[Biochemical, hormonal and genetic evaluation of the families of two Brazilian patients with type 2 familial partial lipodystrophy]. / Avaliação bioquímica, hormonal e genética das famílias de duas pacientes brasileiras portadoras de lipodistrofia parcial familiar tipo 2.

OBJECTIVE: To evaluate clinical, biochemical, hormonal and genetic characteristics of relatives of two patients with familial partial lipodystrophy (FPLD) type 2. MATERIALS AND METHODS: Fifty subjects, members of two non-related Brazilian families from two different probands with FPLD phenotype, were evaluated. A mutation in exon 8 of LMNA gene was confirmed in 18 of them, and a heterozygous substitution at codon 482 was identified, predicting a p.R482W mutation. Based on the presence or absence of the mutation, subjects were classified in affected and unaffected, and compared in terms of clinical, biochemical and hormonal parameters. RESULTS: Affected subjects were 2.8 times more likely to manifest diabetes and PCOS, higher HOMA-IR, insulin and triglyceride levels, and lower levels of leptin. These changes preceded the onset of diabetes, because they were observed in diabetic and non-diabetic affected patients. A phenotypic heterogeneity was found among mutation carriers. CONCLUSION: A mutation in the LMNA gene is a determinant of clinical, biochemical and hormonal changes that imply in metabolic deterioration in mutation carriers.

Avaliação bioquímica, hormonal e genética das famílias de duas pacientes brasileiras portadoras de lipodistrofia parcial familiar tipo 2 / Biochemical, hormonal and genetic evaluation of the families of two Brazilian patients with type 2 familial partial lipodystrophy

OBJETIVO: Avaliar características clínicas, bioquímicas, hormonais e genéticas de familiares de duas pacientes portadoras de lipodistrofia parcial familiar (FPLD) tipo 2. MATERIAIS E MÉTODOS: Foram avaliados 50 indivíduos de duas famílias brasileiras não relacionadas a partir de dois propósitos com fenótipo de FPLD. Foi confirmada a mutação no éxon 8 do gene LMNA em 18 destes e identificada a substituição em heterozigose no códon 482, resultando na mutação p.R482W. Com base na presença ou não da mutação, os indivíduos foram separados em afetados e não afetados, e comparados quanto a parâmetros clínicos, bioquímicos e hormonais. RESULTADOS: Indivíduos afetados tiveram 2,8 vezes mais chance de manifestar diabetes e síndrome dos ovários policísticos (SOP), maiores índices HOMA-IR, níveis de insulina e de triglicérides e menores níveis de leptina. Essas alterações precedem o início do diabetes, pois foram evidenciadas nos afetados diabéticos e não diabéticos. Foi constatada heterogeneidade fenotípica entre os portadores da mutação. CONCLUSÃO: A mutação no gene da LMNA é determinante de alterações clínicas, bioquímicas e hormonais que implicam deterioração metabólica nos portadores da mutação.

OBJECTIVE: To evaluate clinical, biochemical, hormonal and genetic characteristics of relatives of two patients with familial partial lipodystrophy (FPLD) type 2. MATERIALS AND METHODS: Fifty subjects, members of two non-related Brazilian families from two different probands with FPLD phenotype, were evaluated. A mutation in exon 8 of LMNA gene was confirmed in 18 of them, and a heterozygous substitution at codon 482 was identified, predicting a p.R482W mutation. Based on the presence or absence of the mutation, subjects were classified in affected and unaffected, and compared in terms of clinical, biochemical and hormonal parameters. RESULTS: Affected subjects were 2.8 times more likely to manifest diabetes and PCOS, higher HOMA-IR, insulin and triglyceride levels, and lower levels of leptin. These changes preceded the onset of diabetes, because they were observed in diabetic and non-diabetic affected patients. A phenotypic heterogeneity was found among mutation carriers. CONCLUSION: A mutation in the LMNA gene is a determinant of clinical, biochemical and hormonal changes that imply in metabolic deterioration in mutation carriers.

