Cortisol cut-points for the glucagon stimulation test in the evaluation of hypothalamic pituitary adrenal axis.

Diagnosis of adrenal insufficiency requires evaluation by dynamic stimulation tests. The insulin tolerance test (ITT) is accepted as the gold-standard test for the evaluation of hypothalamo-pituitary-adrenal (HPA) axis but the test is unpleasant and dangerous. Although it takes more time, glucagon stimulation test (GST) is a good alternative to ITT. The primary aim of this study was to compare the ITT and GSTs in the evaluation of HPA axe in patients with pituitary disorders. We conducted a prospective study in which ITT and GST were performed within 7 days in 81 patients. Serum cortisol was measured. We divided our population in Group 1 (G1): Adrenal Insufficiency (Peak cortisol under ITT <200 ng/mL) and Group 2 (G2): normal response (Peak cortisol under ITT >200 ng/mL). Receiver-operating characteristic (ROC) analysis was performed to identify the thresholds for GST. The mean peak of cortisol under GST was not significantly different from that obtained after ITT in the whole cohort (182.67 ± 89.07 ng/mL vs. 179.75 ± 79.01 ng/mL), and it was significantly reduced in patients of G1 (p < 10-3). ROC curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cut-off to GST of 167 ng/mL (sensitivity, 89%; specificity, 79%). Using this cut-off, 86.4% of the patients were correctly classified. In our prospective series, GST is a potential accurate and safe alternative test for the assessment HPA. Test-specific cut-offs should be applied to avoid misinterpretation.

Assessing the adrenal axis by the glucagon stimulation test in children with idiopathic growth hormone deficiency.

Approximately 30% of children with idiopathic growth hormone deficiency (IGHD) also suffer from other pituitary hormone deficien-cies. Of children with IGHD, approximately 10% are unable to generate appropriate ACTH levels in response to stress. This study was prospectively designed to test the integrity of the adrenal axis in patients with an established diagnosis of IGHD using the glucagon stimulation test (GST). The study population comprised 39 patients with established childhood-onset IGHD. The diagnosis of GHD was established on the basis of failure of GH to increase over 10 ng/ml after two stimulation tests. The GST was performed by intra-muscular injection of 1 mg glucagon. The criteria followed to define adrenal deficiency was cortisol less than 167 ng/l in response to GST. The mean peak blood glucose level was 8.64 ±1.71 mmol/l. Analysing the cohort using the cut-off of 167 ng/ml to define adrenal insufficiency under GST, there were 25.64% of children diagnosed: 20% among males and 35.7% among females. Subjects with GH and ACTH deficiency had a mean peak GH of 2.07 ±1.79 ng/ml - significantly lower than GH peak of children with IGHD alone (p < 0,001). The frequency of children with combined somatotroph and corticotroph deficiencies with a GH peak < 3 ng/ml was 21% (p < 0,001). The current study identified a prevalence of adrenal insufficiency of 25.64%, which could predict greater risk for children if untreated, especially because a substantial proportion of patients do not present clinical symptoms.

Effects of dermal sub-chronic exposure of pubescent male rats to permethrin (PRMT) on the histological structures of genital tract, testosterone and lipoperoxidation.

Short-term effects of pyrethroids on human health are better and well identified, whereas long-term risk's estimation remains difficult, especially those affecting the reproductive function. The present study, carried out in male rats, is a contribution to explore some effects underlying permethrin (PRMT) toxicity. The aim of the present work was to investigate the effect of different subcutaneous treatments with PRMT low doses on testes and epididymides histopathology, testosterone and oxidative stress in pubescent male rats. Groups of six animals were treated with a dermal daily dose of 0.013, 0.13, or 1.3 mg/kg b.w/day of PRMT in 70% ethanol for 30, 45, and 60 days, respectively. Macroscopic studies showed an influence of PRMT on the testes, the epididymides and body weight. The pyrethroid induces a testis disturbance traduced by a deregulation of spermatogenesis and an epididymis dysfunction by the appearance of strong deformations into the microstructure of the epididymides. A hormonal disruption was evidenced by the measurement of the plasma testosterone concentrations. The findings of the present investigation mentioned a significant increase (p≤0.05) in lipoperoxidation, after 45 or 60 days, when we measured the plasma malondialdehyde (MDA) concentrations. In conclusion the study shows that subcutaneous PRMT treatment causes an arrest of spermatogenesis, and a significant disharmony in testosterone concentration and MDA levels. These effects are related to dose, length of treatment and to the lipid peroxidation, which may be one of the molecular mechanisms involved in PRMT-induced gonads and epididymides toxicity.

Toxic responses to deltamethrin (DM) low doses on gonads, sex hormones and lipoperoxidation in male rats following subcutaneous treatments.

Deltamethrin (DM) is a alpha- cyano pyrethroid insecticide used extensively in pest control. Although initially thought to be least toxic, a number of recent reports showed its toxicity in mammalian and non-mammalian laboratory and wildlife animal species. The present study, carried out in male rats, is a contribution to explore some mechanisms underlying DM toxicity. The aim of the present research was to investigate the effect of different subcutaneous treatments with DM (2 ppm for 30 days, 20 ppm for 45 days and 200 ppm for 60 days) on testes histopathology, sex hormones and oxidative stress from male rats. Our study mentioned an hypospermatogenesis within the testes accompanied by some apoptotic figures in particular cell fragments into the seminiferous tubules (ST)' lumen. The results obtained show that follicule-stimulating hormone (FSH), luteinizing hormone (LH) and testosterone can be differently influenced in rats. In fact, findings of the present investigation mention a significant decrease (p < or = 0.05) of FSH, LH and testosterone at the highest DM dose. Whereas a significant reduction of FSH was noticed after 45 days of treatment. The assessment of oxidative stress by malondialdehyde (MDA) measurements in plasma revealed a significant increase of this parameter after 30 days, 45 days or 60 days. In conclusion the study shows that subcutaneous DM treatment produces an arrest of spermatogenesis, a significant disharmony in sex hormones and MDA levels in rats that is related to dose, length of treatment and to the lipid peroxidation which may be one of the molecular mechanisms involved in DM-induced gonads toxicity.