A patient of
Cushing's disease (CD) characterized by a large
tumor and only subtle symptoms of hormonal hypersecretion was examined. The patient had a germline variant in the
aryl hydrocarbon receptor-interacting protein (AIP) gene. A 50-year-old male presenting with
headache was diagnosed with a large
pituitary tumor by magnetic resonance imaging (MRI). His visual fields were intact and he exhibited no features of CD. Owing to an exuberant response to synacthen, an overnight
dexamethasone suppression test was performed revealing inadequate suppression of plasma
cortisol (419 nmol/l). Owing to
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
tumor remnant. The patient developed skin
hyperpigmentation and a synacthen test demonstrated high basal and stimulated
cortisol levels; an overnight
dexamethasone suppression test showed no suppression (791 nmol/l) and elevated plasma
ACTH levels (135 ng/l). A transcranial operation was performed followed by
radiotherapy. Two months after
radiotherapy, he developed 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, of whom five (including our case) were p.R16H. CD is occasionally dominated by
pituitary tumor growth rather than symptoms of 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.
LEARNING POINTS: CD is occasionally dominated by
pituitary tumor growth rather than symptoms of hypersecretion.Resolution of both
tumor remnant and hormonal hypersecretion may occur within 2 months after postoperative
radiotherapy.The particular AIP gene variant identified in our patient is shared by four other reported cases of CD.