Vitamin D and follicular recruitment in the in vitro fertilization cycle.

OBJECTIVE: Vitamin D (VD) is a fat-soluble steroid hormone, synthesized by the skin, most known for its role in bone mineral balance. Vitamin D receptors (VDR) are also found in the female reproductive system, but their role remains unclear. The objective of this study was to analyze the relationship between serum vitamin D levels and the number of oocytes retrieved after ovarian stimulation. METHODS: This is a retrospective study involving 267 patients undergoing in vitro fertilization (IVF) carried out in the Fertipraxis clinic, a private practice facility. The patients were initially divided into two groups according to their VD levels. Group 1 included 152 patients with VD levels < 30 ng/mL and group 2 had 115 patients with VD levels > 30 ng/mL. They were further analyzed and separated considering their age, anthropometric data, ovarian reserve, amount of gonadotropin used, and follicles obtained until trigger day. RESULTS: In our analysis, there were no difference in the number of follicles and oocytes retrieved, nor in the number of mature oocytes obtained from patients with both vitamin D deficiency and sufficiency. CONCLUSIONS: The results of our study show no difference among number of follicles, oocytes retrieved and mature oocytes obtained after ovarian stimulation according to their vitamin D serum levels. Further higher-quality studies are needed to evaluate the possible roles of serum vitamin D levels in other stages of human fertilization process.

Case Report: Composite pheochromocytoma with ganglioneuroma component: A report of three cases.

Composite pheochromocytoma (CP) is a very rare tumor originating from neural crest cells, predominantly composed of pheochromocytoma (PCC), a chromaffin cell tumor arising in adrenal medulla, and ganglioneuroma, a tumor derived from autonomic ganglion cells of the nervous system. Moreover, CP may be present in the hereditary syndromes of which pheochromocytoma is part. Literature offers scarce data on this subject, and particularly about its biological behavior, clinical evolution, and molecular profile. We report the phenotype and outcome of three cases of CP (PCC and ganglioneuroma components), followed up at the Endocrine Service of the Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, UFRJ, Rio de Janeiro, Brazil. Two nonsyndromic patients (cases 1 and 2) were negative to germline mutations in genes VHL, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and MAX, while the third case (case 3) had clinical diagnosis of neurofibromatosis syndrome. Cases 1, 2, and 3 were diagnosed at 29, 39, and 47 years old, respectively, and were followed up for 3, 17, and 9 years without no CP recurrence. All cases had apparent symptoms of catecholaminergic excess secreted by PCC. Ganglioneuroma, the neurogenic component present in all three cases, had a percentage representation ranging from 5% to 15%. Tumors were unilateral and large, measuring 7.0 cm × 6.0 cm × 6.0 cm, 6.0 cm × 4.0 cm × 3.2 cm, and 7.5 cm × 6.0 cm × 4.5 cm, respectively. All cases underwent adrenalectomy with no recurrence, metastasis, or development of contralateral tumor during follow-up. Genetic testing has been scarcely offered to CP cases. However, a similar frequency of genetic background is found when compared with classic PCC, mainly by the overrepresentation of NF1 cases in the CP subset. By literature review, we identified a notorious increase in cases reported with CP in the last decade, especially in the last 3 years, indicating a recent improvement in the diagnosis of this rare disorder in clinical practice.

Prevalence of subclinical hypercortisolism in type 2 diabetic patients from the Rio de Janeiro Type 2 Diabetes Cohort Study.

AIMS: Subclinical hypercortisolism was reported to be more prevalent among diabetic, obese and hypertensive patients. Our primary aim was to investigate the prevalence of subclinical hypercortisolism in patients from the Rio de Janeiro Type 2 Diabetes (RIO-T2D) Cohort; and secondarily to assess its associated factors. METHODS: From May 2013 to August 2014, 393 diabetic outpatients underwent overnight 1mg dexamethasone suppression test (DST). Patients with non-suppressive morning cortisol (≥1.8µg/dl) were further evaluated with nocturnal salivary cortisol, two readings >0.35µg/dl were considered confirmatory for subclinical hypercortisolism. RESULTS: One-hundred twenty-eight patients (32.6%) failed to suppress morning cortisol, and in 33 patients (8.6%) subclinical hypercortisolism was confirmed. Independent correlates of a positive DST were older age (OR: 1.04; 95% CI: 1.01-1.07; p=0.007), number of anti-hypertensive drugs in use (OR: 1.26; 95% CI: 1.05-1.50; p=0.012), longer diabetes duration (OR: 1.03; 95% CI: 1.004-1.06; p=0.023), and presence of diabetic nephropathy (OR: 1.70; 95% CI: 1.01-2.87; p=0.047). Independent correlates of confirmed subclinical hypercortisolism were a greater number of anti-hypertensive medications (OR: 1.54; 95% CI: 1.14-2.06; p=0.004), shorter diabetes duration (OR: 0.92; 95% CI: 0.87-0.98; p=0.006), and increased aortic stiffness (OR: 2.81; 95% CI: 1.20-6.57; p=0.017); metformin use was protective (OR: 0.27; 95% CI: 0.10-0.73; p=0.010). CONCLUSION: Patients with type 2 diabetes had a high prevalence of subclinical hypercortisolism, and its presence was associated with more severe hypertension and increased aortic stiffness.

