Enhancing Cushing's disease diagnosis: exploring the impact of desmopressin on ACTH gradient during BIPSS.

Introduction: The differential diagnosis between Cushing's disease (CD) and ectopic ACTH syndrome (EAS) is complex, and bilateral inferior petrosal sinus sampling (BIPSS) is considered the gold-standard test. However, BIPSS with corticotropin-releasing hormone (CRH) stimulation is rarely available. Objective: This retrospective cohort study aimed to assess the accuracy of the inferior petrosal sinus to peripheral ACTH gradient (IPS:P) before and after desmopressin stimulation for the differential diagnosis of ACTH-dependent Cushing's syndrome (CS), applying different cutoff values. Methods: A total of 50 patients (48 with CD and 2 with EAS) who underwent BIPSS were included in this study. The sensitivity and specificity of IPS:P in BIPSS before and after desmopressin stimulation were evaluated. Various cutoff values for IPS:P were examined to determine their diagnostic accuracy. Results: Using the traditional IPS:P cutoff, the sensitivity was 85.1% before stimulation, 89.6% after stimulation, and a combined sensitivity of 91.7%. Applying cutoff values of IPS:P >1.4 before and >2.8 after stimulation, the sensitivity was 87.2% and 89.6%, respectively, with a combined sensitivity of 91.7%. Receiver operating characteristic (ROC) curve analysis determined optimal cutoff values of 1.2 before stimulation and 1.57 after stimulation, resulting in a sensitivity of 93.6% and 93.8%, respectively, with a combined sensitivity of 97.9%. Specificity remained at 100% throughout all analyses. Among the 43 patients who responded positively to stimulation, 42 (97.7%) did so within the first three minutes, and all 43 (100%) did so within the first five minutes. None of the assessed clinical variables predicted the ACTH response to stimulation in BIPSS with statistical significance. Discussion: ACTH stimulation with desmopressin during BIPSS improves the accuracy of IPS:P, making it a valuable tool for investigating ACTH-dependent Cushing's syndrome. Considering the low risk of complications, we recommend the use of desmopressin stimulation during BIPSS for the differential diagnosis of ACTH-dependent CS.

Ketoconazole as second-line treatment for Cushing's disease after transsphenoidal surgery: systematic review and meta-analysis.

Introduction: The first-line treatment for Cushing's disease is transsphenoidal surgery for pituitary tumor resection. Ketoconazole has been used as a second-line drug despite limited data on its safety and efficacy for this purpose. The objective of this meta-analysis was to analyze hypercortisolism control in patients who used ketoconazole as a second-line treatment after transsphenoidal surgery, in addition to other clinical and laboratory criteria that could be related to therapeutic response. Methods: We searched for articles that evaluated ketoconazole use in Cushing's disease after transsphenoidal surgery. The search strategies were applied to MEDLINE, EMBASE, and SciELO. Independent reviewers assessed study eligibility and quality and extracted data on hypercortisolism control and related variables such as therapeutic dose, time, and urinary cortisol levels. Results: After applying the exclusion criteria, 10 articles (one prospective and nine retrospective studies, totaling 270 patients) were included for complete data analysis. We found no publication bias regarding reported biochemical control or no biochemical control (p = 0.06 and p = 0.42 respectively). Of 270 patients, biochemical control of hypercortisolism occurred in 151 (63%, 95% CI 50-74%) and no biochemical control occurred in 61 (20%, 95% CI 10-35%). According to the meta-regression, neither the final dose, treatment duration, nor initial serum cortisol levels were associated with biochemical control of hypercortisolism. Conclusion: Ketoconazole can be considered a safe and efficacious option for Cushing's disease treatment after pituitary surgery. Systematic review registration: https://www.crd.york.ac.uk/prospero/#searchadvanced, (CRD42022308041).

Evaluation of ketoconazole as a treatment for Cushing's disease in a retrospective cohort.

