Article

Current predictive models do not accurately differentiate between single and multi gland disease in primary hyperparathyroidism: A retrospective cohort study of two endocrine surgery units

Authors:
Ovie Edafe
Ovie Edafe
Emma Collins at Leeds Teaching Hospitals NHS Trust
Emma Collins
C S Ubhi
C S Ubhi
C S Ubhi
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Sabapathy P Balasubramanian at Sheffield Teaching Hospitals NHS Foundation Trust
Sabapathy P Balasubramanian
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Abstract

Background Minimally invasive parathyroidectomy (MIP) for primary hyperparathyroidism is dependent upon accurate prediction of single-gland disease on the basis of preoperative imaging and biochemistry. The aims of this study were to validate currently available predictive models of single-gland disease in two UK cohorts and to determine if these models can facilitate MIP. Methods This is a retrospectively cohort study of 624 patients who underwent parathyroidectomy for primary hyperparathyroidism in two centres between July 2008 and December 2013. Two recognised models: CaPTHUS (preoperative calcium, parathyroid hormone, ultrasound, sestamibi, concordance imaging) and Wisconsin Index (preoperative calcium, parathyroid hormone) were validated for their ability to predict single-gland disease. Results The rates of single- and multi-gland disease were 491 (79.6%) and 126 (20.2%), respectively. Cure rates in centres 1 and 2 were 93.2% and 93.8%, respectively (P = 0.789). The positive predictive value (PPV) of CaPTHUS score . 3 in predicting single-gland disease was 84.6%, compared with 100% in the original report. CaPTHUS . 4 and 5 had a PPV of 85.1 and 87.1, respectively. There were no differences in Wisconsin Index (WIN) between patients with single- and multi-gland (P = 0.573). A WIN greater than 1600 and weight of excised gland greater than 1 g had a positive predictive value of 86.7% for single-gland disease. Conclusions The use of CaPTHUS and WIN indices without intraoperative adjuncts (such as IOPTH) had the potential to result in failure to cure in up to 15% (CaPTHUS) and 13% (WIN) of patients treated by MIP targeting a single enlarged gland.

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... Usually, the rst line test is sestamibi technetium-99m scintigraphy (MIBI) and later well performed USG can be a con rmatory method [5,17]. Moreover, the use of the single-photon emission computed tomography (SPECT) technique and 4D-CT provides the high possibility of anatomic detail and affords the high likelihood of achieving a safe and successful operation [4,16]. MRI are useful in detection particularly ectopic extra parathyroid mediastinal lesions [9,11]. ...
... The multiple parathyroid gland disease is de ned by Harness and others as: "More than one and fewer than 4 enlarged parathyroid glands at operation, operative nding of at least one normal parathyroid gland, evidence of neither MEN or familial hyperparathyroidism and permanent normocalcemia after resection of enlarged parathyroid glands" [3,13]. Parathyroid lesions are more common in females (3 times more often than in men) 50-70 years old [4,11]. Helpful for diagnosis can be blood studies, measurements of PTH and calcium that are usually elevated. ...
... Female sex is a predisposing factor as well as age over 50 years old. Additionally, some studies suggest that previously performed head and neck radiation procedure can be a predisposing factor for development of adenomas [4,6,14]. Most commonly multiple endocrine neoplasia syndrome type 1, less frequently multiple endocrine neoplasia type 2 and sporadically the hyperparathyroidism -jaw tumor syndrome. ...
Multiglandular Parathyroid Disease
Preprint
Full-text available
  • May 2022
BACKGROUND: Multiglandular parathyroid disease (MGD) is an uncommon cause of primary hyperparathyroidism (pHPT) and has been reported in the literature in 8–33 % of patients with pHPT. The aim of our study was to review the clinical characteristics and management of MGD and evaluation of surgical treatment failures. METHODS: We performed a retrospective study of 163 patients with pHPT undergoing parathyroidectomy (PTX) at the Department of General and Endocrine Surgery, between 1983 and 2018. All these patients were diagnosed with MGD. This group of patients was compared with the group of 856 patients with solitary disease operated for pHPT in the same period. RESULTS: Among 163 patients – 129 (79%) of them had two lesions, 26 (16%) had three and 8 (5%) four. They were prevalently women over the age of 50. The diagnosis was based on PTH and ionized calcium studies and used sestamibi technetium-99m scintigraphy (MIBI) scintigraphy as well for us. Treatment was surgical. CONCLUSIONS: Parathyroidectomy (PTX) for multiglandular parathyroid disease (MGD) is associated with a higher operative risk of failure compared to solitary disease. Preoperative diagnosis and localization of the parathyroid glands is an extremely important element of treatment. Mediastinal MGD is associated with increased surgical treatment failures.
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... The main regulator for parathyroid hormone( PTH ) secretion is the calcium level in the blood, where decrease in serum calcium will stimulate PTH release while a rise in the level will inhibit the secretion by negative feedback. Increase in serum PTH can be primary due to parathyroid gland adenoma, hyperplasia or less commonly carcinoma, or it can be secondary to low levels of serum calcium as in cases of renal failure, and the term tertiary hyperparathyroidism describes hyperplasia of the parathyroid glands in long standing secondary hyperparathyroidism. 1,2 Parathyroid adenomas are the most common cause of primary hyperparathyroidism, accounting for about 80-85% of the causes, while adenoma of two glands occurs in 4-5%, and in about 10% of the cases 4 glands hyperplasia is the main pathology. Parathyroid carcinoma occurs in less than 1%. ...
... The age range for developing adenoma is between 50 and 70 year old with females being affected about 3 times than males. 2,3 Hyperparathyroidism will lead to hypercalcaemia, which can be asymptomatic or may cause bone pain, fatigue, renal stones, psychological upset, abdominal cramps and constipation. 1 Once hyperparathyroidism is confirmed by laboratory investigations, the next step should be imaging of the glands to determine the cause. ...
... In most of the cases, the presentation will be that of hypercalciemia. [1][2][3] In our patients, the main presenting symptoms were fatigue and generalized body aches, recurrent nephrolithiasis, depression and mood changes, recurrent fractures and bony lesions, abdominal colicky pain and constipation. After confirming high level of serum calcium, all patients were sent for serum PTH assessment. ...
Rare And Demanding: Parathyroid Adenoma Localization, Surgery And Outcome. Self Experience With 8 Cases
Article
Full-text available
  • Jan 2020
Objectives: We report our experience with parathyroid adenoma localization and surgical removal Patients and methods: Between June 2017 and June 2019, we had operated 8 cases of parathyroid adenoma. Three patients were males and 5 patients were females. Age ranged from 26 year old to 72 year old with average of 42 year old. Results: preoperative localization was achieved in 7 patients (87%) and intraoperative localization in one case (13%). Seven cases (87%) were sporadic while one case was part of MEN2a. Single adenoma was found in 6 patients (75%) and two adenomas in two patients (25%). The adenomas were located in the neck in 7 patients (87%) and in the anterior mediastinum in one patient (13%). Surgical removal of the adenomas was done without difficulties in all the cases through a neck incision in 7 cases and midline sternotomy in one patient. All the patients had resolution of symptoms within the follow up period. Conclusion: parathyroid surgery is one of the challenging procedures, but with adequate localization and technique, the outcome can be excellent for the patient. ‫الخالصة‬ ‫االهذاف:‬ ‫وانُخبئج.‬ ‫انجزادي‬ ‫انخذاخم‬ ‫انًىقغ،‬ ‫حذذيذ‬ ‫ديذ‬ ‫يٍ‬ ‫انذرقيت‬ ‫جبر‬ ‫انغذد‬ ‫ػقذ‬ ‫يغ‬ ‫انخؼبيم‬ ‫في‬ ‫انشخصيت‬ ‫خبزحُب‬ ‫نخىريق‬ ‫واألساليب:‬ ‫المواد‬ ‫يب‬ ‫دشيزاٌ‬ ‫بيٍ‬ ٧١٠٢ ‫ودشيزاٌ‬ ٧١٠٢ ‫قًُب‬ ، ‫بإجزاء‬ ‫يزضى،‬ ‫نزًبٌ‬ ‫انذرقيت‬ ‫جبر‬ ‫انغذد‬ ‫ػقذ‬ ‫رفغ‬ ‫ػًهيبث‬ ‫انذكىر‬ ‫يٍ‬ ‫رالرت‬ ‫يٍ‬ ‫وخًس‬ ‫اإلَبد‬ ‫حزاودج‬ ، ‫بيٍ‬ ‫اػًبرهى‬ ٧٤ ‫و‬ ٢٧ ‫بًؼذل‬ ‫ػبيب‬ ٢٧ ‫ػبيب‬ ‫النتائج:‬ (‫يزضى‬ ‫سبؼت‬ ‫في‬ ‫انجزادي‬ ‫انخذاخم‬ ‫قبم‬ ‫انؼقذ‬ ‫يىقغ‬ ‫حذذيذ‬ ‫حى‬ ٧٢ ‫وادذ‬ ‫يزيض‬ ‫في‬ ‫انؼًهيت‬ ‫داخم‬ ‫انًىقغ‬ ‫حذذيذ‬ ‫حى‬ ‫فيًب‬)% (٠١ (‫فزديت‬ ‫دبالحهى‬ ‫كبَج‬ ‫يزضت‬ ‫سبؼت‬ .)% ٧٢ ‫يخالسيت‬ ‫يٍ‬ ‫جشءا‬ ‫كبَج‬ ‫ديٍ‬ ‫في‬)% MEN2a (‫وادذ‬ ‫يزيض‬ ‫في‬ ٠١ .)% ‫في‬ (‫يزضى‬ ‫سخت‬ ٢٣ ‫يزيضيٍ(‬ ‫في‬ ‫ارُخيٍ‬ ‫ػقذحيٍ‬ ‫وجذَب‬ ‫بيًُب‬ ‫وادذة‬ ‫ػقذة‬ ‫%)وجذَب‬ ٧٣ .)% (‫يزضى‬ ‫سبؼت‬ ‫في‬ ‫انزقبت‬ ‫في‬ ‫يىجىدة‬ ‫انؼقذ‬ ‫كبَج‬ ٧٢ ‫يزيض‬ ‫في‬ ‫انقص‬ ‫ػظى‬ ‫خهف‬ ‫انصذر‬ ‫في‬ ‫يىجىدة‬ ‫كبَج‬ ‫ديٍ‬ ‫في‬)% ‫وادذ(‬ ٠١ ‫سبؼت‬ ‫في‬ ‫انزقبت‬ ‫في‬ ‫جزوح‬ ‫طزيق‬ ‫ػٍ‬ ‫صؼىببث‬ ‫بذوٌ‬ ‫انًزضى‬ ‫جًيغ‬ ‫في‬ ‫انؼقذ‬ ‫اسخئصبل‬ ‫حى‬ .)% ‫في‬ ‫صذر‬ ‫وفخخ‬ ‫يزضى‬ ‫انًخببؼت.‬ ‫فخزة‬ ‫خالل‬ ‫انؼًهيت‬ ‫بؼذ‬ ‫انًزضى‬ ‫جًيغ‬ ‫حذسٍ‬ ‫وادذ.‬ ‫يزيض‬ ‫االستنتاجات:‬ ‫انًىقغ‬ ‫نخذذيذ‬ ‫انسهيًت‬ ‫انطزق‬ ‫ببحببع‬ ‫ونكٍ‬ ، ‫نهجزاح‬ ‫دقيقيب‬ ‫حذذيب‬ ‫حًزم‬ ‫انذرقيت‬ ‫جبر‬ ‫انغذد‬ ‫في‬ ‫انجزاديت‬ ‫انخذاخالث‬ ‫انُخبئ‬ ‫حكىٌ‬ ‫انالسيت‬ ‫انجزاديت‬ ‫انًهبرة‬ ‫وحىفز‬ ‫انؼًهيت‬ ‫قبم‬ ‫نهًزيض‬ ‫يًخبسة‬ ‫ج‬. ‫الرئيسة:‬ ‫الكلمات‬ ‫سيسخبييبي‬ ‫فذص‬ ‫انذرقيت،‬ ‫جبر‬ ‫انغذة‬ ‫هزيىٌ‬ ‫انذرقيت،‬ ‫جبر‬ ‫ػقذانغذد‬ ‫انهزيزيىَيت،‬ ‫االوراو‬ ‫يخالسيت‬ .