Prevalence and associated factors of subclinical hypercortisolism in patients with resistant hypertension.

BACKGROUND: Subclinical hypercortisolism is a secondary cause of hypertension that had never been evaluated in resistant hypertensive patients, a subgroup of general hypertensive individuals with an expected high prevalence of secondary hypertension. METHODS: Four hundred and twenty-three patients with resistant hypertension and ages up to 80 years were screened for the presence of subclinical hypercortisolism by morning serum cortisol after a midnight 1 mg dexamethasone suppression test (DST). Those with morning cortisol of at least 50  nmol/l had hypercortisolism confirmed by two salivary cortisol of at least 3.6  nmol/l collected at 2300  h. Statistical analysis included bivariate tests between those with positive and negative screening test and with and without confirmed hypercortisolism, and logistic regressions to assess their independent correlates. RESULTS: One hundred and twelve patients (prevalence 26.5%, 95% confidence interval 22.0-31.9%) had the screening test positive for suspected hypercortisolism. None had overt Cushing syndrome. Patients with positive screening were older, more frequently males, had higher prevalences of diabetes and target-organ damage and higher nighttime SBPs than patients with normal screening test results. Thirty-four patients (total prevalence 8.0%, 95% confidence interval: 5.7-11.2%) had confirmed hypercortisolism. Independent correlates of a positive DST were older age (P = 0.007), male sex (P = 0.012) and presence of cardiovascular diseases (P = 0.002) and chronic kidney disease (P = 0.016). Correlates of confirmed subclinical hypercortisolism were older age (P = 0.020), diabetes (P = 0.06) and a nondipping pattern on ambulatory blood pressure monitoring (P = 0.04). CONCLUSION: Patients with resistant hypertension had a relatively high prevalence of subclinical hypercortisolism, and its presence is associated with several markers of worse cardiovascular prognosis.

Influence of obesity on bone density in postmenopausal women.

OBJECTIVE: To evaluate the influence of obesity, age, and years since menopause on bone density. METHODS: A retrospective analysis of bone mineral density (BMD) obtained from 588 women, 41 to 60 years, previously menopaused (1-10 years before). RESULTS: Positive influence of obesity was confirmed by the significant differences in BMD at lumbar spine, femoral neck (FN), and trochanter (TR) between the groups (p < 0.01). Age and years since menopause (YSM) were negatively correlated with BMD at all sites (p = 0.000). Comparing patients within 1 to < 6 YSM versus 6 to 10 YSM, BMD was higher in the former at LS and FN (p < 0.005), despite the higher BMI in the older group (p = 0.01). Obese patients had a lower prevalence of osteoporosis at LS and FN (p = 0.009). Regression analysis identified BMI as the strongest determinant of FN and TR BMD, while YSM was the strongest determinant of LS BMD. CONCLUSION: The protective effect of obesity is overtaken by age and estradiol deficiency. We recommend that even obese postmenopausal women should be screened for osteoporosis.

Influence of obesity on bone density in postmenopausal women

OBJECTIVE: To evaluate the influence of obesity, age, and years since menopause on bone density. METHODS: A retrospective analysis of bone mineral density (BMD) obtained from 588 women, 41 to 60 years, previously menopaused (1-10 years before). RESULTS: Positive influence of obesity was confirmed by the significant differences in BMD at lumbar spine, femoral neck (FN), and trochanter (TR) between the groups (p < 0.01). Age and years since menopause (YSM) were negatively correlated with BMD at all sites (p = 0.000). Comparing patients within 1 to < 6 YSM versus 6 to 10 YSM, BMD was higher in the former at LS and FN (p < 0.005), despite the higher BMI in the older group (p = 0.01). Obese patients had a lower prevalence of osteoporosis at LS and FN (p = 0.009). Regression analysis identified BMI as the strongest determinant of FN and TR BMD, while YSM was the strongest determinant of LS BMD. CONCLUSION: The protective effect of obesity is overtaken by age and estradiol deficiency. We recommend that even obese postmenopausal women should be screened for osteoporosis.