Objective: The first-line treatment for Cushing's disease is transsphenoidal surgery, after which the rates of remission are 60 to 80%, with long-term recurrence of 20 to 30%, even in those with real initial remission. Drug therapies are indicated for patients without initial remission or with surgical contraindications or recurrence, and ketoconazole is one of the main available therapies. The objective of this study was to evaluate the safety profile of and the treatment response to ketoconazole in Cushing's disease patients followed up at the endocrinology outpatient clinic of a Brazilian university hospital. Patients and methods: This was a retrospective cohort of Cushing's disease patients with active hypercortisolism who used ketoconazole at any stage of follow-up. Patients who were followed up for less than 7 days, who did not adhere to treatment, or who were lost to follow-up were excluded. Results: Of the 172 Cushing's disease patients who were followed up between 2004 and 2020, 38 received ketoconazole. However, complete data was only available for 33 of these patients. Of these, 26 (78%) underwent transsphenoidal surgery prior to using ketoconazole, five of whom (15%) had also undergone radiotherapy; seven used ketoconazole as a primary treatment. Ketoconazole use ranged from 14 days to 14.5 years. A total of 22 patients had a complete response (66%), three patients had a partial response (9%), and eight patients had no response to treatment (24%), including those who underwent radiotherapy while using ketoconazole. Patients whose hypercortisolism was controlled or partially controlled with ketoconazole had lower baseline 24-h urinary free cortisol levels than the uncontrolled group [times above the upper limit of normal: 0.62 (SD, 0.41) vs. 5.3 (SD, 8.21); p < 0.005, respectively] in addition to more frequent previous transsphenoidal surgery (p < 0.04). The prevalence of uncontrolled patients remained stable over time (approximately 30%) despite ketoconazole dose adjustments or association with other drugs, which had no significant effect. One patient received adjuvant cabergoline from the beginning of the follow-up, and it was prescribed to nine others due to clinical non-response to ketoconazole alone. Ten patients (30%) reported mild adverse effects, such as nausea, vomiting, dizziness, and loss of appetite. Only four patients had serious adverse effects that warranted discontinuation. There were 20 confirmed episodes of hypokalemia among 10/33 patients (30%). Conclusion: Ketoconazole effectively controlled hypercortisolism in 66% of Cushing's disease patients, being a relatively safe drug for those without remission after transsphenoidal surgery or whose symptoms must be controlled until a new definitive therapy is carried out. Hypokalemia is a frequent metabolic effect not yet described in other series, which should be monitored during treatment.

Cohort cholecystectomies in the Brazilian public system: is access to laparoscopy universal after three decades?

OBJECTIVE: videosurgery in Brazil started in 1990 with the performance of laparoscopic cholecystectomy, being included by the public health system in 2008. We evaluated the current situation of the use of this technology in the Unified Health System (SUS - Sistema Único de Saúde). METHODS: from 2013 to 2019, 1,406,654 patients registered at the SUS Informatics Department (DATASUS) were analyzed to calculate the rate of laparoscopic cholecystectomies (LC) in relation to open cholecystectomies (OC). Patient characteristics, disease presentation and postoperative mortality were evaluated. RESULTS: the LC rate reached 41.5% (growth of 68%) with no decrease in the absolute number of OC. In University Hospitals (UH), the LC rate reached 91.96%. The open technique in emergencies was more associated with male patients, aged 60 years or older, with prolonged hospitalization and in the ICU. Those undergoing LC were less predisposed to postoperative death, both electively (OR 0.49; 95% CI 0.42 - 0.56; NNT=20) and urgently (OR 0.23; 95% CI 0.20 - 0.25; NNT ≅1), providing a protective effect. CONCLUSION: despite the increase in the indication of LC, the open technique during the years studied remained stable and the most used in the public health system in Brazil. The effectiveness of public health policies to shorten the complete implementation of videosurgery in SUS needs to be investigated in future epidemiological studies, as well as its impact on postoperative morbidity and mortality.

Cohort cholecystectomies in the Brazilian public system: is access to laparoscopy universal after three decades? / Colecistectomias em coorte no sistema público brasileiro: o acesso à laparoscopia é universal após três décadas?

ABSTRACT Objective: videosurgery in Brazil started in 1990 with the performance of laparoscopic cholecystectomy, being included by the public health system in 2008. We evaluated the current situation of the use of this technology in the Unified Health System (SUS - Sistema Único de Saúde). Methods: from 2013 to 2019, 1,406,654 patients registered at the SUS Informatics Department (DATASUS) were analyzed to calculate the rate of laparoscopic cholecystectomies (LC) in relation to open cholecystectomies (OC). Patient characteristics, disease presentation and postoperative mortality were evaluated. Results: the LC rate reached 41.5% (growth of 68%) with no decrease in the absolute number of OC. In University Hospitals (UH), the LC rate reached 91.96%. The open technique in emergencies was more associated with male patients, aged 60 years or older, with prolonged hospitalization and in the ICU. Those undergoing LC were less predisposed to postoperative death, both electively (OR 0.49; 95% CI 0.42 - 0.56; NNT=20) and urgently (OR 0.23; 95% CI 0.20 - 0.25; NNT ≅1), providing a protective effect. Conclusion: despite the increase in the indication of LC, the open technique during the years studied remained stable and the most used in the public health system in Brazil. The effectiveness of public health policies to shorten the complete implementation of videosurgery in SUS needs to be investigated in future epidemiological studies, as well as its impact on postoperative morbidity and mortality.

