Severe Rhabdomyolysis Due To Adipsic Hypernatremia After Craniopharyngioma Surgery.

The association of diabetes insipidus and adipsia after craniopharyngioma surgery has high morbidity. Hypernatremia can be caused by adipsia and be aggravated by diabetes insipidus. Rhabdomyolysis rarely occurs. This is the first report of a diabetic patient with craniopharyngioma who developed diabetes insipidus and adipsia after surgery, evolving with severe hypernatremia that caused considerable rhabdomyolysis. The importance of the evaluation of muscle integrity when under hypernatremic states is pointed out. Although adipsia may have a simple solution through volunteer water ingestion, serious consequences such as repeated severe hypernatremia episodes and intense rhabdomyolysis with high morbidity could occur, if adipsia is not diagnosed.511175-

Insulin sensitivity is not decreased in adult patients with hypopituitarism without growth hormone replacement

Decreased insulin sensitivity in patients with hypopituitarism without GH replacement (pHP-WGHR) remains conflicting in literature. It is known that these patients present a decrease in free fat mass and an increase in fat mass. Typically, these kinds of alterations in body composition are associated with a decrease in insulin sensitivity; however, there is no consensus if this association is found in pHP-WGHR. Thus, we investigated pHP-WGHR regarding insulin sensitivity by euglycemic hyperinsulinemic clamp, the gold standard method, and body composition. In a cross-sectional study, we evaluated 15 pHP-WGHR followed up in a Service of Neuroendocrinology and 15 individuals with normal pituitary function as a control group with similar age, gender and body mass index. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp and homeostatic model assessment insulin resistance (HOMA-IR). Kappa coefficient evaluated the agreement between these two methods. Percentage of fat mass, percentage of free fat mass, fat mass weight and free fat mass weight were assessed by electrical bioimpedance. The pHP-WGHR presented similar insulin sensitivity to control group by euglycemic hyperinsulinemic clamp, both by the M-value, (p = 0.0913) and by the area under the glucose infusion rate curve, (p = 0.0628). These patients showed lower levels of fasting glycemia (p = 0.0128), insulin (p = 0.0007), HOMA-IR (p = 0.009). HOMA-IR shows poor concordance with euglycemic hyperinsulinemic clamp (Kappa = 0.16) in pHP-WGHR, while in the control group the agreement was good (Kappa = 0.53). The pHP-WGHR presented higher values of percentage of fat mass (p = 0.0381) and lower values of percentage of free fat mass (p = 0.0464) and free fat mass weight (0.0421) than the control group. This study demonstrated that the insulin sensitivity evaluated by euglycemic hyperinsulinemic clamp in pHP-WGHR was similar to individuals with normal pituitary function, despite the pHP-WGHR presenting higher fatmass percentage. HOMA-IR was not a good method for assessing insulin sensitivity in pHP-WGHR10CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQSem informaçã

Pituitary Macroadenoma Presenting As A Nasal Tumor: Case Report.

Pituitary macroadenomas are rare intracranial tumors. In a few cases, they may present aggressive behavior and invade the sphenoid sinus and nasal cavity, causing unusual symptoms. In this paper, we report an atypical case of pituitary adenoma presenting as a nasal mass. The patient was a 44-year-old woman who had had amenorrhea and galactorrhea for ten months, with associated nasal obstruction, macroglossia and acromegaly. Both growth hormone and prolactin levels were increased. Magnetic resonance imaging showed a large mass originating from the lower surface of the pituitary gland, associated with sella turcica erosion and tumor extension through the sphenoid sinus and nasal cavity. Histopathological analysis demonstrated a chromophobe pituitary adenoma with densely packed rounded epithelial cells, with some atypias and rare mitotic figures. There was no evidence of metastases. Macroadenoma invading the nasal cavity is a rare condition and few similar cases have been reported in the literature. This study contributes towards showing that tumor extension to the sphenoid sinus and nasopharynx needs to be considered and investigated in order to make an early diagnosis when atypical symptoms like nasal obstruction are present.132377-8

Seis novos casos confirmam o perfil clínico molecular de deficiência combinada de 17 alfa-hidroxilase/17,20-liase no Brasil

