Role of insulin and insulin resistance in androgen excess disorders

Insulin has complex effects on cell growth, metabolism and differentiation, and these effects are mediated by a cell-surface bound receptor and eventually a cascade of intracellular signaling events. Among the several metabolic and growth-promoting effects of insulin, insulin resistance is defined as an attenuated effect of insulin on glucose metabolism, primarily the limited export of blood glucose into skeletal muscle and adipose tissue. On the other hand, not all the signaling pathways and insulin-responsive tissues are equally affected, and some effects other than the metabolic actions of insulin are overexpressed. Ovaries and the adrenal glands are two examples of tissues remaining sensitive to insulin actions where insulin may contribute to increased androgen secretion. Polycystic ovary syndrome (PCOS) is the most common form of androgen excess disorder (AED), and its pathogenesis is closely associated with insulin resistance. Patients with idiopathic hirsutism also exhibit insulin resistance, albeit lower than patients with PCOS. Although it is not as evident as in PCOS, patients with congenital adrenal hyperplasia may have insulin resistance, which may be further exacerbated with glucocorticoid overtreatment and obesity. Among patients with severe insulin resistance syndromes, irrespective of the type of disease, hyperinsulinemia promotes ovarian androgen synthesis independently of gonadotropins. It is highly debated in whom and how insulin resistance should be diagnosed and treated among patients with AEDs, including PCOS. It is not suitable to administer an insulin sensitizer relying on only some mathematical models used for estimating insulin resistance. Instead, the treatment decision should be based on the constellation of the signs, symptoms and presence of obesity; acanthosis nigricans; and some laboratory abnormalities such as impaired glucose tolerance and impaired fasting glucose.     

Evaluation of normal appendix vermiformis in adults with multidetector computed tomography

To determine the utility of different contrast enhancement phases (unenhanced, arterial, and venous), slice thicknesses (0.5, 3, and 5 mm), and planes (axial and coronal) in the evaluation of appendix vermiformis (AV) on multidetector computed tomography (MDCT), CT examinations of 600 patients were obtained. No significant difference was found between the different imaging planes, slice thicknesses, and contrast enhancement phases in terms of detection rates of AV. The mean diameter of AV in the axial plane (5.93±0.06 mm) was significantly lower than that in the coronal plane (6.18±0.06 mm). Evaluation of AV on MDCT is enhanced by combined interpretation on axial and coronal planes.     

Effects of 18-month of growth hormone (GH) replacement therapy in patients with Sheehan's syndrome.

OBJECTIVE: Growth hormone deficiency (GHD) in adults is associated with abnormal body composition, altered lipid profile, reduced quality of life and osteoporosis. Replacement with recombinant GH results in significant improvements in most of these altered parameters. The most common cause of adult GHD in previous studies was due to pituitary tumors or their treatment. Sheehan's syndrome classically refers to postpartum hypopituitarism due to pituitary necrosis occurring secondary to massive bleeding at or just after delivery. While severe GHD is a well-established feature of Sheehan's syndrome, the effects of Growth hormone replacement therapy (GHRT) in these patients has not been extensively investigated. The present study was therefore designed to investigate the effects of GHD and GHRT in patients with Sheehan's syndrome. DESIGN: The study comprised 14 severely GH-deficient patients with Sheehan's syndrome with a mean age of 49.4+/-7.9 yr. Treatment with GH was started at a dose of 0.15 mg per day in month 1, was increased to 0.30 mg per day in month 2, and was maintained at 0.66 mg per day until the end of month 18. With the similar maintenance dose adequate age adjusted IGF-I levels for each patient has been achieved. Blood pressure, lipid profile, biochemical parameters, anthropometric measurements including body mass index (BMI), waist and waist to hip ratio (W/H), and bone mineral density (BMD) were investigated before and at 3, 6, 12 and 18 months of the GHRT. RESULTS: The duration of GHD from the onset of the disease was 19.4+/-1.6 yr. The majority of the patients (78%) had panhypopituitarism. At baseline mean total cholesterol, LDL-cholesterol and triglyceride levels were higher than the normal reference ranges but HDL-cholesterol levels were within the lower normal range. During the treatment period total cholesterol and LDL-cholesterol levels decreased and HDL-cholesterol levels increased significantly (P < 0.05). Waist circumference and waist to hip ratio were decreased significantly during the GHRT when compared to basal measurements (P < 0.05). There was a significant positive correlation between the basal waist circumference and the duration of GHD (P < 0.05). CONCLUSIONS: This study clearly demonstrates that Sheehan's syndrome is characterized by severe and long-standing GHD. GHRT have beneficial effects in several parameters including lipid profile and waist circumference. But we could not observe any improvement in BMD after 18 months of GHRT. However interpretations of the present results need to be made with caution because of the uncontrolled design. Further placebo controlled studies with high number of patients with Sheehan's syndrome are warranted.     