RESUMO Introdução: a videocirurgia no Brasil iniciou em 1990 com a realização da colecistectomia laparoscópica, sendo incluída pelo sistema público de saúde em 2008. Avaliamos a situação atual do emprego desta tecnologia no Sistema Único de Saúde (SUS). Métodos: de 2013 a 2019, 1.406.654 pacientes registrados no Departamento de Informática do SUS (DATASUS) foram analisados para calcular a taxa de colecistectomias laparoscópicas (CL) em relação a colecistectomias abertas (CA). Avaliaram-se características dos pacientes, apresentação da doença e mortalidade pós-operatória. Resultados: a taxa de CL atingiu 41,5%, com crescimento de 68%, sem ocorrer diminuição do número absoluto de CA. Já em Hospitais Universitários (HUs) a taxa de CL chegou a 91,96%. A técnica aberta em urgências esteve mais associada a pacientes masculinos, com 60 anos ou mais, à internação prolongada e em UTI. Aqueles submetidos à CL estiveram menos predispostos à morte pós-operatória, tanto em caráter eletivo (OR 0,49; IC 95% 0,42 - 0,56; NNT = 20) como na urgência (OR 0,23; IC 95% 0,20 - 0,25; NNT ≅ 1), conferindo efeito protetor. Conclusão: apesar do aumento da indicação da CL, a cirurgia aberta durante os anos estudados se manteve estável e a técnica mais utilizada no sistema público de saúde do Brasil. A efetividade de políticas de saúde pública para abreviar a completa implementação da videocirurgia no SUS necessita ser investigada em estudos epidemiológicos futuros, assim como seu impacto na morbimortalidade pós-operatória.

Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism.

Hypopituitarism is a disorder characterized by insufficient secretion of one or more pituitary hormones. New etiologies of hypopituitarism have been recently described, including head trauma, cerebral hemorrhage, and drug-induced hypophysitis. The investigation of patients with these new disorders, in addition to advances in diagnosis and treatment of hypopituitarism, has increased the prevalence of this condition. Pituitary hormone deficiencies can induce significant clinical changes with consequent increased morbidity and mortality rates, while hormone replacement based on current guidelines protects these patients. In this review, we will first discuss the different etiologies of hypopituitarism and then address one by one the clinical aspects, diagnostic evaluation, and therapeutic options for deficiencies of TSH, ACTH, gonadotropin, and GH. Finally, we will detail the hormonal interactions that occur during replacement of pituitary hormones.

Brazilian multicenter study on pegvisomant treatment in acromegaly.

OBJECTIVE: Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. SUBJECTS AND METHODS: Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. RESULTS: 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. CONCLUSIONS: In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.

Brazilian multicenter study on pegvisomant treatment in acromegaly

ABSTRACT Objective Investigate the therapeutic response of acromegaly patients to pegvisomant (PEGV) in a real-life, Brazilian multicenter study. Subjects and methods Characteristics of acromegaly patients treated with PEGV were reviewed at diagnosis, just before and during treatment. All patients with at least two IGF-I measurements on PEGV were included. Efficacy was defined as any normal IGF-I measurement during treatment. Safety data were reviewed. Predictors of response were determined by comparing controlled versus uncontrolled patients. Results 109 patients [61 women; median age at diagnosis 34 years; 95.3% macroadenomas] from 10 Brazilian centers were studied. Previous treatment included surgery (89%), radiotherapy (34%), somatostatin receptor ligands (99%), and cabergoline (67%). Before PEGV, median levels of GH, IGF-I and IGF-I % of upper limit of normal were 4.3 µg/L, 613 ng/mL, and 209%, respectively. Pre-diabetes/diabetes was present in 48.6% and tumor remnant in 71% of patients. Initial dose was 10 mg/day in all except 4 cases, maximum dose was 30 mg/day, and median exposure time was 30.5 months. PEGV was used as monotherapy in 11% of cases. Normal IGF-I levels was obtained in 74.1% of patients. Glycemic control improved in 56.6% of patients with pre-diabetes/diabetes. Exposure time, pre-treatment GH and IGF-I levels were predictors of response. Tumor enlargement occurred in 6.5% and elevation of liver enzymes in 9.2%. PEGV was discontinued in 6 patients and 3 deaths unrelated to the drug were reported. Conclusions In a real-life scenario, PEGV is a highly effective and safe treatment for acromegaly patients not controlled with other therapies.

Vitamin D deficiency is independently associated with mortality among critically ill patients

OBJECTIVE: Studies suggest an association between vitamin D deficiency and morbidity/mortality in critically ill patients. Several issues remain unexplained, including which vitamin D levels are related to morbidity and mortality and the relevance of vitamin D kinetics to clinical outcomes. We conducted this study to address the association of baseline vitamin D levels and vitamin D kinetics with morbidity and mortality in critically ill patients. METHOD: In 135 intensive care unit (ICU) patients, vitamin D was prospectively measured on admission and weekly until discharge from the ICU. The following outcomes of interest were analyzed: 28-day mortality, mechanical ventilation, length of stay, infection rate, and culture positivity. RESULTS: Mortality rates were higher among patients with vitamin D levels <12 ng/mL (versus vitamin D levels >12 ng/mL) (32.2% vs. 13.2%), with an adjusted relative risk of 2.2 (95% CI 1.07-4.54; p< 0.05). There were no differences in the length of stay, ventilation requirements, infection rate, or culture positivity. CONCLUSIONS: This study suggests that low vitamin D levels on ICU admission are an independent risk factor for mortality in critically ill patients. Low vitamin D levels at ICU admission may have a causal relationship with mortality and may serve as an indicator for vitamin D replacement among critically ill patients. .