Síndrome de Cushing: um eterno desafio diagnóstico / Cushing syndrome: an eternal clinical challenge

A síndrome de Cushing (SC) é definida como um conjunto de achados decorrentes de um estado crônico de hipercortisolismo, seja de origem endógena ou exógena. Nos casos de etiologia exógena a causa é evidente, secundária ao uso de compostos com ação corticoides. Já no caso de SC de origem endógena, por vezes, a determinação da etiologia do quadro é um desafio aos generalistas e até mesmo aos endocrinologistas. Assim, pode-se acabar cometendo grandes equívocos durante a investigação, caso uma sequência apropriada para a solicitação dos exames complementares não seja seguida, atribuindo-se erroneamente, por exemplo, a etiologia do quadro a um incidentaloma (seja hipofisário e/ou adrenal). Desse modo, este artigo de revisão traz de forma sucinta e clara uma proposta de rotina a ser seguida na investigação diagnóstica de pacientes com quadro clínico-laboratorial compatível com SC.

Perfil clínico de 62 casos de distúrbios da diferenciação sexual / Clinical profile of 62 cases of sexual differentiation disorders

Objetivo: Descrever o perfil clínico dos casos de distúrbios da diferenciação sexual em acompanhamento no Instituto Estadual de Diabetes e Endocrinologia Luiz Capriglione, no Rio de Janeiro, nos últimos cinco anos.Métodos: Revisão dos prontuários dos pacientes, com o diagnóstico de genitália ambígua em acompanhamento nos últimos cinco anos, segundo os critérios clínicos descritos por Danish, em 1982. O registro mais antigo foi feito em 1981 e o mais recente de junho de 2006. Resultados: Foram encontrados 62 casos de genitália ambígua: 26 com registro do sexo feminino e 36 com registro do sexo masculino. O diagnóstico mais freqüente foi o de hiperplasia congênita de supra-renal (33,9%), seguido de quadros sindrômicos (14,5%) e disgenesias gonadais (9,7%). A média de idade ao diagnóstico foi de 7,2 anos (de zero a 42 anos). Conclusões: A ambigüidade genital não é uma doença específica, mas um conjunto de alterações que direcionam o clínico a buscar diagnósticos específicos. A freqüência dessa afecção depende dos critérios diagnósticos utilizados. A adoção de critérios amplos aumenta a chance de detecção precoce do quadro bem como de cuidado adequado a crianças com distúrbios da diferenciação sexual.

Objective: To report patients with ambiguous genitalia assisted at the State Institute of Diabetes and Endocrinology of Rio de Janeiro, Brazil, in the last five years.Methods: Retrospective chart review of all cases of ambiguous genitalia, classified according to Danish criteria (1982), who attended follow-up visits in the last five years. The oldest record is from 1981 and the most recent one, 2006. Results: 62 patients with ambiguous genitalia were found: 26 of them assigned as females and 36 as males. The most frequent diagnosis was congenital adrenal hyperplasia (33.9%), followed by syndromic diseases (14.5%) and gonadal dysgenesis (9.7%). The majority of patients with ambiguous genitalia were detected at birth, however, the mean age at the diagnosis was 7.2 years (zero to 42 years).Conclusions: Genital ambiguity is not a specific disease, but a set of problems that directs the physician to search specific diagnosis. The frequency of this condition depends on the diagnostic criteria used. Adopting amplified criteria in order to diagnose genital ambiguity will increase the possibility of early detention and adequate handling of these patients.

Quality of life in women with microprolactinoma treated with dopamine agonists.

OBJECTIVES: To evaluate QOL in women with microprolactinomas treated with dopamine agonists, comparing the patients with normal versus those with elevated prolactin levels, and to identify clinical and biochemical influences on patients' QOL. MATERIAL AND METHODS: A cross-sectional evaluation was performed in two University referral centers. Fifty women with microprolactinoma answered the SF-36 questionnaire by the time of their clinical evaluation. Their biochemical analysis included PRL, estradiol, testosterone, and SHBG. Fifty women of similar age distribution served as controls. RESULTS: Patients had lower scores than controls in all SF-36 categories: physical functioning, physical role, pain, general health, vitality, social functioning, emotional aspect, and mental health. Within the patients' group, the ones with normal PRL levels had higher scores than those with high PRL levels in all categories but the physical role. The physical functioning score correlated with the free androgen index, while the pain, vitality, social functioning, emotional aspect, and mental health scores were associated with the prolactin levels obtained at study entry. CONCLUSIONS: QOL is impaired in women with microprolactinoma treated with dopamine agonists, and was inversely associated with the PRL levels. This latter finding reinforces the importance of providing adequate disease control for these patients in order to avoid the adverse consequences of hyperprolactinemia on QOL.