In 2004, Costa-Santos and cols. reported 24 patients from 19 Brazilian families with 17&#945;-hydroxylase deficiency and showed that p.W406R and p.R362C corresponded to 50% and 32% of CYP17A1 mutant alleles, respectively. The present report describes clinical and molecular data of six patients from three inbred Brazilian families with 17&#945;-hydroxlyse deficiency. All patients had hypogonadism, amenorrhea and hypertension at diagnosis. Two sisters were found to be 46,XY with both gonads palpable in the inguinal region. All patients presented hypergonadotrophic hypogonadism, with high levels of ACTH (&gt; 104 ng/mL), suppressed plasmatic renin activity, low levels of potassium (< 2.8 mEq/L) and elevated progesterone levels (&gt; 4.4 ng/mL). Three of them, including two sisters, were homozygous for p.W406R mutation and the other three (two sisters and one cousin) were homozygous for p.R362C. The finding of p.W406R and p.R362C in the CYP17A1 gene here reported in additional families, confirms them as the most frequent mutations causing complete combined 17&#945;-hydroxylase/17,20-lyase deficiency in Brazilian patients.Em 2004, segundo Costa-Santos e cols., p.W406R e p.R362C correspondiam a 50% e 32% dos alelos mutantes do gene CYP17A1, respectivamente, em 24 pacientes de 19 famílias brasileiras com deficiência da 17&#945;-hidroxilase. Apresentamos os dados cl&#957;nicos e moleculares de seis pacientes de três famílias consanguíneas brasileiras com deficiência da 17&#945;-hidroxilase. Todas as pacientes apresentavam hipogonadismo, amenorreia e hipertensão ao diagnóstico. Duas irmãs tinham cariótipo 46,XY, ambas com gônadas palpáveis na região inguinal. Todas tinham hipogonadismo hipergonadotrófico, com nível aumentado de ACTH (&gt; 104 ng/mL), atividade de renina plasmática suprimida, baixos níveis de potássio (< 2,8 mEq/L) e progesterona aumentada (&gt; 4,4 ng/mL). Três delas, incluindo duas irmãs, apresentaram homozigose para a mutação p.W406R e as outras três (duas irmãs e uma prima) foram homozigotas para a mutação p.R362C. A recorrência das mutações p.W406R e p.R362C no gene CYP17A1 aqui relatada em famílias adicionais confirma que essas são as mais frequentes causadoras do fenótipo completo da deficiência combinada de 17&#945;-hidroxilase/17,20-liase em pacientes brasileiros.71171

Six New Cases Confirm The Clinical Molecular Profile Of Complete Combined 17α-hydroxylase/ 17,20-lyase Deficiency In Brazil.

In 2004, Costa-Santos and cols. reported 24 patients from 19 Brazilian families with 17α-hydroxylase deficiency and showed that p.W406R and p.R362C corresponded to 50% and 32% of CYP17A1 mutant alleles, respectively. The present report describes clinical and molecular data of six patients from three inbred Brazilian families with 17α-hydroxlyse deficiency. All patients had hypogonadism, amenorrhea and hypertension at diagnosis. Two sisters were found to be 46,XY with both gonads palpable in the inguinal region. All patients presented hypergonadotrophic hypogonadism, with high levels of ACTH (> 104 ng/mL), suppressed plasmatic renin activity, low levels of potassium ( 4.4 ng/mL). Three of them, including two sisters, were homozygous for p.W406R mutation and the other three (two sisters and one cousin) were homozygous for p.R362C. The finding of p.W406R and p.R362C in the CYP17A1 gene here reported in additional families, confirms them as the most frequent mutations causing complete combined 17α-hydroxylase/17,20-lyase deficiency in Brazilian patients.54711-

Long-term Follow-up Of An 8-year-old Boy With Insulinoma As The First Manifestation Of A Familial Form Of Multiple Endocrine Neoplasia Type 1.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant hereditary cancer syndrome characterized mostly by parathyroid, enteropancreatic, and anterior pituitary tumors. We present a case of an 8-year-old boy referred because of hypoglycemic attacks. His diagnosis was pancreatic insulinoma. Paternal grandmother died due to repeated gastroduodenal ulcerations and a paternal aunt presented similar manifestations. At a first evaluation, the father presented only gastric ulceration but subsequently developed hyperparathyroidism and lung carcinoid tumor. During almost 15 years of follow-up, three brothers and the index case presented hyperparathyroidism and hyperprolactinemia. Molecular study showed a G to A substitution in intron 4, at nine nucleotides upstream of the splicing acceptor site, causing a splicing mutation. All affected members of the family have the same mutation. Paternal grandmother and aunt were not studied and the mother does not carry any mutation. MEN1 is a rare condition that requires permanent medical assistance. Early clinical and genetic identification of affected individuals is essential for their own surveillance and also for genetic counseling.54754-6

Repercussões hormonais e metabolicas do uso da pioglitazona na sindrome dos ovarios policisticos

