Frequency of familial pituitary adenoma syndromes among patients with functioning pituitary adenomas in a reference outpatient clinic.

INTRODUCTION: Pituitary adenomas (PA) occur mainly as sporadic disease, but familial syndromes are found in approximately 5% of cases. Identification of these syndromes is important in order to diagnose individuals at risk at an earlier stage. AIMS: To evaluate the frequency of familial PA in a reference outpatient clinic devoted to PA treatment and to identify family members suspected to have pituitary disease. METHODS: Patients with PA were interviewed with respect to the presence of family members with diagnosis of PA or with signs or symptoms suggestive of them. The family members who had a clinical picture suggestive of pituitary disease were further evaluated in an attempt to identify new PA cases. In families with familial disease, the AIP gene was sequenced. RESULTS: 262 patients were evaluated and familial syndrome was found in 13 (5%). Ten (3.8%) patients had familial isolated PA (FIPA) and three (1.2%) had multiple endocrine neoplasia type 1. After evaluation of family members' symptomatology, 110 were considered suspected of having pituitary disease, but only 24 participated in the study. Of these 24, 1 was diagnosed with a corticotropinoma. AIP mutations were found in 20% of FIPA families. CONCLUSION: We found a frequency of familial PA similar to that previously described, as well as a similar frequency of AIP mutations among FIPA families. An active search of the affected family members was able to identify one case of Cushing´s disease. Patients should be aware of pituitary disease's clinical picture to identify possibly affected family members.

Familial Acromegaly and Bilateral Asynchronous Pheochromocytomas in a Female Patient With a MAX Mutation: A Case Report.

Background: There are very few cases of co-occurring pituitary adenoma (PA) and pheochromocytomas (PCC)/paragangliomas caused by MAX mutations. No cases of familial PA in patients with MAX mutations have been described to date. Case Presentation: We describe a 38-year-old female patient, presenting with clinical and biochemical features of acromegaly and PCC of the left adrenal gland. Whole-exome sequencing was performed [NextSeq550 (Illumina, San Diego, CA, USA)] identifying a nonsense mutation in the MAX gene (NM_002382) [c.223C>T (p.R75X)]. The patient had a medical history of PCC of the right adrenal gland diagnosed aged 21 years and prolactinoma diagnosed aged 25 years. Cabergoline treatment was effective in achieving remission of prolactinoma at age 33 years. The patient's father who died at age 56 years of a heart attack had a medical history of PA and prominent acromegalic features, which supports the familial presentation of the disease. Conclusion: This clinical case gives an insight into the clinical presentation of familial PA and PCC probably associated with a MAX mutation.