Bone density in women with prolactinoma treated with dopamine agonists.

OBJECTIVES: (1) to evaluate bone density in women with prolactinoma treated with dopamine agonists and healthy controls, using dual energy x-ray absorptiometry (DXA), (2) to classify the results according to the current International Society for Clinical Densitometry (ISCD) criteria, and (3) to correlate bone density with lean and fat masses, biochemical data and clinical aspects of prolactinomas. MATERIALS AND METHODS: A cross-sectional study was performed in two University referral centers. Forty-five premenopausal women with prolactinoma were submitted to DXA and blood analysis (prolactin, estradiol, testosterone, SHBG, calcium, phosphorus, PTH, C-telopeptides of type 1 collagen, and osteocalcin) by the time of their clinical evaluation. They were compared with 25 control women of similar age and body mass index distribution. RESULTS: Women with prolactinoma had lower lumbar spine Z-score than controls. Femoral neck, trochanter, and total proximal femur Z-scores were similar in patients and controls. Twenty-two percent of the patients had Z-scores below the expected age range vs. 4% in the control group. Lumbar spine, femoral neck, and total proximal femur Z-scores were mainly correlated with the amenorrhea duration. The trochanter Z-score was associated with the gynoid lean/fat mass ratio. CONCLUSIONS: Based on the current ISCD criteria, bone density evaluation in women with prolactinoma reveals bone loss, especially of trabecular type. Bone density in these patients was particularly associated with the duration of amenorrhea, which reinforces the importance of the adequate disease control in women with prolactinoma in order to avoid complications of this disease.

Body fat in nonobese women with prolactinoma treated with dopamine agonists.

OBJECTIVES: To evaluate body fat in nonobese women with prolactinoma treated with dopamine agonists, using whole body dual energy X-ray absorptiometry (DXA) and to correlate DXA results with biochemical data and clinical aspects of the prolactinoma. DESIGN, PATIENTS AND MEASUREMENTS: A cross-sectional study was performed in two University referral centres. Thirty-one nonobese premenopausal women with prolactinoma were subjected to DXA and blood analysis at clinical evaluation. They were compared with 21 control women of similar age and body mass index (BMI). RESULTS: Women with prolactinoma treated with dopamine agonists and controls had similar body fat percentages in all sites evaluated with DXA (arms, legs, trunk, android, gynoid and total body). Patients with normal PRL levels at study entry had lower body fat percentages in all sites. In the patient group, arm, leg, truncal, android, gynoid and total body fat were positively associated with PRL levels. CONCLUSION: Body fat percentage is similar in nonobese women with prolactinoma and in controls. The lower body fat content in patients with normal PRL levels is likely to be due to the metabolic effects of adequate dopamine receptor type 2 (DR2) activation as a result of regular dopamine agonist treatment. This finding reinforces the importance of the appropriate treatment with dopamine agonists in women with prolactinoma, which, besides normalizing PRL levels, reduces body fat content and the consequent risk of developing Metabolic Syndrome and its complications.

[Mucoepidermoid carcinoma of the thyroid: a case report and literature review]. / Carcinoma mucoepidermóide de tireóide: relato de caso e revisão da literatura.

The mucoepidermoid carcinoma is a neoplasia that usually occurs at salivary glands, breast, pancreas and gastrointestinal tract. The primary occurrence on thyroid gland is rare and only 33 cases were previously published. Although the majority of cases of mucoepidermoid carcinoma of the thyroid (MECT) show a benign evolution, this paper describes a patient with an aggressive tumor. A literature review over clinical, histopathological, immunohistochemical features and histogenetic origin was discussed.