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... The contribution of ioPTH increases as the incidence of multiple gland disease increases (6). Although the rate of single gland disease has been reported as 99% in cases where MIBI scan and USG are concordant and a single gland is localized, in some studies it has been reported that multiglandular disease rate may increase to 10%-14% in these patients (18)(19)(20). This situtation suggests that intraoperative PTH measurement may contribute to MIP. ...
... Therefore, it is recommended by some authors that ioPTH should be applied during MIP routinely, not only in selected cases (9,20,26). Also Medas et al. reported in their current meta-analysis that ioPTH reduces surgical failure even in patients in whom the pathological gland can be clearly Frontiers in Surgery localized and concordant with both preoperative imaging method; recommended that routine use of ioPTH should be included in primary hyperparathyroidism surgery in the new guidelines (6). The major (most important) cause of persistent disease is multi-gland disease, and in our study, the rate of multi-gland disease was 6.7% in the series and 85.7% among persistent patients (group 2). ...
Contribution of intraoperative parathyroid hormone monitoring to the surgical success in minimal invasive parathyroidectomy
Article
Full-text available
  • Sep 2022
Background: The contribution of intraoperative parathyroid hormone monitoring to minimally invasive parathyroidectomy remains controversial. We aimed to evaluate whether intraoperative parathyroid hormone monitoring monitoring could contribute to minimally invasive parathyroidectomy in these patients. Methods: The data of the patients whose preoperative ultrasonography and technetium-99 m sestamibi scintigraphy imagings were positive and concordant for one gland and who underwent minimally invasive parathyroidectomy between 2003 and 2018 in our clinic, were evaluated retrospectively. Blood samples were collected at pre-excisional period, and at post-excisional 10 and 20 min; the intaoperative parathyroid hormone was measured, and the surgery was terminated without waiting for the result. Patients were divided into 2 groups according to the postoperative results, as those with normocalcemia (Group 1) and those with persistence (Group 2). Results: There were 195 patients in Group 1 and 14 patients in Group 2. The cure rate at the first surgery was 93.3%. Cure was achieved after the second operation in all patients in Group 2. Recurrent disease developed in 1 patient in group 1 and the overall cure rate was 99.5%. If intraoperative parathyroid hormone had been evaluated, cure could have been achieved at the first surgery with additional exploration, in 10 (71.4%) of 14 patients according to the insufficient decrease in parathyroid hormone value at the 10 min in Group 2, and in 9 (64.3%) of 14 patients according to the parathyroid hormone value at 20 min. However, due to insufficient decrease (false negative) in the parathyroid hormone value at the 10 and 20 min the rate of false negatives and unnecessary exploration would be 9.5% and 2.5%, respectively. With additional exploration, the cure rate in the first surgery could be increased by 4.3%-97.6% according to the 20 min intraoperative parathyroid hormone value. Conclusion: The cure rate in minimally invasive parathyroidectomy can be increased by minimizing unnecessary conversion to bilateral neck exploration, by evaluating intraoperative parathyroid hormone at 10 min in patients with positive and concordant scans, and intraoperative parathyroid hormone at 20 min in patients with inadequate decrease at 10 min intraoperative parathyroid hormone.
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... Usually, the first line test is sestamibi technetium-99m scintigraphy (MIBI), and later, well-performed USG can be a confirmatory method [13,14]. Moreover, the use of the single-photon emission computed tomography (SPECT) technique and 4D-CT provides the high possibility of anatomic detail and affords the high likelihood of achieving a safe and successful operation [15,16]. MRI are useful in the detection of particularly ectopic extra parathyroid Life 2022, 12, 1286 2 of 8 mediastinal lesions [5,17]. ...
... The therapy is based on a surgical approach. In MGD, complete removal of all enlarged parathyroid glands is necessary [15,19]. Appropriate surgical therapy of MGD should consist of a bilateral approach in most patients. ...
Multiglandular Parathyroid Disease
Article
Full-text available
  • Aug 2022
Introduction: Multiglandular parathyroid disease (MGD) is an uncommon cause of primary hyperparathyroidism (pHPT) and has been reported in the literature in 8-33% of patients with pHPT. The aim of our study was to review the clinical characteristics and management of MGD and evaluation of surgical treatment failures. Methods: We performed a retrospective study of 163 patients with pHPT undergoing parathyroidectomy (PTX) at the Department of General and Endocrine Surgery between 1983 and 2018. All these patients were diagnosed with MGD. This group of patients was compared with a group of 856 patients with solitary disease operated for pHPT in the same period. Results: Among 163 patients-127 (79%) of them had two lesions, 28 (16%) had three, and 8 (5%) four. They were prevalently women over the age of 50. The diagnosis was based on PTH and ionized calcium studies and used sestamibi technetium-99m scintigraphy (MIBI) as well for us. Treatment was surgical. Conclusions: Parathyroidectomy (PTX) for multiglandular parathyroid disease (MGD) is associated with a higher operative risk of failure compared to solitary disease. Preoperative diagnosis and localization of the parathyroid glands is an extremely important element of treatment. Diagnosis is based on PTH and calcium levels. Ultrasonography (USG), MRI, and scintigraphy are very helpful in diagnosis. Mediastinal multiglandular parathyroid disease (MGD) is associated with increased surgical treatment failures. The treatment is surgical and consists of the removal of the masses or complete parathyroidectomy. Based on this study, we support the existence of multiple adenomas and advocate the removal of only macroscopically enlarged parathyroid glands in patients with primary hyperparathyroidism.
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... Double adenomas found in 4% -5% patients [3][4][5]. Its Incidence to be 2.5/1000 population. ...
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... PHPT: primary hyperparathyroidism, MIBI: methoxy-isobutyl-isonitrile scintigraphy, PA: parathyroid adenoma, DFI: detective flow imaging 85% and 15% of cases, respectively. Parathyroid carcinoma is an additional, infrequent cause of PHPT 3,4 . When patients are diagnosed with PHPT, an important next step is to detect and localize PT. ...
Ultrasonographic Detective Flow Imaging for Evaluating Parathyroid Adenoma in Patients with Primary Hyperparathyroidism
Article
  • Apr 2024
Background: Detective flow imaging (DFI) is a new imaging technology that displays low-velocity blood flow, which is difficult to visualize on conventional color Doppler ultrasonography (CDU). In this study, we compared the usefulness of DFI with that of CDU and methoxy-isobutyl-isonitrile (MIBI) scintigraphy for detecting parathyroid adenoma (PA) in patients with primary hyperparathyroidism (PHPT). Methods: From March 2021 to March 2023, 87 PHPT patients underwent surgery, and 66 had a single PA. We performed preoperative conventional ultrasonography with CDU, MIBI scintigraphy, and DFI for 42 patients (5 males and 37 females; mean age: 61.6 ± 15.4 years). Results: MIBI scintigraphy detected PA in 85.7% (36/42) patients, and both CDU and DFI detected PA in all patients. The rates of vascularity in PA detected by CDU and DFI were 71.4% (30/42) and 85.7% (36/42), respectively. Vascularity was detected by DFI in 6 patients who were negative for vascularity on MIBI scintigraphy. Furthermore, DFI detected blood supply in 6 of the 12 patients with undetectable blood supply on CDU. Fisher's exact test revealed that high or low blood flow, as determined by DFI, was significantly associated with detection of feeding vessels in PA by CDU (P < 0.001). Conclusions: DFI was useful for preoperative detection of PA blood flow.
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... Primary hyperparathyroidism (pHPT) is a common endocrine disorder, with an estimated prevalence of seven cases per 1000 adults (1) worldwide, being threefold higher in females than in males (2). The classical presentation of symptomatic hypercalcemia as an initial sign has become increasingly rare, as primary hyperparathyroidism is typically diagnosed during routine screening that reveals increased serum levels of calcium and parathyroid hormone (PTH), or by clinical manifestation of pathological bone density, which prompts the measurement of PTH. ...
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... This hyperplasia results from heightened parathyroid cell proliferation, insufficiently compensated by a concurrent increase in parathyroid cell apoptosis [3]. Additionally, primary hyperparathyroidism can be induced by causes such as parathyroid hyperplasia, multiple parathyroid adenomas, and parathyroid carcinoma [4]. Even in the absence of symptoms, the hyperfunction of the parathyroid glands should be treated with complete excision to prevent life-threatening arrhythmias and associated severe complications [5]. ...
