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Bone disease in primary hyperparathroidism
Abstract
The classic bone disease of primary hyperparathyroidism, osteitis fibrosa cystica, was characterized by subperiosteal bone resorption, osteopenia, and "brown tumors." Since the description of this skeletal disorder, the clinical profile of primary hyperparathyroidism has evolved markedly. The disease today is often characterized by no more than asymptomatic hypercalcemia, and severe bone disease is a distinct rarity. However, as we have endeavored to show in this article, newer and more sensitive techniques show significant evidence of the effect of excess parathyroid hormone on the skeleton. Bone density as measured by photon absorptiometry and bone histomorphometry show a deficit of cortical bone and a preservation or increase in cancellous bone elements in mild primary hyperparathyroidism with no clinical evidence of skeletal disease. Important questions exist as to the therapeutic implications of these data. Does the presence of parathyroid hormone effect on sophisticated testing portend the development of clinical bone disease? Should these data be used as a rationale for surgical intervention in patients who might otherwise be followed conservatively with mild primary hyperparathyroidism? The answers to these questions must await further data collection and study.
... Here, we observed a moderate enrichment of the osteoid surface, areas with fibrotic bone marrow, but also increased numbers of osteoclasts (Fig 4D and E). Since these observations represent three typical histological features of hyperparathyroidism (Parisien et al, 1990), and neonatal hyperparathyroidism has been occasionally reported in MLII patients (Unger et al, 2005), we determined serum concentrations of PTH together with the urinary concentrations of desoxypyridinoline (Dpd), a type I collagen degradation product, corresponding to crosslaps in mice ( Fig 4F). In comparison to the reported children reference ranges (Cioffi et al, 2000;Husain et al, 1999) we found that the serum PTH concentration was not pathologically altered in the MLII patient. ...
... Skeletal radiographs of newborn MLII patients resemble those seen in neonatal hyperparathyroidism (Parisien et al, 1990). In the MLII mice and the MLII patient described here, we did not find increased serum PTH concentrations which is in agreement with reports on more than 25 MLII patients with normal PTH and parathyroid receptor protein concentrations (David-Vizcarra et al, 2010;Otomo et al, 2011). ...
... Only some cases of MLII are associated with marked elevation of serum PTH levels (Unger et al, 2005). Our data also exclude tissue hypersensitivity (pseudohyperparathyroidism) to PTH postulated as pathogenetic mechanism for the osteopenia (David-Vizcarra et al, 2010;Parisien et al, 1990), since the secretion of Rankl in osteoblasts from MLII mice was not affected in response to PTH stimulation. ...
Mucolipidosis type II (MLII) is a severe multi-systemic genetic disorder caused by missorting of lysosomal proteins and the subsequent lysosomal storage of undegraded macromolecules. Although affected children develop disabling skeletal abnormalities, their pathogenesis is not understood. Here we report that MLII knock-in mice, recapitulating the human storage disease, are runted with accompanying growth plate widening, low trabecular bone mass and cortical porosity. Intralysosomal deficiency of numerous acid hydrolases results in accumulation of storage material in chondrocytes and osteoblasts, and impaired bone formation. In osteoclasts, no morphological or functional abnormalities are detected whereas osteoclastogenesis is dramatically increased in MLII mice. The high number of osteoclasts in MLII is associated with enhanced osteoblastic expression of the pro-osteoclastogenic cytokine interleukin-6, and pharmacological inhibition of bone resorption prevented the osteoporotic phenotype of MLII mice. Our findings show that progressive bone loss in MLII is due to the presence of dysfunctional osteoblasts combined with excessive osteoclastogenesis. They further underscore the importance of a deep skeletal phenotyping approach for other lysosomal diseases in which bone loss is a prominent feature.
... Von Recklinghausen was the first to describe the characteristic bone disease of hyperparathyroidism (HPT). The Brown Tumors develop mainly in the facial bones, pelvis, ribs, and femur, and can be multifocal [2]. In this case we report a patient with PHPT who developed two Brown Tumors including one at the talus and the second in the lateral malleolus. ...
... In several studies, differantial effects of the PTH on cancellous and cortical bone have been evaluated. It was found that the PTH affects mostly the cortical bone and the most significant postoperative improvements in bone mineral density occurs in cancellous bone [2,11]. Brown Tumors' histopathological diagnosis include; extravasated blood cells areas of hemorrhage, histiocytosis including hemosiderin, trabeculation of unmineralized new bone and a mixture of osteoblasts, mononuclear cells and multiloculated giant cells [3]. ...
Excess production and secretion of parathormone (PTH) from parathyroid glands causes primary hyperparathyroidism (PHPT). Orthopaedic surgeons should be aware of skeletal manifestations, labaratory abnormalities, and the treatment options of hyperparathyroidism (HPT). Elevated serum calcium or pathognomonic findings of HPT on plain radiographs should alert the orthopaedic surgeon. In these cases serum intact PTH and additional diagnostic tools should be obtained for proper diagnosis. We report a 43 year-old patient with PHPT who developed two Brown Tumors including one at the talus and second in the lateral malleolus. The present case is the first report of Brown Tumor of the lateral malleolus and talus in the literature. In additon we reviewed literature pertaining to HPT, from orthopaedic surgeons%u2019 aspect.
... Parathyroid hormone (PTH) excess in PHPT produces cortical bone loss but is purported to preserve bone at trabecular sites [3][4][5][6][7][8][9][10]. This notion is based on finding normal or increased so-called 'trabecular' bone volumetric bone mineral density (vBMD) when assessed by noninvasive imaging and normal volume/total volume (BV/TV) using histomorphometry [3][4][5][6][7][8][9][10]. ...
... Parathyroid hormone (PTH) excess in PHPT produces cortical bone loss but is purported to preserve bone at trabecular sites [3][4][5][6][7][8][9][10]. This notion is based on finding normal or increased so-called 'trabecular' bone volumetric bone mineral density (vBMD) when assessed by noninvasive imaging and normal volume/total volume (BV/TV) using histomorphometry [3][4][5][6][7][8][9][10]. ...
