Endocrine Abstracts

Introduction: Adrenal adenoma is one of the extraintestinal lesions associated with familial adenomatous polyposis (FAP). Only four cases of Cushing’s syndrome due to adrenal adenoma complicated by FAP, including ours, have been reported to date.

Case report: A 37-year-old woman presented with pretibial edema and hirsutism. She was diagnosed with FAP at 8 years old. She had undergone resection of craniopharyngioma at 10 years old and repeated removal of desmoid tumors. Polyposis was observed in the stomach, duodenum, upper jejunum, and large intestine. Polypectomy was performed for a large intestine lesion. Her mother and younger sister also had FAP, but her mother had died of colorectal cancer. The patient had developed hypertension and menstrual abnormalities at the age of 35 years. She also had diabetes (HbA1c 7.7%) and was obese (BMI 31.1 kg/m²). Upon physical examination at our hospital, facial fullness, morbid obesity, a buffalo hump, striae, pretibial edema, subcutaneous bleeding spots, and hypertrichosis were detected. Laboratory assays revealed hypercortisolism (17.2 μg/dl), indicating the circadian rhythm loss of cortisol secretion, no suppression in the low- and high-dose dexamethasone suppression tests, and high levels of urine free cortisol (240 μg/day). ACTH levels were always suppressed (< 2 pg/ml). There was no excess catecholamine, and the renin-angiotensin system was normal. CT revealed a left adrenal mass measuring 5.3×5.2×4.7 cm. She underwent left laparoscopic adrenalectomy. She was diagnosed with Cushing’s syndrome owing to the left adrenal gland tumor, which was pathologically diagnosed as adenoma. Genetic analysis of APC via the direct sequence method showed a mutation in codon 1517 (CAG (Gln) → TAG (STOP)), which has been reported in patients with an extraintestinal manifestation of FAP.

Discussion: Brain tumors, papillary adenocarcinoma of the thyroid, hepatoblastoma, retinal pigment epithelium hyperplasia (CHRPE), osteoma, desmoid tumors, and adrenal adenomas are known extraintestinal manifestations of FAP. FAP is an autosomal dominant hereditary disease that occurs due to an APC mutation on the chromosome locus 5q21-22. APC consists of 15 exons and 2844 codons. The highest cumulative mutation frequencies in extra-colonic manifestations are found between codons 976–1067 and 1310–2011, for example, desmoid tumors, which frequently show mutations in codons 1309–1580. However, no genotype-phenotype correlations have been established for adrenal adenoma or functional adrenal adenoma. This association will likely be elucidated with more reports like this case study.