Abstract
Introduction: Multiple Endocrine Neoplasia type 1 (MEN1) is characterized by tumours of the parathyroid glands, neuroendocrine pancreatic tumour (PNET), and anterior pituitary. Studies suggest that MEN1 gen is not etiologically related to the oncogenesis of the papillary thyroid carcinoma (PTC). Expression of menin is preserved in human normal thyroid tissue and THc. Papillary thyroid carcinoma (PTC) combined with multiple endocrine neoplasia type 1 is a rare association. Cushing Syndrome (CS) is another rare associated condition with MEN-1. In patients with MEN1, CS can result from pituitary, adrenal, or other endocrine tumours. In large series of MEN-1 CS has low frequency (0.5%) or not described. Clinical Case: A.M.F.A, 49 years, female. In 2007, cytological study of thyroid nodules resulted in PTC, underwent total thyroidectomy. Anatomopathological (AP) confirmed PTC. She was followed with an excellent response to therapy. In 2018, abdominal ultrasound due to epigastric pain showed pancreatic lesion. MRI confirmed lesion in the head and body of the pancreas of 8.2cm. She underwent total gastroduodenopacreatectomy (TGDP), AP showed a well-differentiated PNET (KI67: 2%). Before TGDP, tests for MEN-1 were collected: IGF-1 of 450 ng/ml (RV for age: 90-249 ng/ml); calcium: 1,46 nmol/l (RV: 1,12-1,40), PTH: 91,7 pg/ml (RV: 15-65), prolactin 13,3 ng/ml (RV: 5-23), gastrin 22pg/ml (RV 13-115), and late night salivary cortisol (LNSC): 8,3 nmol/l (RV <7,6). Pituitary MRI showed a 0.5cm intrasellar nodule. Genetic study revealed c654 + 1G>T mutation in heterozygosity. O3 family members had the same mutation. To investigate hypercortisolism, it was made basal ACTH (56,1 pg/ml (VR 46 pg/ml), urine free cortisol (UFC) of 261,0 mcg/24h, 1mg DST of 15,2 mcg/dl (RV <1,8), basal cortisol of 16,5 mcg/dl and 8mg DST of 13,7 mcg/dl (not 50% suppressing of basal value). Another measurement of IGF-1 (after the PNET surgery) was normal. A petrosal venous sinus catheterization (PVSC) was made, which was compatible with Cushing’s disease (CD). She had brittle hair, facial plethora, proximal muscle weakness and easily bruising, without other clinical CS aspects. Treatment with ketoconazole was initiated and she was referred to transesphenoidal surgery. Conclusion: Patient had two rare presentation of MEN1, first manifestation was PTC. PNET and CD was diagnosed 11 years late during clinical follow up. In this patient, MEN1 syndrome may have predisposed the patient to developing PTC. Currently, little is known about the prevalence of THc in MEN1 and it is unclear whether tumorigenesis is related. Further studies and additional case reports are required to clarify this connection. Also, we observed IGF-1 value normalized after TGDP, so it could be caused by a functional PNET. Rare causes of acromegaly are excess secretion of GH-releasing hormone (GHRH) by hypothalamic tumours, and ectopic GHRH or GH secretion by NET.
A Germline Mutation, 1001delC, of the Multiple Endocrine Neoplasia Type 1 (MEN 1) Gene in a Japanese Family.