In primary hyperparathyroidism (PHPT), protracted elevation of serum parathyroid hormone (PTH) is held to be associated with cortical, but not trabecular, bone loss. However, an alternative explanation for the apparent preservation of trabecular bone is fragmentation of the cortex by intracortical remodeling. The cortical fragments resemble trabeculae and so may be erroneously included in the quantification of 'trabecular' bone density. To test this hypothesis, we compared bone microarchitecture in 43 patients with untreated PHPT (mean 62.9years, range 31-84) with 47 healthy age-matched controls and 25 patients with surgically treated PHPT (63.6years, 30-82). Images of the distal radius and tibia were acquired using high-resolution peripheral quantitative CT and analysed using StrAx1.0, a new software program that quantifies bone morphology in-vivo. Results were expressed as the mean number of standardized deviations (SD) from the age-specific mean (Z scores, mean±SEM). In subjects with PHPT, total tibial cortical area was reduced -0.26±0.08 SD; p=0.002). Cortical volumetric bone mineral density (vBMD) was reduced (-0.29±0.06 SD; p<0.001) due to higher cortical porosity (0.32±0.06 SD; p<0.001) and lower tissue mineralization density (-0.21±0.06 SD; p=0.002). Medullary area was increased (0.26±0.08 SD; p=0.002) and trabecular vBMD was reduced (-0.14±0.04 SD; p<0.001). In subjects who underwent successful parathyroidectomy, cortical area (-0.18±0.10 SD; NS) and medullary area (0.18±0.10 SD; NS) did not differ from controls. Cortical vBMD was reduced (-0.15±0.05 SD; p=0.003) due to high porosity (0.15±0.05 SD; p=0.006), values numerically lower than in untreated PHPT. Tissue mineralization density (-0.26±0.04 SD; p<0.001) and trabecular vBMD were reduced (-0.16±0.04 SD, p<0.001). The results were similar in the distal radius. In PHPT, chronically elevated endogenous PTH does not spare trabecular bone; it causes bone loss and microarchitectural deterioration in both cortical and trabecular compartments of bone.
... Deposition of haemosiderin gives the tumor its characteristic brown colour. It has been reported to develop in facial bones, clavicle, ribs, pelvis, tibia and femur 3,4 . Craniofacial BT are extremely rare, with mandibular involvement being more common than maxillary involvement. ...
Unusual presentation of primary hyperparathyroidism, first suspected after a visit to the dentist
... Hypercalcemia in an adult who is asymptomatic is usually due to PHPT. 2 Skeletal changes can occur in both PHPT and secondary hyperparathyroidism (SHPT), and the extent of these changes depends on the severity and duration of the underlying disease. 3,4 Hypercalcemia in association with lytic bone lesions as seen in our case raised the suspicion of a metastatic bone involvement. The key screening tools in such cases are the medical history, routine laboratory tests, imaging techniques, and a bone marrow examination to rule out a primary tumor. ...
Multiple osteolytic lesions are usually associated with metastatic involvement of the bone; however, metabolic bone diseases should also be included in the differential diagnosis. In this study, we describe a case of primary hyperparathyroidism (PHPT) with multiple osteolytic lesions that was diagnosed initially as having metastatic bone involvement. The laboratory results showed hypercalcemia and raised alkaline phosphatase along with fibrosis in the bone marrow biopsy with no increase in tumor markers and normal serum protein electrophoresis. The parathyroid hormone levels were high, which pointed toward a diagnosis of PHPT. Sestamibi scan revealed uptake at the level of the left inferior pole of the thyroid gland, which was suggestive of parathyroid adenoma. The possibility of hyperparathyroidism should be kept in mind when a patient presents with multiple osteolytic lesions and hypercalcemia.
... Dual-energy X-ray absorptiometry (DXA) demonstrates preferential loss of bone mineral density (BMD) at cortical sites such as the distal third of the forearm in PHPT while cancellous sites such as the lumbar spine are relatively spared [1]. This pattern is thought to reflect the catabolic vs. anabolic effects of parathyroid hormone (PTH) upon different skeletal compartments [2]. ...
Lower vitamin D and higher parathyroid hormone (PTH) levels are associated with higher volumetric BMD and bone strength at the lumbar spine as measured by central quantitative computed tomography in primary hyperparathyroidism (PHPT), but there are no differences in bone microarchitecture as measured by trabecular bone score (TBS).
Introduction
The purpose of this study was to evaluate the association between 25-hydroxyvitamin D (25OHD) and volumetric bone mineral density (vBMD) and the TBS at the lumbar spine (LS) in PHPT.
Methods
This is a cross-sectional analysis of PHPT patients with and without low 25OHD. We measured vBMD with quantitative computed tomography (cQCT) and TBS by dual-energy X-ray absorptiometry (DXA) at the LS in 52 and 88 participants, respectively.
Results
In the cQCT cohort, those with lower vitamin D (<20 vs. 20-29 vs. ≥30 ng/ml) tended to be younger (p = 0.05), were less likely to use vitamin D supplementation (p < 0.01), and had better renal function (p = 0.03). Those with 25OHD <20 ng/ml had 80 and 126 % higher serum PTH levels respectively vs. those with 25OHD 20–29 ng/ml (p = 0.002) and 25OHD ≥30 ng/ml (p < 0.0001). Covariate-adjusted integral and trabecular vBMD were higher in those with 25OHD 20–29 vs. those with 25OHD ≥30 ng/ml, but those with 25OHD <20 did not differ. Because there were few participants with 25OHD deficiency, we also compared those with vitamin D <30 vs. ≥30 ng/ml. Covariate-adjusted integral and trabecular vBMD were 23 and 30 % higher respectively (both p < 0.05) in those with vitamin D <30 vs. ≥30 ng/ml. TBS was in the partially degraded range but did not differ by vitamin D status.
