Endocrine Abstracts

Introduction: Carney Complex (CNC) is a rare syndrome characterized by multiple endocrine and non-endocrine tumors, which may be accompanied by macular pigmentation of the skin. This is an autosomal dominant disorder with high penetrance and heterogeneous expression. It is caused by inactivating pathogenic variants in the PRKAR1A gene in over 70% of cases which encodes the regulatory type 1 alpha subunit of protein kinase A. Diagnosis is made by identifying specific criteria. At least two criteria are necessary, but only one is needed if the patient or a first-degree relative has the genetic alteration.

Case report: An 11-year-old girl with a history of polycystic kidney disease with dysplastic, nonfunctional left kidney and compensatory enlargement of right kidney. She also had a history of melanotic shwannomas on the abdomen, scalp, and lower eyelid. She was referred for suspicion of Cushing’s syndrome (CS) due to a one-year history of weight gain, moon face, truncal obesity, purplish streaks, dorsocervical fat pad, and mild hirsutism. On biochemical study, 24 h urinary cortisol (24hUC) was inconsistent: 3.397 ->132->1270 mg reference range (RR:21-143) and midnight salivary cortisol 0.75 mg/dl (RR:<0.27). We found a nonsuppressible serum cortisol (SC): 6.7 mg/dl (RR:6-18), after dexamethasone (DST) 1 mg followed by administration of DST 8 mg finding SC remained high after 48h: 12.10 mg/dl, with also elevated 24 hUC: 403 mg, undetectable serum ACTH <5 pg/ml (RR:5-60), and low dehydroepiandrosterone sulfate: 25.9 mg/dl (RR:33.9-280), confirming an ACTH-independent CS (ACTHICS) with a cyclic pattern. In addition, a paradoxical increase in 24 hUC was detected at day 6, measuring 6,137 mg/24 h. This finding is consistent with primary pigmented nodular adrenocortical disease (PPNAD), which is the most common endocrine neoplasm in CNC and one of the main diagnostic criteria, in addition to the mentioned schwannomas. A contrast-enhanced CT scan of the abdomen revealed normal-appearing adrenal glands, and genetic testing identified a likely pathogenic variant in heterozygosis of the PKRAR1A gene (Chr17: c.658_659 of p(Asn220 Cysfs*12). Histopathological confirmation of PPNAD was obtained after performing bilateral adrenalectomy and left nephrectomy. A search for potential relatives was conducted, but yielded no results.

Conclusion: CNC should be considered in the differential diagnosis of ACTHICS, especially if it has a cyclic pattern and the imaging studies appear to be normal. We present a novel variant of the PKRAR1A mutation, with pathogenic implication. Timely diagnosis and treatment of the patient, in conjunction to screening first-degree relatives who may be affected, can help prevent further complications.