Aldosterone secretion in patients with septic shock: a prospective study / Secreção de aldosterona em pacientes com choque séptico: estudo prospectivo

OBJECTIVE: To assess serum levels of the main factors that regulate the activation of the zona glomerulosa and aldosterone production in patients with septic shock, as well as their response to a high-dose (250 µg) adrenocorticotropic hormone (ACTH) stimulation test. SUBJECTS AND METHODS: In 27 patients with septic shock, baseline levels of aldosterone, cortisol, ACTH, renin, sodium, potassium, and lactate were measured, followed by a cortrosyn test. RESULTS: Renin correlated with baseline aldosterone and its variation after cortrosyn stimulation. Baseline cortisol and its variation did not correlate with ACTH. Only three patients had concomitant dysfunction of aldosterone and cortisol secretion. CONCLUSIONS: Activation of the zona glomerulosa and zona fasciculata are independent. Aldosterone secretion is dependent on the integrity of the renin-angiotensin-aldosterone system, whereas cortisol secretion does not appear to depend predominantly on the hypothalamic-pituitary-adrenal axis. These results suggest that activation of the adrenal gland in critically ill patients occurs by multiple mechanisms.

OBJETIVO: Avaliar os níveis séricos dos principais fatores que regulam a ativação da zona glomerulosa e a produção de aldosterona em pacientes com choque séptico, assim como sua resposta ao teste de cortrosina em alta dose (250 µg). SUJEITOS E MÉTODOS: Em 27 portadores de choque séptico, foram aferidos níveis basais de aldosterona, cortisol, ACTH, renina, sódio, potássio e lactato, bem como realizado teste de cortrosina. RESULTADOS: Renina se correlacionou com níveis basais de aldosterona e sua variação após teste de cortrosina. Cortisol basal e sua variação não se correlacionaram com ACTH. Apenas três pacientes apresentaram disfunção concomitante da secreção de aldosterona e cortisol. CONCLUSÕES: Ativação das zonas fasciculada e glomerulosa são independentes. Secreção de aldosterona é dependente da integridade do sistema renina-angiotensina-aldosterona, enquanto secreção de cortisol não parece predominantemente dependente do eixo hipotálamo-hipófise-adrenal. Esses resultados sugerem que a ativação da adrenal em pacientes críticos ocorre por múltiplos mecanismos.

Effects of oral and transdermal estrogen on IGF1, IGFBP3, IGFBP1, serum lipids, and glucose in patients with hypopituitarism during GH treatment: a randomized study.

OBJECTIVE: To evaluate the effects of oral estradiol and transdermal 17ß-estradiol on serum concentrations of IGF1 and its binding proteins in women with hypopituitarism. DESIGN: Prospective, comparative study. METHODS: Eleven patients with hypopituitarism were randomly allocated to receive 2 mg oral estradiol (n=6) or 50 µg/day of transdermal 17ß-estradiol (n=5) for 3 months. RESULTS: The oral estrogen group showed a significant reduction in IGF1 levels (mean: 42.7%±41.4, P=0.046); no difference was observed in the transdermal estrogen group. There was a significant increase in IGFBP1 levels (mean: 170.2%±230.9, P=0.028) in the oral group, but not in the transdermal group. There was no significant difference within either group in terms of median IGFBP3 levels. In relation to lipid profiles, there was a significant increase in mean high-density lipoprotein cholesterol levels in the oral group after 3 months of treatment, (27.8±9.3, P=0.003). We found no differences in the anthropometric measurements, blood pressure, heart rate, glucose, insulin, C-peptide, or the homeostasis model assessment index after treatment. CONCLUSIONS: Our preliminary data indicate that different estrogen administration routes can influence IGF1 and IGFBP1 levels. These findings in patients with hypopituitarism have an impact on their response to treatment with GH, since patients receiving oral estrogen require increased GH dosage. These results suggest that oral estrogens may reduce the beneficial effects of GH replacement on fat and protein metabolism, body composition, and quality of life.

Diabetes mellitusin a cohort of patients with acromegaly / Diabetes melito em uma coorte de pacientes com acromegalia

OBJECTIVES: To evaluate the presence of diabetes mellitus (DM) in a cohort of patients with acromegaly. METHODS: This was a cross sectional study. RESULTS: Fifty-eight acromegalic patients were assessed. Only 29 percent met the criteria for cure, and 27 percent had the disease controlled. Twenty-two had DM; HbA1c was equal to 7.34 ± 2.2 percent. Most of the diabetic patients (18 out of 22, 82 percent) did not meet criteria for cure. They were more often hypertensive [16/22 (73 percent) vs. 17/36 (46 percent), p = 0.04], and used statins more frequently [14/22 (64 percent) vs. 8/36 (21 percent), p = 0.004]. After regression analysis, hypertension was associated with diabetes [odds ratio (OR): 9.28 (95 percent CI: 1.59 - 54.00), p = 0.01], and cured/ controlled acromegaly was associated with protection against the presence of diabetes [OR: 0.17 (95 percent CI: 0.03 - 0.78), p = 0.02]. CONCLUSIONS: The presence of DM was associated with active acromegaly and presence of hypertension. However, absolute levels of GH and IGF-1 did not differ between patients with and without diabetes.

