Background: Hereditary hyperparathyroidism has been reported to occur in 5-10 % of cases of primary hyperparathyroidism in the context of multiple endocrine neoplasia (MEN) types 1, 2A and 4; hyperparathyroidism-jaw tumour (HPT-JT); familial isolated hyperparathyroidism (FIHPT); familial hypocalciuric hypercalcaemia (FHH); neonatal severe hyperparathyroidism (NSHPT) and autosomal dominant moderate hyperparathyroidism (ADMH). This paper aims to review the controversies in the main genetic, clinical and pathological features and surgical management of hereditary hyperparathyroidism.
Methods: A peer review literature analysis on hereditary hyperparathyroidism was carried out and analyzed in an evidence-based perspective. Results were discussed at the 2015 Workshop of the European Society of Endocrine Surgeons devoted to hyperparathyroidism due to multiple gland disease.
Results: Literature reports scarcity of prospective randomized studies; thus, a low level of evidence may be achieved.
Conclusions: Hereditary hyperparathyroidism typically presents at an earlier age than the sporadic variants. Gene penetrance and expressivity varies. Parathyroid multiple gland involvement is common, but in some variants, it may occur metachronously often with long disease-free intervals, simulating a single-gland involvement. Bilateral neck exploration with subtotal parathyroidectomy or total parathyroidectomy + autotransplantation should be performed, especially in MEN 1, in order to decrease the persistent and recurrent hyperparathyroidism rates; in some variants (MEN 2A, HPT-JT), limited parathyroidectomy can achieve long-term normocalcemia. In FHH, surgery is contraindicated; in NSHPT, urgent total parathyroidectomy is required. In FIHPT, MEN 4 and ADMH, a tailored case-specific approach is recommended.
Keywords: ADMH; FHH; FIHPT; Familial primary hyperparathyroidism; HPT-JT; Hereditary primary hyperparathyroidism; MEN 1; MEN 2; MEN 4; Multiple gland disease; NSHPT; Parathyroidectomy.