Conclusion
In mild PHPT, lower 25OHD is associated with higher PTH, but vitamin D deficiency and insufficiency using current clinical thresholds did not adversely affect lumbar spine skeletal health in PHPT. Further work is needed to determine if higher vBMD in those with lower vitamin D is due to an anabolic effect of PTH.
... The condition called osteitis fibrosa cystica (OFC), or brown tumor, constitutes a small percentage of osteolytic lesions in people with either primary or secondary hyperparathyroidism. 1 OFC represents a focal bone lytic lesion that often develops at multiple sites. 2 The radiographic findings of OFC can mimic bone malignancy, while the simultaneous involvement of multiple skeletal segments can be interpreted as diffuse metastatic disease. 3 In both presentations, the hypersecretion of PTH is observed, which results in increased osteoclastic activity, osteopenia and subperiosteal bone resorption. ...
Case summary
A 4-month-old cat had bilateral swellings of the mandible, maxilla, humerus and femur, and angular deviations in the axial and appendicular skeleton. The biochemical profile indicated hypercalcemia, hyperphosphatemia and increased parathyroid hormone levels. Because of the poor prognosis, the cat was euthanized. At necropsy, malleable and fragile bones, associated with numerous cystic areas containing yellowish and translucent liquid, were observed. Histologically, the bones showed marked diffuse proliferation of fibrous connective tissue, and large numbers of osteoclasts surrounding numerous cystic structures were also observed within fibrotic areas at the periphery of the trabecular bone. In addition, enlargement of the parathyroid glands, which was associated with increased serum concentrations of calcium, phosphorus and parathyroid hormone, was detected.
Relevance and novel information
The changes observed in this cat are consistent with hyperparathyroidism-associated osteitis fibrosa cystica, which is an unusual presentation in the cat. Hyperparathyroidism, either primary (neoplastic) or secondary (nutritional or renal), is the primary cause of this condition.
... 10 Patients with undiagnosed HPT presenting with severe bone disease such as a brown tumour are becoming increasingly less common as a result of earlier diagnosis and improved treatment. 11 This case posed two diagnostic challenges. Firstly, identifying primary HPT as the cause of the tumour, and secondly, identifying parathyroid carcinoma as the cause of the primary HPT prior to surgery. ...
This is a report of a maxillary brown tumour caused by primary hyperparathyroidism (HPT) secondary to parathyroid carcinoma. A 62-year-old man presented with a large swelling in the right maxilla, which caused right-sided nasal obstruction, intermittent bleeding and diplopia. A computed tomography scan demonstrated an expansible, destructive soft tissue mass centred on the right ethmoid sinus, extending from the maxilla to the orbital floor. Histology showed a central giant cell granuloma of bone, thought to be a brown tumour of HPT and this was supported by serum calcium of 3.0 mmol/l and serum parathyroid hormone of 880 ng/l (normal 7 to 40 ng/l). Parathyroid imaging was consistent with a left lower parathyroid adenoma. The patient underwent removal of the parathyroid gland, left hemithyroidectomy and central node dissection. Histology confirmed parathyroid carcinoma. Surgical removal of the brown tumour was offered but declined. The symptoms improved and the maxillary swelling gradually reduced in size. The management of brown tumours is controversial, but a pragmatic approach is essential to a successful outcome. The general consensus seems to be adequate treatment of the HPT and surgical excision of the brown tumour only if the mass effect of the lesion is troublesome.
... Common sites include the long bones, ribs, pelvis, and facial bones. [33] The lesions improve with treatment, often becoming sclerotic. If lesions fail to improve in appearance with treatment, an alternative diagnosis should be considered. ...
Focal lesions in bone are very common and many of these lesions are not bone tumors. These bone tumor mimickers can include numerous normal anatomic variants and non-neoplastic processes. Many of these tumor mimickers can be left alone, while others can be due to a significant disease process. It is important for the radiologist and clinician to be aware of these bone tumor mimickers and understand the characteristic features which allow discrimination between them and true neoplasms in order to avoid unnecessary additional workup. Knowing which lesions to leave alone or which ones require workup can prevent misdiagnosis and reduce patient anxiety.
... On histological exam the lesion may mimic a giant cell tumour of bone [35], therefore a bone biopsy may be quite contributing or even decisive [20,29,30], but not in all cases. ...
We report a case of 66-years-old woman mistakenly diagnosed as a metasases’ dissemination on a basis of mulitifocal skeleton lesion showed by 99mTc-MDP scanning, high serum calcium level and a vague breast tumour history. Additionally she suffered had humer and femur fractures. Immobilised and diagnosed as a cancer patient, she he was referred to palliative care. In hospice for the first time the suspicion of hyperparathyroidism was raised. When 99mTc-MIBI SPECT/CT scan revealed a parathyroid adenoma, also considering her biochemical parameters, she underwent the surgery. Following this her biochemical parameters normalised. This case illustrates a pitfall, which sometimes happens in this rare disease. A review of literature is provided.
Brown tumor represents a terminal stage of bone remodeling process due to an imbalance between osteoclastic and osteoblastic activity. It represents a reparative cellular process, rather than a neoplastic process mostly associated with primary or secondary hyperparathyroidism. Although parathyroidectomy is the first treatment of choice for brown tumors, several cases don’t resolve even after normalization of parathyroid hormone levels which leads to surgical intervention. Therefore, to avoid multiple bone surgeries in the same patient, it is crucial to have a conservative approach like targeted therapy which could block certain molecules involved in bone resorption. In this string, we have recognized and quantified three molecules namely sclerostin, MCP-1 and CD73 in brown tumors and correlated their expression with bone resorption pathogenesis and potential therapeutic approach.