OBJETIVOS: Avaliar a presença de diabetes melito (DM) em uma coorte de acromegálicos. MÉTODOS: Este é um estudo transversal. RESULTADOS: Cinquenta e oito pacientes acromegálicos foram analisados. Apenas 29 por cento preencheram critérios de cura e 27 por cento estavam com a doença controlada. Vinte e dois pacientes (38 por cento) apresentaram DM, HbA1c 7,34 ± 2,2 por cento. Destes, 18 não preencheram critérios de cura. Pacientes com DM foram mais frequentemente hipertensos [16/22 (73 por cento) vs. 17/36 (46 por cento), p = 0,04] e usavam mais estatina [14/22 (64 por cento) vs.8/36 (21 por cento), p = 0,004]. Após regressão múltipla, hipertensão foi associada a DM [razão de chances (RC): 9,28 (95 por cento CI: 1,59 - 54,00), p = 0,01], e acromegalia curada/controlada foi fator protetor para presença de diabetes [OR: 0,17 (95 por cento CI: 0,03-0,78), p = 0,02]. CONCLUSÕES: A presença de DM esteve associada com acromegalia ativa e com a presença de hipertensão. No entanto, os níveis absolutos de GH e IGF-1 não diferiram entre aqueles com e sem diabetes.

Hypertension-related factors in patients with active and inactive acromegaly / Fatores implicados com a hipertensão em pacientes com acromegalia ativa e inativa

INTRODUCTION: There are several complications of the cardiovascular system caused by acromegaly, especially hypertension. OBJECTIVES: To evaluate hypertension characteristics in patients with cured/controlled acromegaly and with the active disease. PATIENTS AND METHODS: Cross-sectional study of the follow-up of forty-four patients with acromegaly submitted to clinical evaluation, laboratory tests and cardiac ultrasound. Patients with cured and controlled disease were evaluated as one group, and individuals with active disease as second one. RESULTS: Forty-seven percent of the patients had active acromegaly, and these patients were younger and had lower blood pressure levels than subjects with controlled/cured disease. Hypertension was detected in 50 percent of patients. Subjects with active disease showed a positive correlation between IGF-1 and systolic and diastolic blood pressure levels (r = 0.48, p = 0.03; and r = 0.42, p = 0.07, respectively), and a positive correlation between IGF-1 and urinary albumin excretion (UAE) rates. In patients with active disease, IGF-1 was a predictor of systolic blood pressure, although it was not independent of UAE rate. For individuals with cured/controlled disease, waist circumference and triglycerides were the predictors associated with systolic and diastolic blood pressure. CONCLUSIONS: Our findings suggest that blood pressure levels in patients with active acromegaly are very similar, and depend on excess GH. However, once the disease becomes controlled and IGF-1 levels decrease, their blood pressure levels will depend on the other cardiovascular risk factors.

INTRODUÇÃO: Existem várias complicações no sistema cardiovascular causadas pela acromegalia, especialmente a hipertensão. OBJETIVOS: Avaliar as características da hipertensão em pacientes com acromegalia curada/controlada e com doença ativa. PACIENTES E MÉTODOS: Estudo transversal com 44 pacientes com acromegalia seguidos em nosso serviço. Eles foram submetidos a avaliação clínica, exames laboratoriais e ecocardiograma. Pacientes com doença curada/controlada foram avaliados como um grupo único e os indivíduos com doença ativa como outro grupo. RESULTADOS: Quarenta e sete por cento dos pacientes apresentaram acromegalia ativa. Esses indivíduos foram mais jovens e apresentaram níveis mais baixos de pressão arterial que os indivíduos com doença controlada/curada. A hipertensão foi detectada em 50 por cento da amostra. Indivíduos com doença ativa mostraram uma correlação positiva entre os níveis de IGF-1 e os níveis de pressão arterial sistólica e de pressão arterial diastólica (r = 0,48, p = 0,03; e r = 0,42, p = 0,07, respectivamente) e também apresentaram uma correlação positiva entre IGF-1 e excreção urinária de albumina (EUA). Em pacientes com doença ativa, o IGF-1 foi um preditor da pressão arterial sistólica, embora não tenha sido independente da taxa de EUA. Para indivíduos com doença curada/controlada, a circunferência da cintura e os triglicérides foram os preditores associados aos níveis de pressão arterial sistólica e diastólica. CONCLUSÕES: Nossos resultados sugerem que os níveis pressóricos em pacientes com acromegalia ativa dependem do excesso de GH. No entanto, uma vez que a doença torna-se controlada e os níveis de IGF-1 reduzem, os níveis de pressão arterial dependerão de outros fatores de risco cardiovasculares.

