Introduction: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder which typically presents with colorectal cancer in early adult life secondary to extensive adenomatous polyps of the colon. Gardner's syndrome is a variant of FAP in which desmoid tumors, osteomas and pigmented retinal lesions occur together with intestinal manifestations. The APC gene (adenomatous polyposis coli) at 5q21 is a tumor suppressor gene which is mutant in FAP.
Patient: A 36 year old woman presented with a history of polyposis ventriculi, ovarian desmoid cysts, and disseminated desmoid tumors. Her familial history was unremarkable. On admission she complained weight gain, secondary amenorrhea, and episodes of hypertension followed by paroxysmal headache.
Results: Elevated urinary free cortisol (878 microg/24h), suppressed basal ACTH (< 5 pg/ml) and insuppressible serum cortisol after low dose dexamethasone (189 ng/ml) revealed adrenal Cushing's syndrome. Abdominal NMR showed an adrenal mass two centimeter in diameter with inhomogeneous contrast enhancement. Unilateral adrenalectomy was performed and an adrenal adenoma was diagnosed by histological criteria. For mutational detection DNA from peripheral blood leucocytes was extracted. A protein truncation test was performed, which revealed a termination mutation between codon 1099 and 1623 of the APC gene. Direct sequencing showed a point mutation in exon 15 of the APC gene at position 1542 (CAG --> TAG). This region is known to be altered in patients with extraintestinal manifestation of FAP.
Conclusion: In patients with Gardner's syndrome adrenal tumors leading to hormonal excess should be considered. Whether mutations in the APC gene have implications in sporadic adrenal tumorigenesis needs to be proven.