OBJETIVO: Avaliar a influência de obesidade, idade e anos de menopausa sobre a densidade óssea. MÉTODOS: Análise retrospectiva da densidade mineral óssea (DMO) obtida em 588 mulheres de 41 a 60 anos, já menopausadas (1-10 anos antes). RESULTADOS: A influência positiva da obesidade foi confirmada através de diferenças significativas da DMO entre os grupos na coluna lombar (CL), colo de fêmur (CF) e trocânter (TR) (p < 0,01). Idade e anos desde a menopausa (ADM) foram correlacionados negativamente com DMO em todos os sítios (p = 0,000). Comparando-se pacientes entre 1 e < 6 ADM vs 6 e 10 AMD, a DMO foi maior no primeiro grupo na CL e CF (p < 0,005), apesar de maior DMO no grupo de mais idade (p = 0,01). Pacientes obesas tiveram uma prevalência mais baixa de osteoporose na CL e CF (p = 0,009). Análise de regressão identificou o IMC como o determinante mais forte da DMO de CF e trocânter, enquanto a ADM foi o determinante mais forte da DMO na CL. CONCLUSÃO: O efeito protetor da obesidade é sobrepujado pela deficiência de estradiol. Recomendamos que mesmo mulheres obesas na pós-menopausa devam ser examinadas para osteoporose.

[Lipid profile and alteration of body composition in growth hormone deficient adults]. / Perfil lipídico e composição corporal na deficiência do hormônio de crescimento em adultos.

BACKGROUND: The growth hormone deficiency (GHD) syndrome in adults and the increased associated cardiovascular risk have been extensively studied in recent years. Abnormal body composition with excess of visceral adiposity and adverse lipid profile are important features of this syndrome. Abnormal lipid profile has been described with increased levels of total cholesterol (C), LDL-cholesterol (LDL-C), triglycerides, decreased levels of HDL-cholesterol (HDL-C) and apolipoproteins abnormalities. METHODS: Lipid profile and the amount of visceral adipose tissue were studied in 31 GHD adults compared with a control group of healthy subjects matched for age, gender and body mass index (BMI). Visceral adipose tissue was evaluated by abdominal computed tomography and anthropometric measurements--BMI (kg/m2) and waist circumference (cm). The lipid profile was studied by measurement of C, LDL-C, HDL-C, triglycerides, apolipoproteins A and B, and Lipoprotein (a). RESULTS: The GHD adults showed increased visceral adipose tissue (156.66 +/- 72.72 vs. 113.51 +/- 32.97 cm2, p = 0.049), higher levels of triglycerides (158.58 +/- 80.29 vs. 97.17 +/- 12.37 mg/dl; p = 0.007) and lower HDL- cholesterol (45.41 +/- 13.30 vs. 55.34 +/- 14.31 mg/dl; p = 0.002). There were no differences in others aspects of lipid profile and anthropometric measurements. CONCLUSION: Growth Hormone Deficient adults showed increased visceral adipose tissue, higher levels of triglycerides and lower HDL- cholesterol levels.

Perfil lipídico e composição corporal na deficiência do hormônio de crescimento em adultos / Lipid profile and alteration of body composition in growth hormone deficient adults

OBJETIVO: A síndrome da deficiência de hormônio de crescimento (DGH) no adulto e o conseqüente aumento no risco cardiovascular têm sido bastante estudados nos últimos anos. De grande relevância clínica são as alterações na composição corporal com aumento do tecido adiposo visceral e perfil lipídico adverso. MÉTODOS: Estudou-se o perfil lipídico e o tecido adiposo visceral de 31 adultos com DGH comparado com um grupo controle de indivíduos saudáveis pareados por idade, sexo e índice de massa corporal (IMC). A avaliação da gordura visceral foi feita por tomografia computadorizada de abdome e por medidas antropométricas, através do IMC (Kg/m²) e da medida da cintura (cm). A avaliação do perfil lipídico foi obtida através de dosagens laboratoriais de colesterol (CT), triglicerídeos (TG), HDL, LDL, apolipoproteínas A e B e lipoproteína (a). RESULTADOS: Foi observado aumento do tecido adiposo visceral nos pacientes DGH (156,66 ± 72,72 vs. 113,51 ± 32,97 cm²; p-valor = 0,049), além de aumento nos níveis de TG (158,80 ± 80,29 vs. 97,17 ± 12,37 mg/dl; p-valor = 0,007) e diminuição nos níveis de HDL (45,41 ± 13,30 vs. 55,34 ± 14,31 mg/dl; p-valor = 0,002). Não houve diferença entre os demais parâmetros do perfil lipídico e nas medidas antropométricas. CONCLUSÃO: Adultos deficientes de GH apresentam aumento da adiposidade visceral e aumento das concentrações de TG com diminuição das concentrações de HDL.