An Ectopic Parathyroid Adenoma of the Retropharynx in a Patient with Primary Hyperparathyroidism and Papillary Thyroid Cancer—A Rare Case
Article
Full-text available
  • Jan 2024
The frequency of concurrent thyroid cancer in patients with primary hyperparathyroidism (pHPT) varies. While the pathological association between thyroid and parathyroid disorders is frequently noted, the co-occurrence of parathyroid adenoma and papillary thyroid cancer is exceptionally rare. Furthermore, an ectopic parathyroid adenoma in the retropharyngeal space is exceedingly rare. Therefore, anatomical variations through the utilization of relevant diagnostic tools play a crucial role in guiding decisions pertaining to clinical manifestations, diagnostic methods, surgical interventions, and operative strategies for parathyroid tumors. We present a case of a 51-year-old female patient with papillary thyroid carcinoma in the right thyroid lobe and an ectopic parathyroid adenoma in the retropharyngeal space confirmed through surgical intervention. The elevated preoperative levels of serum calcium and parathyroid hormone, along with low serum phosphate, returned to normal ranges after surgery. This case sheds light on the unusual occurrence of an ectopic parathyroid adenoma in the retropharyngeal region within a thyroid cancer patient, providing valuable insights into the realm of thyroid malignancies.
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... Parathyroid adenomas exhibiting tissue invasion and lacking concurrent hyperparathyroidism are uncommon [2]. Additionally, primary hyperparathyroidism can be induced by causes such as parathyroid hyperplasia, multiple parathyroid adenomas, and parathyroid carcinoma [3]. Even in the absence of symptoms, the hyperfunction of the parathyroid glands should be treated with complete excision to prevent life-threatening arrhythmias and associated severe complications [4]. ...
An Ectopic Parathyroid Adenoma of the Retropharynx in a Patient with Primary Hyperparathyroidism and Papillary Thyroid Cancer – A Rare Case
Preprint
Full-text available
  • Dec 2023
The frequency of concurrent thyroid cancer in patients with primary hyperparathyroidism (pHPT) varies. While the pathological association between thyroid and parathyroid disorders is frequently noted, the co-occurrence of parathyroid adenoma and papillary thyroid cancer is exceptionally rare. Furthermore, the occurrence of an ectopic parathyroid adenoma in the retropharyngeal space is exceedingly rare. Ectopic parathyroid glands present considerable complexities in both diagnosis and surgical management, especially within the realm of surgical intervention. The potential inability to accurately identify and excise ectopic parathyroid adenomas during the initial surgery may lead to an increased morbidity and recurrence, requiring high-risk reoperations. Therfore, the evaluation of anatomical variations through the utilization of relevant diagnostic tools plays a crucial role in guiding decisions pertaining to clinical manifestations, diagnostic methods, surgical interventions, and operative strategies for parathyroid tumors. We present the case of a 51-year-old female patient with papillary thyroid carcinoma in the right thyroid lobe and an ectopic parathyroid adenoma in the retropharyngeal space confirmed through surgical intervention. This case sheds light on the unusual occurrence of an ectopic parathyroid adenoma in the retropharyngeal region within a thyroid cancer patient, providing valuable insights within the realm of thyroid malignancies.
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... Аденома паращитовидных желез чаще встречается в возрасте 50-70 лет, тем не менее они могут наблюдаться в любом периоде жизни. Согласно полученным данным практически 1/3 (35%) пациентов находились в возрастном интервале 56-65 лет, причем женщины в 13 раз чаще, чем мужчины, страдают этой патологией [21]. ...
Parathyroid adenoma: multimodal diagnosis capabilities: A retrospective study
Article
Full-text available
  • Nov 2023
Background. Primary hyperparathyroidism is a common endocrinological disease caused mainly by parathyroid adenoma. The main treatment method is surgery (parathyroidectomy). Therefore, the exact determination of adenoma localization is crucial. Aim. To evaluate the current possibilities of multimodal diagnosis of parathyroid adenomas. Materials and methods. A retrospective analysis of 49 patients with primary hyperparathyroidism aged 24 to 82 (median 57.9 years) was performed. Modern radionuclide and hybrid technologies were used for topical diagnosis and metabolic assessment of parathyroid adenomas: scanning, single-photon emission computed tomography, single-photon emission computed tomography combined with computed tomography, positron emission tomography combined with computed tomography with 18F-deoxyglucose and 18F-choline. The diagnosis of primary hyperparathyroidism was confirmed by a biochemical blood test: the level of parathyroid hormone and ionized and total calcium. Results. The study included 43 (87.8%) females and 6 (12.2%) males. The female/male ratio was 7.2:1. Most cases (78.1%) were the hypercalcemic type of primary hyperparathyroidism, and the normocalcemic type was diagnosed in 21.9% of patients. The mean parathyroid hormone level was 145.43 pg/mL, exceeding the reference values by 2.2 times. Parathyroid hormone concentration in patients with primary hyperparathyroidism was 156.38 pg/mL, and mean ionized and total blood calcium levels were 1.43 and 3.04 mmol/L, respectively. The asymptomatic type occurred in 76.7% of patients. The symptomatic type of hyperparathyroidism had 23.3%, manifested with nephrolithiasis, pancreatitis, and bone lesions. Parathyroid adenomas were more often located in the left lobe (42.9%). In 77.6% of patients with primary hyperparathyroidism, solitary adenomas were detected. Ectopia of the parathyroid glands was detected in 16.3% of patients, with intrathyroidal location in the left lobe being the most common. Rare locations include the anterior and posterior mediastinum and the esophageal wall. Conclusion. Modern diagnostic multimodal options based on radionuclide and hybrid technologies are crucial in the personalized treatment of primary hyperparathyroidism.
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... Parathyroid adenomas are almost 3 times more common in women and may occur at any age [1]. This is usually an incidental finding, when patients are evaluated for the classical 'moans, bones and groans' symptoms, like in this case. ...
Reflections of the Anesthetic Management in a Case of Parathyroid Adenoma: A Case Report
Article
Full-text available
  • Oct 2023
Parathyroid adenomas are usually an incidental finding and present more commonly in women. The parathyroid gland releases parathyroid hormone(PTH), which is essential to maintain calcium homeostasis. Hence, the removal of parathyroid glands will result in hypocalcemia and if not treated could be life threatening. We present the case of a young female patient who presented with vague complaints and was evaluated and diagnosed with primary hyperparathyroidism. She was optimized and taken for surgical removal of parathyroid glands. The anesthetic considerations in the perioperative period and an intraoperative event during positioning are mentioned herewith.
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... It can predict MGPD in those with positive imaging but is unreliable in patients with mild disease and low adenoma weight which are more common presentations of MGPD [15,31]. Whilst useful, [32], both the Wisconsin index and CaPTHUS score have been found to have variable sensitivity, specificity, positive and negative predictive values [33][34][35][36] and thus have not found universal acceptance and do not feature in national guidelines on the surgical management of hyperparathyroidism [37][38][39]. ...
A contemporary analysis of the pre- and intraoperative recognition of multigland parathyroid disease
Article
Full-text available
  • Oct 2023
  • LANGENBECK ARCH SURG
Background Despite advances in biochemical and radiological identification of parathyroid gland enlargement, primary hyperparathyroidism (PHPT) due to sporadic multigland parathyroid disease (MGPD) remains a perioperative diagnostic dilemma. Failure to recognise MGPD pre- or intraoperatively may negatively impact surgical cure rates and result in persistent PHPT and ongoing patient morbidity. Methods We have conducted a comprehensive review of published literature in attempt to determine factors that could aid in reliably diagnosing sporadic MGPD pre- or intraoperatively. We discuss preoperative clinical features and examine pre- and intraoperative biochemical and imaging findings concentrating on those areas that give practicing surgeons and the wider multi-disciplinary endocrine team indications that a patient has MGDP. This could alter surgical strategy. Conclusion Biochemistry can provide diagnosis of PHPT but cannot reliably discriminate parathyroid pathology. Histopathology can aid diagnosis between MGPD and adenoma, but histological appearance can overlap. Multiple negative imaging modalities indicate that MGPD may be more likely than a single parathyroid adenoma, but the gold standard for diagnosis is still intraoperative identification during BNE. MGPD remains a difficult disease to both diagnose and treat.
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... It is usually diagnosed when patients present with hypercalcemia; specifically, a single parathyroid adenoma is responsible for 80-85% of hyperparathyroidism, double adenomas are observed in 4-5% of cases and parathyroid hyperplasia in 10-12% of patients. Additionally, parathyroid carcinomas are very rare causes of hyperparathyroidism and account for less than 1% of the disease cause [45,46]. ...
Adrenal Incidentalomas and Other Endocrine-Related Adenomas: How Much Does Cortisol Secretion Matter?
Article
Full-text available
  • Sep 2023
Simple Summary This article reflects a comprehensive analysis between cortisol secretion and the presence of other endocrine-related adenomas (specifically thyroid, parathyroid and pituitary). Cortisol has anti-inflammatory properties but has also been related to impaired cell proliferation and function. Specifically, its role in the presence of other benign lesions has not been described. For these reasons, we analyzed the prevalence of these other endocrine-related benign lesions in patients with nonfunctioning adrenal incidentalomas and with mild autonomous cortisol secretion. We observed that mild autonomous hypercortisolism does not affect the prevalence of other endocrine-related adenomas but is associated with increased metabolic comorbidities and mortality in these patients. Abstract Background: Adrenal incidentalomas (AI) are frequent findings in clinical practice. About 40% of AIs are associated with hypercortisolism of variable severity. Although mild autonomous cortisol secretion (MACS) has been associated with the impaired clinical outcome of several diseases, its effect on the development of benign neoplasms is unknown. Aim: To compare the prevalence of adenomas (thyroid, parathyroid, pituitary and other locations) in patients with nonfunctioning AIs (NFAIs) and MACS. Methods: A multicenter, retrospective study of patients with AIs evaluated in four tertiary hospitals was performed. Results: A total of 923 patients were included. Most patients were male (53.6%), with a mean age at diagnosis of 62.4 ± 11.13 years; 21.7% presented with bilateral AIs. MACS was observed in 29.9% (n = 276) of patients, while 69.9% (n = 647) were NFAIs. Adenomas in locations other than the adrenal gland were observed in 36% of the studied population, with a similar distribution in patients with MACS and NFAIs (33% vs. 32%; p > 0.05). There were no statistically significant differences in the prevalence of pituitary, thyroid, parathyroid or other endocrine-related adenomas between both groups, but the prevalence of metabolic comorbidities and mortality was increased in patients with MACS, specifically in patients with thyroid and other endocrine-related adenomas (p < 0.05). Conclusions: Adenomas in locations other than the adrenal glands occur in one third of patients with AIs. Mild autonomous hypercortisolism does not affect the prevalence of other endocrine-related adenomas but is associated with increased metabolic comorbidities and mortality, especially in patients with thyroid adenomas and adenomas in other locations.
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... The Wisconsin Index (WIN) predicts the probability of additional hyperfunctioning glands during surgery and uses preoperative parathyroid hormone (PTH) levels and lesion weight during surgery (13). Their clinical values have been validated (14,15). However, neither of them can be used to improve the efficacy of MGD diagnosis preoperatively. ...
