Despite the fact that many research articles have been written about stress and stress-related diseases, no scientifically accepted definition of stress exists. Selye introduced and popularized stress as a medical and scientific idea. He did not deny the existence of stressor-specific response patterns; however, he emphasized that such responses did not constitute stress, only the shared nonspecific component. In this review we focus mainly on the similarities and differences between the neuroendocrine responses (especially the sympathoadrenal and the sympathoneuronal systems and the hypothalamo-pituitary-adrenocortical axis) among various stressors and a strategy for testing Selye's doctrine of nonspecificity. In our experiments, we used five different stressors: immobilization, hemorrhage, cold exposure, pain, or hypoglycemia. With the exception of immobilization stress, these stressors also differed in their intensities. Our results showed marked heterogeneity of neuroendocrine responses to various stressors and that each stressor has a neurochemical "signature." By examining changes of Fos immunoreactivity in various brain regions upon exposure to different stressors, we also attempted to map central stressor-specific neuroendocrine pathways. We believe the existence of stressor-specific pathways and circuits is a clear step forward in the study of the pathogenesis of stress-related disorders and their proper treatment. Finally, we define stress as a state of threatened homeostasis (physical or perceived treat to homeostasis). During stress, an adaptive compensatory specific response of the organism is activated to sustain homeostasis. The adaptive response reflects the activation of specific central circuits and is genetically and constitutionally programmed and constantly modulated by environmental factors.

/pdf/stressor-specificity-of-central-neuroendocrine-responses-3hrslqz38s.pdf

Stressor specificity of central neuroendocrine responses: implications for stress-related disorders.

http://www.svemonline.org/wp-content/uploads/2016/02/endotips-vol-03-2.pdf

Diagnosis, Evaluation, and Treatment of Hyponatremia: Expert Panel Recommendations

Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future.

/pdf/advances-in-the-treatment-of-prolactinomas-5a8n14833q.pdf

Advances in the treatment of prolactinomas.

Systemic osmoregulation is a vital process whereby changes in plasma osmolality, detected by osmoreceptors, modulate ingestive behaviour, sympathetic outflow and renal function to stabilize the tonicity and volume of the extracellular fluid. Furthermore, changes in the central processing of osmosensory signals are likely to affect the hydro-mineral balance and other related aspects of homeostasis, including thermoregulation and cardiovascular balance. Surprisingly little is known about how the brain orchestrates these responses. Here, recent advances in our understanding of the molecular, cellular and network mechanisms that mediate the central control of osmotic homeostasis in mammals are reviewed.

http://www.med.uottawa.ca/courses/nsc5104/assets/documents/dr_renaud2009/nrn2400.pdf

Central mechanisms of osmosensation and systemic osmoregulation.

Hyponatremia

OBJECTIVE The best dynamic test for the assessment of the hypothalamic–pituitary–adrenal axis and the interpretation of the cortisol levels, remain a matter of controversy. We aimed to establish normal ranges with current assays, for both the short Synacthen (SST) and insulin stress tests (IST) and then to use these data to examine whether the SST can satisfactorily substitute for the IST in assessment of the hypothalamic–pituitary–adrenal axis.

DESIGN Thirty SSTs and 27 ISTs were performed on different healthy volunteers. The results of all paired tests performed on patients in the last three years are reviewed.

SETTING Programmed Investigation Unit.

SUBJECTS Fifty-seven healthy volunteers and 166 patients.

MAIN OUTCOME MEASURES Basal serum cortisol concentration and cortisol values obtained at 30 and 60 minutes during the SST compared to the maximum obtained with adequate hypoglycaemia (plasma glucose < 2mmol/l) during an IST.

RESULTS From normal data the mean-2SD 30-minute value during the SST was 392 nmol/l and 60-minute value was 497 nmol/l. The maximal cortisol response (mean − 2SD) during the IST was 519 nmol/l. Sixty patients failed the IST, none of whom had a basal cortisol > 450 nmol/l and only six (10%) had a 30-minute cortisol value > 600 nmol/l. The 30-minute value provided a better index than the 60-minute value. The basal, 30 and 60-minute values during the SST all correlated positively and significantly with the maximal cortisol on IST. The correlations persisted for all microadenomas and macroadenomas secreting prolactin, gonadotrophins or growth hormone, patients undergoing either pre or post-adenomectomy evaluation, and in those patients who had received long-term steroids provided that the medication had been reduced and stopped two days prior to admission.

CONCLUSIONS Using a 30-minute cortisol value > 600 nmol/l as a cut-off, the short Synacthen test provides a suitable substitute for the insulin stress test. Adopting this policy will decrease the number of insulin stress tests performed by one-quarter and thus provide a substantial saving without detriment to patient care.

The short Synacthen and insulin stress tests in the assessment of the hypothalamic-pituitary-adrenal axis

The relationship between thirst perception and plasma osmolality was studied during hypertonic and physiological saline infusion in ten healthy volunteers. Thirst perception was quantified using a linear visual analogue scale which volunteers marked at intervals during the infusion periods. Infusion of hypertonic saline caused a steady rise in plasma osmolality together with a progressive linear increase in thirst perception and also plasma arginine vasopressin. No significant changes in thirst, plasma osmolality or plasma arginine vasopressin occurred during infusion of physiological saline. Linear regression analysis of the results defined the functions. Thirst (cm) = 0.3 (plasma osmolality-281) (r = +0.92, P less than 0.001) and plasma arginine vasopressin (pmol/l) = 0.4 (plasma osmolality-285) (r = +0.96, P less than 0.001). The osmolar threshold for thirst onset thus defined (281 mosmol/kg) was much lower than in previous studies and similar to the theoretical osmolar threshold for vasopressin release (285 mosmol/kg). We conclude that thirst perception rises in a progressive fashion throughout a wide range of plasma osmolality and that the osmolar threshold for thirst onset is similar to the theoretical osmolar threshold for vasopressin release. The results are compatible with the concept of either a single osmoreceptor subserving both thirst and vasopressin release, or two osmoreceptors sharing similar functional characteristics.

