Endocrine Abstracts

Introduction: The association between pituitary adenoma and hyperparathyroidism is the main feature of multiple endocrine neoplasia (MEN) 1 but also for a novel MEN4 syndrome. Germline mutations in the cyclin-dependent kinase (CDK) inhibitor 1b gene (CDKN1B) were identified in patients with MEN4. The most common phenotype of the 19 established cases of MEN4 that have been described since now is primary hyperparathyroidism (PHPT) followed by pituitary adenomas. There are a limited number of cases with MEN4 and that way the association between phenotype and genotype is very difficult in order to have a positive diagnosis.

Aim: Tto present the discovery in uncommon circumstances of multiple endocrine tumors in a patient with no signs or symptoms of endocrine disorders and the difficulty to classify a possible MEN 1 or 4 syndromes.

Case presentation: We report the case of a 74-year-old female without significant family history of endocrine disease who was discovered with pituitary tumor (12/9.5 mm) and right adrenal incidentaloma (34/19 mm) at CT scan. The medical history revealed the presence of hypertension and a hip fracture at the age of 60. The patient was overweight (BMI = 26 kg/m²) with no particular signs of endocrine dysfunctions. The endocrine panel taking into account both pituitary and adrenal tumors revealed GH nadir during OGGT = 23.7 pg/ml, IGF1 = 456 ng/ml (64–188) with central thyroid insufficiency (TSH = 0.027 µUI/ml, fT4 = 1.39 ng/dl) and normal values for: prolactine, ACTH, plasma cortisol, free urinary cortisol, 24-hour urinary fractionated metanephrines. The ultrasound of the neck area discovered the presence of multiple thyroid macronodules and o nodular lesion located posterior to the right thyroid lobe suggestive for parathyroid adenoma. High levels of parathyroid hormone (186.2 pg/ml), hypercalcemia (11.04 mg/dl) along with osteoporosis (distal forearm T-score = –3.1 S.D.) and normal values of vitamin D were consistent with the diagnosis of PHPT. The parathyroid 99mTc-MIBI scintigraphy revealed the presence of multiple adenomas in all four glands. Regarding the thyroid the level of calcitonine was normal also the fine needle aspiration biopsy. The patient declines the surgical treatment for GH secreting pituitary adenoma and also PHPT. Somatostatin analogues and close surveillance was the decision for this patient.

Conclusion: In the absence of genetic result of possible mutation is very difficult to decide the MEN type or to conclude for simple concomitance. The phenotype otherwise extremely suggestive for MEN is not enough for delimitation between the type 1 and 4.

Keywords: MEN1, MEN4, fenotype, genotype.