Multiple Endocrine Neoplasia is characterised by the occurrence of tumours involving two or more endocrine glands within a single patient. MEN are autosomal dominant disorders. Four forms have been described: MEN 1 due to menin mutations, MEN2 (previously MEN2A) due to mutations of a tyrosine kinase receptor encoded by the rearranged during transfection (RET) protoncogene, MEN3 (previously MEN2B) due to RET mutations and MEN4 due to cyclin-dependent kinase inhibitor (CDNK1B) mutations. Each MEN is associated with the occurrence of specific tumours. MEN4 is characterized by the occurrence of parathyroid and anterior pituitary tumours in association with tumours of the adrenals, kidneys, and reproductive organs.
We are presenting the case of a 31 year old female referred to our Endocrine Clinic by the Fertility Clinic with hyperprolactinaemia (PRL: 1158 mu/L) in March 2010. Her MRI pituitary revealed a microprolactinoma and was started on cabergoline with good response (PRL: 156 mu/L). In August 2016, she came back in Clinic for her routine follow up. Her prolactin levels remained normal but hypercalcaemia (CorrCa: 2.70 mmol/L) was noted. Her PTH was subsequently tested and found to be elevated (9.9 pmol/L) and her Vitamin D levels were normal (79 nmol/L). The results were in keeping with primary hyperparathyroidism. Her MIBI and USS parathyroid didnt reveal any distinct adenoma. The suspicion of MEN was raised and she was referred for genetic testing. Mutation analysis of the AIP, CDKN1B, MEN1 and RET genes was requested. The patient was found to be heterozygous for a novel CDKN1B frameshift mutation consistent with a diagnosis of MEN4.
This case illustrates the required level of clinical suspicion when encountering cases of patients with more than one endocrinopathies in order to refer the appropriate cases for genetic testing. It also underlines that the management of these cases requires multidisciplinary approach and input from various specialities (endocrinologists, clinical geneticists, radiologists, oncologists).