Prevalence of hypothyroidism in patients with frozen shoulder.

BACKGROUND: Hypothyroidism and frozen shoulder (FS) have been associated, although this relationship remains uncertain. The main objective of this study was to determine the prevalence of hypothyroidism in patients with FS. METHODS: A case-control study was performed to compare FS patients (cases) with patients who visited an orthopedic service for other clinical conditions (controls). FS was diagnosed according to specific criteria based on anamnesis, physical examination, and shoulder radiographs. A specific questionnaire was applied, and measurements of serum thyroid-stimulating hormone (TSH) and free tetraiodothyronine were performed in all subjects. RESULTS: We evaluated 401 shoulders from 93 FS patients and 151 controls. The prevalence of hypothyroidism diagnosis was significantly higher in the FS group (27.2% vs. 10.7%; P = .001). There was also a tendency for higher prevalence of bilateral FS among patients with elevated TSH levels (P = .09). Mean serum TSH levels were higher in patients with bilateral FS compared with those with unilateral compromise (3.39 vs. 2.28; P = .05) and were higher in patients with severe FS compared with those with mild and moderate FS together (3.15 vs. 2.21; P = .03). Multivariate analysis showed that FS was independently related to a diagnosis of hypothyroidism (odds ratio, 3.1 [1.5-6.4]; P = .002). There was a trend toward independent association between high serum TSH levels and both severe (odds ratio, 3.5 [0.8-14.9]; P = .09) and bilateral (odds ratio, 11.7 [0.9-144.8]; P = .05) compromise. CONCLUSION: The prevalence of hypothyroidism was significantly higher in FS patients than in controls. The results suggest that higher serum TSH levels are associated with bilateral and severe cases of FS.

Thyroid Volume in Pregnancy is Associated with Parity, Gestational Age, and Body Mass Index in an Iodine-sufficient Area.

OBJECTIVE: We compared thyroid volume (TV) and presence of nodular goiter (NG) in pregnant vs. non-pregnant women in an iodine-sufficient area. We also evaluated the relationship between gestational age, parity, and TV in the pregnant women group, and determined the 2.5th and 97.5th percentiles of normal TV in pregnancy. METHODS: This cross-sectional study included 299 healthy women (216 pregnant) without previous thyroid diseases. Thyroid ultrasounds were performed and compared between pregnant and non-pregnant women. The range of normal distribution of TV (2.5th and 97.5th percentiles) in pregnancy was determined after excluding individuals with positive thyroid antibodies, NG, and/or abnormal serum thyrotropin (TSH) or free thyroxine (FT4). RESULTS: Thyroid volume was larger among pregnant compared to non-pregnant women (8.6 vs 6.1 cm3; p < 0.001) and was positively correlated with gestational age (rs = 0.221; p = 0.001), body mass index (BMI, rs 0.165; p = 0.002), and FT4 levels (rs 0.118 p = 0.021). Nodular goiter frequency did not differ between the two groups. There was a negative correlation between TV and TSH (rs -0.13; p = 0.014). Thyroid volume was lower among primiparous compared to multiparous patients (7.8 vs 8.9; p < 0.001) and was positively correlated with parity (rs 0.161; p = 0.016). The 2.5th and 97.5th percentiles of TV were 4.23 and 16.47 cm3, respectively. CONCLUSION: Thyroid volume was higher in pregnant compared to non-pregnant women and was positively related to parity, BMI, and gestational age in a normal iodine status population. Pregnancy did not interfere with the development of NG.

