Primary Hyperparathyroidism and Familial Hypocalciuric Hypercalcemia: Relationships and Clinical Implications

Eldeiry, Leslie S.; Ruan, Daniel T.; Brown, Edward M.; Gaglia, Jason L.; Garber, Jeffrey R.

doi:10.4158/ep11272.ra

Cited by 33 publications

(21 citation statements)

References 21 publications

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“…In addition to the previously described cancer predisposition syndromes, a group of familial ‘hypercalcemic’ syndromes (FHH-1, FHH-2, FHH-3, neonatal severe HPT, familial hypercalciuric hypercalcaemia) has been reported to cause HPT, due to aberrant inactivation of CaSR signalling in the parathyroid glands, kidneys and skeletal bones 13 32 42 75 76 77 141. These conditions are generally inherited in an autosomal-dominant manner and appear to have near-complete penetrance for the phenotypical expression of hypercalcaemia 13 32 42 75–77 141 167.…”

Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

Clinicopathological correlates of hyperparathyroidism

2015

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Hyperparathyroidism is a common endocrine disorder with potential complications on the skeletal, renal, neurocognitive and cardiovascular systems. While most cases (95%) occur sporadically, about 5% are associated with a hereditary syndrome: multiple endocrine neoplasia syndromes (MEN-1, MEN-2A, MEN-4), hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH-1, FHH-2, FHH-3), familial hypercalciuric hypercalcaemia, neonatal severe hyperparathyroidism and isolated familial hyperparathyroidism. Recently, molecular mechanisms underlying possible tumour suppressor genes (MEN1, CDC73/HRPT2, CDKIs, APC, SFRPs, GSK3β, RASSF1A, HIC1, RIZ1, WT1, CaSR, GNA11, AP2S1) and proto-oncogenes (CCND1/PRAD1, RET, ZFX, CTNNB1, EZH2) have been uncovered in the pathogenesis of hyperparathyroidism. While bi-allelic inactivation of CDC73/HRPT2 seems unique to parathyroid malignancy, aberrant activation of cyclin D1 and Wnt/β-catenin signalling has been reported in benign and malignant parathyroid tumours. Clinicopathological correlates of primary hyperparathyroidism include parathyroid adenoma (80–85%), hyperplasia (10–15%) and carcinoma (<1–5%). Secondary hyperparathyroidism generally presents with diffuse parathyroid hyperplasia, whereas tertiary hyperparathyroidism reflects the emergence of autonomous parathyroid hormone (PTH)-producing neoplasm(s) from secondary parathyroid hyperplasia. Surgical resection of abnormal parathyroid tissue remains the only curative treatment in primary hyperparathyroidism, and parathyroidectomy specimens are frequently encountered in this setting. Clinical and biochemical features, including intraoperative PTH levels, number, weight and size of the affected parathyroid gland(s), are crucial parameters to consider when rendering an accurate diagnosis of parathyroid proliferations. This review provides an update on the expanding knowledge of hyperparathyroidism and highlights the clinicopathological correlations of this prevalent disease.

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Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

Clinicopathological correlates of hyperparathyroidism

2015

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“…In the Fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism, they suggested the use of urinary calcium and calcium-creatinine clearance ratio (UCCR) to differentiate BFHH from PHPT with an UCCR less than 0.01 in favor of BFHH. Unfortunately, UCCR has limitations (vitamin D deficiency, renal failure, and African-American origins) and patients with BFFH have been misdiagnosed to have PHPT in more than 20% of cases [8,9]. Moreover, 20% of patients with BFHH have UCCR greater than 0.01.…”

Section: Resultsmentioning

confidence: 99%

Persistent and recurrent hyperparathyroidism

et al. 2017

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Despite remarkable progress in imaging modalities and surgical management, persistence or recurrence of primary hyperparathyroidism (PHPT) still occurs in 2.5-5% of cases of PHPT. The aim of this review is to expose the management of persistent and recurrent hyperparathyroidism. A literature search was performed on MEDLINE using the search terms "recurrent" or "persistent" and "hyperparathyroidism" within the past 10 years. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Before considering reoperation, the surgeon must confirm the diagnosis of PHPT. Then, the patient must be evaluated with new imaging modalities. A single adenoma is found in 68% of cases, multiglandular disease in 28%, and parathyroid carcinoma in 3%. Others causes (<1%) include parathyromatosis and graft recurrence. The surgeon must balance the benefits against the risks of a reoperation (permanent hypocalcemia and recurrent laryngeal nerve palsy). If surgery is necessary, a focused approach can be considered in cases of significant imaging foci, but in the case of multiglandular disease, a bilateral neck exploration could be necessary. Patients with multiple endocrine neoplasia syndromes are at high risk of recurrence and should be managed regarding their hereditary pathology. The cure rate of persistent-PHPT or recurrent-PHPT in expert centers is estimated from 93 to 97%. After confirming the diagnosis of PHPT, patients with persistent-PHPT and recurrent-PHPT should be managed in an expert center with all dedicated competencies.

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“…Interestingly, 6 of 14 (42.9%) FHH patients in our investigation presented CCCR values of >0.01. Furthermore, treatment with thiazide may result in a distorted 24hU CE and a low CCCR . Consecutively, the specificity of CCCR would be reduced.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, treatment with thiazide may result in a distorted 24hU CE and a low CCCR. 15,16 Consecutively, the specificity of CCCR would be reduced. Therefore, thorough knowledge of a given patient's medical history is necessary.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of calcium excretion and calcium/creatinine clearance ratio in the differential diagnosis of familial hypocalciuric hypercalcemia and primary hyperparathyroidism

et al. 2018

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Background Twenty‐four‐hour renal calcium‐excretion (CE) and calcium/creatinine‐clearance‐ratio (CCCR), respectively, are widely used to rule out familial hypocalciuric hypercalcemia (FHH) in patients with suspected primary hyperparathyroidism before surgery. The aim was to evaluate the practicability of CE compared to CCCR. Patients and Methods We analyzed biochemical parameters, surgical treatment, gene mutation results, and long‐term follow‐up data of 198 patients (including 14 patients with FHH) and the discriminative power of CE and CCCR. Results Twenty four patients (12.1%) had a low CE and 35 patients (20.2%) had a CCCR indicating FHH. However, eight patients with FHH (57.1%) had a normal or increased CE. Correspondingly, only eight cases of FHH (57.1%) were correctly predicted by CCCR. Sensitivity/specificity were 42.9%/89.9% for CE and 64.3%/79.9% for CCCR, showing no statistical differences (P = 0.482) between both methods. Conclusion Neither CE nor CCCR was able to distinguish between PHPT and FHH but may help to narrow down potential FHH patients.

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Primary Hyperparathyroidism and Familial Hypocalciuric Hypercalcemia: Relationships and Clinical Implications

Cited by 33 publications

References 21 publications

Clinicopathological correlates of hyperparathyroidism

Clinicopathological correlates of hyperparathyroidism

Persistent and recurrent hyperparathyroidism

Efficacy of calcium excretion and calcium/creatinine clearance ratio in the differential diagnosis of familial hypocalciuric hypercalcemia and primary hyperparathyroidism

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