Subclinical alveolar involvement in ulcerative colitis

BACKGROUND: Although pulmonary dysfunction has been described in patients with ulcerative colitis (UC), the pathogenesis remains unclear. Our aim was to study alveolar epithelial damage using technetium-99m diethylene triamine penta acetic acid (Tc-99m DTPA) aerosol scintigraphy in patients with UC but without respiratory symptoms. METHODS: We enrolled 32 patients (18 women and 14 men; mean age, 36.4 +/- 11.6 yr) with active UC, 10 patients with inactive UC (6 women and 4 men; mean age, 43.4 +/- 11.8 yr), and 31 healthy controls (24 women and 7 men; mean age, 40 +/- 10 yr). Tc-99m DTPA aerosol scintigraphy was performed on all patients and controls. The relationship between alveolar epithelial permeability and the activity, localization, and duration of the disease was studied. RESULTS: There was a significant difference between alveolar epithelial permeability results in patients with active UC and those of the controls (P < 0.001). The same correlation was also found between the patients with inactive UC and the control group (P < 0.001). There was no correlation between Tc-99m DTPA alveolar scintigraphic test results and the stage of activity, localization, and duration of the disease. CONCLUSIONS: A latent pulmonary involvement may exist in patients with active and inactive UC. The alveolar involvement may be the earliest pulmonary damage, and a DTPA clearance test may show the early changes in pulmonary epithelial permeability that precedes clinical symptoms. Increased alveolar epithelial permeability is an extraintestinal manifestation in patients with UC and is not related to the activity of the colitis.     

The comparison of low and standard dose ACTH and glucagon stimulation tests in the evaluation of hypothalamo-pituitary-adrenal axis in healthy adults

Evaluation of the HPA axis is still a challenge; due to different sensitivities and stimulation efficiencies of dynamic tests, lack of standard assays for cortisol measurement and lack of data regarding the effects of age and gender on the results of the HPA axis evaluation with different dynamic tests. This study was performed to compare 1 μg ACTH, 250 μg ACTH and glucagon tests in the evaluation of HPA axis. The study was carried out on 55 healthy individuals (28 men, 27 women). 10–12 volunteers were included from every decades between 20 and 70 years. Low dose short synacthen test (1 μg ACTH), standard dose short synacthen test (250 μg ACTH) and glucagon tests were performed consecutively. The mean peak cortisol response to standard dose ACTH stimulation test was found to be significantly higher than the low dose ACTH and glucagon stimulation tests. The mean peak cortisol responses to low dose ACTH and the glucagon stimulation tests were not significantly different. The mean peak cortisol responses did not differ significantly between different age or sex groups. The lowest peak cortisol responses obtained after low dose ACTH and glucagon stimulation tests were 12.5 and 9.1 μg/dl respectively in the volunteers who all had cortisol responses higher than 20 μg/dl after standard dose ACTH stimulation test. The lowest cortisol responses obtained during 250 μg ACTH, 1 μg ACTH and glucagon stimulation tests were found to be 20.1, 12.5 and 9.1 μg/dl in a known group of healthy people. So the consideration of appropriate hormonal cut-off levels for each test seems reasonable. The age, sex and body mass indeces were not shown to affect the cortisol response to dynamic stimulation tests.     

Helicobacter pylori has no effect on plasma ghrelin levels

OBJECTIVE: Helicobacter pylori is the major etiologic agent for chronic active gastritis, and it also plays a crucial role in gastric and duodenal ulcer disease, as well as in gastric carcinoma. H. pylori infection has been shown to decrease plasma somatostatin (SST) and increase plasma gastrin concentrations. Ghrelin is a recently discovered peptide produced mostly in the stomach of rodents and humans and is secreted into the bloodstream. There is no data in the literature about the relationship between H. pylori and ghrelin. DESIGN: Thirty-nine age- and BMI-matched H. pylori infection positive and negative women, from whom biopsy specimens were taken during gastric endoscopy, were included in the study. METHODS: Total ghrelin was measured by enzyme immunoassay (EIA) in Medistek. All samples were measured in duplicate and averaged; results differing by more than 20% were re-assayed. Two biopsy specimens from antrum, corpus and fundus were obtained. RESULTS: Fifteen of the subjects were H. pylori negative and 24 were H. pylori positive. Age, BMI, lipid profile and insulin sensitivity indices of the groups were similar. Plasma ghrelin levels (375.92+/-7.10 vs 370.00+/-4.14 pmol/l; P>0.05) of H. pylori negative and positive groups did not differ significantly. CONCLUSION: H. pylori has no effect on plasma ghrelin concentration.     