OBJETIVO: Comparamos o volume tireoidiano (VT) e a presença de bócio nodular (BN) em mulheres grávidas e não grávidas em uma área suficiente em iodo. Também avaliamos a relação entre idade gestacional, paridade e VT no grupo de gestantes e determinamos os percentis 2,5 e 97,5 de VT normal na gestação. MéTODOS: Este estudo transversal incluiu 299 mulheres saudáveis (216 grávidas) sem doenças tireoidianas prévias. Ultrassonografias de tireoide foram realizadas e comparadas entre mulheres grávidas e não grávidas. A faixa de distribuição normal de VT (percentis 2,5 e 97,5) na gestação foi determinada após a exclusão de indivíduos com anticorpos tireoidianos positivos, BN e/ou tireotropina sérica (TSH) ou tiroxina livre (T4L) anormais. RESULTADOS: O VT foi maior entre as gestantes em comparação com as mulheres não grávidas (8,6 vs 6,1 cm3; p < 0,001) e foi positivamente correlacionado com a idade gestacional (rs = 0,221; p = 0,001), índice de massa corporal (IMC, rs 0,165; p = 0,002) e níveis de T4L (rs 0,118 p = 0,021). A frequência de BN não diferiu entre os dois grupos. Houve correlação negativa entre VT e TSH (rs -0,13; p = 0,014). O VT foi menor entre as primíparas em comparação com as multíparas (7,8 vs 8,9; p < 0,001) e foi positivamente correlacionado com a paridade (rs 0,161; p = 0,016). Os percentis 2,5 e 97,5 de VT foram 4,23 e 16,47 cm3, respectivamente. CONCLUSãO: O VT foi maior em gestantes em comparação com mulheres não grávidas e foi positivamente relacionado à paridade, IMC e idade gestacional em uma população com status iódico normal. A gravidez não interferiu no desenvolvimento de BN.

Sellar and suprasellar mixed germ cell tumor mimicking a pituitary adenoma.

Germ cell tumors (GCT) are a heterogeneous group of lesions whose origin is not well established. Several cases of primary intrasellar germinomas have been reported, however non-germinomatous GCT have rarely been described. We report the case of a young adult male patient with a mixed GCT that presented with a sellar tumor with suprasellar extension. The patient seeked medical attention because of seizures and magnetic resonance imaging evidenced a tumor of the sellar region. Hyperprolactinemia was also present and dopamine agonist therapy was started. As there was a rapid tumor growth and the patient had concomitant central diabetes insipidus and elevated testosterone levels, a GCT was suspected and confirmed by elevated serum concentration of ß-human chorionic gonadotrophin. Patient underwent surgical resection of the tumor and histopathological examination confirmed the diagnosis of a mixed GCT. Chemotherapy was initiated, followed by conventional radiotherapy. In conclusion, although pituitary adenomas respond for the vast majority of sellar tumors, concomitant symptoms such as central diabetes insipidus and rapid tumor growth should raise the suspicion of a diverse diagnosis. The present report intend not only to show a rare case of sellar and suprasellar mixed GCT but also to remind clinicians that if laboratory findings do not fit into patient's diagnosis (such as high testosterone levels in our patient), then the diagnosis should be reviewed.

Effects of 5 years of growth hormone (GH) replacement therapy on cardiac parameters and physical performance in adults with GH deficiency.

The purpose of this study was to evaluate the effects of 5 years of GH substitution on cardiac structure and function, physical work capacity and blood pressure levels in adults with GH deficiency (GHD). Fourteen patients were clinically assessed every 3 months for 5 years. Transthoracic echocardiography and exercise test were performed at baseline, 24, 48 and 60 months. Blood pressure (BP) was measured by means of ambulatory monitoring of blood pressure at baseline, 6, 12, 24 and 60 months. Left ventricular mass and its index increased progressively during the 5 years of GH substitution (P = 0.008 and 0.007, respectively). There were no significant changes in all others cardiac parameters evaluated. It was observed a significant improve in functional capacity (P < 0.001) and maximal oxygen uptake (P = 0.006) during the treatment. Diurnal systolic BP increased by 15 mmHg (P = 0.024) and diurnal diastolic BP by 4.5 mmHg (P = 0.037). There was no change in dirnal systolic pressure load but a considerable but non-statistically significant reduction in diurnal diastolic pressure load was observed during the study. During the night diastolic BP increased by 4 mmHg (P = 0.012) despite a substantial but non-statistically significant reduction in diastolic pressure load. We observed an increase in the proportion of persons with a non-physiological nocturnal fall (non-dippers) throughout the study (from 36.4% at baseline to 54.6% after 60 months of therapy). We concluded that 5 years of GH replacement promoted positive effects on exercise capacity and maximum oxygen uptake in spite of a modest increase in BP levels and left ventricular mass. Continuous monitoring is mandatory to arrive at further conclusions concerning the effects of GH substitution in adults on cardiovascular parameters with respect to possible unfavorable long term effects.

Effects of Metformin on TSH Levels and Benign Nodular Goiter Volume in Patients Without Insulin Resistance or Iodine Insufficiency.