O recordatório de 24 horas como instrumento na avaliação do consumo alimentar de cálcio, fósforo e vitamina D em crianças e adolescentes de baixa estatura / The 24-hour recall for the assessment of dietary calcium, phosphorus and vitamin D intakes in stunted children and adolescents

OBJETIVO: Verificar em que medida o Recordatório Alimentar de 24 horas como instrumento de avaliação do consumo alimentar contribui para a avaliação de parâmetros biológicos envolvidos no metabolismo de cálcio, fósforo e vitamina D em crianças e adolescentes de baixa estatura. MÉTODOS: Foram avaliados 59 crianças e adolescentes com baixa estatura do Ambulatório de Baixa Estatura do Serviço de Endocrinologia do Hospital das Clínicas de Porto Alegre. Causas orgânicas, genéticas e endócrinas de baixa estatura foram excluídas da avaliação. Foram dosados cálcio, fósforo, creatinina, vitamina D, paratormônio fosfatase alcalina no soro e cálcio, fósforo, creatinina e sódio em urina de Recordatório Alimentar de 24h foi empregado para estimar o consumo dietético. RESULTADOS: Foi constatada ingestão reduzida de cálcio e vitamina D, em relação ao recomendado para idade e sexo. Verificou-se correlação negativa entre paratormônio e vitamina D dietética (r= -0,46; p<0,01), consumo de cálcio (r= -0,41; p<0,001), calciúria (r= -0,41; p<0,001) e o índice de excreção de cálcio na urina de 24 horas (r= -0,36; p<0,01). CONCLUSÃO: Quando comparados os resultados do Recordatório Alimentar de 24 horas com seus parâmetros bioquímicos, este instrumento pareceu adequado na estimativa do consumo dietético de micronutrientes de crianças e adolescentes.

OBJECTIVE: The objective of this study was to verify the extent to which the 24 hour recall, used as a tool to assess dietary intake, contributes to the assessment of biological parameters involved in the metabolism of calcium, phosphorus and vitamin D in stunted children and adolescents. METHODS: A total of 59 stunted children and adolescents seen at the outpatient clinic that specializes in stunting of the Endocrinology Service of Hospital das Clínicas in Porto Alegre, were assessed. Organic, genetic and endocrine causes of stunting were excluded from the assessment. Serum calcium, phosphorus, creatinine, vitamin D, parathormone and alkaline phosphatase and urine calcium, phosphorus, creatinine and sodium were measured. The 24 hour recall was used to determine dietary intake of these nutrients. RESULTS: Calcium and vitamin D intakes were low according to the values recommended for the two genders and studied age groups. There was a negative correlation between parathormone and dietary vitamin D (r= -0.46; p<0.01), calcium intake (r= -0.41; p<0.001), urine calcium (r= -0.41; p<0.001) and the calcium excretion index in the 24 hour urine (r= -0.36; p<0.01). CONCLUSION: When the 24-hour recall results were compared with their biochemical parameters, this instrument seemed to estimate the dietary micronutrient intakes of children and adolescents correctly.

Variação sazonal de níveis de 25-hidroxivitamina d sérica e ingestão dietética de vitamina d em crianças e adolescentes com baixa estatura / Seasonal variation of 25-hydroxyvitamin d serum levels and vitamin d dietary intake in short children and adolescents

Introdução: A baixa estatura sem causa clínica evidente pode estar relacionada com deficiências nutricionais. A vitamina D é um hormônio fundamental para o desenvolvimento ósseo, obtida através da dieta e exposição solar. Objetivo: Avaliar os níveis séricos de 25(OH)D, a variação sazonal deste metabólito e a ingestão de vitamina D em crianças e adolescentes com o déficit estatural sem causas clínicas evidentes. Métodos: Cinquenta e cinco crianças e adolescentes com baixa estatura, sem doenças crônicas, endócrinas ou genéticas, responderam a três recordatórios de 24h para estimar o consumo de vitamina D. O nível sérico de 25(OH)D foi avaliado por Cromatografia Líquida de Alta Eficiência (HPLC) no Laboratório Fleury/SP. A classificação do fototipo foi realizada através dos parâmetros de Fitzpatrick. Os dados meteorológicos foram obtidos junto ao VIII Distrito de Meteorologia de Porto Alegre, do Instituto Nacional de Meteorologia. Resultados: Verificou-se o consumo dietético de Vitamina D abaixo do recomendado em 96% (N=53) dos pacientes e níveis insuficientes de 25(OH)D (<30 ng/ml) em 60% (N=33). A concentração de 25(OH)D sérica foi mais alta nas amostras coletadas durante o outono (P<0,05), não se correlacionando com a insolação (P =0,13) ou consumo dietético de Vitamina D (P=0,32). A média de 25(OH)D sérica foi maior (P<0,05) no grupo de pacientes com fototipos I, II e III. Conclusão: A 25(OH)D sérica apresentou variação sazonal. Níveis séricos de 25(OH)D baixos reforçam a importância da vitamina D obtida através da dieta ou suplementação nos meses onde há uma menor incidência de radiação ultravioleta.

