SUMMARY Prader-Willi syndrome (PWS) is a genetic disorder frequently characterized by obesity, growth hormone deficiency, genital abnormalities, and hypogonadotropic hypogonadism. Incomplete or delayed pubertal development as well as premature adrenarche are usually found in PWS, whereas central precocious puberty (CPP) is very rare. This study aimed to report the clinical and biochemical follow-up of a PWS boy with CPP and to discuss the management of pubertal growth. By the age of 6, he had obesity, short stature, and many clinical criteria of PWS diagnosis, which was confirmed by DNA methylation test. Therapy with recombinant human growth hormone (rhGH) replacement (0.15 IU/kg/day) was started. Later, he presented psychomotor agitation, aggressive behavior, and increased testicular volume. Laboratory analyses were consistent with the diagnosis of CPP (gonadorelin-stimulated LH peak 15.8 IU/L, testosterone 54.7 ng/dL). The patient was then treated with gonadotropin-releasing hormone analog (GnRHa). Hypothalamic dysfunctions have been implicated in hormonal disturbances related to pubertal development, but no morphologic abnormalities were detected in the present case. Additional methylation analysis (MS-MLPA) of the chromosome 15q11 locus confirmed PWS diagnosis. We presented the fifth case of CPP in a genetically-confirmed PWS male. Combined therapy with GnRHa and rhGH may be beneficial in this rare condition of precocious pubertal development in PWS.

A síndrome de Cushing secundária à hiperplasia adrenal macronodular independente de ACTH (AIMAH) pode estar associada com respostas anômalas a estímulos sobre receptores hormonais expressos de maneira aberrante no córtex adrenal. O objetivo deste trabalho foi caracterizar a fisiopatologia do hipercortisolismo in vitro na síndrome de Cushing responsiva a beta-bloqueadores decorrente de AIMAH. Em cultura de células, a secreção de cortisol apresentou resposta aumentada ao salbutamol (agonista beta2-adrenérgico), à cisaprida (agonista de receptor 5-HT4) e à vasopressina, na AIMAH mas não no córtex adrenal normal. O estudo de receptores aberrantes por RT-PCR demonstrou que o gene do receptor beta2-adrenérgico estava superexpresso (e não expresso ectopicamente) nos fragmentos da AIMAH quando comparado ao tecido normal. A expressão de MC2R foi semelhante em ambos. Curiosamente, o nível basal de secreção de cortisol pelas células da AIMAH foi 15 vezes superior às células normais, não havendo resposta das células AIMAH ao estímulo com ACTH. A análise do meio de cultura das células AIMAH revelou a presença de ACTH, que foi confirmada por estudo imuno-histoquímico. Em suma, este estudo demonstrou: a) aumento dos níveis de cortisol in vitro em resposta a catecolaminas, 5-HT4 e vasopressina, correspondendo aos resultados dos testes clínicos para pesquisa de receptores aberrantes; b) expressão anormal de receptores beta2-adrenérgicos em algumas áreas de hiperplasia; c) produção autócrina de ACTH. Estes resultados envolvendo ativação de receptores aberrantes e estímulo hormonal autócrino no mesmo tecido favorecem a hipótese da existência de alterações moleculares múltiplas na hiperplasia adrenal macronodular.