Objectives: To evaluate the impact of metformin (MTF) use on TSH levels, thyroid volume and volume of benign thyroid nodules (TNs). Additionally, to study if iodine status influences the outcomes. Methods: A total of 23 euthyroid patients (42 TNs) with benign thyroid nodules, diagnosed by fine needle aspiration biopsy, were randomly assigned to MTF or placebo (P) use for 6 months. Serum TSH, homeostatic model assessment for insulin resistance (HOMA-IR), and urinary iodine concentrations (UIC) were assessed. Ultrasound was used to evaluate TNs and thyroid volumes (TV) and their variations throughout the study. Diabetic patients, those undergoing levothyroxine replacement, and/or using thyroid- or insulin level-influencing drugs were excluded. Results: The sample consisted predominantly of patients without IR. Both intervention groups were similar regarding several confounding variables and showed a comparable median UIC. Serum TSH decreased significantly after MTF (-0.21 vs. 0.09 mUI/L in the P group; p = 0.015). At 6 months, no significant variations were found between groups with respect to TN volumes, TV, HOMA-IR, or body mass index (BMI). However, a tendency toward enlargement of TV with placebo (16.0%; p = 0.09) and a protective effect of MTF on growing TN (OR: 0.25; CI 0.05-1.20) was detected after excluding patients with IR (a lower UIC subgroup). The reduction on TSH levels with MTF maintained in the population without iodine insufficiency (-0.24 vs. +0.07 in the P group; p = 0.046) and was accentuated in those with excessive or more than adequate UIC (-0.69; p = 0.043). A protective effect of MTF on growing TN was suggested (OR: 0.11; IC: 0.02-0.84) in those with higher UIC. Conclusions: This study demonstrated that MTF caused a reduction in TSH levels in benign nodular goiter. This effect was more accentuated in patients with higher levels of UIC and was accompanied by a suggested protective effect on TN enlargement.

Impact of 5 years of growth hormone replacement therapy on cardiovascular risk factors in growth hormone-deficient adults.

The benefits of long-term effects of growth hormone (GH) substitution on carbohydrate and lipid metabolism in GH-deficient (GHD) adults are still controversial. The purpose of this study was to evaluate the effects of 5 years of GH substitution on body composition, glucose and lipid metabolism, and carotid artery intima-media thickness (IMT) in GHD adults. Fourteen patients were clinically assessed every 3 months for 5 years. Serum insulin-like growth factor 1 levels, lipid profile, oral glucose tolerance test, and ultrasonography of the carotid arteries were performed at baseline, 6 months, and every year during replacement. Visceral fat was measured by computed tomographic scan at baseline and at 6, 12, 24, and 60 months. The waist circumference was reduced after 6 months but increased during the next months toward baseline values. Visceral fat decreased during the study. Fasting glucose and insulin levels did not change, as well as the homeostasis model assessment of insulin resistance index. Despite an initial increase in frequency of abnormal glucose tolerance, mean 2-hour oral glucose tolerance test glucose levels decreased during the last 2 years. There was an increase in apolipoprotein A-1 levels during the treatment. Apolipoprotein B levels were reduced after 6 months and remained stable thereafter. A reduction in carotid artery IMT was observed during replacement. We concluded that 5 years of GH replacement therapy promoted positive effects on visceral fat, lipid profile, and carotid artery IMT in GHD adults. Long-term therapy improves insulin sensitivity through a reduction in visceral fat, and continuing monitoring is mandatory in terms of glucose metabolism.

Thyroid Volume in Pregnancy is Associated with Parity, Gestational Age, and Body Mass Index in an Iodine-sufficient Area / O volume tireoidiano em gestantes está associado à paridade, idade gestacional e índice de massa corporal em uma área suficiente em iodo