Predicting multigland disease in primary hyperparathyroidism using ultrasound and clinical features
Article
Full-text available
  • Mar 2023
Background The identification of multigland disease (MGD) in primary hyperparathyroidism (PHPT) patients is essential for minimally invasive surgical decision-making. Objective To develop a nomogram based on ultrasound (US) findings and clinical factors to predict MGD in PHPT patients. Materials and methods Patients with PHPT who had surgery between March 2021 and January 2022 were consecutively enrolled to this study. Biochemical and clinicopathological data were recorded. US images were analyzed to extract US features for prediction. Logistic regression analyses were used to identify MGD risk factors. A nomogram was constructed based on these factors and its performance evaluated by area under the receiver operating characteristic curve (AUC), calibration curve, Hosmer-Lemeshow tests, and decision curve analysis (DCA). Results A total of 102 PHPT patients were included; 82 (80.4%) had single-gland disease (SGD) and 20 (19.6%) had MGD. Using multivariate analyses, MGD was positively correlated with age (odds ratio (OR) = 1.033, 95% confidence interval (CI): 0.190–4.047), PTH levels (OR = 1.001, 95% CI: 1.000–1.002), multiple endocrine neoplasia type 1 (MEN1) (OR = 29.730, 95% CI: 3.089–836.785), US size (OR = 1.198, 95% CI: 0.647–2.088), and US texture (cystic-solid) (OR = 5.357, 95% CI: 0.499–62.912). MGD was negatively correlated with gender (OR = 0.985, 95% CI: 0.190–4.047), calcium levels (OR = 0.453, 95% CI: 0.070–2.448), and symptoms (yes) (OR = 0.935, 95% CI: 0.257–13.365). The nomogram showed good discrimination with an AUC = 0.77 (0.68–0.85) and good agreement in predicting MGD in PHPT patients. Also, 65 points was recommended as a cut-off value, with specificity = 0.94 and sensitivity = 0.50. Conclusion US was useful in evaluating MGD. Combining US and clinical features in a nomogram showed good diagnostic performance for predicting MGD.
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... demonstrated that WIN did not accurately differentiate between single and multigland disease in a large cohort of 624 patients (20). In contrast to WIN, our Ca*PTH cutoffs were derived through ML without supervision, and our prediction tree incorporates imaging criteria of 4D-CT and MIBI and may be further adapted using ML to potentially predict multigland disease. ...
Machine Learning-derived Clinical Decision Algorithm for the Diagnosis of Hyperfunctioning Parathyroid Glands in Patients with Primary Hyperparathyroidism
Preprint
Full-text available
  • Jan 2023
Purpose In patients with primary hyperparathyroidism (PHPT), planning for parathyroid surgery currently relies on the synthesis of clinical, laboratory, and imaging data by the clinician. Machine learning may assist in analyzing and integrating data to facilitate surgical decision making. To train and validate a Machine Learning-derived Clinical Decision Algorithm (MLCDA) for the diagnosis of abnormal hyperfunctioning parathyroid glands using preoperative variables. Methods Four hundred and fifty-eight consecutive patients were evaluated from a single-institution retrospective dataset of PHPT patients who underwent combined 4D-CT and sestamibi SPECT/CT (MIBI) with subsequent parathyroidectomy from February 2013 to September 2016. Study cohort was divided into training (first 400 patients) and validation sets (remaining 58 patients). Sixteen preoperative clinical, laboratory, and imaging variables were evaluated. A random forest algorithm was programmed to select the best predictor variables and output a single clinical decision algorithm with the highest performance (MLCDA). The MLCDA was trained to predict the probability of a hyperfunctioning vs. normal gland for each of four parathyroid glands in a patient. Reference standard was 4-quadrant location on operative reports and pathological confirmation of adenoma or hyperplasia. Accuracy of MLCDA was prospectively validated. Results Of 16 variables, the algorithm selected 3 variables for optimal prediction: combined 4D-CT and MIBI using 1) sensitive reading and 2) specific reading, and 3) crossproduct of serum calcium and parathyroid hormone levels, and outputted a MLCDA using five probability categories for hyperfunctioning glands. The MLCDA demonstrated excellent accuracy for correct classification in the training set (4D-CT + MIBI: 0.91 [95%CI 0.89–0.92]), and in the validation set (4D-CT + MIBI: 0.90 [95%CI 0.86–0.94], 4D-CT: 0.88 [95%CI 0.84–0.92], and MIBI: 0.88 [95%CI 0.84–0.92]). Conclusion Machine learning generated a clinical decision algorithm that accurately diagnosed hyperfunctioning parathyroid gland through classification into probability categories, which can be implemented for improved preoperative planning and convey diagnostic certainty.
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... Primary hyperparathyroidism (PHPT) is a pathological idiopathic condition caused by persistent PTH hypersecretion, independent of serum calcium levels. PHPT is caused by PTs in approximately 85% of cases and by multiple hyperplastic parathyroids in approximately 15% of cases, with a low percentage owing to parathyroid carcinoma (PC) [4,5]. ...
Usefulness of ultrasonographic detective flow imaging to diagnose parathyroid tumors: two case reports
Article
  • Oct 2022
Parathyroid tumors (PTs) are sometimes difficult to diagnose because they are small and have a low-velocity blood flow, which can be missed by current imaging modalities. PTs consist of parathyroid adenoma (PA), parathyroid cyst, and parathyroid carcinoma (PC). Detective flow imaging (DFI) is a new imaging technology that displays a low-velocity blood flow. Herein, we report two cases in which DFI was useful for the diagnosis of PTs. One case consisted of a PA and a parathyroid cyst in close proximity, and the other was a PC. To the best of our knowledge, this is the first report to demonstrate the usefulness of DFI in the diagnosis of PTs.
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... Among the above cases, eight were female and four were male patients. Hyperplasia and adenomas showed characteristic female 6 preponderance. Typical hyperparathyroidism symptoms were found in eight cases, comprising of generalized malaise, weakness, muscle pains, renal stones and psychological disturbances. ...
STUDY OF PARATHYROID DISEASE SPECTRUM AND ANALYSIS
Article
  • Sep 2022
Proliferative Parathyroid (PT) lesions are rare and frequently missed due to vague presentation. Many cases present with generalized weakness, musculoskeletal symptoms, renal stones, pancreatitis and neuropsychiatric symptoms due to associated hyperparathyroidism. Aim of this study is to evaluate the spectrum of PT lesions.
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... Decisions regarding medical or surgical treatment were guided by MDT discussions in these two studies, as in this cohort, but we note that some patients in these studies underwent surgery despite having only mild hypercalcaemia (< 2.85 mmol/L) [16]. Based on observational data, it appears that the success rate of parathyroid surgery and other surgery-related outcomes are lower in the pregnancy cohort than in the general population [20,21]. There may be several reasons for this including the limitations of preoperative imaging in pregnant patients and the higher likelihood of multi-gland disease in this population. ...
Primary hyperparathyroidism in pregnancy: experience of a tertiary centre
Article
Full-text available
  • Sep 2022
Background and purpose The management of primary hyperparathyroidism (PHPT) during pregnancy is challenging and there is no clear consensus on whether it increases the risk of complications in pregnancy. We conducted this study to review the maternal and fetal outcomes of pregnant women treated for PHPT in a single centre. Methods Data on relevant clinical parameters, demographics, management strategies, maternal and fetal outcomes were collected from the medical records of pregnant patients with PHPT diagnosed between 2012 and 2019. Results Of 15 pregnant women with PHPT, 6 were managed medically and 9 underwent surgery. The median age at their index pregnancy was 28 years [range 19–42]. The median highest adjusted calcium level in the medical group was 2.90 [range 2.61–3.25] mmol/L vs. 3.11 [2.78–4.95] mmol/L in the surgical group. There was one miscarriage and the stillbirth of twins in the medical group, but no such outcomes in the surgical group. The median gestational ages were 39 + 3 weeks [range 24 + 2–41 + 2 weeks] and 39 + 4 weeks [range 37 + 1–39 + 5 weeks] in the medical and surgical groups, respectively. No birth was complicated by neonatal tetany or convulsions. Conclusion More complications developed in the pregnant PHPT patients who were managed medically than in those who underwent surgery. Surgery performed during the second trimester resulted in good outcomes. Multi-centre prospective studies are required to ascertain the risk of various complications in women with PHPT during pregnancy.
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... However, it can neither detect parathyroid glands nor differentiate abnormal parathyroid glands from normal glands. Another challenge is parathyroid hyperplasia, where the gland mass is smaller than that of parathyroid adenoma [6]. ...
Artificial intelligence-augmented, label-free molecular imaging method for tissue identification, cancer diagnosis, and cancer margin detection
Article
Full-text available
  • Aug 2021
Label-free high-resolution molecular and cellular imaging strategies for intraoperative use are much needed, but not yet available. To fill this void, we developed an artificial intelligence-augmented molecular vibrational imaging method that integrates label-free and subcellular-resolution coherent anti-stokes Raman scattering (CARS) imaging with real-time quantitative image analysis via deep learning (artificial intelligence-augmented CARS or iCARS). The aim of this study was to evaluate the capability of the iCARS system to identify and differentiate the parathyroid gland and recurrent laryngeal nerve (RLN) from surrounding tissues and detect cancer margins. This goal was successfully met.
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... So, based on this article we could not estimate the possibility of a second adenoma clearly, because the chance of finding another adenoma correlates positively with the WIN but negatively with the weight based on the nomogram. In addition, a recent study demonstrates that there is a significant failure to cure PHPT in up to 13%, when only WIN is used to predict multi gland disease without ioPTH assay [28]. We are wondering whether it is worth reassessing the validity of the WIN index nomogram in future cohort studies in order to create a new more sophisticated system which will give us the possibility of a second pathologic parathyroid gland, after having calculated the WIN preoperatively, based on the weight of the first adenoma found intraoperatively. ...
