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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 0.2 mg/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 1 year 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.

To investigate the effects of GH replacement on lipid profile, carotid artery intima-media thickness (IMT), glucose metabolism and visceral fat in patients with Sheehan’s syndrome, ten patients, mean age 44.8 ± 9.5 yr, compared with 10 controls matched for age and body mass index were studied. Total cholesterol, Triglycerides (TG), HDL-c, LDL-c, Apolipoprotein A and B (apoA and apoB) and Lipoprotein (a), serum IGF-1, ultrasonography of the carotid arteries, oral glucose tolerance test (OGTT), HOMA insulin resistance index, insulin sensitivity index (ISI)-composite and abdominal CT scan were performed. When compared to a control group, patients presented lower HDL concentrations (p = 0.05) and 2-h OGTT insulin levels (p < 0.04) and increased TG levels (p < 0.04). After 24 months of GH replacement a reduction in the relation ApoB/ApoA (p = 0.04) was observed, as well as an increase in HDL (p < 0.004). A decrease in carotid artery IMT and in visceral fat over time was found, p < 0.03 and p < 0.04 respectively, though without any significant differences during post hoc comparisons of means, which may be explained by the small number of cases studied, but there was a tendency, p = 0.08 and p = 0.09 respectively. The 2-h OGTT insulin levels increased (p < 0.02) as well as the prevalence of glucose intolerance (prevalence = 42.8%, p < 0.05). GH replacement therapy promoted favorable effects on carotid artery IMT, lipid profile and visceral fat in patients with Sheehan’s syndrome. On the other hand, patients developed abnormal glucose tolerance probably due to an increase in insulin resistance, demonstrated by higher insulin levels, despite favorable changes in body composition.

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.

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.

The aim of this study was to evaluate the effect of 24 months of growth hormone (GH) replacement on glucose metabolism and visceral fat in 17 adults with GH deficiency: 9 men and 8 women; age 40 +/- 1.8 yr. [range 20-61] and body mass index 25 +/- 0.8 Kg/m2. Glucose metabolism was evaluated by a standard oral glucose tolerance test (OGTT), by the homeostatic model assessment (HOMA) insulin resistance index and by the insulin sensitivity index (ISI)-composite derived from the OGTT. Visceral fat was evaluated by CT scan.Twenty-four months of GH replacement induced an increase in the prevalence of abnormal glucose tolerance, with significant progressive increment in 2h-OGTT insulin levels at 3, 12 and 24 months (p = 0.005). Plasma glucose levels and ISI-composite did not alter during the study. HOMA-IR index increased only in the group of patients (n = 8) who had abnormal OGTT at 24 months (p = 0.012). Visceral fat reduced at month 12 and remained decreased until the end of the study (p = 0.009). In conclusion, the present study suggests that adults with GH deficiency after twenty-four months of GH replacement developed abnormal glucose tolerance, probably due to an increase in insulin resistance, associated with higher insulin levels, despite favorable alterations in body composition.

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.

Este relato mostra o caso de uma paciente com mucocele gigante do seio esfenoidal, apresentando-se como massa intracraniana, invadindo a sela túrcica e levando à disfunção hipofisária com deficiência córtico e somatotrófica. Revendo a literatura, não foram encontrados casos semelhantes, Desta forma, serão discutidos alguns relatos de caso de mucoceles que se apresentaram como massa intracraniana e a reversibilidade da função hipofisária após a cirurgia descompressiva.

Discutimos um caso incomum de doença de Paget do osso, de apresentação nos maxilares. Esta forma rara de manifestação de uma doença sistêmica levou à dificuldade inicial em estabelecer o diagnóstico, sendo a etiologia firmada apenas pela biópsia da lesão. Utilizamos bisfosfonatos com boa resposta. Ressaltamos no artigo a necessidade do acompanhamento multidisciplinar desses pacientes devido às complicações odontológicas da doença quando localizada nos maxilares.

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.

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.

To evaluate the variation of serum IGF-1 levels during GH replacement and observe gender differences, 29 adults with GH deficiency (mean age 42.5 +/- 10.1 year), were studied. Serum IGF-1 was assessed every 4 weeks during the titration period and afterwards every 3 months of GH therapy. At baseline 77.7% of women and 45.4% of men had serum baseline IGF-1 levels below the lower limit of normal age-related reference range. The time to reach the maintenance dose was lower in men than women (p0.05). There was an increase in IGF-1 levels after one year of GH therapy, significant only in men (p0.01). IGF-1 concentrations were higher in men than women (p0.05), at the 12th and 18th months of GH therapy. GH dose was reduced by 25% in men (p0.01). At the end of the study the mean GH dose was lower in men than in women (p0.05). The factor responsible for these findings is not known, however a possible role of androgens has been suggested.

The aim of the present study was to evaluate the bioequivalence and therapeutic equivalence of the two most commonly prescribed L-thyroxine (monsodium L-thyroxine hydrate, CAS 25416-65-3) formulations in Brazil in patients treated for hypothyroidism. Twenty-four patients received 100 micrograms L-thyroxine daily of either Puran T4 (test) or the Brazilian reference formulation (reference) during 42 days, in a two-period crossover design. Serum samples obtained over a 24-h interval were analyzed for their total T4 concentration by a chemiluminescent immunoassay. Content and uniformity of the tablets and dissolution studies were also assessed according to USP 24 monograph using an isocratic HPLC-UV system and a rotating-paddle method. The mean pharmacokinetic parameters for total T4, expressed as geometric means (CV), for the test and reference were, respectively: Cmax (microgram/dl) 9.8 (14.3%) and 10.8 (14.9%); AUC0-24 h (microgram/dl.h) 206.8 (13.9%) and 230.4 (14.9%). Median values (90% CI) for Tmax (h) were 3 (2-3) and 2 (2-4) for the test and reference, respectively. 90% CI for ratios of LogCmax and LogAUC0-24 h were 86.6-94.9 and 86.3-93.4, respectively. Although the test exhibited values of Cmax and AUC0-24 h around 10% lower than the reference, these formulations must be considered bioequivalent since the 90% CI for both Cmax and AUC0-24 h mean ratio were within the 80-125% interval as proposed by the US Food and Drug Administration and the Brazilian legislation. TSH dosages within the normal range further support therapeutic equivalence between the two formulations. Dissolution data were roughly in agreement with in vivo results since both formulations comply with the USP dissolution criteria although the test tablets had a slower dissolution rate than the reference tablets. As a conclusion, the two oral formulations of L-thyroxine are both bioequivalent and therapeutically equivalent although presenting a small difference in their extent of absorption. Noteworthy, the dissolution profiles of the tablets correlate well with their bioavailability in the present experimental conditions.