Abstract Objective We compared thyroid volume (TV) and presence of nodular goiter (NG) in pregnant vs. non-pregnant women in an iodine-sufficient area. We also evaluated the relationship between gestational age, parity, and TV in the pregnant women group, and determined the 2.5th and 97.5th percentiles of normal TV in pregnancy. Methods This cross-sectional study included 299 healthy women (216 pregnant) without previous thyroid diseases. Thyroid ultrasounds were performed and compared between pregnant and non-pregnant women. The range of normal distribution of TV (2.5th and 97.5th percentiles) in pregnancy was determined after excluding individuals with positive thyroid antibodies, NG, and/or abnormal serum thyrotropin (TSH) or free thyroxine (FT4). Results Thyroid volume was larger among pregnant compared to non-pregnant women (8.6 vs 6.1 cm3; p< 0.001) and was positively correlated with gestational age (rs = 0.221; p= 0.001), body mass index (BMI, rs 0.165; p= 0.002), and FT4 levels (rs 0.118 p= 0.021). Nodular goiter frequency did not differ between the two groups. There was a negative correlation between TV and TSH (rs -0.13; p= 0.014). Thyroid volume was lower among primiparous compared to multiparous patients (7.8 vs 8.9; p< 0.001) and was positively correlated with parity (rs 0.161; p= 0.016). The 2.5th and 97.5th percentiles of TV were 4.23 and 16.47 cm3, respectively. Conclusion Thyroid volume was higher in pregnant compared to non-pregnant women and was positively related to parity, BMI, and gestational age in a normal iodine status population. Pregnancy did not interfere with the development of NG.

Resumo Objetivo Comparamos o volume tireoidiano (VT) e a presença de bócio nodular (BN) em mulheres grávidas e não grávidas em uma área suficiente em iodo. Também avaliamos a relação entre idade gestacional, paridade e VT no grupo de gestantes e determinamos os percentis 2,5 e 97,5 de VT normal na gestação. Métodos Este estudo transversal incluiu 299 mulheres saudáveis (216 grávidas) sem doenças tireoidianas prévias. Ultrassonografias de tireoide foram realizadas e comparadas entre mulheres grávidas e não grávidas. A faixa de distribuição normal de VT (percentis 2,5 e 97,5) na gestação foi determinada após a exclusão de indivíduos com anticorpos tireoidianos positivos, BN e/ou tireotropina sérica (TSH) ou tiroxina livre (T4L) anormais. Resultados O VT foi maior entre as gestantes em comparação com as mulheres não grávidas (8,6 vs 6,1 cm3; p< 0,001) e foi positivamente correlacionado com a idade gestacional (rs = 0,221; p= 0,001), índice de massa corporal (IMC, rs 0,165; p= 0,002) e níveis de T4L (rs 0,118 p= 0,021). A frequência de BN não diferiu entre os dois grupos. Houve correlação negativa entre VT e TSH (rs -0,13; p= 0,014). O VT foi menor entre as primíparas em comparação com as multíparas (7,8 vs 8,9; p< 0,001) e foi positivamente correlacionado com a paridade (rs 0,161; p= 0,016). Os percentis 2,5 e 97,5 de VT foram 4,23 e 16,47 cm3, respectivamente. Conclusão O VT foi maior em gestantes em comparação com mulheres não grávidas e foi positivamente relacionado à paridade, IMC e idade gestacional em uma população com status iódico normal. A gravidez não interferiu no desenvolvimento de BN.

Growth hormone and cortisol secretion in the elderly evaluated using the glucagon stimulation test.

OBJECTIVES: The glucagon stimulation test is a reliable alternative test to assess growth hormone and cortisol secretion, but has not been widely used in the elderly population. The aim of this study was to evaluate growth hormone and cortisol secretion using the glucagon stimulation test in an elderly population without known hypothalamic-pituitary disease and to correlate growth hormone and cortisol peaks with age (less than or greater than 80 years) and body mass index. METHODS: Forty-two subjects (67-88 years) from the geriatric ambulatory unit were submitted and 41 subjects completed the glucagon stimulation test. RESULTS: Median growth hormone peak was 5.99 µg/L and median cortisol peak was 21.6 µg/dL. Growth hormone peak was >3 µg/L in 73.2%, and cortisol peak was >18 µg/dL in 65.8% of patients. There was a statistically significant positive correlation between the growth hormone peak and the cortisol peak. The cortisol peak was significantly different between subjects stratified by growth hormone peak of < or >3 µg/L (15.7 and 21.8 µg/dL, respectively). There was a statistically significant difference in cortisol peak according to age < or > 80 years (22.4 and 18.5 µg/dL, respectively). Considering lower cut-offs recently proposed for growth hormone peak (1.0 µg/L for overweight subjects) and cortisol peak (9.1 µg/dL), only two patients had a growth hormone peak below this value, and all patients had preserved cortisol secretion. CONCLUSIONS: We did find a positive correlation between growth hormone and cortisol peaks in the glucagon stimulation test in the elderly, confirming the capacity of the glucagon stimulation test to stimulate both axes. According to the new proposed cut-points for growth hormone and cortisol, we had 95% of normal growth hormone and 100% of normal cortisol responses.

