Abstract
Introduction
The Carney complex (CNC) is a rare syndrome with autosomal dominant inheritance pattern characterized by spotty skin pigmentation, myxomas and endocrine hyperactivity. The incidence of this disease is not well established, but there were approximately 160 index cases known in 2006 after review of cumulative reports from Mayo Clinic, Cochin center in France and Cornell Center in New York. Here we present a case of CNC in a young woman that was diagnosed as a child and later developed ACTH-independent Cushing's Disease.
Case Report
Patient is a 29-year-old woman dependent of an active duty sailor who was diagnosed with CNC in Mayo clinic at the age of 5. Diagnosis was confirmed by a skin biopsy obtained from a blue nevus. Genetic testing was positive for a heterozygous mutation in the PRKAR1A Gene. Her childhood medical history was complicated by multiple cutaneous myxomas, most of which have been resected from her head, forearm and vaginal area. Annual surveillance screening with transthoracic echocardiograms and lab work were all normal until 15 years later when she re-presented with gradual development of cushingoid features. Baseline ACTH was suppressed and a dexamethasone suppression text was consistent with an ACTH-independent Cushing's Disease. Cross sectional imaging of adrenal glands via a Computed Tomography scan was normal in appearance and without evidence of nodularity or abnormal enhancement. She underwent bilateral adrenalectomy in 2009 and both adrenal glands were noted to have diffuse spotty hyperpigmentation on gross examination intra-operatively. Pathology reports revealed normal sized adrenal glands with brown micro- and macro-nodules in the area of the cortex that was consistent with Primary Pigmented Nodular Adrenocortical Disease (PPNAD). She subsequently developed iatrogenic adrenal insufficiency and also has a multi-nodular goiter that was negative for evidence of papillary thyroid carcinoma on fine needle aspiration. The patient,s youngest child was diagnosed with CNC at 6 months of age and her 7-year-old son has not been tested.
Discussion
Systematic CNC was first described in 1985 after review of Mayo Clinic Tissue registry that identified individuals with at least two of the following features: Cushing's syndrome, cardiac or cutaneous myxoma, myxoid mammary fibroadenoma or spotty pigmentation of the skin. Although this complex has only recently been described, there has been major genetic advancement in the diagnosis of this complex. Clinical diagnosis is made by establishing at least two if its main manifestations or a single manifestation is sufficient with confirmed germline PRKAR1A mutation and/or a first degree relative is affected. PPNAD is a rare cause of Cushing's syndrome, but it is the most common endocrine finding in CNC with a frequency of 25–60%. Other endocrine anomalies observed in CNC patients include growth hormone secreting pituitary adenomas (however, prolactinomas have also been described in one family), thyroid tumors (most often benign, although some patients present with carcinoma), testicular tumors (specifically Large-Cell Calcifying Sertoli Cell Tumor) or ovarian cysts. There are no current evidence-based recommendations on surveillance screening for CNC patients, but general consensus has been to work-up all manifestations of CNC annually. The importance of this case is to highlight the complexity of this disease and to review its clinical manifestations, genetics and management.
Conflict of Interest
The authors report no conflict of interest.