Evaluation of cortisol precursors for the diagnosis of pituitary-dependent hypercortisolism in dogs

The serum concentrations of cortisol, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, 21-deoxycortisol and 11-deoxycortisol were measured in 19 healthy dogs, 15 dogs with pituitary-dependent hypercortisolism (pdh) and eight dogs with other diseases before and one hour after an injection of synthetic adrenocorticotrophic hormone (acth). At both times the dogs with pdh had significantly higher concentrations of cortisol, 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone and 21-deoxycortisol than the healthy dogs. Basal 11-deoxycortisol concentrations were also significantly higher in dogs with pdh compared with healthy dogs. When compared with the dogs with other diseases, the dogs with pdh had significantly higher basal and post-acth cortisol and basal 21-deoxycortisol, and significantly lower post-acth 11-deoxycortisol concentrations. The dogs with other diseases had significantly higher post-acth cortisol, 17alpha-hydroxyprogesterone and 11-deoxycortisol concentrations than the healthy dogs. In general, the post-acth concentrations of 17alpha-hydroxypregnenolone, 17alpha-hydroxyprogesterone, 11-deoxycortisol and 21-deoxycortisol were more variable than the post-acth concentrations of cortisol, resulting in large overlaps of the concentrations of these hormones between the three groups. A two-graph receiver operating characteristic (ROC) analysis was used to maximise the sensitivity and specificity of each hormone for diagnosing hypercortisolism; it showed that the post-acth concentration of cortisol had the highest sensitivity and specificity. The overlaps between the healthy dogs, the dogs with pdh and the dogs with other diseases suggested that the individual precursor hormones would not be useful as a screening test for hypercortisolism

Serum concentrations of cortisol and cortisone in healthy dogs and dogs with pituitary-dependent hyperadrenocorticism treated with trilostane

The serum concentrations of cortisol and cortisone were measured in 19 healthy dogs and in 13 dogs with pituitary-dependent hyperadrenocorticism (PDH) before and one hour after an injection of synthetic adrenocorticotropic hormone (ACTH). In the dogs with pdh, the cortisol and cortisone concentrations were measured before and after one to two weeks and three to seven weeks of treatment with trilostane. The dogs with PDH had significantly higher baseline and poststimulation concentrations of cortisol and cortisone, and higher baseline cortisol:cortisone ratios than the healthy dogs. During the treatment with trilostane, the poststimulation cortisol, the baseline and poststimulation cortisone concentrations, and the baseline and poststimulation cortisol:cortisone ratios decreased significantly. The decrease in poststimulation cortisone was significantly smaller than the decrease in cortisol

Neuroendocrine changes in patients with acute space occupying ischaemic stroke

Objective: To evaluate neuroendocrine changes in critical care patients with acute space occupying hemispheric stroke. Methods: 22 patients with acute space occupying hemispheric stroke were studied (mean age 57.7 years; five women, 17 men). Plasma levels of prolactin, thyrotropin (TSH), total thyroxine (T4), free thyroxine (FT4), and total triiodothyronine (T3) were measured on admission and thereafter on days 3, 5, 7, and 9. Cortisol and ACTH levels were analysed at 8.00, 16.00, and 24.00 hours each day. A TRH stimulation test with measurements of TSH and prolactin was done on day 3. Results: Nine patients underwent decompressive craniectomy and nine were treated with moderate hypothermia. All patients received vasopressor drugs because of arterial hypotension. Plasma ACTH and cortisol values were abnormally low despite systemic hypotension and acute systemic illness, and remained low throughout the observation period. The diurnal rhythm of cortisol was not preserved. Prolactin levels increased during the observation period, and were well above normal on day 9. Thyroid function was slightly suppressed until day 7. TRH stimulation of plasma TSH and prolactin was low. Conclusions: Patients with an acute space occupying cerebral infarct show profound neuroendocrine changes. The central regulation of adrenal and thyroid function and prolactin release is impaired, which may compromise the clinical course of affected patients and have implications for therapeutic management

Loss of G(q/11) Family G Proteins in the Nervous System Causes Pituitary Somatotroph Hypoplasia and Dwarfism in Mice

