HomeHyperparathyroidism in MEN1 Syndrome
Multiple Endocrine Neoplasia Type 1 syndrome
Multiple Endocrine Neoplasia Type 1 syndrome is caused by a germline mutation in the multiple endocrine neoplasia type 1 gene encoding the tumor-suppressor protein menin. This syndrome is presentated with: primary hyperparathyroidism (PHPT) in 95% of patients, pancreatic neuroendocrine tumors (NET) in 40–70% of patients (gastrinomas (40%), insulinomas (10%), glucagonomas (1%), VIPoma (1%), PPomas and nonfunctioning), anterior pituitary tumors in 30–40% of patients (prolactinomas (20%), somatotrophinomas (10%), corticotropinomas (5%), and nonfunctioning adenomas (5%)). In addition: adrenocortical tumors (40%), pheochromocytoma (1%), bronchopulmonary NET (2%), thymic NET (2%), gastric NET (10%), lipomas (30%), angiofibromas (85%), collagenomas (70%), meningiomas (8%), thyroid tumors (adenomas, colloid goiters, carcinomas) (25%) could be seen as well.
The diagnosis is established either clinically: occurrence of 2 or more MEN1-related NET in a single patient, or by blood test for the MEN 1 gene mutation.
About 1336 mutations were characterized (1133 germline and 203 somatic) in the MEN1 gene (> 600 different mutations reported in the Human Gene Mutation Database). Approximately 30 of them - Familial Isolated Hyperparathyroidism (FIHP) syndrome. Penetrance of the MEN1 gene is almost complete after the 7th decade of life. No genotype-phenotype correlations have been identified: the same mutation in unrelated families can present with different phenotypes, unique to each family. There is a variation within the family as well.
Primary Hyperparathyroidism in Multiple Endocrine Neoplasia Type 1 syndrome
Presentation of hypercalcemia in MEN Type 1 syndrome is usually mild; parathyroid cancers are very rare (less than 1%). The age of onset of the hypercalcemia is earlier (20 to 25 years old). It has been reported, however, that there is a greater reduction in bone density than in non-MEN1 primary hyperparathyroidism. The most common findings are hyperplasia of all four parathyroid glands, with asynchronous, asymmetric growth; even if some glands appear macroscopically normal, pathological evaluation will still show hyperplasia. It has been reported that supernumerary glands are present in up to 20% of MEN1 patients, which explains the limitations of preoperative studies. Because of an uncontrollable growth pattern and the presence of supernumerary (ectopic) glands, the rate of persistent diseases is higher and described as less than 20% in an expert surgeon and 40–60% in a non-expert (the definition of an expert parathyroid surgeon is someone who performs more than 50-100 parathyroid surgeries a year)
Initial treatment of primary hyperparathyroidism in MEN1 is recommended to be first as a subtotal parathyroidectomy (3&1/2) with transcervical partial thymectomy. A total parathyroidectomy with autotransplantation may be reserved for those patients with extensive disease either at first or at repeat surgery. Prophylactic transcervical thymectomy should be performed in all patients (consider the presence of supernumerary parathyroid glands to prevent the development of thymic carcinoid. With a subtotal parathyroidectomy (3&1/2 glands), 40 to 60% of patients will have persistence or recurrence of primary hyperparathyroidism within 10 years after surgery; and 10 to 30% of patients will have persistent hypoparathyroidism
References:
R. Thakker, J Clin Endocrinol Metab 97: 2990–3011, 2012
Lemos MC, Thakker RV. Hum Mutat 2008, 29:22–32
Giusti F, Brandi ML. Clinics (Sao Paulo). 2012;67 Suppl 1:141-4.
R. Thakker, J Clin Endocrinol Metab 97: 2990–3011, 2012
Neuroendocrine Thymic Carcinoma Metastatic to the Parathyroid Gland that was Reimplanted into the Forearm in a Patient with Multiple Endocrine Neoplasia Type 1 Syndrome: A Challenging Management Dilemma. Shifrin A, Livolsi V, Zheng M, Lann D, Fomin S, Naylor E, Mencel P, Fay A, Erler B, Matulewicz T. Endocr Pract. 2013 Sep 6:1-14.