Brown tumors are benign bone tumors that rarely complicate hyperparathyroidism, manifesting as fibrous and erosive lesions secondary to rapid and localized osteoclast turnover. These lesions are typical of primary hyperparathyroidism, but they are not often observed. We present the case of a 72-year-old woman presenting with asthenia, bone pain, and hemiplegia. Biological analysis showed primary hyperparathyroidism, cervical ultrasound a right parathyroid adenoma that fixed on scintigraphy. When cross-sectional imaging was performed, it revealed multiple bone tumors of the axial and peripheral trunk with spinal cord compression which were diagnosed as brown tumors related to parathyroid adenoma. We illustrate through this case the importance of multidisciplinary imaging techniques before raising the diagnosis, especially in unusual pathologies such as brown tumors.
A 48-year-old female with long-standing type 2 diabetes mellitus presented with acute onset of bilateral lower limb weakness. She had been previously well and denied any constitutional symptoms. Physical examinations revealed generalized lower limb weakness with bilateral lower limb hypotonia, power of 0 over 5, reduced deep tendon reflexes, and loss of peripheral sensations up to the level of T10. Upper limb functions were normal. Rectal examination showed a lax anal tone and reduced anal grip. Blood investigations showed elevated serum alkaline phosphatase, corrected serum calcium, and parathyroid hormone. Magnetic resonance imaging of the spine revealed an expansile mass at the posterior element of the ninth thoracic vertebrae, causing spinal compression with possible impingement of the right T9 exiting spinal nerve. An urgent surgical decompression and tissue biopsy were performed for stabilization of the spine. Intraoperative findings included spinal cord compression secondary to an epidural tumour mass extending from T9 to T10 disc levels. Histopathological analysis showed a giant cell tumour of the spine. A 99m Tc Sestamibi-SPECT parathyroid scintigraphy showed an ectopic parathyroid adenoma at the left suprasternal region. A diagnosis of Brown tumour secondary to ectopic parathyroid adenoma was made. She underwent an exploratory parathyroidectomy procedure with removal of the ectopic parathyroid gland, which resulted in a normalization of the serum calcium and parathyroid hormone. Unfortunately, her lower limb functions did not return to normal, and she remained paraplegic at 6 months postoperatively.
Primary hyperparathyroidism presenting with diffuse skeletal involvement, such as discrete osteoclastic bone lesions, is rare. We describe a 35-year-old woman who presented with a left mandibular mass that rapidly enlarged over 3 weeks. Radiological, histological, and biochemical investigations led to the diagnosis of brown tumor secondary to primary hyperparathyroidism. A neck ultrasound revealed a 1.5 × 2.3 × 4.6 cm mass at the lower pole of the left thyroid lobe, suggestive of a parathyroid adenoma. Bone scan showed additional abnormal foci of increased uptake in the maxilla, both femora, skull, and scapula. Brown tumors are treated primarily by correcting the underlying endocrine disorder, and a parathyroidectomy was performed.
A 23-year-old girl with hyperparathyroidism was referred for parathyroid scintigraphy in 1986 following a previously failed parathyroidectomy. The patient had raised serum calcium and parathormone. On examination, there was a palpable nodule in the left lobe of the thyroid.
Abstract Brown tumours do not represent neoplastic process, but they are focal bony lesions due to bone remodelling from either primary or secondary hyperparathyroidism. Their incidence is also low. The current literature on brown tumour is mainly in the form of case reports that focus on single affected sites. This pictorial review describes the full imaging workup and pathway of suspected brown tumour in the setting of both primary and secondary hyperparathyroidism. It aims to illustrate the management strategy to aid both clinicians and radiologists in suspected cases of brown tumour. We highlight the complementary roles that different imaging modalities can play in different settings including the importance of parathyroid ultrasound, 99mTc-sestamibi scintigraphy and SPECT/CT in the localisation of the parathyroid adenoma. We present cases with full clinical and imaging workup in both the acute and chronic setting and scenarios that require exclusion of primary and secondary bone malignancies.
Introduction:
The purpose of this study was to investigate the difference in surgical outcomes between symptomatic and asymptomatic patients with primary hyperparathyroidism (PHPT) and between patients with high serum calcium and those with normal blood calcium, as well as to explore the epidemiological trend of PHPT in northern China.
Methods:
Clinicopathologic data of 197 patients (50 men and 147 women) with PHPT who underwent surgery at the First Affiliated Hospital of Harbin Medical University from 2008 to 2017 were analyzed. Changes in clinicopathology were compared among different subgroups of patients. Patients were categorized into subgroups based on serum calcium levels, whether or not they presented with symptoms, and admission time.
Results:
Of the total patients, 82.23% had hypercalcemic primary hyperparathyroidism (HCPHPT), 17.77% had normocalcemic primary hyperparathyroidism (NCPHPT), 45.18% had symptomatic primary hyperparathyroidism (SPHPT), and 54.82% had asymptomatic primary hyperparathyroidism (ASPHPT). Seventy-seven cases of PHPT involved thyroid nodules, with 22 confirmed as papillary thyroid carcinoma, and 29 confirmed as nodular goiter. There was no significant difference in the success rate of surgery, postoperative recurrence rate, and the symptoms of temporary hypocalcemia between the HCPHPT and NCPHPT groups, and between the SPHPT and ASPHPT groups. The incidence of PHPT has increased threefold since 2013.
Conclusions:
Symptoms and serum calcium levels did not affect the results of surgical treatment for PHPT. The incidence of PHPT in northern China is increasing. Moreover, PHPT manifestation has shifted from the symptomatic to the asymptomatic form. Thyroid surgery should be performed in PHPT patients with thyroid nodules.
Objective: Mediastinal parathyroid adenomas are rare in clinical practice. We report a case that mimicked cancer metastatic to bone on initial workup to increase awareness of this differential diagnosis in the evaluation of patients presenting with multiple foci of uptake on technetium bone scanning without an established primary neoplasm. We also outline other diagnostic pitfalls that may be encountered in the workup and management of this uncommon condition.
