Evidence for a positive correlation between serum cortisol levels and IL-1beta production by peripheral mononuclear cells in anorexia nervosa.

A hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis has been reported in anorexia nervosa (AN), together with some immunological abnormalities, involving citokine - and particularly Tumor Necrosis-Factor-alpha (TNF-alpha) - production by polymorphonuclear cells. The ability of pro-inflammatory cytokines to activate the HPA axis is well known; however, there are no data demonstrating an interdependence between immunological and endocrine response in AN. To investigate the presence of a correlation between immune response and pituitary-adrenal function, plasma ACTH and serum cortisol concentrations were measured in 13 AN patients and in the same number of controls. TNF-alpha and interleukin (IL)-1beta production by ex-vivo unstimulated and LPS-stimulated peripheral mononuclear cells was also assessed. Circulating cortisol concentrations were higher (p<0.01) in AN (156.7 +/- 45.1 microg/l, mean +/- SD) than in controls (105.9 +/- 25.7 microg/l). Unstimulated IL-1beta release in supernatants of mononuclear cell cultures was slightly but not significantly higher in AN than in controls, while TNF-alpha release was similar in the two groups. A positive correlation was found between IL-1beta concentrations in unstimulated culture supranatants and serum cortisol levels in AN (r=0.782, p=0.002), while in normal subjects there was a trend toward a negative correlation; a slight positive correlation, while not significant, between IL-1beta and plasma ACTH, as well as between TNF-alpha and serum cortisol was also found in AN. These data suggest that the normal relationship between pro-inflammatory cytokines release, particularly IL-1beta, and cortisol secretion is deranged in AN.

[Primary hyperaldosteronism. Update on a topic of physiopathology and clinical features]. / L'iperaldosteronismo primitivo. Attualità in tema di fisiopatologia e clinica.

The authors examine the various forms of primary hyperaldosteronism, outlining the most recent acquisitions in terms of etiopathogenesis and physiopathology. While Conn's original description of primary hyperaldosteronism is a syndrome based on corticoadrenal aldosteronesecreting adenoma, it was later seen that this condition could recognise other anatomic substrates, such as carcinoma and in particular bilateral corticoadrenal hyperplasia. A peculiar form of the latter can be suppressed with glucocorticoids sustained by an anomalous recombination of aldosterone-synthase and 11-beta-hydroxylase. The main focus in this paper is on clinical management, in particular the current diagnostic criteria which show that primary hyperaldosteronism affects a higher percentage of the hypertense population that was estimated in the past. Above all, the significance of the aldosterone/PRA (ARR) ratio in screening for this condition is discussed, above all in normokalemic forms, together with the role of molecular biology in identifying glucocorticoid-suppressible forms. Lastly, the principles of medical and surgical management are outlined, emphasising the role of laparoscopic surgery.

Evidence for an interaction between alpha-MSH and opioids in the regulation of gonadotropin secretion in man.

Gonadotropin secretion is inhibited by the endogenous opioids and stimulated by their antagonist naloxone. LH secretion is stimulated by alpha-MSH, a tridecapeptide derived from the post-translational processing of POMC. The possibility that alpha-MSH interacts with the opioids, as suggested by the experimental evidence, was investigated in 7 normal males aged 24-29 through the performance of seven tests: naloxone (0.8 mg i.v. bolus, followed by infusion of 1.6 mg/h for 120'); alpha-MSH (2.5 mg i.v. bolus); naloxone + alpha-MSH (2.5 mg i.v. 15' after commencement of the naloxone infusion); naloxone + GnRH (100 micrograms i.v. 15' after commencement of the naloxone infusion); alpha-MSH + GnRH (respectively 2.5 mg and 100 micrograms at time 0), GnRH alone (100 micrograms at time 0), placebo (150 nmol/l NaCl solution). The LH AUCs during both naloxone (30.3 +/- 2.7 mIU/ml.min-1) and alpha-MSH test (32.9 +/- 4.6 mIU/ml.min-1) were significantly greater (p < 0.005) than that observed during placebo (16.9 +/- 3.6 mIU/ml.min-1). The LH AUC during alpha-MSH + naloxone (37.6 +/- 2.6 mIU/ml.min-1) was not significantly different from that recorded during their separate administration. GnRH injected alone, during the naloxone infusion and with alpha-MSH produced similar increases in LH, that were significantly higher than that observed during the other tests (AUCs: GnRH 89.4 +/- 10.6, GnRH + naloxone 100.5 +/- 9.1, GnRH + alpha-MSH 94.6 +/- 7.9 mIU/ml.min-1, p < 0.001). Significant increase in FSH (p < 0.001) was only observed during GnRH, GnRH + naloxone and GnRH + aMSH tests (AUCs: placebo 13.3 +/- 1.7; naloxone 14.7 +/- 2.5; alpha-MSH 15.5 +/- 2.3; alpha-MSH + naloxone 16.9 +/- 1.9; GnRH 19.1 +/- 1.1; GnRH + alpha-MSH 20.7 +/- 1.3; GnRH + naloxone 21.2 +/- 1.8 mIU/ml.min-1). These results are in line with the possibility of an interaction between alpha-MSH and the opioids in the regulation of gonadotropin secretion, perhaps with opposing effects on a final common pathway.