Heterotrimeric G proteins of the G(q/11) family transduce signals from a variety of neurotransmitter and hormone receptors and have therefore been implicated in various functions of the nervous system. Using the Cre/loxP system, we generated mice which lack the genes coding for the α subunits of the two main members of the G(q/11) family, gnaq and gna11, selectively in neuronal and glial precursor cells. Mice with defective gnaq and gna11 genes were morphologically normal, but they died shortly after birth. Mice carrying a single gna11 allele survived the early postnatal period but died within 3 to 6 weeks as anorectic dwarfs. In these mice, postnatal proliferation of pituitary somatotroph cells was strongly impaired, and plasma growth hormone (GH) levels were reduced to 15%. Hypothalamic levels of GH-releasing hormone (GHRH), an important stimulator of somatotroph proliferation, were strongly decreased, and exogenous administration of GHRH restored normal proliferation. The hypothalamic effects of ghrelin, a regulator of GHRH production and food intake, were reduced in these mice, suggesting that an impairment of ghrelin receptor signaling might contribute to GHRH deficiency and abnormal eating behavior. Taken together, our findings show that G(q/11) signaling is required for normal hypothalamic function and that impairment of this signaling pathway causes somatotroph hypoplasia, dwarfism, and anorexia

Ausdauer-Leistungsfahigkeit von Triathlon-Athleten mit Typ-1-Diabetes

BACKGROUND AND OBJECTIVE: Treatment of type 1 diabetes mellitus (DM) aims to prevent complications by strictly optimizing blood glucose levels. Although physical exercise is an important part of metabolic control, endurance sports are considered hazardous for patients with type 1 diabetes because of the extreme physiological stress they represent. To further elucidate the metabolic challenge this form of exercise presented we investigated the performance of triathlon competitors with type 1 diabetes. PATIENTS AND METHODS: Ten patients (32-61 years) with type 1 diabetes (disease duration 2-35 years) were followed for three years, during which each year they participated in one triathlon long-distance competitions (2.4 miles swimming, 26.2 miles running and 112 miles cycling; Ironman Germany 2005-2007). Glucose, cortisol, aldosterone, renin, thyroid hormones, testosterone, growth hormone and catecholamines were measured in blood and saliva. Five non-diabetic competitors served as controls. RESULTS: The performance equalled those of age-matched healthy athletes. Several participants experienced hyperglycemia early in the bike leg, whereas all of them developed low blood glucose levels during the marathon leg. Basal insulin supply was reduced up to 50 % on race day. Hormone levels in athletes with type 1 DM and healthy controls were similar. CONCLUSIONS: Patients with type 1 DM can successfully sustain extreme endurance challenges. Physiological alterations of the metabolic state complicated by type 1 DM can readily be compensated by adapting intensified insulin therapy and nutritional modifications. Thus 1 DM should not be regarded a contraindication to participating in high endurance sports

Rapid screening test for primary hyperaldosteronism: ratio of plasma aldosterone to renin concentration determined by fully automated chemiluminescence immunoassays.

Contains fulltext : 57887.pdf (publisher's version ) (Closed access)BACKGROUND: The ratio of plasma aldosterone concentration to plasma renin activity (PAC/PRA) is the most common screening test for primary hyperaldosteronism (PHA), but it is not standardized among laboratories. We evaluated new automated assays for the simultaneous measurement of PAC and plasma renin concentration (PRC). METHODS: We studied 76 healthy normotensive volunteers and 28 patients with confirmed PHA. PAC and PRC were measured immunochemically in EDTA plasma on the Nichols Advantage chemiluminescence analyzer, and PRA was determined by an activity assay. RESULTS: In volunteers, PAC varied from 33.3 to 1930 pmol/L, PRA from 1.13 to 19.7 ng.mL(-1).h(-1) (0.215 ng.mL(-1).h(-1) = 1 pmol.L(-1).s(-1)), and PRC from 5.70 to 116 mU/L. PAC/PRA ratios ranged from 4.35 to 494 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios from 0.69 to 71.0 pmol/mU. In PHA patients, PAC ranged from 158 to 5012 pmol/L, PRA from 0.40 to 1.70 ng.mL(-1).h(-1), and PRC from 0.80 to 11.7 mU/L. PAC/PRA ratios were between 298 and 6756 (pmol/L)/(ng.mL(-1).h(-1)) and PAC/PRC ratios between 105 and 2328 pmol/mU. Whereas PAC or PRC showed broad overlap between PHA patients and volunteers, the PAC/PRC ratio indicated distinct discrimination of these two groups at a cutoff of 71 pmol/mU. CONCLUSION: The PAC/PRC ratio offers several practical advantages compared with the PAC/PRA screening method. The present study offers preliminary evidence that it may be a useful screening test for PHA. Further studies are required to validate these results, especially in hypertensive cohorts