Results: A 26 year-old man presented with a several month history of back and pelvic pain. Initial plain radiography showed multiple lytic lesions in the pelvis. Technetium bone scanning revealed multiple foci of increased uptake in the thoracic vertebrae, ribs, clavicles, pelvis and extremities. A CT scan demonstrated a mediastinal mass and an initial diagnosis of metastatic disease from a mediastinal primary malignancy was entertained. Further workup revealed a markedly elevated serum ionized calcium of 1.97 mmol/L (N 1.19–1.31) and parathyroid hormone (PTH) of 154.8 pmol/L (N 2.0–9.4). Parathyroid scintigraphy showed intense tracer accumulation in the anterior mediastinal mass. A median sternotomy was performed and histopathology was consistent with a parathyroid adenoma. Post-operatively the patient's ionized calcium and PTH levels normalized and pain resolved.
Conclusion: This case illustrates two clinical pearls: 1) brown tumor secondary to hyperparathyroidism is an important differential in the evaluation of patients presenting with widespread lytic bone lesions on CT or multiple foci of uptake on bone scan; and 2) the mediastinum is a rare location but should be considered in the workup of primary hyperparathyroidism.
IntroductionBasic Calcium PhysiologyParathyroid Hormone HypercalcaemiaPTH-Related Causes of HypercalcaemiaHypoparathyroidismEvidence AppraisalReferencesMultiple Choice Questions
The term “circumscribed myositis ossificans” designates a benign limited heterotopic ossification developing in muscle tissue usually secondary to trauma. In practice this label is less restrictive, as it may be argued that the lesion is not always situated in a muscle, and that in some cases development of the lesion is preceded by a quite characteristic infective process. In other cases there is neither a traumatic nor an infective history. These qualifications explain the numerous terms under which the lesion has been reported. Even if the term myositis ossificans is arrived at arbitrarily, it properly describes the majority of cases and recognition of its essentially benign nature avoids long arguments.
Der Serumkalziumspiegel wird normalerweise in engen Grenzen gehalten, um die ungestörte Gewebefunktion zu gewährleisten. Regelgröße ist hierbei der Spiegel des freien Kalziums (Normalwert: 1,1-1,3 mmol/l), das etwa 50% des Gesamtserumkalziums (Normalwert: 2,2-2,65 mmol/l) ausmacht. Etwa 40 % des Gesamtserumkalziums sind an Albumin gebunden, während etwa 10% als Phosphatoder Zitratsalzkomplexe vorliegen.
Nuclear medicine studies have important roles in the evaluation and localization of the diverse group of endocrine and neuroendocrine tumors that includes tumors of the parathyroid glands, tumors originating in neural crest-derived cells in the sympathetic nervous system, and neuroendocrine tumors. Nuclear medicine evaluation of these tumors typically has relied on single-photon emitting radiopharmaceuticals. Parathyroid imaging most commonly is performed with 99mTc-sestamibi. Imaging of other neuroendocrine tumors typically has used radioiodinated (123I, 131I) meta-iodobenzylguanidine (MIBG) and 111In-pentetreotide. There is a developing role for PET using 18F-FDG, as well as newer PET radiopharmaceuticals labeled with 18F, 11C, and 68Ga. © 2014 Springer Science+Business Media New York. All rights reserved.
Introduction:
Severe osteoporosis represents a disease of high mortality and morbidity. Recognition of what constitutes and causes severe osteoporosis and aggressive intervention with pharmacological agents with evidence to reduce fracture risk are outlined in this review. Areas Covered: This review is a blend of evidence obtained from literature searches from PubMed and The National Library of Medicine (USA), clinical experience and the author's opinions. The review covers the recognition of what constitutes severe osteoporosis, and provides up-to-date references on this sub-set of high risk patients. Expert Opinion: Severe osteoporosis can be classified by using measurements of bone densitometry, identification of prevalent fractures, and, knowledge of what additional risk factors contribute to high fracture risk. Once recognized, the potential consequences of severe osteoporosis can be mitigated by appropriate selection of pharmacological therapies and modalities to reduce the risk for falling.
Brown tumours (BT), an expression of osteitis fibrosa cystic due to primary hyperparathyroidism (pHPT), can occasionally be mistaken for malignancy. Among 615 patients who underwent parathyroidectomy for pHPT in our institution, the medical records of three patients affected by BT were reviewed. The first patient underwent surgical removal of the orbital mass for a suspected lachrymal gland neoplasm. The remaining two patients underwent, respectively, leg amputation and femur resection for a suspected bone malignancy. Final histology showed a BT in three cases. All three patients were admitted to our Division and underwent successful parathyroidectomy for parathyroid adenoma in two cases and for parathyroid carcinoma in the remaining case. When faced with an osteolithic bone lesion, complete evaluation of medical history, biochemical and radiographic findings can help to reach a correct diagnosis and avoid unnecessary bone resections.
We present the case of a female patient who had an intervention in a cervical nodule in the context of moderate hypercalcemia, with a histological diagnosis of a possible parathyroid carcinoma, whose later development made it necessary to rethink the diagnosis.
Intravenous disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate (pamidronate disodium) was used to treat 39 patients (22 males and 17 females, age range 48-85 years) with symptomatic Paget's disease. Patients were stratified into three groups based on the biochemical severity of the disease as assessed by fasting urinary hydroxyproline excretion (HypE, mumol/liter GF, glomerular filtrate): group I (n = 23), HypE < 5.0, treated with 120 mg total dose over 2 or 4 days; group II (n = 6), 5.0 < or = HypE < or = 10.0, 180 mg over 3 or 6 days; and group III (n = 10), HypE > 10.0, 240 mg over 4 or 8 days. Bone mineral density (BMD) was measured before and 3 and 6 months following treatment in the spine (L1-4) using dual-energy x-ray absorptiometry and in the forearm at an ultradistal and a shaft site using single-photon absorptiometry. When groups I-III were combined, nonpagetic and pagetic lumbar spinal BMD had both risen significantly at 3 months compared with the pretreatment values (p < 0.001). In each group, lumbar spinal BMD in pagetic vertebrae rose markedly by 3 months, with no further significant change at 6 months. The percentage rises in the three groups were not different from each other at 3 or 6 months. Nonpagetic lumbar spinal BMD followed a similar and significant trend but with a significantly smaller rise than for pagetic bone. (For the combined groups, nonpagetic BMD rose 5.1 +/- 1.1% SEM, above pretreatment at 6 months; pagetic BMD rose 17.8 +/- 1.6%: significance of comparison = p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Zusammenfassung Die meisten der heute diagnostizierten Patienten mit primärem Hyperparathyreoidismus (pHpt) sind asymptomatisch oder oligosymptomatisch.