Background: Short stature without evident medical cause may be related to nutritional deficiencies. Vitamin D is an essential hormone for bone development, being obtained through diet and sun exposure. Aim: To evaluate 25(OH)D serum levels, as well as the seasonal variation of this metabolite and vitamin D intake in children and adolescents with short stature without evident clinical causes. Methods: Fifty-five short children and adolescents, without endocrine or genetic chronic diseases, completed three 24-hour dietary recalls to estimate the intake of vitamin D. 25(OH)D serum levels were evaluated using high performance liquid chromatography (HPLC) at Laboratory Fleury, state of São Paulo, Brazil. The phototype classification was performed using the Fitzpatrick parameters. Meteorological data were obtained from the VIII District of Meteorology of Porto Alegre, National Institute of Meteorology. Results: The dietary intake of vitamin D was lower than recommended in 96% (N= 53) of patients and there were insufficient levels of 25(OH)D (<30 ng/ml) in 60% (N=33). The concentration of 25(OH)D levels was higher in samples collected during the fall (P<0.05), without correlation with sunshine (P=0.13) or dietary intake of vitamin D (P=0.32). The mean 25(H)D level was higher (P<0.05) in patients with phototypes I, II and III. Conclusion: 25(OH)D levels showed seasonal variation. Low serum 25(OH)D levels reinforce the importance of vitamin D obtained from diet or supplements in the months during which there is lower incidence of ultraviolet radiation.

Diabetes melito e acromegalia: interações entre hormônio de crescimento e insulina / Diabetes mellitus and acromegaly: interactions between growth hormone and insulin

Introdução: o hormônio de crescimento humano (GH) possui um importante papel na fisiologia do metabolismo glicêmico, lipídico e protéico. O excesso deste hormônio, como encontrado na acromegalia, induz a um estado de resistência insulínica que pode estar associado à presença de diabetes melito (DM). Objetivo: descrever a frequência de DM e as características dos indivíduos com acromegalia e DM em acompanhamento no Hospital de Clínicas de Porto Alegre (HCPA). Métodos: estudo transversal avaliando o perfil clínico e laboratorial de uma coorte de pacientes com acromegalia. Os critérios utilizados para cura da doença foram os sugeridos pelo consenso de 2000 e, para considerar-se sob remissão, a presença de IGF-1 normal para sexo e idade em uso de medicação para controle da acromegalia. As dosagens de IGF-1 foram realizadas pelo método imunoradiométrico e as de GH por quimioluminescência. Resultados: cinquenta e nove pacientes com acromegalia foram analisados. Desses, 24% preencheram critérios de cura e 25% estavam em remissão da doença, os restantes apresentavam doença ativa. Trinta e sete por cento dos pacientes apresentavam DM, com HbA1c média de 7,3±2,2%. Entre os pacientes com DM, 86% não preencheram critérios de cura e mais frequentemente eram hipertensos [16/22 (73%) vs. 17/37 (46%), P=0,04] e faziam mais uso de estatina [14/22 (64%) vs. 8/37 (21%), P=0,004] em relação aos pacientes sem DM. Após análise de regressão logística múltipla, a presença de DM foi associada à presença de acromegalia ativa [razão de chances: 17,4 (IC 95%: 1,08-28,0), P=0,04] e essa associação foi independente do ajuste para idade, níveis de IGF-1 ou GH, hipertensão arterial e níveis séricos de triglicerídeos. Conclusões: O DM foi frequente entre os pacientes com acromegalia e significativamente relacionado ao controle da doença.

Background: human growth hormone (GH) plays an important role in the physiology of glucose, lipid and protein metabolism. The excess of this hormone, such as in cases of acromegaly, leads to a state of insulin resistance that can be associated with diabetes. Aim: to describe the frequency of diabetes in the sample of patients with acromegaly followed up at Hospital de Clínicas de Porto Alegre (HCPA). Methods: cross-sectional study assessing the metabolic profile of a cohort of acromegalic patients. The criteria used for cure of the disease were those suggested in the 2000 consensus, and the remission criteria were presence of normal IGF-1 levels for age and gender. IGF-1 was measured using the immunoradiometric assay and GH levels were measured using chemiluminescence. Results: fifty-nine acromegalic patients were analyzed. Only 24% met criteria for cure and 25% were in remission, the remaining had active disease. Thirty-seven percent of patients had diabetes, with a mean HbA1c of 7.3±2.2%. Among patients with diabetes, 86% did not meet criteria for cure and they were more often hypertensive [16/22 (73%) vs. 17/37 (46%), P=0.04] and were on statins [14/22 (64%) vs. 8/37 (21%), P=0.004] compared with patients without diabetes. After the multiple regression analysis, the presence of diabetes was associated with the presence of active acromegaly [odds ratio: 17.4 (95% CI: 1.08-28.0), P=0.04], and this association was independent from adjustment for age, IGF-1 levels or GH levels, hypertension, and triglycerides levels. Conclusions: diabetes was frequent among patients with acromegaly and it was closely related to the control of the underlying disease.

Distúrbios cardiovasculares na acromegalia: [revisão] / Cardiovascular disturbances in acromegaly: [review]

A acromegalia acarreta uma série de distúrbios ao sistema cardiovascular, decorrentes da exposição crônica a níveis elevados de GH e IGF-1. Estes distúrbios são os principais responsáveis pelo aumento da mortalidade de acromegálicos. Entre as várias formas de acometimento cardiovascular, destaca-se a miocardiopatia acromegálica, entidade caracterizada, inicialmente, pelo estado hiperdinâmico, seguido de hipertrofia ventricular esquerda concêntrica e disfunção diastólica por déficit de relaxamento, culminando com disfunção sistólica e, por vezes, insuficiência cardíaca franca. Além disso, são também relevantes as arritmias, as valvulopatias, sobretudo mitral e aórtica, a cardiopatia isquêmica, a hipertensão e os distúrbios dos metabolismos glicêmico e lipídico. Nesta revisão são abordados os principais aspectos clínicos e prognósticos destas entidades, os efeitos do tratamento da acromegalia sobre elas e as repercussões correspondentes sobre a sobrevida dos pacientes.