Carcinoma mucoepidermóide de tireóide: relato de caso e revisão da literatura / Mucoepidermoid carcinoma of the thyroid: a case report and literature review / Mucoepidermoid carcinoma of the thyroid: a case report and literature review

O carcinoma mucoepidermóide é um tipo de neoplasia encontrada geralmente nas glândulas salivares, mamas, pâncreas e trato digestivo. O acometimento primário da glândula tireóide é muito raro, apenas 33 casos na literatura. Embora a maioria dos casos de carcinoma mucoepidermóide de tireóide (CMET) tenha evolução favorável, o caso clínico relatado descreve uma paciente com tumor agressivo e, a partir deste relato, é apresentada revisão da literatura quanto aos aspectos clínico, histopatológico, imunohistoquímico e origem histogenética dessa neoplasia.

The mucoepidermoid carcinoma is a neoplasia that usually occurs at salivary glands, breast, pancreas and gastrointestinal tract. The primary occurrence on thyroid gland is rare and only 33 cases were previously published. Although the majority of cases of mucoepidermoid carcinoma of the thyroid (MECT) show a benign evolution, this paper describes a patient with an aggressive tumor. A literature review over clinical, histopathological, imunohistochemical features and histogenetic origin was discussed.

Síndrome de Cushing por uso abusivo de descongestionante nasal contendo dexametasona: Relato de caso / Cushing syndrome after abusive use of a nasal preparation containing dexamethasone: A case report

Os glicocorticóides têm sido largamente utilizados na prática clínica desde os princípios de 1950. Enquanto são bem conhecidos os efeitos adversos relacionados ao seu uso oral ou parenteral, não existem muitos relatos na literatura sobre efeitos adversos relacionados ao seu uso tópico. Relatamos o caso clínico de um rapaz de 16 anos com rinite alérgica que desenvolveu síndrome de Cushing exógena por uso abusivo de descongestionante nasal à base de dexametasona numa dose diária que variava de 0,5-0,7mg durante um período de 4 anos. O desmame do glicocorticóide foi iniciado substituindo-se o descongestionante em uso por outro sem glicocorticóide associado a doses progressivamente decrescentes de dexametasona administrada via oral, medicação esta que foi definitivamente suspensa 3 meses após o início do desmame - época na qual foi constatada recuperação do eixo hipotálamo-hipófise-adrenal. Chamamos a atenção para a importância do acompanhamento criterioso dos pacientes em uso, a longo prazo, de toda e qualquer medicação que contenha glicocorticóide, eventualmente até com monitorização mais rigorosa através da determinação do cortisol livre urinário ou do cortisol plasmático após teste de estímulo com o ACTH dose baixa (1mcg), permitindo assim o diagnóstico de insuficiência adrenal, mesmo que incipiente, mas que na presença de stress leve a moderado poderia oferecer risco de vida. Diante da possibilidade de severos efeitos colaterais sistêmicos mesmo quando utilizados esteróides nasais, devemos sempre que possível dar preferência aos glicocorticóides de menor biodisponibilidade e insistir junto ao paciente para que seja respeitada a dose assim como o tempo de uso prescrito.

Síndrome de Cushing: Estudo comparativo de métodos diagnósticos / Cushing's syndrome: A comparative study of diagnostic methods

Comparamos as respostas dos corticosteróides urinários:17-hidroxicorticosteróides (17-OHCS), 17-cetosteróides (17-KS) e cortisol livre (FC) à supressäo com dexametasona (baixa dose - 2 mg e alta dose - 8mg) em 71 pacientes com síndrome de Cushing (45 com doença de Cushing, 12 com carcinoma adrenal, oito com adenoma adrenocortical e seis com hiperplasia nodular da córtex adrenal). Os pacientes com doença de Cushing e hiperplasia nodular da córtex adrenal näo apresentam supressäo suficiente com 2 mg de dexametasona,porém o fazem com 8 mg. Os tumores adrenais näo demonstram supressäo adequada. A resposta hiperativa dos 17-OHCS, 17-KS e FC ao hormônio adrenocorticotrópico (ACTH) exógeno foi comparada na doença de Cushing. Concluimos que a determinaçäo urinária dos 17-OHCS, 17-KS e FC säo parâmetros diagnósticos úteis, embora a dosagem do FC mostrou ser um índice mais sensível da hiperfunçäo adrenocortical