Orientadores: Denise Engelbrecht Zantut Wittmann, Marcos Antonio TambasciaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: O hiperandrogenismo da Síndrome dos Ovários Policísticos (SOPC) pode resultar de hiperinsulinemia decorrente da resistência periférica à ação da insulina. Assim, as drogas sensibilizadoras da ação da insulina tornam-se possível opção terapêutica para as pacientes. A relação entre hormônio luteinizante e hormônio folículo-estimulante (LH/FSH) encontra-se aumentada na SOPC, ocorrendo hiper-resposta do LH ao estímulo com hormônio liberador das gonadotrofinas hipofisárias (GnRH). Entretanto, permanece sem elucidação como a hiperinsulinemia induz ao hiperandrogenismo e se as ações da insulina na hipófise alterariam a liberação de gonadotrofinas. O objetivo deste estudo foi avaliar os efeitos do tratamento com pioglitazona sobre a resposta de insulina ao teste oral de tolerância à glicose (GTTO), o perfillipídico, os níveis séricos de andrógenos e globulina transportadora de hormônios sexuais (SHBG) e a resposta das gonadotrofinas hipofisárias frente ao estímulo com GnRH. Para detectar possíveis efeitos colaterais da droga avaliaram-se os perfis hepático, renal e hematológico.Foram selecionadas 15 pacientes obesas com SOPC, tratadas com pioglitazona 30mg/dia por 58 dias, submetidas a avaliações clínicas e laboratoriais antes, durante e ao final do tratamento. Verificou-se, de modo estatisticamente significativo, diminuição de 34,9% na resposta de insulina ao GTT, redução dos níveis séricos de testosterona total (1,48 ± 0,47vs 0,83 ± 0,27) e livre (8,94 ± 5,2 vs 3,69 ± 2,03), elevação de SHBG (21 ,87 ± 8,68 vs 25,62 ± 10,06) e diminuição de 14,8% na resposta do LH ao estímulo com GnRH. Resultados semelhantes são descritos utilizando-se metformina e troglitazona, porém não se encontraram na literatura avaliações com a pioglitazona ou estudos sobre alteração da resposta de LH ao teste de estímulo com GnRH. Concluindo, observou-se diminuição da resposta de insulina ao GTT acompanhada por redução significativa nos níveis de testosterona livre e total e aumento na concentração sérica de SHBG com o uso da pioglitazona. Adicionalmente, houve queda significativa na resposta do LH ao estímulo com GnRH. Novas investigações com o uso da pioglitazona devem ser conduzidas para que sejam estabelecidos os riscos e beneficios, auxiliando no entendimento fisiopatológico da SOPCAbstract: The hyperandrogenism found in Polycystic Ovarian Syndrome(PCOS) can be a consequence of hyperinsulinemia as a result of peripheral resistance to insulin. Therefore, drugs used to induce insulin sensitizationhave become a possible therapeutic option for these patients. The relationship between luteinizing hormone/follicle-stimulating hormone (LH/FSH) is increased in PCOS and there is hyperresponsivity of LH to stimulation with gonadotropin-releasing hormone (GnRH). However, the reason why hyperinsulinemia produces hyperandrogenism and whether insulin action on the hypophysis alters gonadotropin liberation remains unknown. Our objective was to evaluate the resultsof treatment with pioglitazone on insulin response to the oral glucose tolerance test (GTT), serum levels of androgens and sexual hormone binding globulin (SHBG), lipidic profile and hypophyseal gonadotropin response to GnRH stimulation. In order to detect possible side effects of the drug the hepatic, renal and hematologic profiles were evaluated. We selected 15 obese patients with PCOS treated with pioglitazone 30mg/day for 58 days who had clinical and laboratorial evaluations before, during and after treatment. The outcome was a statistically significant decrease in insulin response to GTT by 34,9%, serum levels of total testosterone (1.48 ± 0.47vs 0.83 ± 0.27)and free testosterone (8.94 ± 5.2vs 3.69 ± 2.03), increase of SHBG (21.87 ± 8.68 vs 25.62 ± 10.06) and decrease in LH response to GnRH stimulation by 14,8%. Similar results are described using metformin and troglitazone, but we did not find in the literature pioglitazone evaluations or studies on alteration of LH response to GnRH stimulation test. In conclusion, a decrease in insulin response to GTT, accompanied by a significant reduction in free and total testosterone levels as well as increase in serum concentration of SHBG with pioglitazone was observed. In addition, there was a significant reduction in LH responseto GnRH stimulation. Further research with pioglitazone should be carried out to establish risks and benefits, assisting in the pysiopathologic comprehension of PCOSDoutoradoMedicina InternaDoutor em Ciências Médica