Complexo de Carney: relato de um caso e revisão da literatura

Abstract

RESUMOComplexo de Carney (CNC) pode ser definido como uma forma de neoplasia endócrina múltipla familial associada a alteração de pigmentação cutânea e de mucosa, doença nodular pigmentosa primária das adrenais, mixomas cardíacos e cutâneos, adenomas hipofisários produtores de GH e PRL, neoplasia testicular, adenoma ou carcinoma de tireóide, além de cistos ovarianos. CNC tem herança autossômica dominante e possui manifestações clínicas que são, em alguns aspectos, similares às da síndrome de McCune-Albright. Recentemente, genes envolvidos na via de sinalização dependente de AMPc foram implicados na etiologia do CNC. Vamos apresentar, inicialmente, um caso de um paciente masculino de 17 anos com doença adrenal nodular pigmentosa, lentiginose facial e osteoporose severa. A seguir, procuramos analisar os aspectos clínicos e a genética molecular do CNC, assim como descrever os critérios diagnósticos e recomendações para o seguimento. Carney complex (CNC) is a familial multiple neoplasia syndrome associated with abnormal skin and mucosal pigmentation, primary pigmented nodular adrenocortical disease (PPNAD), cardiac and cutaneous myxomas, GH and PRL pituitary adenoma, testicular tumors, thyroid adenoma or carcinoma and ovarian cysts. CNC is inherited as an autosomal dominant trait and has some clinical similarities to McCuneAlbright syndrome. Recently, genes related to stimulation of the cAMP signaling pathway have been considered candidates for causing CNC. We report a 17-yr-old man with PPNAD, lentigines on the face and severe osteoporosis. In this article we aim at describing the clinical aspects and molecular genetics of CNC and also summarizing diagnostic criteria for CNC and recommendations for follow-up.

Primary pigmented nodular adrenocortical disease associated with Carney complex: case report and literature review

“…In studies on autopsies of patients with CNC, PPNAD was observed in almost all cases. 4,10,11 Although our patient presented a classical picture of Cushing's syndrome, her two-year history of amenorrhea, which was thought to have been caused previously by PCOS, and her short stature could be indicative of a disease that emerged atypically a long time earlier.…”

“…7,11 Paradoxical cortisol secretion responses after performing the Liddle test (two days of baseline collection, two days of dexamethasone 0.5 mg orally every six hours followed by two days of 2 mg orally every six hours and a new sample on the sixth day of the test) showed an increase of more than 50% in 24-hour urinary free cortisol (UFC) in relation to the baseline value. This is considered to be one of the major criteria for CNC.…”

Possible association between Carney complex and multiple endocrine neoplasia type 1 phenotypes

“…In general, osseous alterations found in CNC patients are a consequence of associated hypercortisolism. Thus, because PTH signaling also depends on PKA activation, the osseous metabolism alterations found in CNC patients can also be related to the excessive action of this hormone (2). In this case report the patient presented increased calcium and PTH intact after surgery, but these parameters subsequently normalized.…”

“…Loss of PKA regulatory subunits increases its catalytic activity, providing cellular proliferation in various tissues, which results in endocrine hyperfunction and the development of neoplasias. They are germ mutations, in heterozygosis, resulting from an unexpressed allele, which leads to haploinsufficiency (2). On the other hand, in MEN1 the causative gene, located in the 11q13 chromosome, consists of 10 exons and encodes a protein, composed of 610 amino acids, called menin (3,5).…”

“…NC is an autosomal dominant multiple endocrine neoplasia syndrome (OMIM 160980) (1,2). It is associated with skin and mucosal pigmen-tation, cardiac and mucocutaneous myxomas, breast myxoma, primary pigmented nodular adrenocortical disease (PPNAD), prolactin and growth-hormone-producing adenoma, thyroid adenoma or carcinoma, psammomatous melanotic schwannoma, blue nevus, breast ductal adenoma, and osteochondromyxoma.…”