Sie werden aufgrund von Screeninguntersuchungen im Rahmen der Differentialdiagnose einer zufällig entdeckten Hyperkalzämie
erkannt. Die Sicherung der Diagnose erfolgt durch den Nachweis einer persistierenden Hyperkalzämie und die Bestimmung eines
erhöhten intakten Parathormonspiegels. Unter Berücksichtigung von bestimmten Kriterien, insbesondere nur gering erhöhtem Serumkalzium
und weitgehend normalem Knochen-und Nierenstatus, ist eine sichere Langzeitbeobachtung von asymptomatischen Patienten mit
pHpt möglich.
Parathyroid hormone (PTH) and vitamin D are the most important hormones regulating calcium metabolism. In primary hyperparathyroidism (PHPT) excessive amounts of PTH are produced. Bone turnover is enhanced, leading to reduced bone mineral density and elevated levels of serum calcium. The aim of this study was to investigate relations between serum levels of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)(2)D) and bone mineral density, as well as known genetic polymorphisms in the vitamin D receptor and enzymes metabolising vitamin D in patients with PHPT.
We conducted a cross-sectional study of 52 patients with PHPT.
Mean level of 25(OH)D was 58.2 nmol/L and median 1,25(OH)(2)D level was 157 pmol/L. Among our patients with PHPT 36.5% had 25(OH)D levels below 50 nmol/L. Serum 1,25(OH)(2)D was inversely correlated to bone mineral density in distal radius (p = 0.002), but not to bone mineral density at lumbar spine or femoral neck. The vitamin D receptor polymorphism Apa1 (rs7975232) was associated with bone mineral density in the lumbar spine.
The results suggest that PHPT patients with high blood concentrations of 1,25(OH)(2)D may have the most deleterious skeletal effects. Randomized, prospective studies are necessary to elucidate whether vitamin D supplementation additionally increases serum 1,25(OH)(2)D and possibly enhances the adverse effects on the skeleton in patients with PHPT.
Brown tumours (BT), an expression of osteitis fibrosa cystic due to primary hyperparathyroidism (pHPT), can occasionally be mistaken for malignancy. Among 615 patients who underwent parathyroidectomy for pHPT in our institution, the medical records of three patients affected by BT were reviewed. The first patient underwent surgical removal of the orbital mass for a suspected lachrymal gland neoplasm. The remaining two patients underwent, respectively, leg amputation and femur resection for a suspected bone malignancy. Final histology showed a BT in three cases. All three patients were admitted to our Division and underwent successful parathyroidectomy for parathyroid adenoma in two cases and for parathyroid carcinoma in the remaining case. When faced with an osteolithic bone lesion, complete evaluation of medical history, biochemical and radiographic findings can help to reach a correct diagnosis and avoid unnecessary bone resections.
Intravenous disodium 3-amino-1-hydroxypropylidene-1,1-bisphosphonate pentahydrate (pamidronate disodium) was used to treat 39 patients (22 males and 17 females, age range 48-85 years) with symptomatic Paget's disease. Patients were stratified into three groups based on the biochemical severity of the disease as assessed by fasting urinary hydroxyproline excretion (HypE, mumol/liter GF, glomerular filtrate): group I (n = 23), HypE < 5.0, treated with 120 mg total dose over 2 or 4 days; group II (n = 6), 5.0 < or = HypE < or = 10.0, 180 mg over 3 or 6 days; and group III (n = 10), HypE > 10.0, 240 mg over 4 or 8 days. Bone mineral density (BMD) was measured before and 3 and 6 months following treatment in the spine (L1-4) using dual-energy x-ray absorptiometry and in the forearm at an ultradistal and a shaft site using single-photon absorptiometry. When groups I-III were combined, nonpagetic and pagetic lumbar spinal BMD had both risen significantly at 3 months compared with the pretreatment values (p < 0.001). In each group, lumbar spinal BMD in pagetic vertebrae rose markedly by 3 months, with no further significant change at 6 months. The percentage rises in the three groups were not different from each other at 3 or 6 months. Nonpagetic lumbar spinal BMD followed a similar and significant trend but with a significantly smaller rise than for pagetic bone. (For the combined groups, nonpagetic BMD rose 5.1 +/- 1.1% SEM, above pretreatment at 6 months; pagetic BMD rose 17.8 +/- 1.6%: significance of comparison = p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
We previously demonstrated an increase in cancellous bone volume and trabecular number in patients with mild primary hyperparathyroidism (PHPT). To test the hypothesis that this increase is due to preservation of cancellous bone architecture, we conducted a trabecular strut analysis using a new method that measures trabecular connectivity. Iliac crest biopsies from 37 patients with PHPT, 14 men (28–68 years) and 23 women (26–68 years), were examined histomorphometrically and compared to cadaveric samples from 24 age-matched subjects, 17 men and 7 women. Two-dimensional indices of cancellous structure–node number (N.Nd), terminus number (N.Tm), node to node (Nd.Nd), node to terminus (Nd.Tm), and terminus to terminus (Tm.Tm) strut lengths, and total strut length (TSL)–were measured and the ratio of node number to terminus number (N.Nd/N.Tm) calculated. TSL, N.Nd, and Nd.Nd were significantly higher in patients than in controls. TSL and Nd.Nd, but not N.Nd or Nd/Tm, decreased significantly with age in PHPT, indicating that age-related bone loss in PHPT occurs without significant loss of trabecular connectivity. Two-dimensional indices reflecting connectivity or the amount of bone, that is, N.Nd, Nd.Nd, N.Nd/N.Tm, and TSL, correlated positively with cancellous bone volume (BV/TV) and trabecular number (Tb.N) and negatively with trabecular spacing (Tb.Sp) in both PHPT and controls. Trabecular thickness (Tb.Th) correlated positively with Nd.Nd and Tb.N and negatively with Tm.Tm in PHPT but not in controls. The present data show that in PHPT there is not only greater cancellous bone volume and trabecular number but preserved trabecular connectivity as well. The data further support the hypothesis that in PHPT cancellous bone architecture is maintained.
