Genetic testing in patients with primary hyperparathyroidism: when is screening worthwhile?


N Chander, C Camenzuli, A Paspala, NS Tolley, A Di Marco, J Todd, F Wernig, FF Palazzo, Imperial Healthcare NHS Trust, London


CC216706Background: Primary hyperparathyroidism (pHPT) affects 1:1000 of the population but increases in prevalence with age, such that 2% of post-menopausal women have the condition. Approximately 95% of pHPT is sporadic and 5% related to familial inherited disorders, most commonly Multiple Endocrine Neoplasia type 1 syndrome (MEN1). Almost all MEN1 patients develop pHPT, and the disease is biochemically evident in over 90% by the age of 20 years. According to international guidelines, it is therefore recommended that genetic testing be performed in patients diagnosed with pHPT below the age of 30 years; however, the threshold age for testing remains controversial. The purpose of this study was to assess the use of genetic testing in early onset pHPT, to determine the yield of genetic abnormality and possibly the optimal age for genetic testing.


Methods: This was a retrospective observational study of a prospectively collected database of all patients 40 years and under, that underwent parathyroidectomy between February 2010 and February 2019. Electronic patient records were used to identify: age at operation; number of parathyroid glands removed; whether a referral for genetic testing was made and the results of any genetic tests. For patients referred for genetic testing, the genes most commonly tested for mutations included MEN1, MEN2, CASR, CDC73, CDKN1A, CDKN1B, CDKN2B and CDKN2C.


Results: An initial database search yielded a total number of 158 patients that fulfilled the above criteria, of which 70 patients were identified that had all required electronic notes available for analysis. Of these 70 patients, 48 had undergone genetic testing, and 15 were confirmed to have a gene mutation causing pHPT. A small proportion of patients who tested positive, were determined to have variations of uncertain significance. The age of patients who tested positive ranged from 19 to 40 years old, with a mean age of 30 years.


Conclusions: Our study demonstrates a high yield of causal genetic abnormalities in young patients undergoing parathyroidectomy. Genetic testing is therefore justified in younger patients diagnosed with pHPT, even up to the age of 40 years, since it may impact on surgical strategy and patient informed consent for surgery.