Clinical aspects of pancreatogenic diabetes secondary to hereditary pancreatitis.

BACKGROUND: Hereditary pancreatitis is a rare inherited form of pancreatitis, characterized by recurrent episodes of acute pancreatitis with early onset and/or chronic pancreatitis, and presenting brittle diabetes, composed of episodes of nonketotic hyperglycemia and severe hypoglycemia. The existing literature regarding this form of diabetes is scarce. In this report, clinical features of pancreatogenic diabetes secondary to hereditary pancreatitis are presented along with recommendations for appropriate medical treatment. RESULTS: Clinical data from five patients of a family with pancreatogenic diabetes secondary to hereditary pancreatitis were analyzed. The average time between hereditary pancreatitis and diabetes diagnosis was 80 ± 24 months (range: 60-180 months) with a mean age of 25.6 ± 14.7 years (range: 8-42 years), four patients used antidiabetic agents for 46 ± 45 months and all progressed to insulin therapy with a mean dose of 0.71 ± 0.63 IU/kg (range: 0.3-1.76 IU/kg). The glycemic control had a high variability with average capillary blood glucose of 217.00 ± 69.44 mg/dl (range: 145-306 mg/dl) and the average HbA1c was 9.9 ± 1.9% (range: 7.6-11.6%). No ketoacidosis episodes occurred and there were several episodes of hospitalization for severe hypoglycemia. CONCLUSIONS: Diabetes mellitus secondary to hereditary pancreatitis presents with early onset, diverse clinical presentation and with extremely labile glycemic control. Diabetes treatment varies according to the presentation and insulin is frequently necessary for glycemic control.

Carotid artery intima-media thickness and lipid profile in adults with growth hormone deficiency after long-term growth hormone replacement.

To investigate the effects of growth hormone (GH) replacement on carotid artery intima-media thickness (IMT) and lipid profile, 29 adults with GH deficiency (GHD), mean age 42.5 +/- 10.1 years, were studied and compared with 29 control subjects matched for sex, age, body mass index, and smoking habits. Lipid profile (total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, apolipoproteins A and B, and lipoprotein), serum insulin-like growth factor 1 (IGF-1) levels, and ultrasonography of the carotid arteries were performed at baseline and at 6, 12, and 24 months during GH therapy on maintenance dose. At baseline, when compared with the control group, patients presented increased carotid artery IMT (P < .05) and triglyceride levels (P < .001) and lower HDL concentrations (P < .01). In a linear regression analysis, age and known mean duration of GHD were correlated with carotid artery IMT. After 24 months of GH replacement, a reduction in the mean of carotid artery IMT was observed (P < .01). The apolipoprotein B levels decreased significantly after the first 3 months of GH treatment (P < .001) and remained stable thereafter. Women also presented an increase in HDL cholesterol levels (P < .01). No differences were observed in the other lipids measured. Carotid artery IMT at baseline was inversely correlated with the change in carotid artery IMT (Delta = 24 months - baseline), r = 0.63, P < .001. In conclusion, 24 months of GH replacement therapy promoted favorable effects on carotid artery IMT and lipid profile in patients with GHD. Long-term follow-up studies are required to show whether these beneficial effects will result in reduction of morbidity and mortality from vascular disease.

Potential risks of glucagon stimulation test in elderly people.