The osmotic thresholds for thirst and vasopressin release are similar in healthy man

GFR and renal plasma flow (RPF) decrease in preeclampsia, a serious hypertensive complication of pregnancy. Serial data derived in late pregnancy (LP) and >5 mo postpartum (PP) in 13 healthy controls and 10 preeclamptic women (13 and 5, respectively) returning PP for theoretical analysis of neutral dextran sieving curves (theta(D)), are presented and are used to calculate the key determinants of glomerular ultrafiltration. Normal LP hyperfiltration was associated with increases in RPF and the ultrafiltration coefficient (K(f)), as well as in the nondiscriminatory shunt pathway (omega(0)) and the SD of pore size (S). Preeclamptic LP showed the largest omega(0) and S values, indicating a loss of size-selectivity, accompanying reduced K(f) and RPF, both of which are implicated in the relative hypofiltration. Despite a 100-fold increase in urinary albumin excretion (UAE), LP preeclamptic theta(D) values were reduced for the equivalent neutral dextran (36A), providing indirect evidence for a loss of glomerular barrier charge-selectivity. All the determinants of GFR and all modeled parameters were comparable across both groups PP, strong evidence that preeclamptic glomerular dysfunction resolves.

/pdf/glomerular-ultrafiltration-in-normal-and-preeclamptic-1e45851wid.pdf

Glomerular Ultrafiltration in Normal and Preeclamptic Pregnancy

Our understanding of the mechanisms that regulate water balance in mammals began over 40 years ago with the classic studies of Professor E. B. Verney and his colleagues in Cambridge, England. In a series of experiments on conscious, trained dogs with permanent exteriorized carotid arteries to allow rapid injections of solutions into the cerebral circulation, Verney demonstrated that hypertonic solutions of sodium chloride, sucrose and glucose caused antidiuresis; observations which formed the basis of the concept of the ‘osmoreceptor’. Verney proposed that cells within the central nervous system altered their volume thus regulating the release of an antidiuretic hormone which acted upon the kidney (Verney, 1947). The results of subsequent experiments suggested that these osmotically sensitive cells were located in the anterior hypothalamus (Jewel1 & Verney, 1957). Recent work from independent laboratories has identified probably the most important putative osmoreceptor concerned with the vasopressin secretion, the organum vasculosum of the lamina terminalis which is an area within the circumventricular organs of the anterior hypothalamus (McKinley et al., 1978; Thrasher er al., 1982). There is evidence that other sites associated with the circumventricular organs (e.g. the subfornical organ) might also act as osmoreceptors (Iovino & Steardo, 1984; Ferguson & Kasting, 1986), and possibly even the supra-optic nucleus itself, which synthesizes most of the osmoregulated vasopressin, may play a similar role (Leng et al., 1985). Progress in characterization of the functional aspects of osmoregulated vasopressin secretion was hampered by the lack of sensitive and reproducible assays to measure circulating vasopressin. UntiI the early 1970s only bioassays were available; but a major advance in our understanding of osmoregulation was heralded by the development of specific and sensitive radioimmunoassays able to detect vasopressin at the extremely low concentrations found in the body fluids of mammals (Robertson etal., 1970; Oyama et al., 1971). Over the next decade, the functional characteristics of osmoregulated vasopressin release were defined in healthy man (Robertson et al., 1976), data which confirmed Verney’s original observations in the dog. In more recent years physiological and

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2265.1988.tb03704.x

Osmoregulation of vasopressin secretion and thirst in health and disease.

Studies on intact animals and isolated rat hepatocytes have shown that arginine vasopression (AVP) stimulates glycogen phosphorylase to break down glycogen and raise plasma glucose concentrations. Since no similar work has been performed on healthy human adults, the effect of moderate (25 pmol/min) and high (75 pmol/min) dose AVP infusion on plasma glucose, intermediary metabolites, glucose kinetics, and circulating glucagon and insulin concentrations was investigated. After AVP infusion, plasma glucose rose from 4.9 +/- 0.1 to a peak of 5.7 +/- 0.2 mmol/l (P less than 0.001), but no changes in blood lactate, pyruvate, alanine, glycerol or 3-hydroxybutyrate concentrations were observed. The glucose rise was accounted for entirely by an increase in the rate of appearance of glucose from 11.19 +/- 0.43 to 13.38 +/- 0.63 mu mol/kg/min (P less than 0.001). Infusion of AVP also increased plasma glucagon concentrations from 38 +/- 8 to 79 +/- 20 pg/l (P less than 0.01). The hyperglycaemic effect of AVP may be mediated solely by stimulation of glucagon release, but we cannot exclude direct stimulation of glycogen phosphorylase activity.

Peter H Baylis

Papers

The short Synacthen and insulin stress tests in the assessment of the hypothalamic-pituitary-adrenal axis

The osmotic thresholds for thirst and vasopressin release are similar in healthy man

Glomerular Ultrafiltration in Normal and Preeclamptic Pregnancy

Osmoregulation of vasopressin secretion and thirst in health and disease.

The effect of vasopressin infusion on glucose metabolism in man