STATIN‐D Study: Comparison of the Influences of Rosuvastatin and Fluvastatin Treatment on the Levels of 25 Hydroxyvitamin D

Several studies have shown that low 25‐hydroxyvitamin D levels are associated with higher risk of cardiovascular disease and an increase in 25‐hydroxyvitamin D levels protects against cardiovascular disease. In this study, we aimed to compare the effects of rosuvastatin and fluvastatin on vitamin D metabolism. The study population consisted of 134 hyperlipidemic patients who had not previously been treated with lipid lowering medications. Patients were randomized in a 1:1 ratio to rosuvastatin 10 mg or fluvastatin 80 mg XL during the study. Lipid parameters, 25 hydroxyvitamin‐D, and bone alkaline phosphatase (BALP) were obtained at baseline and after 8 weeks of rosuvastatin and fluvastatin treatment. Sixty‐nine patients were administered rosuvastatin, and 65 patients fluvastatin. Total Cholesterol and LDL cholesterol decreased after 8 weeks of both rosuvastatin and fluvastatin treatments. Rosuvastatin was significantly more effective than fluvastatin on lowering total (P < 0.001) and LDL cholesterol (P < 0.001). There was a significant increase in 25‐hydroxyvitamin D with rosuvastatin treatment (P < 0.001), whereas no significant change in 25‐hydroxyvitamin D was observed with fluvastatin treatment. Mean BALP fell from 18.5 to 9.6 u/I (P < 0.001) with rosuvastatin and from 17.0 to 12.8 with fluvastatin (P= 0.004). There was no significant difference in BALP levels between rosuvastatin and fluvastatin treatment (P= 0.368). The present study demonstrated that 25‐hydroxyvitamin D levels increased with rosuvastatin treatment; whereas fluvastatin treatment had no effect on 25‐hydroxyvitamin D. This disparity could be related to the potency or the bioavailability of these two statins. Further studies are needed to clarify the relationship between statins and the vitamin D physiology.     

Posterior pituitary functions are not altered after growth hormone replacement therapy in hypopituitarism due to Sheehan's syndrome

ObjectiveThe aim of the present study was to investigate the effects of growth hormone (GH) replacement on posterior pituitary functions of GH-deficient Sheehan's syndrome (SS) patients.DesignTen patients with SS and 14 healthy control women were included in this prospective study. All patients were given appropriate hormone replacement therapy other than GH, according to present hormone deficiencies. Patients were euthyroid and eucortisolemic at the time of baseline evaluation. Patients and the control group were evaluated with water-deprivation and saline-infusion tests at baseline and the tests were repeated in patients with SS after 3 months of GH replacement therapy.ResultsAccording to the water deprivation test, 3 patients had partial central DI at baseline. Urine osmolalities of the patients were slightly lower and plasma osmolalities were significantly higher than the control group at baseline, after water deprivation and following DDAVP injection and after hypertonic saline infusion. The osmotic threshold of serum for thirst perception was found to be significantly higher in SS patients than the control group, GH replacement therapy did not influence the results of water deprivation and saline infusion tests in SS patients.ConclusionPatients with SS have subtle abnormalities in posterior pituitary functions and the threshold for thirst perception is increased. However GH replacement therapy does not seem to reverse or adversely affect the mildly deteriorated posterior pituitary functions of SS patients.     

Investigation of insulin resistance in patients with normocalcemic primary hyperparathyroidism

While derangements in glucose metabolism in patients with primary hyperparathyroidism are well-defined, this issue is not investigated in patients with normocalcemic primary hyperparathyroidism (NPHPT). The aim of this study was to investigate the presence of insulin resistance in patients with NPHPT. Eighteen patients with NPHPT (two males and 16 females) and 18 healthy volunteers were enrolled into the study. Secondary causes of parathyroid hormone elevations were excluded in all patients. Blood samples were obtained for the measurement of serum calcium, phosphate, alkaline phosphatase (ALP), albumin, creatinine, glucose, and serum lipid levels. Glucose and insulin responses to oral glucose tolerance test (OGTT) were obtained. Homeostasis model assessment (HOMA-IR) was also used as an indice of insulin resistance. Patients and control subjects had similar age, body mass index, and sex distribution. Although within normal limits, serum calcium and ALP levels were higher in patients than in the control subjects. None of the patients and the control subjects had diabetes mellitus, while eight patients and six control subjects had impaired glucose tolerance. Insulin responses to OGTT and HOMA-IR were not significantly different among the patient and control subjects. In addition, both groups have similar serum lipid levels. Patients with NPHPT do not exhibit insulin resistance and glucose intolerance. Since so little is known about this form of disease, subjects should be monitored regularly for the metabolic aspects of the disease as well as the progression of their disease.