UNLABELLED: The glucagon stimulation test (GST) is a reliable measure for assessing growth hormone (GH) and adrenocorticotropic hormone (ACTH) secretion. The GST is considered to be a safe test, with few mild side effects, especially in adults and in the elderly in whom underlying co-morbidities may be present. OBJECTIVE: To describe the side effects of the GST in elderly people. DESIGN AND SETTING: The study was performed with patients of the geriatric ambulatory of our hospital who were recruited to voluntarily participate in a research study concerning the GH and ACTH axis in the elderly people. Forty-two subjects (n=5 males and 37 females) aged 67-88 years, without hypothalamic-pituitary disease, were submitted to the GST. The GST was performed by intramuscular injection of 1mg of glucagon. Blood samples were collected at baseline, and 90, 120, 150, and 180 min after glucagon injection for GH and cortisol measurements. RESULTS: During the test, 9 subjects (21.4%) had side effects, which included: nausea (14.2%), indisposition (11.9%), hypotension (9.5%), vomiting (7.1%), sweating (4.7%), and dizziness (2.3%). There were four cases of severe symptomatic hypotension, with inaudible blood pressure in two cases. In one case of severe hypotension, the subject suffered two episodes of generalized tonic seizures. Patients who had side effects at GST had statistically higher peak of cortisol (28.9 ± 6.67 µg/dL) and a statistical trend to higher GH peak (8.74 ± 5.96 µg/L). In the group of patients who did not have side effects, the mean cortisol and GH peak were 19.05 ± 5.36 µg/dL and 5.32 ± 3.52 µg/L, respectively. CONCLUSION: Although the GST is a reliable alternative test to the ITT, it should be cautiously used in the elderly because this population may have co-morbidities including vascular and cardiac diseases that could be potentiated with side effects of the test, such as severe hypotension.

Hereditary Pancreatitis Associated With the N29T Mutation of the PRSS1 Gene in a Brazilian Family: A Case-Control Study.

Hereditary pancreatitis (HP) is an autosomal-dominant disease with incomplete penetrance manifesting as early-onset chronic relapsing pancreatitis. A mutation in the PRSS1 gene is present in greater than 70% of HP kindreds and leads to a gain-of-function characterized by the increased autocatalytic conversion of trypsinogen to active trypsin, promoting autodigestion and damage to acinar cells. Other genetic defects observed in the pathogenic mechanism of pancreatitis include mutations in the genes encoding SPINK1, CTRC, and CPA1. There are few reports of HP in Latin America, and no families have been investigated in Brazil. A case-control observational study was conducted at Clementino Fraga Filho University Hospital in Brazil. Patients with suspected HP and healthy controls were enrolled in this study, and a detailed questionnaire was administered to patients with HP. PRSS1 and SPINK1 genes were analyzed by DNA sequencing, and a family that fit the HP diagnostic criteria was identified. The neutral polymorphism c.88-352A > G in the SPINK1 gene was found to be prevalent in the individuals studied, but no important alterations were found in this gene. Ten out of 16 individuals in this family carried the N29T mutation in the PRSS1 gene, with 2 clinically unaffected mutation carriers. The median age of HP onset was 6 years. Pancreatic exocrine failure occurred in 6 patients, 5 of whom also had diabetes mellitus. Surgical procedures were performed on 3 affected members, and no cases of pancreatic cancer have been reported thus far. This study identified the first PRSS1 gene mutation in a Brazilian family with HP.

Biochemical definitions of disease activity in acromegaly.

UNLABELLED: In acromegaly the therapeutic outcome is difficult to assess and depends on the biochemical method. We have ascertained disease activity in 70 acromegalic patients by means of a GH profile (8 hourly samples) and a single IGF-I measurement as compared to a healthy control group. As an estimate of the "stiffness" of the GH profile we calculated the SD/nadir(GH) from the GH profile. In the control group the following upper normal limits were obtained: IGF-I (microg/l) 217; mean GH (microg/l) 2.16; nadir GH (g/l) 0.3. Based on ROC plot analysis a value of 2.0 for the SD/nadir ratio was used as cut-off. This translated into the following surgical cure rates (%): IGF-I 47; mean GH 77; nadir GH 65; SD/nadir 30. Some of the patients post-surgery had elevated IGF-I levels despite "normal" GH levels. Abnormal SD/nadir versus normal IGF-I and vice versa were recorded in many patients post-surgery. IN CONCLUSION: (1) cure rates of acromegaly depend strongly on the criteria being used and (2) estimates of GH secretion pattern may yield important information about GH status in acromegaly.

Evaluation of growth hormone stimulation tests in cured acromegalic patients.