Double ipsilateral parathyroid adenomas, with one supernumerary and ectopic at the same time: a case report
Article
Full-text available
  • Apr 2021
  • J Med Case Rep
Background Double adenomas (DA) represents a distinct clinical entity of primary hyperparathyroidism (PHPT). DA may follow various embryologic distribution patterns and could be supernumerary and/or ectopic. Case presentation We describe the first case of PHPT which comes as a result of double ipsilateral adenoma, of which one was both ectopic and supernumerary. A 45 year-old Greek male patient with diagnosed PHPT due to a single lower right parathyroid adenoma was admitted to our department for surgical treatment. The preoperative tests (neck US, Sestamibi scan) were conclusive for single gland disease. The patient underwent focused parathyroidectomy. The frozen section revealed a parathyroid adenoma with a slight possibility for parathyroid carcinoma. Ten minutes after the excision, intact PTH (iPTH) dropped >50% related to preoperative values and was within normal range. Right hemithyroidectomy with additional ipsilateral central neck dissection was performed, because of the possibility for parathyroid carcinoma. The final pathology report showed that the first excised tissue proved to be a parathyroid adenoma, while a second subcapsular one and a normal right upper parathyroid gland were also found. Conclusions Preoperative localization of DA using routine imaging tests and the utility of intraoperative parathyroid hormone assay are still unreliable in detecting multiple adenomas. Furthermore, a slight possibility of a second and simultaneously supernumerary and ectopic adenoma maybe present. Therefore, it would be advisable to establish the use of more advanced imaging tests (such as 4D-CT, 4D-MRI) or other diagnostic tools when DA are suspected.
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... In 2017, Edafe et al. (23) simultaneously applied CaPTHUS and WIN to discriminate between SGD and MGD in their two-center cohort comprising 624 patients. The PPV for predicting SGD of the CaPTHUS ≥3 model was 84.6%. ...
Usefulness of the Wisconsin and CaPTHUS indices for predicting multiglandular disease in patients with primary hyperparathyroidism in a southern European population
Article
Full-text available
  • Mar 2021
Background: Focused parathyroidectomy is a safe technique for the treatment of primary hyperparathyroidism. The CaPTHUS score and the Wisconsin index are preoperative diagnostic tools designed to distinguish between single- and multigland disease. The aim of the study is to evaluate the usefulness of these models for predicting multiglandular disease in a European population. Methods: Retrospective review of a database of patients operated upon for primary hyperparathyroidism at a referral center. The sensitivity, specificity, positive and negative predictive values, and reliability of both scores for the prediction of multiglandular disease, were calculated. Receiver operating characteristic (ROC) curves were constructed to assess the sensitivity and specificity of CaPTHUS score and Wisconsin Index for predicting single-gland disease. A level of P<0.05 was accepted as significant. Results: Two hundred and eighty-one patients who underwent successful surgery from January 2001 to December 2018 were included. Single-gland disease was detected in 92.5%, and 73.7% had a CaPTHUS score of ≥3. The sensitivity, specificity, positive and negative predictive values of this model for predicting single-gland disease with a score of ≥3 were 76.9%, 66.7%, 96.6%, and 18.9% respectively. The area under the curve value of the CaPTHUS score for predicting single-gland disease was 0.74. A Wisconsin Index >2,000 and an excised gland weight above one gram presented a positive predictive value for single-gland disease of 92.5%. Conclusions: Despite the good performance of both scales, the established cut-off points did not definitively rule out parathyroid multiglandular disease in our population. In cases with a minimal suspicion of this condition, additional intraoperative techniques must be used, or bilateral neck explorations should be performed.
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... Adenomas are most common in any individuals of 50 to 70 years old; however, they can occur at any age. Women are more affected by 3-times as often as men [3,4]. Almost everyone who inherited MEN syndromes developed overactivity of the parathyroid glands (hyperparathyroidism) that develop noncancerous (benign) tumours. ...
Identification of key regulators in parathyroid adenoma using an integrative gene network analysis
Article
Full-text available
  • Nov 2020
  • Bioinformation
Parathyroid adenoma (PA) is marked by a certain benign outgrowth in the surface of parathyroid glands. The transcriptome analysis of parathyroid adenomas can provide a deep insight into actively expressed genes and transcripts. Hence, we analyzed and compared the gene expression profiles of parathyroid adenomas and healthy parathyroid gland tissues from database name. We identified a total of 280 differentially expressed genes (196 up-regulated, 84 down-regulated), which are involved in a wide array of biological processes. We further constructed a gene interaction network and analyzed its topological properties to know the network structure and its hidden mechanism. This will help to understand the molecular mechanisms underlying parathyroid adenoma development. We thus identified 13 key regulators (PRPF19, SMC3, POSTN, SNIP1, EBF1, MEIS2, PAX9, SCUBE2, WNT4, ARHGAP10, DOCK5, CAV1 and VSIR), which are deep-rooted from top to bottom in the gene interaction network forming a backbone for the network. The structural features of the network are probably maintained by crosstalk between important genes within the network along with associated functional modules. Thus, gene-expression profiling and network approach could be used to provide an independent platform to glen insights from available clinical data.
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... However a multiglandular disease is encountered in 15-23.5% of cases. 2,3 Surgery to remove the abnormal parathyroid gland is the only curative treatment. Bilateral neck exploration of the four parathyroid glands has been the gold standard in the surgical management of PHPT for a long time. ...
Utility of a Second 99mTc-MIBI Scintigraphy Before Reoperation for Patients With Persistent Sporadic Primary Hyperparathyroidism: Results of a Retrospective Multicenter Study
Article
Full-text available
  • Apr 2020
Background Persistent primary hyperparathyroidism (PHPT) occurs in 2.5% to 15% of cases after parathyroidectomy. Few studies have evaluated the best pre-reoperative imaging approaches for persistent sporadic PHPT. This retrospective multicenter study aimed to evaluate the benefit of a second pre-reoperative 99mTc-methoxy-isobutyl-isonitrile (MIBI) scintigraphy for patients with persistent PHPT who had a 99mTc-MIBI before their initial surgery.Methods The study enrolled 50 patients with persistent sporadic PHPT who had reoperation between 2006 and 2016 in three French University Hospitals (Angers, Nantes, and La Pitié Salpêtrière-Paris). Preoperative 99mTc-MIBI scan was performed before each operation.ResultsAfter the reoperation, 42 patients (84%) were cured. By the second 99mTc-MIBI, 31 patients (62%) had a removed gland identified. A new pathologic gland was identified by a second 99mTc-MIBI in 25 patients (50%), and this imaging permitted correction of an initial surgical error in six patients (12%). A second 99mTc-MIBI showed a sensitivity of 63%, a specificity of 89%, a positive predictive value (PPV) of 78%, and a negative predictive value (NPV) of 80%. A concordant second 99mTc-MIBI and ultrasonography (17 patients) showed a sensitivity of 70%, a specificity of 81%, a PPV of 70%, and an NPV of 81%.Conclusions Performing a second 99mTc-MIBI scan permitted 62% of the persistent PHPT patients to be cured, allowing identification of new pathologic glands in 50% of the cases and correction of an initial surgical error in 12% of the cases, with high specificity and PPV. These results reinforce the fact that a second 99mTc-MIBI scan should be performed at first intention before reoperation of patients with persistent PHPT, regardless of the result from the initial 99mTc-MIBI scan.
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... There are single gland disease predicting models such as Wisconsin Index (preoperative calcium, parathyroid hormone) in practice. They are not found to accurately predict single-gland disease in PHPT [13]. It is not possible to suggest a selection criterion for US only investigation based on clinical information. ...
Stepwise Approach for Parathyroid Localisation in Primary Hyperparathyroidism
Article
  • Nov 2019
Introduction Primary hyperparathyroidism (PHPT) is a relatively common condition in surgical practice. Availability of localisation studies has shifted the treatment from bilateral neck exploration to selective parathyroidectomy. Several imaging modalities, each with varying sensitivities, are available to detect abnormal parathyroid glands. Ultrasound is almost universally accepted as the first line radiological investigation however its sensitivity is particularly heterogeneous and operator-dependent. Material and methods We studied 250 consecutive patients with PHPT who underwent parathyroidectomy in our hospital over a period of 33 months. Pre-operative neck ultrasound, 99mTc-sestamibi and single-photon emission computed tomography (SPECT CT) were performed in 249, 237 and 198 patients respectively. Unilateral and bilateral neck exploration was performed in 190 and 60 patients, respectively. Sensitivity, positive predictive value (PPV) and accuracy were calculated comparing the results with surgical and pathology findings. Results Mean pre and postoperative PTH and adjusted calcium were, 11 ± 10.6 pmol/L, 1.9 ± 3.6, 2.81 ± 0.2 and 2.45 ± 0.2 mmol/L. There were 71 (29.95%) discordant results between US, compared to sestamibi and SPECT CT. An average of 1.9 parathyroid glands were removed with a mean weight of 0.92 g. Overall success rate based on postoperative PTH levels was 94.8%. Overall sensitivity, PPV and accuracy for US were 80.80%, 92.35%, and 75.73% respectively; for sestamibi were 71.82%, 94.61%, 69.00% and for SPECT CT were; 70.21%, 97.78%, 69.11% respectively. Conclusion Ultrasound performed by an experienced specialist sonographer is highly sensitive in localising abnormal parathyroid glands. It can be used as a main and sole investigation in the majority of patients. Sestamibi, SPECT CT and other investigations should be performed in a step-wise manner and reserved for patients with negative US, failed primary procedure and recurrences.
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Machine learning-derived clinical decision algorithm for the diagnosis of hyperfunctioning parathyroid glands in patients with primary hyperparathyroidism
Article
Full-text available
  • Oct 2024
  • EUR RADIOL
To train and validate machine learning-derived clinical decision algorithm (MLCDA) for the diagnosis of hyperfunctioning parathyroid glands using preoperative variables to facilitate surgical planning. This retrospective study included 458 consecutive primary hyperparathyroidism (PHPT) patients who underwent combined 4D-CT and sestamibi SPECT/CT (MIBI) with subsequent parathyroidectomy from February 2013 to September 2016. The study cohort was divided into training (first 400 patients) and validation sets (remaining 58 patients). Sixteen clinical, laboratory, and imaging variables were evaluated. A random forest algorithm selected the best predictor variables and generated a clinical decision algorithm with the highest performance (MLCDA). The MLCDA was trained to predict the probability of a hyperfunctioning vs normal gland for each of the four parathyroid glands in a patient. The reference standard was a four-quadrant location on operative reports and pathology. The accuracy of MLCDA was prospectively validated. Of 16 variables, the algorithm selected 3 variables for optimal prediction: combined 4D-CT and MIBI using (1) sensitive reading, (2) specific reading, and (3) cross-product of serum calcium and parathyroid hormone levels and outputted an MLCDA using five probability categories for hyperfunctioning glands. The MLCDA demonstrated excellent accuracy for correct classification in the training (4D-CT + MIBI: 0.91 [95% CI: 0.89–0.92]) and validation sets (4D-CT + MIBI: 0.90 [95% CI: 0.86–0.94]. Machine learning generated a clinical decision algorithm that accurately diagnosed hyperfunctioning parathyroid glands through classification into probability categories, which can be implemented for improved preoperative planning and convey diagnostic certainty. Question Can an MLCDA use preoperative variables for the diagnosis of hyperfunctioning parathyroid glands to facilitate surgical planning? Findings The developed MLCDA demonstrated excellent accuracy for correct classification in the training (0.91 [95% CI: 0.89–0.92]) and validation sets (0.90 [95% CI: 0.86–0.94]). Clinical relevance Using standard preoperative variables, an MLCDA for diagnosing hyperfunctioning parathyroid glands can be implemented to improve preoperative parathyroid localization and included in radiology reports for surgical planning.