Acromegaly causes a number of disorders in the cardiovascular system, resulting from chronic exposure to high levels of GH and IGF-1. Such disorders are the main responsible for increased mortality rates among acromegalic patients. Among several forms of cardiovascular impairment is acromegalic cardiomyopathy, an entity that is initially characterized by a hyperdynamic state, followed by concentric left ventricular hypertrophy and diastolic dysfunction due to relaxation deficit, culminating in systolic dysfunction and sometimes heart failure. In addition, arrhythmias and heart valve diseases are also relevant, especially mitral and aortic, ischemic heart disease, hypertension, and glucose and lipid metabolism disorders. This review approaches the main clinical and prognostic aspects of these entities, the effects of acromegaly treatment on them, and the respective consequences on patient survival.

Micronutrientes envolvidos no crescimento / Micronutrients involved in growth

Os hábitos alimentares infantis têm sofrido modificações drásticas nas ultimas décadas. A aversão a frutas, verduras, carnes e laticínios, juntamente à predileção por produtos artificiais e industrializados observada entre crianças, tem despertado preocupação entre os profissionais da saúde. Isso porque estudos têm demonstrado a influência negativa do consumo insuficiente de alguns nutrientes no crescimento e desenvolvimento infantil. Cientes deste problema, desenvolvemos este artigo visando esclarecer algumas dúvidas quanto a função e importância de alguns micronutrientes como o zinco, ferro, vitamina A, ácido fólico, cálcio e vitamina D, bem como suas recomendações nutricionais, como auxilio a elaboração de tratamento e estratégias nutricionais que poderão garantir o crescimento e desenvolvimento normais entre as crianças

The infant habits have suffered drastic alterations in the last decades. The avoidance of fruits, vegetables, meat and milk products, with the preference to artificial and industrialized products observed among children have raised concerned among the health working groups. This is due to the studies that have demonstrated the negative influence of insufficient intake of some nutrients on infant growth and developing. Considering this problem, we wrote this article to clarify some doubts about the functions and importance of some micronutrients such as zinc, iron, vitamin A, folic acid, calcium and vitamin D, as well as nutritional recommendations, as a contribution to the elaboration of treatment and nutritional strategies that would ensure children growth and development

Esteróides anabolizantes no esporte / Anabolic steroids in sports

Os hormônios esteróides anabólicos androgênicos (EAA) compreendem a testosterona e seus derivados. Eles são produzidos nos testículos e no córtex adrenal, e promovem as características sexuais secundárias associadas à masculinidade. Na medicina, os EAA são utilizados geralmente no tratamento de sarcopenias, do hipogonadismo, do câncer de mama e da osteoporose. Nos esportes, são utilizados para o aumento da força física e da massa muscular; entretanto, os efeitos sobre o desempenho atlético permanecem, ainda, controversos. Os EAA podem causar diversos efeitos colaterais, como psicopatologias, câncer de próstata, doença coronariana e esterilidade. Estudos epidemiológicos apontam a problemática acerca do uso de EAA, nos esportes; todavia, no Brasil não existem publicações substanciais sobre esse tema. Esta revisão analisa esse assunto, procurando despertar a curiosidade e o interesse dos leitores para a produção científica de novos trabalhos relacionados ao tema.

Cardiopatia carcinóide associada ao carcinoma medular de tireóide: relato de caso / Carcinoid heart disease associated to medullar thyroid carcinoma: report of case

A associação entre o Carcinoma Medular de Tireóide (CMT) e a Síndrome Carcinóide é bem estabelecida. Entretanto, não existem relatos na literatura da presença de cardiopatia Carcinóide (CC), um dos componentes da síndrome, em pacientes com CMT. Relatamos o caso de uma paciente de 36 anos, branca, submetida à tireoidectomia por apresentar nódulos tireoidianos de crescimento progressivo, cujo diagnóstico, feito pelo exame anátomo-patológico, demonstrou CMT, confirmado pelo exame imunohistoquímico, positivo para calcitonina. A paciente apresentava metástases ósseas, renais e pancreáticas. Um ano após, apresentou quadro progressivo de insuficiência cardíaca, com espessamento das valvas tricúspide e aórtica, dilatação de cavidades diretas e derrame pericárdico à ecocardiografia. A presença de síndrome carcinóide foi estabelecida pela pesquisa de ácido 5-hidroxindolacético urinário fortemente positiva. Muito embora cerca de 20 por cento dos pacientes com Síndrome Carcinóide possam desenvolver a CC, esta alteração não havia sido descrita em associação com o Carcinoma Medular de Tireóide.