ESPE Abstracts

Background: “Carney complex” is an autosomal dominant inheritance extremely rare genetic syndrome, usually determined by PRKAR1A (17q22-24) gene mutations. The clinical picture is characterized by speckled skin pigmentation; cardiac, cutaneous and mammary myxomas; schwannomas; endocrinopathies (acromegaly, Cushing syndrome due to primary pigmented nodular adrenocortical disease) and tumors of the endocrine glands.

Case report: A 10 years-old boy first came to our ambulatory due to severe obesity. Height was 134.2 cm (-0.86 SD), within target height, BMI 27.1 kg/m2 (+3.05 SDS). On physical examination acanthosis nigricans was observed. Hyperinsulinemia was documented by OGTT. During the first three months of follow-up the statural growth rate was regular but the dietary response was poor. When the patient came back to our observation 10 months after the last visit, there was evidence of worsening of obesity (BMI +3.22 SDS), statural growth failure (growth velocity 0.7 cm/year), hypertension and the occurrence of striae rubrae at the trunk and root of the limbs. Endocrinological causes of obesity associated with statural growth failure have been investigated. The circadian rhythm of cortisol (22 mg/dl at 7 a.m., 23.3 mg/dl at 4 p.m. and 15.5 mg/dl at midnight) and ACTH (persistently <1.5 pg/ml) and cortisoluria (568 mg/24hour) were suggestive of ACTH-independent hypercortisolemia. Iatrogenic causes were ruled out. Adrenal ultrasound and CT scan were performed, suspecting the presence of a nodule or hyperplasia of the medial arm of the left adrenal gland. Conversely, MRI showed a significant increase in the global dimensions of the adrenals. For the suspicion of bilateral adrenal hyperplasia, a genetic investigation was performed, which found a mutation in the PRKAR1A gene (c.46C>T p.(Arg16*) of exon 2) pathogenic for 'Carney complex'. Other related diseases were ruled out. Patient started and well tolerated therapy with Metyrapone, an adrenal steroidogenesis inhibitor, 250 mg daily. The clinical picture has slightly improved (disappearance of striae rubrae, reduction in mean blood pressure, slight weight loss, spontaneous onset of pubertal development), cortisoluria is again within normal limits, but ACTH suppression persists.

Conclusions: Our patient, suffering from "Carney's complex", had onset symptoms related to ACTH-independent hypercortisolemia. No established protocols are currently available for the management of this condition. Bilateral adrenectomy is often the only resolving treatment approach for hypercorisolemia. In our case, a two-years fair clinical-biochemical response to Metyrapone was observed, but it cannot be ruled out that other medical therapies or bilateral adrenectomy will have to be considered.