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Adenoma weight: the only predictive factor for multiple gland disease in primary hyperparathyroidism
Article
  • Apr 2023
Background: Predicting a multiple gland disease (MGD) in primary hyperparathyroidism (pHPT) remains challenging. This study aimed to evaluate predictive factors for MGD. Methods: A retrospective chart review was performed of 1211 patients with histologically confirmed parathyroid adenoma or hyperplasia between 2007-2016. Localization diagnostics, laboratory parameters, and the weight of the resected parathyroid glands were evaluated concerning their predictive value of a multiple-gland disease. Results: A number of 1111 (91.7%) had a single-gland disease (SGD), and 100 (8.3%) a multiple-gland disease (MGD). US and MIBI scans were comparable for either negative or positive adenoma localization and suspected MGD. While the PTH level was similar, the calcium level was higher in SGD (2.8 mmol/L versus 2.76 mmol/L, P=0.034). MGD had a significantly lower gland weight (0.78 g versus 0.31 g; P<0.001). A gland weight of 0.418 grams was a predictive factor for MGD with a sensitivity of 72% and a specificity of 66%. Conclusions: Only the weight of the resected parathyroid adenoma was meaningful in predicting MGD. A cut-off value of 0.418 g can differentiate SGD from MGD.
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A study of patient satisfaction with healthcare in Zenica-Doboj Canton
Article
Full-text available
  • Nov 2020
Abstract Aim: Patient satisfaction and patient evaluation of healthcare can be seen as important results of provided care, as they reflect the level to which the patient’s subjective and objective needs have been met. The aim was to evaluate patient satisfaction with healthcare and compare the results for 2017 with the results from 2011. Methods:The study was conducted in the territory of Zenica-Doboj Canton in May 2011 and in October 2017. A questionnaire was filled out by 2,008 examinees in 2011 and by 2,000 examinees in 2017 outside healthcare institutions (in the street), using the EUROPEP questionnaire as a research instrument. The average age of the respondents was 38.4. The participants in the study were 52 % male and 48 % female. Student’s T-test was used to compare the results between the two samples. Results: A statistically significant difference was observed between the mean patient satisfaction in 2011 (3.19 ± 0.3, min. = 2.6, max. = 3.83, P = 0.00032) and the mean patient satisfaction in 2017 (3.47 ± 0.17, min. = 3.14, max. = 3.94, P = 0.000647), t(23) = 3.75. Increase in patien t satisfaction in 2017 is evident compared to their satisfaction in 2011. Conclusion: Surveying the satisfaction of healthcare recipients should be a common method of work as it gives the patients the impression that their opinion is valued, while at the same time it indicates to healthcare staff that their attitudes may need to be changed, their knowledge expanded and the organization of work improved, if they want to provide services of improved quality.
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Intravagal parathyroid adenomas: Case report and literature review
Article
Full-text available
  • Apr 2020
Intravagal parathyroid adenomas remain an exceedingly rare diagnosis; however, their true incidence may be higher than currently known. It is important to keep intravagal sites within the list of potential ectopic locations of parathyroid adenomas.
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The surgical management of sporadic primary hyperparathyroidism
Article
  • Dec 2018
Sporadic primary hyperparathyroidism (pHPT) is the commonest cause of hypercalcaemia in the ambulatory population. It has a female preponderance and its incidence is increasing. In 85% of cases it is caused by a single parathyroid adenoma, with four gland hyperplasia in up to 20%. Parathyroidectomy is the only cure and bilateral neck exploration remains the gold standard to achieve this. Several adjuncts have been developed to improve success rates or limit the extent of surgery. Pre-operative localisation permits planned targeted surgery. Ultrasound scanning and scintigraphy are the most commonly employed, although 4DCT has become a useful modality in complex cases. However, excellent rates of biochemical cure can be achieved in specialist centres when pre-operative imaging is negative. Pre-operative prediction models and intra-operative parathyroid hormone (ioPTH) assist, with high sensitivity, to predict single gland disease. Reoperations present a major challenge to the endocrine surgeon.
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The CaPTHUS score as predictor of multiglandular primary hyperparathyroidism in a European population
Article
Full-text available
  • Nov 2016
  • LANGENBECK ARCH SURG
Purpose: Focused parathyroidectomy has been proven to be a safe technique for the treatment of single-gland primary hyperparathyroidism (PHPT). The CaPTHUS scoring model has been reported to be an accurate preoperative diagnostic tool for distinguishing single-gland (SGD) from multiglandular disease (MGD), including preoperative serum calcium and PTH values plus ultrasound and Sestamibi scanning. The purpose of the present study was to validate the CaPTHUS model for the population in southern Europe, since the North American and the European populations show different clinicopathological profiles in PHPT. Methods: This is a retrospective review of a prospectively maintained database of patients diagnosed with PHPT who underwent surgical treatment in a single referral center. Differences between SGD and MGD groups were analyzed using chi-square and Fisher's exact tests for categorical variables and Student's t test for continuous variables. Overall diagnostic accuracy of the scoring model was assessed by the area under the receiver operating characteristic (ROC) curve (AUC). A p < 0.05 level was accepted as significant. Results: From January 2001 to November 2014, 241 patients were included in the study, of whom 92.1 % had SGD and 71.8 % had a CaPTHUS score ≥3. SGD was distinguished from MGD (p < 0.001) using the dichotomous scoring model based on an AUC value of 0.762. Scores ≥3 had a sensitivity of 76.5 % and a positive predictive value of 96 % for SGD. Conclusions: Despite good test performance, a CaPTHUS score ≥3 does not discard MGD definitely. Intraoperative adjuncts are still needed to further reduce the risk of missing MGD during selective parathyroidectomy.
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Sporadic multiple parathyroid gland disease-a consensus report of the European Society of Endocrine Surgeons (ESES)
Article
Full-text available
  • Dec 2015
  • LANGENBECK ARCH SURG
Background: Sporadic multiglandular disease (MGD) has been reported in literature in 8-33 % of patients with primary hyperparathyroidism (pHPT). This paper aimed to review controversies in the pathogenesis and management of sporadic MGD. Methods: A literature search and review was made to evaluate the level of evidence concerning diagnosis and management of sporadic MGD according to criteria proposed by Sackett, with recommendation grading by Heinrich et al. and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system. Results were discussed at the 6th Workshop of the European Society of Endocrine Surgeons entitled 'Hyperparathyroidism due to multiple gland disease: An evidence-based perspective'. Results: Literature reports no prospective randomised studies; thus, a relatively low level of evidence was achieved. Appropriate surgical therapy of sporadic MGD should consist of a bilateral approach in most patients. Unilateral neck exploration guided by preoperative imaging should be reserved for selected patients, performed by an experienced endocrine surgeon and monitored by intraoperative parathormone assay (levels of evidence III-V, grade C recommendation). There is conflicting or equally weighted levels IV-V evidence supporting that cure rates can be similar or worse for sporadic MGD than for single adenomas (no recommendation). Best outcomes can be expected if surgery is performed by an experienced parathyroid surgeon working in a high-volume centre (grade C recommendation). Levels IV-V evidence supports that recurrent/persistence pHPT occurs more frequently in patients with double adenomas hence in situations where a double adenoma has been identified, the surgeon should have a high index of suspicion during surgery and postoperatively for the possibility of a four-gland disease (grade C recommendation). Conclusions: Identifying preoperatively patients at risk for MGD remains challenging, intraoperative decisions are important for achieving acceptable cure rates and long-term follow-up is mandatory in such patients.
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CaPTHUS Scoring Model in Primary Hyperparathyroidism: Can It Eliminate the Need for ioPTH Testing?
Article
  • Sep 2014
  • ANN SURG ONCOL
Background: The CaPTHUS model was reported to have a positive predictive value of 100 % to correctly predict single-gland disease in patients with primary hyperparathyroidism, thus obviating the need for intraoperative parathyroid hormone (ioPTH) testing. We sought to apply the CaPTHUS scoring model in our patient population and assess its utility in predicting long-term biochemical cure. Methods: We retrospective reviewed all parathyroidectomies for primary hyperparathyroidism performed at our university hospital from 2003 to 2012. We routinely perform ioPTH testing. Biochemical cure was defined as a normal calcium level at 6 months. Results: A total of 1,421 patients met the inclusion criteria: 78 % of patients had a single adenoma at the time of surgery, 98 % had a normal serum calcium at 1 week postoperatively, and 96 % had a normal serum calcium level 6 months postoperatively. Using the CaPTHUS scoring model, 307 patients (22.5 %) had a score of ≥ 3, with a positive predictive value of 91 % for single adenoma. A CaPTHUS score of ≥ 3 had a positive predictive value of 98 % for biochemical cure at 1 week as well as at 6 months. Conclusions: In our population, where ioPTH testing is used routinely to guide use of bilateral exploration, patients with a preoperative CaPTHUS score of ≥ 3 had good long-term biochemical cure rates. However, the model only predicted adenoma in 91 % of cases. If minimally invasive parathyroidectomy without ioPTH testing had been done for these patients, the cure rate would have dropped from 98 % to an unacceptable 89 %. Even in these patients with high CaPTHUS scores, multigland disease is present in almost 10 %, and ioPTH testing is necessary.
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Operative Failure in Minimally Invasive Parathyroidectomy Utilizing an Intraoperative Parathyroid Hormone Assay
Article
  • Jan 2014
  • ANN SURG ONCOL
Minimally invasive parathyroidectomy (MIP) is a targeted operation to cure primary hyperparathyroidism utilizing intraoperative parathyroid hormone monitoring (IOPTH). The purpose of this study was to quantify the operative failure of MIP. Utilizing institutional parathyroid surgery database, demographic, operative, and biochemical data were analyzed for successful and failed MIP. Operative failure was defined as <6 months of eucalcemia after operation. Five hundred thirty-eight patients (96.6 %) had successful MIP with mean follow-up of 13 months, and 19 (3.4 %) had operative failure. The major cause of operative failure (11 of 19) was the result of surgeons' inability to identify all abnormal parathyroid glands. The remaining eight operative failures were the result of falsely positive IOPTH results. Eleven of 19 patients whose MIP had failed underwent a second parathyroid surgery. All but one of these patients achieved operative success, and 9 patients had missed multigland disease. Only 46 (8.3 %) of 557 patients had conversion to bilateral cervical exploration (BCE). Eighty percent of patients had more than 70 % IOPTH decrease, and all had successful operations. Patients with a marginal IOPTH decrease (50-59 %) had a treatment failure rate of 20 %. The most common cause of operative failure in MIP utilizing IOPTH was the result of surgeons' failure to identify all abnormal parathyroid glands. Falsely positive IOPTH is rare, and a targeted MIP utilizing IOPTH can achieve an excellent operative success rate without routine BCE. Selective BCE on patients with marginal IOPTH decrease may improve surgical outcome.
