An unusual case of an ACTH-secreting macroadenoma with a germline variant in the aryl hydrocarbon receptor-interacting protein ( AIP ) gene

[摘要] A patient of Cushing’s disease (CD) characterized by a large tumor and only subtle symptoms of hormonal hypersecretion wasexamined. The patient had a germline variant in the aryl hydrocarbon receptor-interacting protein (AIP) gene. A 50-year-oldmale presenting with headache was diagnosed with a large pituitary tumor by magnetic resonance imaging (MRI). His visualfields were intact and he exhibited no features of CD. Owing to an exuberant response to synacthen, an overnightdexamethasone suppression test was performed revealing inadequate suppression of plasma cortisol (419 nmol/l). Owingto tumor growth and visual field impairment, he underwent transsphenoidal surgery and developed hypocortisolemia.The pathology specimen revealed a sparsely granulated corticotrope adenoma. Postoperative MRI showed a large tumorremnant. The patient developed skin hyperpigmentation and a synacthen test demonstrated high basal and stimulatedcortisol levels; an overnight dexamethasone suppression test showed no suppression (791 nmol/l) and elevated plasma ACTHlevels (135 ng/l). A transcranial operation was performed followed by radiotherapy. Two months after radiotherapy, hedeveloped secondary adrenocortical failure. Genetic testing revealed an AIP variant of unknown significance (p.R16H)without loss of the normal AIP allele in the tumor. A literature review showed ten CD patients with AIP gene variants, ofwhom five (including our case) were p.R16H. CD is occasionally dominated by pituitary tumor growth rather than symptomsof hypersecretion. The particular AIP gene variant identified in our patient is shared by four other reported cases of CD.Future studies are needed to assess whether the reported AIP gene variant is more than just coincidental.

[学科分类] 血液学

[关键词] Adult;Male;White;Denmark;Pituitary;Pituitary;Cortisol;Cushing's syndrome;Cushing's disease;Pituitary adenoma;Diabetes insipidus - neurogenic/central;AIP gene variant;Headache;Polydipsia;Polyuria;Nocturia;Hyperpigmentation;ACTH;ACTH stimulation;MRI;Cortisol (serum);IGF1;Dexamethasone suppression test;Transsphenoidal surgery;Radiotherapy;Hydrocortisone;Glucocorticoids;Prednisolone;Somatostatin analogues;GH;Levothyroxine;Testosterone;Desmopressin;Genetics;Unique/unexpected symptoms or presentations of a disease;January;2015