Cushing's syndrome due to ACTH-independent macronodular adrenal hyperplasia (AIMAH) can be associated with abnormal responses of aberrantly expressed adrenocortical receptors. This study aimed to characterize in vitro the pathophysiology of hypercortisolism in a b-blocker-sensitive Cushing's syndrome due to AIMAH. Cortisol secretion profile under aberrant receptors stimulation revealed hyperresponsiveness to salbutamol (beta2-adrenoceptor agonist), cisapride (5-HT4 receptor agonist), and vasopressin in AIMAH cultured cells, but not in normal adrenocortical cells. By RT-PCR, AIMAH tissues revealed beta2-adrenoceptor overexpression rather than ectopical expression. MC2R expression was similar in both AIMAH and normal adrenocortical tissues. Curiously, cortisol levels of AIMAH cells under basal condition were 15-fold higher than those of control cells and were not responsive to ACTH. Analysis of culture medium from AIMAH cells could detect the presence of ACTH, which was immunohistochemically confirmed. Finally, the present study of AIMAH cells has identified: a) cortisol hyperresponsiveness to catecholamines, 5-HT4 and vasopressin in vitro, in agreement with clinical screening tests; b) abnormal expression of beta2-adrenoceptors in some areas of the hyperplastic adrenal tissue; c) autocrine loop of ACTH production. Altogether, the demonstration of aberrant responses to hormonal receptors and autocrine hormone production in the same tissue supports the assumption of multiple molecular alterations in adrenal macronodular hyperplasia.

Nódulos tireoideanos impalpáveis, descobertos principalmente por ultra-sonografia (USG), são denominados "incidentalomas". Sua importância, além da alta prevalência, está na possibilidade da detecção de "carcinoma oculto". Este trabalho objetiva estudar características ultra-sonográficas dos incidentalomas de tiróide confrontadas com diagnóstico citopatológico obtido pela punção-biópsia aspirativa por agulha fina (PBAAF) guiada por USG. Realizou-se um estudo transversal descritivo dos nódulos tireoideanos classificados como "incidentalomas", cujos pacientes, sabidamente portadores dos mesmos por exames prévios, foram submetidos à PBAAF-USG, de janeiro/1996 a maio/1998, em clínica radiológica. Os estudos ultra-sonográfico e citopatológico foram realizados pela mesma equipe médica, considerando-se a citopatologia como padrão-ouro. Nódulos > 1,5cm foram excluídos. No período de estudo, 110 nódulos foram examinados (95 pacientes, alguns portadores de nódulos múltiplos). À citopatologia, 74% dos nódulos eram benignos, 10% malignos e 16% com citodiagnóstico de lesão indeterminada (desconsiderados da análise estatística). Os nódulos malignos apresentaram predomínio das seguintes características à USG: conteúdo sólido (100%), margens irregulares (54%) e microcalcificações (54%), com diferenças estatisticamente significantes dos benignos. Em 72% dos nódulos malignos, havia pelo menos 3 das 5 características indicativas de malignidade: hipoecogenicidade, conteúdo sólido, halo ausente, margem irregular e microcalcificações. A maioria dos incidentalomas estudados foi benigna. As características ultra-sonográficas - conteúdo sólido, margens irregulares e microcalcificações, principalmente quando associadas, devem ser valorizadas ao se investigar malignidade.

Thyroid incidentalomas are incidentally found nodules by investigation methods; usually diagnosed by ultrasound (US), which are not evident by palpation. Besides their high prevalence, the possibility of the detection of "occult" carcinoma makes the thyroid incidentalomas an important finding. The aim of the present study was to describe the ultrasonografic features of thyroid incidentalomas according to the cytological diagnosis obtained by US-guided fine-needle aspiration cytology (FNA). A cross-sectional study was conducted from January/1996 to May/1998. Ninety-five patients of a radiologic clinic with a previous finding of incidentaloma were selected and their thyroid nodules were studied (US features and cytological analysis), being considered the cytologic study as gold standard. Nodules > 1.5cm were excluded. In the study period, 110 nodules were examined (95 patients, some of that with multiple nodules), being 74% were benign, 10% malign and 16% of the nodules with cytological diagnoses of uncertain lesion (excluded of the statistical analysis). Malign nodules presented the following US features: solid content (100%), irregular margins (54%) and microcalcifications (54%), with statistically significant differences of the benign ones. In 72% of the malign nodules, there were at least 3 of the 5 indicative features of malignancy: hipoechogenicity, solid content, absent halo, irregular margin and microcalcifications. Most of the studied incidentalomas was benign. Our findings suggest that certain features found in the US of incidentalomas as solid content, irregular margins and microcalcifications, are important due to their association with malignancy, mainly if they were found associated.