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Cure Predictability During Parathyroidectomy
Article
  • Nov 2013
  • WORLD J SURG
A mathematical model for primary hyperparathyroidism (1°HPTH) was developed and embedded in software to yield intraoperative predictability curves. A total of 1,754 consecutive 1°HPTH operative cases were screened to select 617 [554 single adenoma (SA), 63 multigland] patients with complete preoperative, intraoperative (pre-exploration, time 0, every 5 min post-resection), and postoperative parathyroid hormone (PTH) and calcium data. Data transformations and models were hypothesized and tested, including inverse functions, differences, half-lives, differences from projected half-lives, second-order kinetics, second-order derivatives, and time-dependent ratios. Sub-models of ratios were developed for time-dependent and initial-value combinations. For each time segment the log odds were modeled using multiple logistic stepwise regression. An idealized model was selected, embedded in software, and installed in a laptop computer to enable intraoperative decision analyses, PTH curve plotting, and storage and transmission of data. A subsequent cohort of 100 consecutive unselected patients [81 SAs, 19 multigland (13 hyperplasia, 2 MEN1, 1 lithium, 3 double adenomas)] inclusive of seven remedial cervical explorations were tested. The model predicted an overall curative resection in 95 % of patients. In SA patients, cure was predicted in 78/81 patients with a mean probability of 99.3 % at 11.8 ± 10.4 min post-resection. In three cured patients, the software failed to suggest cure, because of a low baseline PTH or delayed clearance. The model also correctly predicted residual hyperfunctioning tissue in all tested multigland patients. All multigland patients underwent additional exploration with resection of residual disease resulting in a mean predicted cure rate of 97.9 % at 10.6 ± 7.3 min post-resection completion in 17 patients. In two patients, the software predicted a mean cure rate of 22 % due to either a low PTH baseline or delayed clearance. Overall, the software accurately predicted cure in 95 of 100 cured cases. This intraoperative prediction software expedites termination of surgery with a high level of curative confidence. Alternatively, the model accurately predicts residual disease prompting additional exploration. Because the model is based on a large set of multivariate regression curves, PTH values obtained at any post-resection sampling interval generate prediction data with far greater accuracy than existing algorithms. The software is designed for convenient operative use and can print, store, and electronically transmit probability analyses and PTH curves in real-time.
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Safety and efficacy of minimally-invasive parathyroidectomy (MIP) under local anaesthesia without intra-operative PTH measurement
Article
  • Feb 2013
  • Int J Surg
Background: Minimally invasive parathyroidectomy (MIP) is the choice of treatment in patients with sporadic adenomas localized on preoperative imaging. Currently there is no centre in the UK which performs this procedure under local anaesthesia. The aim of this study was to assess the efficacy and safety of MIP under local anaesthesia in patients with sporadic primary hyperparathyroidism (pHPT). Methods: This is a prospective, nonrandomized study of 86 patients with pHPT localized with Tc99m Sestamibi scan and ultrasound. MIPs were performed under local anaesthesia and sedation at the Oxford University Hospitals. Serum Ca and PTH were measured before discharge, at 6 weeks follow up, and at 6 months. Main outcome measures were cure at 6 months, complications with the procedure and operative time. Results: 86 patients (58 females: 28 males) with a mean age of 65 (range 24-87) underwent MIP under local anaesthesia and sedation. All patients (100%) were normocalcaemic at 6 months following surgery. There was no incidence of temporary or permanent recurrent laryngeal nerve palsy or persistent hypercalcaemia. Two patients had temporary hypocalcaemia that resolved in 6 weeks. In one patient the neck incision needed extension for bleeding, with no incidence of wound haematoma or infection. Conclusion: This study demonstrates that MIP (without ioPTH) can be safely performed under local anaesthesia for patients with sporadic primary hyperparathyroidism.
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Creation of a “Wisconsin Index” Nomogram to Predict the Likelihood of Additional Hyperfunctioning Parathyroid Glands During Parathyroidectomy
Article
  • Jul 2012
  • ANN SURG
Objective: The aim of our study was to create a preoperative "index" that could predict the likelihood of additional hyperfunctioning parathyroid glands and let the surgeon determine whether to wait for the intraoperative parathyroid hormone (ioPTH) or to explore further. Background: During parathyroidectomy for primary hyperparathyroidism (PHPT), discovering a minimally "enlarged" parathyroid gland creates a dilemma for the surgeon regarding the need for further exploration. Although ioPTH testing can potentially solve this problem after a 20- to 30-minute period, several surgeons recognize that further operative exploration may be more effective. Methods: We analyzed a prospective database of 1235 consecutive patients who underwent parathyroidectomy for PHPT at our institution between March 2001 and August 2010. The Wisconsin Index (WIN) was defined as the multiplication of preoperative serum calcium by preoperative parathyroid hormone (PTH). Patients were divided into 3 WIN categories: low (<800), medium (801-1600), and high (>1600). The utility of the WIN was then validated on a subsequent cohort of 216 patients. Results: The median age of the patients was 61 years (range, 10-91), and 77% of the patients were female. The mean preoperative calcium and PTH levels were 11.0 ± 0 mg/dL and 127 ± 3 pg/mL, respectively. The mean WIN for the entire cohort was 1461 ± 38 and highly correlated with gland weight (P < 0.000001). A single adenoma was identified in 1000 patients (81%), double adenoma in 100 patients (8%), and hyperplasia in 135 patients (11%). The mean gland weights for the 3 WIN catagories were low = 370 ± 33 mg, medium = 532 ± 39 mg, and high = 985 ± 28 mg, respectively (P < 0.000001). A WIN nomogram, consisting of the combination of WIN and parathyroid gland weight, accurately predicted the likelihood of additional hyperfunctioning parathyroid glands. For example, for a WIN of less than 800 and a gland weight of 500 mg, there is a 9% chance for additional hyperfunctioning parathyroid glands based on the WIN nomogram. In contrast, for the same gland weight, if the WIN is 801 to 1600, these chances increase to 28%, and if the WIN is more than 1600, the chance of multigland disease is 61%. Comparison between the predicted chances for another gland with the actual chance in the validation cohort identified an R(2) value of 0.96. Conclusions: The WIN nomogram predicts the likelihood of additional hyperfunctioning parathyroid glands during parathyroidectomy. This simple intraoperative tool may be used to guide the decision of whether to wait for ioPTH results or to proceed with further neck exploration.
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A Predictive Model of Suitability for Minimally Invasive Parathyroid Surgery in the Treatment of Primary Hyperthyroidism
Article
  • Dec 2011
  • WORLD J SURG
Improved preoperative localizing studies have facilitated minimally invasive approaches in the treatment of primary hyperparathyroidism (PHPT). Success depends on the ability to reliably select patients who have PHPT due to single-gland disease. We propose a model encompassing preoperative clinical, biochemical, and imaging studies to predict a patient's suitability for minimally invasive surgery. For the purposes of the present study, 180 consecutive patients were included for analysis. A 5-variable model based on preoperative ionized serum calcium (>1.4 mmol/l), intact parathyroid hormone level (≥ 2 times the upper limit of normal), positive sestamibi scan for a single affected gland, positive ultrasound scan for a single gland, and concordance between the two imaging modalities for single-gland disease at a similar location was employed, where a score of 1 was allocated for each variable present. Of the 180 patients, 62 (34%) underwent bilateral exploration, 63 (36%) underwent unilateral exploration, and 55 (30%) underwent minimally invasive parathyroidectomy. The results showed that 92% had single-gland disease, 3% had double adenomas, and 5% had hyperplasia. Biochemical cure was achieved in 98.9%. Mean follow-up was 153 days (range: 80-342 days). With the predictive scoring model, a score of ≥ 3 had a positive predictive value of 100% for single-gland disease. A scoring model encompassing preoperative biochemical and imaging data can be successfully employed to predict suitability for minimally invasive surgery in the majority of patients with single-gland disease.
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1000 minimally invasive parathyroidectomies without intra-operative parathyroid hormone measurement: Lessons learned
Article
  • May 2011
  • ANZ J SURG
Minimally invasive parathyroidectomy (MIP) has become the procedure of choice in the treatment of primary hyperparathyroidism where a single adenoma can be localized preoperatively. The role for intra-operative parathyroid hormone measurement (IOPTH) is controversial. Some experts recommend that IOPTH is a mandatory requirement for successful MIP while others state that the technique is not needed. We reviewed 10 years of MIP in a single unit without the use of IOPTH in order to examine causes of failure. This study is a retrospective review of the University of Sydney Endocrine Surgery Database from May of 1998 to August of 2008. The database was queried for MIPs performed as well as for failed operations. Patient record analysis was completed to determine the reason for failure of the operation. In the period January 1998 to August 2008, a total of 2343 parathyroidectomy procedures were performed. Of these, 1020 were MIPs with 23 (2.2%) failures. One patient was found to have benign familial hypercalcemia, whereas five were lost to follow-up. Reasons for failure in the remaining 17 patients were: 10 patients (59%) were found to have double adenomas, 3 (17%) patients with hyperplasia and 4 (24%) patients with single gland disease were missed at initial operation. All 17 were cured on repeat exploration. MIP can be performed safely and with 98% success without the need for IOPTH. The most common cause of failure after MIP is an occult double adenoma. Given that repeat sestamibi scan correctly identifies persistent disease in most cases, consideration can be given to MIP as a choice of procedure for repeat operation.
