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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.

Glucagon stimulation test for the diagnosis of GH deficiency in adults

The insulin tolerance test (ITT) is considered the test of choice for the diagnosis of GH deficiency (GHD). However, in patients with contraindications to ITT, alternative provocative tests must be used with appropriate cut-offs. The glucagon stimulation test has proved to be a safe, low-cost and effective means of stimulating GH secretion, and therefore can be considered as a suitable alternative to the ITT. We have studied the GH response to the glucagon test in 33 patients with known pituitary disease, 12 males and 21 females, aged between 21 and 60 yr (41.18±9.47 yr); 5 had isolated GHD and 28 had panhypopituitarism. We also evaluated a control group of 25 individuals, matched for age and sex (8 males and 17 females), aged between 20 and 60 yr (39.28±12.10 yr). They were selected via the ITT if their peak GH response was >5.0 ng/ml. GH peak after glucagon was significantly lower in the group of patients compared to the control group (0.49±0.85 vs 8.69±5.85 ng/ml, p=0.0001). Receiver-operating characteristic (ROC) plot analyses of the control and GHD group showed an area under the curve of 0.982 for GH peak response to glucagon. The response value of 3.0 ng/ml showed the best pair of sensitivity (97%)/specificity (88%), and was chosen as the cut-off defining GHD. After evaluation of positive predictive values (PPV) and negative predictive values (NPV) through simulation of different prevalences of the disease, we concluded that the cut-off point of 3.00 ng/ml maximizes both PPV and NPV (100%). In conclusion, we have shown that the glucagon stimulation test has a good performance and great diagnostic accuracy for the diagnosis of GHD.

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.

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.

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.

Glucose Metabolism and Visceral Fat in GH Deficient Adults: Two Years of GH-Replacement

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.

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.

Growth Hormone Therapy in Adults

The importance of growth hormone (GH) deficiency in adults became evident 10 to 15 years ago, when the first clinical studies on GH replacement therapy in adults were published. Since then, a number of studies have been reported showing that GH replacement therapy can improve this condition. Adult GH deficiency (GHD) is now recognized as a specific clinical syndrome and the first reports of long-term use of GH (up to 10 years) are now being published. The aim of this paper was to review the accumulated data on the various clinical aspects of adult GHD.

Aspectos diagnósticos e terapêuticos da síndrome de Sheehan

Sheehans syndrome is characterized by hypopituitarism that occurs as a result of ischemic pituitary necrosis due to severe postpartum hemorrhage. Nowadays it is not usually seen in developed countries because of the improvements in obstetric care. However, in developing countries it is still frequent and probably one of the most common causes of hypopituitarism. Most patients usually present it months to years later, with a history of failure of postpartum lactation, failure to resume menses and other signs of panhypopituitarism. In mild forms of the disease, patients may remain undetected and do not receive treatment for many years. Early diagnosis and appropriate treatment are important to reduce the morbimortality of the patients with Sheehans syndrome. The aim of this review is to describe clinical, laboratorial and therapeutic aspects of Sheehans syndrome, including our experience in the replacement of recombinant GH in these patients.

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.