Background: Primary hyperparathyroidism (PHPT) is the third most frequently diagnosed endocrine disorder worldwide. The aim of our study was to evaluate quantitative ultrasound (QUS) parameters of the hand in postmenopausal women with PHPT preoperatively, so that we may develop an effective method to compare the benefits of the patients after a successful parathyroidectomy. We hypothesized in this study that QUS evaluation of the hand may have an extra advantage in the assessment of cortical bone quality in patients with PHPT than standard bone density measurements with dual energy X-Ray absorptiometry (DXA). Methods: Sixteen postmenopausal women who had been diagnosed with primary hyperparathyroidism and 16 age-matched post-menopausal women were enrolled in the study. Bone mineral density (BMD) measurements were performed by dual-energy X-ray Absorptiometry (DXA) at the lumbar spine (L1-L4) and proximal femur (neck and total). Ultrasound measurements were performed at the 1/3 distal radius (RAD) and proximal phalanges of the third finger (PLX) on the non-dominant hand. Results: All parameters of the QUS measurements (T-scores for RAD and PLX, ORI™) were significantly lower in the PHPT group than in the control group (p < 0.05). However, there was no significant difference between the patients with PHPT and the control group when evaluated by DXA. Conclusions: This study indicates that QUS could be an alternative diagnostic approach in evaluating bone mass in post-menopausal women with PHPT since reflects early bone loss in these patients better than DXA measurement.
Parathyroid pathology is usually manifested clinically as hyperparathyroidism (HPT), resulting from parathormone (PTH) excess.
PTH is the chief hormone product of the parathyroid glands and can be overproduced in several complexly interrelated settings,
termed primary (PHPT), secondary (SHPT), and tertiary hyperparathyroidism (THPT). PHPT can arise sporadically or from inherited
syndromes that include multiple endocrine neoplasia type 1 (MEN1), multiple endocrine neoplasia type 2A (MEN2A), isolated
familial hyperparathyroidism (FHPT), and familial hyperparathyroidism-jaw tumor syndrome (FHJT). SHPT is secondary to hypocalcemia,
renal insufficiency, and/or severe vitamin D deficiency. THPT by definition occurs with a history of renal failure and long-standing
SHPT.
Almost any time a physician treats a bony lesion or fracture pathological to the spine, the world of poor bone quality is
entered. In order to improve understanding (and control) of the normal and diseased skeletal system, it is necessary to be
conversant with a basic knowledge of these disorders affecting the spine. Therefore, basic laboratory tests, which can aid
in the diagnostic work-up and evaluation of tumor recurrence, are reviewed in this chapter. It should be noted, though, that
this chapter provides only an overview on the subject and it does not provide a complete review of all laboratory tests and
prognostic factors applicable to spine tumor patients.
DA - 19970520
IS - 0140-6736 (Print)
IS - 0140-6736 (Linking)
LA - eng
PT - Journal Article
PT - Research Support, Non-U.S. Gov't
PT - Research Support, U.S. Gov't, P.H.S
PT - Review
RN - 0 (Parathyroid Hormone)
SB - AIM
SB - IM
Osteoanabolic therapy is an attractive therapeutic option for men with osteoporosis because it directly stimulates bone formation, an action not shared by any antiresorptive drug. Teriparatide (recombinant human PTH(1-34)) and PTH(1-84) are available in many countries but PTH(1-84) is not available in the United States. Only teriparatide is approved for the treatment of osteoporosis in men. It is also indicated in glucocorticoid-induced osteoporosis. Teriparatide is associated with major gains in bone density at the lumbar spine and, to a lesser extent, in the hip regions. Vertebral and nonvertebral fractures are reduced in postmenopausal women treated with teriparatide. Fracture reduction data in men are less secure because the number of study subjects is small and the studies have not been powered to document this endpoint. Nevertheless, observational data in men suggest a reduction in vertebral fractures with teriparatide. Attempts to show further beneficial effects of teriparatide in combination with antiresorptive agents have not been demonstrated yet to be superior to monotherapy with teriparatide alone. The duration of therapy with teriparatide is limited to 2 years. Thereafter, it is necessary to treat with an antiresorptive drug to maintain, and perhaps increase, densitometric gains. Teriparatide is well tolerated with a good safety profile.
Although the capacity of exogenous PTH1-34 to enhance the rate of bone repair is well established in animal models, our understanding of the mechanism(s) whereby PTH induces an anabolic response during skeletal repair remains limited. Furthermore it is unknown whether endogenous PTH is required for fracture healing and how the absence of endogenous PTH would influence the fracture-healing capacity of exogenous PTH.
Closed mid-diaphyseal femur fractures were created and stabilized with an intramedullary pin in 8-week-old wild-type and Pth null (Pth(-/-)) mice. Mice received daily injections of vehicle or of PTH1-34 (80 µg/kg) for 1-4 weeks post-fracture, and callus tissue properties were analyzed at 1, 2 and 4 weeks post-fracture. Cartilaginous callus areas were reduced at 1 week post-fracture, but were increased at 2 weeks post-fracture in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice respectively. The mineralized callus areas, bony callus areas, osteoblast number and activity, osteoclast number and surface in callus tissues were all reduced in vehicle-treated and PTH-treated Pth(-/-) mice compared to vehicle-treated and PTH-treated wild-type mice, but were increased in PTH-treated wild-type and Pth(-/-) mice compared to vehicle-treated wild-type and Pth(-/-) mice.
