Endocrine Abstracts

Background and Aim: Primary hyperparathyroidism (PHPT) is a common endocrine disorder. A small proportion of these patients may have syndromic conditions such as multiple endocrine neoplasia (MEN) or familial hypocalciuric hypercalcemia (FHH). The UK national guidelines recommend genetic testing for familial hyperparathyroidism in individuals under 50 or any age with specific criteria such as family history, multi glandular disease, hyperplasia, or parathyroid carcinoma. Genetic testing for familial hypocalciuric hypercalcemia (FHH) is recommended in patients with hypercalcemia with hypocalciuria (urinary calcium creatinine clearance ratio <0.02). The aim of our study was to assess the uptake and utility of genetic testing and its diagnostic yield in patients referred to endocrine clinic with possible primary hyperparathyroidism.

Methods: A retrospective analysis of the genetic tests performed in patients with primary hyperparathyroidism over 7 years was done. Along with routine testing with PTH, bone profile and vitamin D, all patients underwent screening for FHH with urinary calcium/creatinine ratio and/or 24 h urine calcium excretion. Data on additional hormonal tests (fasting gut hormone profiles, pituitary profile, catecholamine level), and imaging to evaluate pathological glands (Ultrasound (US) and MIBI scan) was collected.

Results: A total of 33 patients underwent genetic testing for PHPT, and results were available for 26. 70% (n=23) were females. The mean age at diagnosis was 44 years (range 16-66). Additional hormonal testing was conducted for 25 patients. Ultrasound of parathyroid glands was performed in 30 patients, with 21 positive results. Additionally, 28 patients underwent Nuclear Medicine Parathyroid MIBI scans with 12 positive results. Various indications and numbers tested were: a) 14 patients due to age <50 years old. b) 8 for failed localization on imaging modalities. c) 4 for low urine calcium creatinine ratio. d) 2 for recurrence of primary hyperparathyroidism. e) 2 for parathyroid hyperplasia on post-operative histology. f) 2 for associated hormone problems (one each with elevated gastrin and chromogranin A). 1 for coexistent pituitary adenoma. Genetic tests confirmed CASR gene mutation in 2 patients confirming FHH. None of the patients had MEN-1 or MEN-2 gene mutations.

Conclusion: Our data indicates that, despite a high index of suspicion for MEN and FHH based on risk factors and clinical presentation, the actual prevalence is low in this highly selected cohort, with sporadic occurrence being the most common presentation.