RP (a 60 yr-old male) was found to have multiple atrial myxomata, whilst being investigated for recurrent attacks of amaurosis fugax affecting his left eye. During the preceding twenty years he had undergone repeated resections of cutaneous tumours, which were reported as neurofibromata. A clinical diagnosis of Carney Complex (CNC) was made based on the presence of multiple cutaneous nodules and atrial myxomata. RP displayed mild acromegalic features, but no pigmentation abnormalities. Screening of the PRKAR1A gene on chromosome 17q23-24 revealed a novel c1067_1070 del AACG ins GCCCA mutation within exon 11. RP has two sons, one of whom (TP, 35 yr-old) also has multiple cutaneous tumours. Nodular swellings in both testes were noted on clinical examination. Genetic testing of TP confirmed the same mutation. Both RP and TP were investigated for endocrine manifestations of CNC: primary pigmented nodular adrenocortical disease (PPNAD); growth hormone producing pituitary adenoma; large-cell calcifying Sertoli cell tumours (LCCSCT); and thyroid nodules. Positive findings for RP included: failure of growth hormone suppression during a glucose tolerance test (trough GH 4.6 mU/L at 90 min) and a persistent mildly elevated IGF-1 (32.7 nmol/L, age/sex-matched ULN 30 nmol/L). Positive findings for TP included: an elevated midnight cortisol (264 nmol/L) with undetectable ACTH (<10 ng/L); after low and high dose dexamethasone suppression, plasma cortisol failed to suppress (397 nmol/L), and the 24 hr urinary free cortisol rose paradoxically (pre- 67 nmol/24 hr; post- 299 nmol/24 hr) suggestive of PPNAD. Scrotal ultrasound of TP revealed innumerable, calcified, nodular lesions consistent with LCCSCT. Annual surveillance of RP and TP has been arranged in the cardiac genetic and endocrine clinics. TP is also under active urological follow-up. Genetic testing of other relatives is ongoing. This kindred illustrates the phenotypic variation of CNC secondary to PRKAR1A gene mutations. Practical issues concerning the care of patients with CNC and the clinical applications of molecular genetics in the diagnosis and screening of patients with CNC will be discussed.
06 - 07 Nov 2006
Society for Endocrinology