UNLABELLED: We have evaluated the GH peak response to insulin tolerance test (ITT) and to GHRH+arginine in 11 patients cured of acromegaly after treatment with surgery/radiotherapy and compared them to a control group matched for age and sex. GH peak response was significantly higher in the control group than in the patient group (11.21+/-6.98 vs. 4.46+/-6.90 ng/ml, p=0.010). Seven patients had a GH peak response of less than 3 ng/ml, compatible with the diagnosis of GH deficiency. Peak GH response after GHRH+arginine was significantly lower in the group of patients with GH peak of less than 3 ng/ml during ITT as compared to the group with GH peak of more than 3 ng/ml, and in all cases the diagnosis of GH deficiency was confirmed. Mean IGF-I level was not different between the patients and controls, as well as between patients with and without GH deficiency diagnosed by the stimulation tests. CONCLUSION: The incidence of GHD diagnosed by stimulation tests is high in patients cured of acromegaly.

Glucose metabolism and visceral fat in GH deficient adults: 1 year of GH replacement.

The aim of the current study is to evaluate the effects of 12-month growth hormone (GH) replacement on glucose metabolism and visceral fat in 24 adults with GH deficiency (11 men, 13 women, age 41+/-1.9 year, BMI 27+/-1.2 kg/m2. Glucose metabolism was measured in the fasting state by the homeostatic model assessment (HOMA) insulin resistance index and during a standard oral glucose tolerance test (OGTT). Data were analyzed by HOMA and the insulin sensitivity index (ISI)-composite derived from the OGTT. Visceral fat was evaluated by CT scan. GH-deficient adults had increased visceral fat (P=0.029) with lower fasting glucose levels (P=0.004) than the control group on baseline evaluation. GH replacement induced deterioration in glucose metabolism, with progressive increment in fasting insulin levels at 6 and 12 months (P=0.024) and in 2-h-OGTT insulin levels at 3, 6 and 12 months (P=0.001). Plasma glucose levels did not change during the study. There was a deterioration in insulin sensitivity index observed by an increase in HOMA-IR (P=0.049) and a reduction in the ISI-composite (P=0.028), both at 12 months of replacement. Visceral fat and waist-to-hip-ratio (WHR) reduced not only at month 6 but also at month 12 (P=0.0001 and 0.023, respectively). In conclusion, 12 months of GH replacement seem to impair glucose homeostasis, despite favorable alterations in body composition.

Arterial hypertension and metabolic profile in patients with polycystic ovary syndrome.

PURPOSE: To evaluate parameters related with arterial pressure and metabolic profile in women with polycystic ovary syndrome (POS). METHODS: This monocentric study at the University Hospital Endocrinology Section included 60 women aged 18-45 years, 42 being diagnosed with POS and acting as 18 controls. All women were subjected to transvaginal ultrasound and monitored for arterial pressure for 24 h in the ambulatory (MAP). Venous blood samples were taken between 07.00 and 09.00, after 12 h fasting. Basal (BG) and fasting glucose concentrations, total cholesterol and its fractions, triglycerides and insulin (to calculate the homeostatic assay insulin-resistance, HOMA-IR) were measured. Collected data were the mean arterial blood pressure (24-h awake/sleep cycle), arterial pressure nocturnal descensus, glycemia and fasting glucose for HOMA-IR, and lipid profile. The Student's t test was used to compare homogeneous variables; the Mann-Whitney test was used to compare non-homogeneous variables; the Pearson's correlation coefficient was used to search for correlation between the variables. The χ(2) test was used for comparison of the absence of nocturnal descensus. Significance was taken as p<0.05. RESULTS: The mean age of the patients with POS was 27.4 ± 5.5 (18-45 years, n=42) and the body mass index (BMI) was 30.2 ± 6.5 kg/m(2) (18.3-54.9). In the Control Group, the mean age was 31.4 ± 6.1 (18-45 years) and the BMI was 27.1 ± 6.2 kg/m(2) (18.3-54.9, n=18). No difference in the metabolic parameters and insulin resistance was observed between the two groups. Comparison between these parameters and MAP showed that the only parameter with a correlation was the BMI, independent of the POS diagnosis. This was not seen in nocturnal descensus, which was uncorrelated with POS and any of the other studied parameters. CONCLUSION: POS women do not show higher arterial blood pressure, glycemia, HDL-col, TG, HOMA-IR and BMI compared to non-POS women. However, POS patients showed correlation between arterial pressure and BMI, suggesting that obesity is a primary factor involved in arterial pressure changes in these patients.