Deficiência de GH em adultos: resultados do estudo multicêntrico brasileiro / GH deficiency in adults: results of the Brazilian multicenter study

Avaliamos 70 pacientes com deficiência de GH, 39 mulheres e 31 homens, com idades entre 18 e 69 anos (média de 38,3±13,5), provenientes de 3 centros no Brasil. A dose de reposiçäo variou entre os centros, bem como a resposta do IGF-1, que mostrou maior aumento nos centros com maior dose de GH. Reposiçäo de GH levou a um aumento significativo nos níveis de IGF-1 e HDL colesterol, bem como da densidade mineral óssea (DMO), e a uma reduçäo significativa nos níveis de colesterol total e LDL colesterol, semelhante nos 3 centros. Encontramos aumento mais significativo de HDL colesterol nas mulheres e aumento mais acentuado da DMO nos pacientes do sexo masculino. Concluimos que reposiçäo de GH leva à melhora do perfil lipídico e da DMO, e que doses menores apresentam o mesmo benefício, provavelmente com menor incidência de efeitos colaterais

Avaliação do metabolismo glicídicoe da gordura visceral em adultos deficientes de hormônio de crescimento / Evaluation of glucose metabolism and visceral adiposity in growth hormone deficient adults

A síndrome da deficiência de hormõnio de crescimento (DGH) no adulto e o conseqüente aumento no risco cardiovascular têm sido bastante estudados nos últimos anos. Com o objetivo de avaliar as alterações na composição corporal e a presença de resistência à insulina em adultos com DGH, estudamos 27 pacientes comparados a 27 indivíduos saudáveis pareados por idade, sexo e índice de massa corporal, através de tomografia computadorizada de abdomen para medida da gordura visceral e teste de tolerância oral à glicose (TTOG), com curva de glicose e insulina e estimativa da resistência à insulina pelo Homeostasis Model Assessment (HOMA). Observamos, nos pacientes, aumento do tecido adiposo visceral (p= 0,008) sem aumento da freqüência de alterações no TTOG. As glicemias e insulinemias basais e após 2 horas de sobrecarga oral de glicose e as áreas sob as curvas de glicose e insulina foram semelhantes ao grupo controle (p> 0,05). Não houve diferença na sensibilidade à insulina pelo método HOMA (p= 0,989). Houve correlação positiva significativa da medida de gordura visceral nos pacientes com as dosagens de glicemia (r= 0,583; p= 0,001) e insulina (r= 0,728; p= 0,001) após sobrecarga de glicose e as áreas sob a curvas de glicose (r= 0,403; p= 0,040) e insulina (r= 0,713; p= 0,001), porém sem correlação significativa nos controles (r< 0,40; p> 0,05). Em conclusão, não houve alteração significativa no metabolismo glicídico, apesar do aumento da adiposidade visceral observada em adultos DGH.

Ambulatory monitoring of blood pressure in growth hormone-deficient adults.

The aim of this study was to evaluate the 24-h pattern of blood pressure in adults with growth hormone deficiency using ambulatory blood pressure monitoring. We therefore evaluated the mean systolic and diastolic blood pressures, systolic and diastolic blood pressure loads and diurnal blood pressure rhythm. We used an auscultatory-type monitor, the measurements being made at 10-15 min intervals during the day and 20-30 min intervals at night. We included patients with a growth hormone peak of less than 3 ng/ml in at least two stimulation tests: the insulin tolerance and glucagon tests. The exclusion criteria were mental illnesses, pregnancy, diabetes mellitus, blood pressure higher than 160/90 mmHg, the use of growth hormone in the previous 12 months, severe acute illnesses, chronic liver or kidney disease and a history of malignancy. The results were interpreted according to the II Brazilian Consensus for the utilization of ambulatory monitoring. The study population comprised 27 adult patients with growth hormone deficiency, 11 male and 16 female, with an age range of 21-62 years. Five had developed the condition during childhood, whereas the remainder had adult-onset growth hormone deficiency. The mean systolic (115 +/- 16.7 mmHg) and diastolic blood pressure loads (75.51 +/- 1.90 mmHg) were normal. There was a tendency towards a lower blood pressure in patients with childhood-onset growth hormone deficiency when compared with their adult-onset counterparts. Men had a lower systolic blood pressure than women, the same pattern being found for mean diastolic blood pressure. Multiple regression analysis showed that age was the only independent variable with the statistical power to explain the variance of blood pressure in this group of patients. The incidence of non-dippers was 37.03%. Growth hormone deficiency thus seems to be associated with a change in the 24-h blood pressure pattern, with a high incidence of non-dippers.

