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

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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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... 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. ...
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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 .
... 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]. ...
Article
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.
... 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. ...
Article
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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.
... 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%. ...
Article
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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.
... 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. ...
Article
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.
... 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. ...
Article
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.
... 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. ...
Article
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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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 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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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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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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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.
Article
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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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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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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.
Article
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.