Pituitary development: a complex, temporal regulated process dependent on specific transcriptional factors.

Pituitary organogenesis is a highly complex and tightly regulated process that depends on several transcription factors (TFs), such as PROP1, PIT1 (POU1F1), HESX1, LHX3 and LHX4. Normal pituitary development requires the temporally and spatially organised expression of TFs and interactions between different TFs, DNA and TF co-activators. Mutations in these genes result in different combinations of hypopituitarism that can be associated with structural alterations of the central nervous system, causing the congenital form of panhypopituitarism. This review aims to elucidate the complex process of pituitary organogenesis, to clarify the role of the major TFs, and to compile the lessons learned from functional studies of TF mutations in panhypopituitarism patients and TF deletions or mutations in transgenic animals.

Comparison of two dose regimens of growth hormone (GH) with different target IGF-1 levels on glucose metabolism, lipid profile, cardiovascular function and anthropometric parameters in gh-deficient adults.

OBJECTIVE: To compare the effects of two regimens of GH therapy with different target IGF-1 levels on anthropometric parameters, glucose metabolism, lipid profile and cardiac function in adults with GH deficiency (GHD). PATIENTS AND METHODS: Retrospective analysis of 14 GHD adults from Clementino Fraga Filho University Hospital, Rio de Janeiro, Brazil, who were treated with a GH regimen aimed at maintaining serum IGF-1 levels between the median and upper reference limit (high dose group - HDGH) and 18 GHD adults from Federal University Hospital, Curitiba, Brazil, who received a fixed GH dose of 0.2mg/day in the first year of treatment, followed by titration to maintain serum IGF-1 levels between the median and lower reference limit (low dose group - LDGH). All patients were followed for 2 years with analysis of anthropometric parameters, serum levels of IGF-1, glucose, insulin, HOMA-IR, lipid profile, and transthoracic echocardiography. RESULTS: Changes on weight, BMI and waist circumference were similar between the two groups. Insulin levels increased and HOMA-IR worsened in the LDGH group at 1year and improved thereafter. Total cholesterol and triglycerides did not change with therapy. LDL cholesterol reduced in both groups, while HDL-cholesterol significantly increased only in the HDGH group (p=0.007 vs LDGH). No significant variations on echocardiographic parameters were observed. CONCLUSION: The HDGH and LDGH regimens resulted in similar changes on anthropometric, echocardiographic, glucose and lipid parameters in GHD adults, except for increase in HDL cholesterol that was only observed in the HDGH regimen.

Orbital pseudotumor: a differential diagnosis of Graves' ophthalmopathy.

The objective of this study is to report and discuss a rare and inflammatory cause of exophthalmos. This report describes a patient with exophthalmos, who was initially diagnosed with euthyroid Graves' with good response to therapy. After 8 years of follow-up, she had recurrence of symptoms and a new evaluation revealed the final diagnosis of orbital pseudotumor. Orbital pseudotumor is an uncommon disorder that both radiologically and clinically mimics a malignant process or other inflammatory disease, such as Graves' ophthalmopathy.

Growth hormone secretion in response to glucagon stimulation test in healthy middle-aged men.

OBJECTIVE: To investigate the growth hormone (GH) response to glucagon stimulation test (GST) in a population of healthy men over 50 years old in comparison to insulin tolerance test (ITT), analysis of the spontaneous 24-hour GH profile and insulin-like growth factor 1 (IGF-I). METHODS: 27 healthy men aged between 51 and 65 years were tested. RESULTS: Using non-parametric correlation analysis, a positive correlation between GH peak after GST and mean IGF-I (r = 0.528; p = 0.005) was found, as well with GH peak in 24-hour profile (r = 0.494; p = 0.009). No correlation was found comparing GH peak after ITT with the same parameters. Ten subjects presented GH peak of less than 3.0 microg/L after GST, none confirmed in ITT. CONCLUSIONS: GH peak response to GST was lower than ITT, but it showed a positive correlation with mean IGF-I and also with GH peak in 24-hour profile. However, GST should not be used to differentiate organic growth hormone deficiency (GDH) from the expected decline on GH secretion due to aging.