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Epidemiology of primary hyperparathyroidism in Tayside, Scotland, UK
Article
  • Oct 2009
  • CLIN ENDOCRINOL
To evaluate prevalence and incidence of diagnosed primary hyperparathyroidism (PHPT) in adults between 1997 and 2006 in Tayside, Scotland, UK. Population-based incidence and prevalence study. All Tayside residents aged 20 years and over with an increased serum calcium level (> 2.55 mmol/l) between 1997 and 2006 were included as potential participants. Using a unique patient identifier, data-linkage enabled a data set of PHPT patients to be created from an algorithm of biochemistry records, nuclear scan records, histology records, hospital clinic letters and community based prescription records. Persons having tertiary hyperparathyroidism (14.0%) were also identified and were excluded. Age and sex adjusted incidence density and period prevalence were calculated for each year. We identified 2709 patients (70.8% female) diagnosed with PHPT by the end of 2006. The mean age of women (68 years SD = 14) was older than that of men (64 years SD = 15) at baseline. The prevalence of diagnosed PHPT in Tayside increased from 1.82 per 1000 population in 1997 to 6.72 per 1000 population in 2006 (P < 0.001). Prevalence of PHPT is higher in females, and the female preponderance increases with age; the annual prevalence ratio between women and men is stable at around 2.5 each year. There was a 3-4-year cyclical incidence rate varying from 4.13 to 11.30 per 10 000 person-years. We observed a general increase in the prevalence of diagnosed PHPT in Tayside, Scotland. The incidence of diagnosis is greater in females than in males and increases with age. The annual incidence followed an apparent cyclic curve during the study period.
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Hyperparathyroidism
Article
  • Aug 2009
  • LANCET
Hyperparathyroidism is due to increased activity of the parathyroid glands, either from an intrinsic abnormal change altering excretion of parathyroid hormone (primary or tertiary hyperparathyroidism) or from an extrinsic abnormal change affecting calcium homoeostasis stimulating production of parathyroid hormone (secondary hyperparathyroidism). Primary hyperparathyroidism is the third most common endocrine disorder, with the highest incidence in postmenopausal women. Asymptomatic disease is common, and severe disease with renal stones and metabolic bone disease arises less frequently now than it did 20-30 years ago. Primary hyperparathyroidism can be cured by surgical removal of an adenoma, increasingly by minimally invasive parathyroidectomy. Medical management of mild disease is possible with bisphosphonates, hormone replacement therapy, and calcimimetics. Vitamin D deficiency is a common cause of secondary hyperparathyroidism, particularly in elderly people. However, the biochemical definition of vitamin D deficiency and its treatment are subject to much debate. Secondary hyperparathyroidism as the result of chronic kidney disease is important in the genesis of renal bone disease, and several new treatments could help achieve the guidelines set out by the kidney disease outcomes quality initiative.
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Primary Hyperparathyroidism: Role of the Preoperative Oral Calcium Loading Test in the Differential Diagnosis Between Adenoma and Hyperplasia
Article
  • Dec 2008
  • CALCIFIED TISSUE INT
Whereas the sensitivity of the membrane calcium receptors is decreased in parathyroid adenoma, extracellular calcium may reduce parathyroid hormone (PTH) secretion through the protein kinase C pathway in parathyroid hyperplasia. The aim of this study was to determine the role of a preoperative oral calcium loading test in the differential diagnosis between adenoma and hyperplasia. Twenty-two subjects with adenoma (group A, age +/- standard error 56 +/-2 years, female/male 15/7), 10 individuals with hyperplasia (group H, age 54 +/-3, female/male 8/2), and 32 age and gender pair-matched controls (group C) underwent the test. Calcium and PTH were measured before and 60, 120, and 180 min after oral administration of 1 g of calcium (as gluconolactate). Product P was defined as minimal PTH concentration (pg/mL) x maximal calcium concentration (mg/dL) during the test. Ratio R was defined as relative PTH decline/relative calcium increase. The PTH decline during the test in group H was comparable to that of the controls. PTH decline <30%, Product P > 1,100, and Ratio R < 4 diagnosed adenoma with specificity of 100%, 90%, and 100%, respectively. PTH decline >60% diagnosed hyperplasia with specificity of 100%. The total accuracy of the test (65%) was comparable to that of technetium-99 m sestamibi scintigraphy (66%) and better than that of ultrasonography (58%). The test may discriminate patients with sporadic diffuse hyperplasia from individuals with solitary adenoma in cases of primary hyperparathyroidism with an indication for surgery.
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Predicting the Success of Limited Exploration for Primary Hyperparathyroidism Using Ultrasound, Sestamibi, and Intraoperative Parathyroid Hormone
Article
  • Sep 2008
  • ANN SURG
The aim of this study was to determine the success of limited neck exploration (LE) for primary hyperparathyroidism (1 degrees HPT). Between 1999 and 2007, 1407 patients with hyperparathyroidism underwent bilateral neck exploration (BE). Of these, 1158 patients with first-time sporadic 1 degrees HPT were analyzed prospectively. Based on surgeon-performed ultrasound (US) and sestamibi scan (MIBI), LE was initially performed. Regardless of results, BE followed to identify the presence of additional parathyroid pathology. Of 1158 patients, 242 (21%) were found to require concomitant thyroid surgery thus excluding LE. Of the remaining 916 patients, a single abnormal gland was identified on MIBI in 682 (74%), US in 731 (80%), and concordance of both in 588 (64%). Unsuspected multiglandular disease (MGD) was identified at BE in 22%, 22%, and 20% of patients, respectively. Adding intraoperative parathyroid hormone sampling (IOPTH) further reduced the rate of unsuspected MGD to 16%, 17%, and 16%. Overall, IOPTH correctly predicted MGD in only 22%. Neither concomitant nonsurgical thyroid disease nor more stringent selection criteria (preop Ca>11 mg/dL and PTH>120 pg/dL) altered success rates. In patients with MGD, a subsequent gland identified was larger than the index gland in 23%. Ninety-eight percent of BE patients were cured of 1 degrees HPT. This is the largest study to evaluate the prevalence of additional parathyroid pathology in patients who are candidates for LE. Limitations in localizing studies and IOPTH fail to identify MGD in at least 16% of patients, risking future recurrence.
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Kebebew E, Hwang J, Reiff E, Duh QY, Clark OH. Predictors of single-gland vs multigland parathyroid disease in primary hyperparathyroidism: a simple and accurate scoring model. Arch Surg. 2006;141:777-82
Article
  • Aug 2006
  • ARCH SURG-CHICAGO
Preoperative clinical, biochemical, and imaging studies could be used to reliably select patients with single-gland primary hyperparathyroidism who could undergo minimally invasive parathyroidectomy and to determine whether additional perioperative testing is necessary. Retrospective analysis. Tertiary referral center. A total of 238 patients who underwent neck surgical exploration and parathyroidectomy for primary hyperparathyroidism from January 7, 2002, to December 23, 2004. Demographic, clinical, biochemical, and imaging factors that predict single-gland vs multigland parathyroid disease, and biochemical cure. Of the 238 patients, 75.2% had a single adenoma, 21.4% had asymmetric 4-gland hyperplasia, and 3.4% had double adenomas. A biochemical cure was achieved in 99.2% of the patients. Preoperative calcium and intact parathyroid hormone levels were significantly higher (P = .03 and .04, respectively) and ultrasound and sestamibi scan results were more likely to be positive (both P<.001) in single-gland primary hyperparathyroidism. A dichotomous scoring model based on preoperative total calcium level (>/=3 mmol/L [>/=12 mg/dL]), intact parathyroid hormone level (>/=2 times the upper limit of normal levels), positive ultrasound and sestamibi scan results for 1 enlarged gland, and concordant ultrasound and sestamibi scan findings reliably distinguished single-gland vs multigland cases (P<.001). The positive predictive value of this scoring model to correctly predict single-gland disease was 100% for a total score of 3 or higher. Preoperative biochemical and imaging study results reliably distinguished single-gland vs multigland parathyroid disease in primary hyperparathyroidism. Our findings suggest that patients with a score of 3 or higher can undergo a minimally invasive parathyroidectomy without the routine use of intraoperative parathyroid hormone or additional imaging studies, and those with a score of less than 3 should have additional testing to ensure that multigland disease is not overlooked.
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Minimally invasive parathyroidectomy without intraoperative parathyroid hormone monitoring in patients with primary hyperparathyroidism
Article
  • Jan 2007
Minimally invasive parathyroidectomy (MIP) is the preferred operation for patients with primary hyperparathyroidism (HPT) and positive preoperative imaging. This non-randomized case series assessed the long-term results of MIP performed without the use of intraoperative parathyroid hormone (ioPTH) monitoring. The study involved prospective collection of demographic, biochemical and operative details on a consecutive, unselected cohort of 298 patients who underwent surgery for non-familial primary HPT during a 5-year interval. The mean preoperative serum calcium level was 3.00 mmol/l with a mean parathyroid hormone concentration of 25.8 pmol/l. (99m)Tc-labelled sestamibi scanning and neck ultrasonography were performed in 262 patients. Sestamibi scan showed unilateral uptake in 182 patients and a single parathyroid adenoma was confirmed on ultrasonography in 161 patients. MIP was performed in 150 patients. The mean duration of operation was 25 (range 8-65) min. Four patients needed conversion to conventional neck exploration. There was one postoperative haematoma and three cases of temporary recurrent laryngeal nerve neuropraxia. All but four patients were normocalcaemic after MIP. All the parathyroid tumours removed were adenomas, with a mean weight of 1.3 (range 0.1-17.4) g. No patient developed recurrent HPT after a median follow-up of 16 (range 3-48) months. The outcome of MIP without ioPTH monitoring was comparable to that reported in series that used ioPTH monitoring.
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Parathyroid hormone assay predicts hypocalcaemia after total thyroidectomy
Article
  • Sep 2007
Postoperative parathyroid gland function after total thyroidectomy (TT) has traditionally been monitored by the measurement of serum calcium concentrations. The purpose of this study is to determine whether measurement of parathyroid hormone (PTH) concentrations in the early postoperative period accurately predicts patients at risk of developing hypocalcaemia. A prospective cohort study of patients undergoing TT was carried out. PTH concentrations were measured preoperatively and at 4 and 23 h postoperatively. Serum calcium concentration was measured preoperatively and twice daily for 48 h after surgery. One hundred patients undergoing TT were recruited into the study in the period June 2004 to July 2005. Benign multinodular goitre was the most common indication for surgery (77%). The incidence of temporary hypocalcaemia (Ca < 2.0 mmol/L) was 18%. The mean PTH concentration at 4 h after surgery was 22.3 ng/L and was not significantly different from the 23-h concentration of 23.2 ng/L (P = 0.18). A PTH concentration of < or = 3 ng/L measured at 4 h after surgery had a sensitivity, specificity and likelihood ratio of 0.71, 0.94 and 11.3, respectively, for predicting postoperative hypocalcaemia. The accuracy of a single PTH concentration at 4 h was good for predicting hypocalcaemia (area under receiver-operator characteristic curve 0.90; confidence interval 0.81-0.96). There was no significant difference in accuracy between the 4- and 24-h PTH concentrations (P = 0.14). A single measurement of PTH concentration in the early postoperative period after TT reliably predicts patients who are likely to develop hypocalcaemia. This approach facilitates early discharge and may decrease the need for multiple postoperative blood tests.
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