Absence of endogenous PTH1-84 impedes bone fracture healing. Exogenous PTH1-34 can act in the absence of endogenous PTH but callus formation, including accelerated endochondral bone formation and callus remodeling as well as mechanical strength of the bone are greater when endogenous PTH is present. Results of this study suggest a complementary role for endogenous PTH1-84 and exogenous PTH1-34 in accelerating fracture healing.
Brown tumor or Osteitis Fibrosa Cystica (OFC) is a rare clinical entity complicating hyperparathyroidism. It may occur in the head and neck, with the mandible being the most frequent site. Primary hyperparathyroidism is usually associated with hypercalcemia. We report a 35 years old female with mandibular brown tumor secondary to primary hyperparathyroidism. In this case in spite of primary hyperparathyroidism and the bony lesion the serum calcium level was within normal limit. This case demonstrates that in osteolytic bony lesions a hyperparathyroidism complication can be expected even with normal serum calcium level. The presence of normocalcemia in hyperparathyroidism should prompt the physician to measurement of ionized calcium and look for vitamin D deficiency, magnesium deficiency, impaired renal function, use of interacting drugs and associated disorders. If there weren’t these factors, normocalcemic primary hyperparathyroidism should be considered. Sci Med J 2010; 9(5):529-534
Disturbances in mineral and bone metabolism are common in patients with chronic kidney disease. The purpose of this follow-up study was to compare the change of bone mineral density in patients with chronic kidney disease to those who have received the renal transplant.
The study included 47 children and adolescents: 16 with mild to moderate kidney disease, 14 on dialysis and 17 patients with renal transplant. At the baseline and follow-up visits, regular biochemistry, anthropometry and bone mineral density were measured. To minimize the effect of skeletal size, bone mineral apparent density (BMAD; g/cm3) was calculated.
The mean height was below one standard deviation from reference values in patients on dialysis and in those with renal transplant. After correction for age, baseline and follow-up BMAD did not differ significantly between patients after transplantation and those with chronic kidney disease. The increase of BMAD between two measurements (mean period 16.0 +/- 4.4 months) was not significantly higher in patients with kidney transplant compared to those with chronic kidney disease. The significant predictors of BMAD were PTH in patients with chronic kidney disease and duration of steroid therapy in patients with renal transplant.
The results showed that bone density in children and adolescents, even several years after kidney transplantation, did not significantly change over time comparing to patients with chronic kidney disease. Hyperparathyroidism and steroid therapy were the most important risk factors for the slow increase of bone density.
A 73 year old woman was referred because of hypophosphataemia and raised serum alkaline phosphatase. She was a chronic hepatitis B carrier and regular monitoring had shown a persistently raised alkaline phosphatase (415-495 U/l; normal range 47-124). All other liver enzymes were within the normal range, and ultrasound of the liver was unremarkable.Further assessment showed low serum phosphate (0.51-0.63 mmol/l; 0.88-1.45), but normal albumin adjusted calcium (2.53-2.63 mmol/l; 2.24-2.63) and creatinine (40 µmol/l; normal 49-82). Her serum parathyroid hormone was extremely high at 689 ng/l (normal 9-52), serum calcidiol (25-hydroxyvitamin D) was low at 23.5 nmol/l (normal >50), and serum calcitriol (1,25-dihydroxycalciferol) was raised at 240.5 pmol/l (60.2-158.6).She was diagnosed with vitamin D insufficiency with secondary hyperparathyroidism and was prescribed cholecalciferol 800 IU/day. After three months of treatment, serum phosphate remained persistently low at 0.52 mmol/l and she had developed hypercalcaemia (albumin adjusted calcium 2.73 mmol/l). Her 24 hour urine for calcium was normal (7.1 mmol/day; 2.0-7.4) and parathyroid hormone remained raised at 691 ng/l.Questions1 What is the most likely diagnosis?2 What further investigations are needed before treatment can be started?3 What is the treatment of choice?Answers1 What is the most likely diagnosis?Short answerThe patient has primary hyperparathyroidism; vitamin D replacement seemed to unmask the hypercalcaemia.Long answerPrimary hyperparathyroidism is a common endocrine disorder. Up to 80% of patients have no symptoms of hypercalcaemia and only a small proportion present with associated complications such as hypercalciuria, renal stones, osteoporosis, and fractures.Vitamin D insufficiency is also a common problem worldwide, which often goes unrecognised. A serum calcidiol concentration of below 50 nmol/l is suggestive of vitamin D insufficiency. Recently, the National Institute of Health of the United States recommended a calcidiol value of greater than 75 nmol/l to reduce fracture risk, improve lower extremity function, and protect against development of colorectal cancer. …
El no disponer de valores normales de la densidad vertebral (DOV) por TCc en nuestra área geográfica ha hecho plantearse la posibilidad de obtener tablas propias pues es bien conocida la influencia de los factores genéticos, étnicos, nutricionales y otros en la mineralización ósea. Por otro lado, la presencia de una mayor osteopenia en un grupo de pacientes menopáusicas, con hiperpatiroidismo primario, osteodistrofia renal, nefrolitiasis cálcica y en tratamiento esteroideo crónico, hizo que se estudiara la DOV y algunos parámetros bioquímicos relacionados con el metabolismo óseo, con el fin de identificar a aquellos pacientes de riesgo. El análisis de los resultados muestra algunas diferencias entre nuestros valores de pacientes normales y la de los americanos sobre sobre todo en el grupo de mujeres. La determinación de la densidad ósea vertebral es importante sobre todo aquellas pacientes con menopausia quirúrgica, siendo las determinaciones de desoxipiridolina de parámetro que mejor predecía la DOV en las menopausias fisiológicas y el calcitriol en las menopausias quirúrgicas.
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