Fracture risk is increased in patients with GH deficiency or untreated prolactinomas--a case-control study.

OBJECTIVE: The pituitary secretes many hormones of significance to bone turnover and thus skeletal integrity. The aim of this study was to examine fracture risk in patients with pituitary disorders with special reference to GH deficiency and hyperprolactinaemia. DESIGN: Case-control study. MEASUREMENTS: Fracture occurrence. PATIENTS: A self-administered questionnaire was issued to 537 consecutive patients with pituitary disorders excluding Cushing's disease. A total of 426 (79%) returned the questionnaire and 422 of these could be analysed. Each respondent was compared to three age- and gender-matched control respondents to the same questionnaire drawn randomly from the background population. RESULTS: The patients had a mean age of 51.4 +/- 14.8 years. One hundred and eight patients had acromegaly, 86 had prolactinomas, 136 had non-functioning pituitary adenomas (NFPA), 23 had craniopharyngiomas, and 73 had other types of pituitary disorders. For the total group the fracture risk was not elevated either before or after confirmed diagnosis compared to controls. However, among the patients with prolactinomas, the fracture risk was significantly increased before (relative risk, RR = 1.6, 95% CI: 1.1--2.3) but not after diagnosis. In patients with NFPA, fracture risk was borderline significantly elevated following diagnosis (RR = 1.6, 95% CI: 1.0--2.6). Patients with subnormal stimulated peak GH values suggestive of GH deficiency had a significantly higher risk of fractures after diagnosis than patients who had normal stimulated peak GH values (odds ratio, OR = 4.90, 95% CI: 1.10--21.88). CONCLUSIONS: Untreated prolactinomas were associated with a significant increase in fracture risk. Growth hormone deficiency was also associated with a higher fracture risk.

Efeitos do treinamento físico contra resistência sobre a composiçäo corporal e a potência muscular em adultos deficientes de hormônio do crescimento / Effects of physical training against resistance over the corporal composition and the muscular potency in deficient adults of growth hormone

A síndrome de deficiência do hormônio de crescimento (GH) no adulto está bem esclarecida, assim como os benefícios da terapia de reposiçäo com o GH recombinante. Dentre as alteraçöes observadas nesses pacientes, as da composiçäo corporal estäo entre as mais estudadas, sendo caracterizadas por um aumento da gordura corporal total com predomínio de gordura no tronco, diminuiçäo da massa magra, da força muscular e da água corporal total. Todas säo quase completamente revertidas após tratamento de reposiçäo com GH. Estudamos a composiçäo corporal e potência muscular de 11 pacientes com deficiência de GH, antes e após serem submetidos a um programa de treinamento com exercícios contra resistência por 12 semanas, sem reposiçäo com o GH. Avaliamos a composiçäo corporal através de medidas de circunferências, dobras cutâneas, peso, altura, cálculo do índice de massa corporal e relaçäo cintura-quadril. A potência muscular localizada foi avaliada em vários grupos musculares através de cinco exercícios numa unidade de exercícios musculares localizados, onde foi acoplado um tensiômetro. Após análise dos resultados, observamos que näo houve mudança na composiçäo corporal destes pacientes, em relaçäo ao índice de massa corporal, relaçäo cintura-quadril e peso. Quando estudamos separadamente a soma das dobras cutâneas centrais e periféricas, houve diminuiçäo no volume da soma das dobras centrais. Em relaçäo à força e potência muscular, näo houve ganho de força de preensäo manual medida através do dinamômetro (p>0,05), já a potência mostrou um aumento significativo após treinamento (p<0,01). Concluímos que esses pacientes, se submetidos a um programa de treinamento de exercícios contra resistência realizado em casa, ganham potência muscular e que esta forma de exercício é uma alternativa terapêutica para que possam melhorar sua qualidade de vida, quando näo for possível a utilizaçäo do GH.