The inhibitory effect of glucose on growth hormone secretion is lost in obesity but not in hypertension.

In obesity there is a clear reduction of both spontaneous and stimulated GH secretion. Furthermore, in obese patients the somatotrope responsiveness to provocative stimulation is selectively refractory to the inhibitory effect of glucose load. It has been hypothesized that hyperinsulinism of obese patients could play a role in the pathogenesis of these alterations. Aim of the present study was to verify the GH response to GHRH and the ability of glucose load to inhibit it in patients with essential hypertension in whom hyperinsulinism and insulin resistance are frequently present. To this goal, 7 patients with essential hypertension (HP, age, mean +/- SE: 29.6 +/- 2.4 yr, 3 females and 4 males, BMI: 21.7 +/- 1.2 kg/m2), 7 obese (OB, 4 females and 3 males, 31.9 +/- 4.1 yr, 35.6 +/- 2.0 kg/m2) and 7 normal subjects (NS, 4 females and 3 males, 28.3 +/- 3.9 yr, 21.0 +/- 1.6 kg/m2) underwent the following tests: GHRH (1 microgram/kg i.v. at time 0) alone and preceded by oral glucose load (OGTT, 100 g po at -45 min). Basal insulin levels were similar in HP and OB (11.3 +/- 0.5 and 12.7 +/- 2.2 microU/ml, respectively); these, in turn, were higher (p < 0.005) than those in NS (6.8 +/- 0.8 microU/ml). Basal plasma glucose levels in HP were similar to those in OB and NS (80.3 +/- 3.6, 86.9 +/- 6.7 and 84.4 +/- 1.7 mg/dl, respectively). In HP and OB and NS basal GH (1.0 +/- 0.5, 1.0 +/- 0.6 and 0.3 +/- 0.1 micrograms/l, respectively) and IGF-I levels (132.6 +/- 14.8, 137.3 +/- 13.2 and 138.8 +/- 12.2 micrograms/l, respectively) were similar. In HP the GH response to GHRH (AUC: 1058.8 +/- 347.8 micrograms/l/min) was similar to that observed in NS (959.0 +/- 167.8 micrograms/l/min) and higher than that in OB (344.8 +/- 67.2 micrograms/l/min, p < 0.01). OGTT clearly blunted (p < 0.01) the GHRH-induced GH response in HP as well as in NS (401.8 +/- 104.4 and 521.6 +/- 76.6 (g/l/min, respectively) but not in OB (387.4 +/- 78.8 (g/l/min). The OGTT-induced insulin levels in HP did not differ from those of OB, both being higher (p < 0.05) than those recorded in NS. Glucose levels after OGTT were similar in the three groups. In conclusion, this study demonstrates that, like in normal subjects but differently from in obese patients the GH response to GHRH is normal in patients with essential hypertension and it is normally inhibited by oral glucose load even when these patients show high insulin levels. Thus, it is unlikely that the low somatotrope secretion and its refractoriness to inhibition by glucose load in obesity is due to hyperinsulinism.