Evaluation of adrenal function in patients with hypothalamic and pituitary disorders: comparison of serum cortisol, urinary free cortisol and the human-corticotrophin releasing hormone test with the insulin tolerance test.

OBJECTIVE: This study aimed to evaluate the performance of screening tests (serum cortisol and 24-h urinary free cortisol) and the human-corticotrophin releasing hormone (h-CRH) test in the assessment of adrenal function in patients with hypothalamic-pituitary disorders. DESIGN: Summary receiver operating characteristics (SROC) curve analysis was applied with the insulin tolerance test (ITT) as reference test. A peak serum cortisol response to ITT > or = 500 nmol/l indicated adrenal sufficiency. The sensitivity at the intersect of the diagonal between sensitivity = 1 and (1-specificity) = 1 with the SROC curve, where sensitivity and specificity are equal, and the corresponding weighted kappa, an estimate of agreement with the ITT, served as parameters of test performance. The diagnostic yield, representing the proportion of tests obviating the need for an ITT, was also calculated. MEASUREMENTS: Serum cortisol at 0800 h (n = 122), at 1600 h (n = 116), 24-h urinary free cortisol (n = 115) and the peak serum cortisol to h-CRH (n = 129) were compared with the peak serum cortisol to ITT. PATIENTS: Eighty patients with hypothalamic-pituitary disorders in whom 75 ITT's were performed pre- and 57 post-operatively. RESULTS: Sensitivity at the intersect and weighted kappa were higher for 0800 h serum cortisol (0.873 and 0.763 respectively) than for 1600 h serum cortisol (0.769 and 0.561) and 24-h urinary free cortisol (0.777 and 0.576). These parameters were 0.868 and 0.756 for the h-CRH test. The diagnostic yield was 63.9% for 0800 h serum cortisol compared to 25.9% for 1600 h serum cortisol (P < 10(-8)), 23.5% for 24-h urinary free cortisol (P < 10(-8)) and 60.5% for the h-CRH test (NS). CONCLUSIONS: Serum cortisol measurement at 0800 h is better than 1600 h and 24-h urinary free cortisol to evaluate adrenal function in this patient category. The diagnostic applicability of the h-CRH test is not superior to 0800 h serum cortisol measurement.

Analysis of urinary nitric oxide metabolites in healthy subjects.

Nitric oxide (NO) has divergent actions under physiological and pathological conditions. NO is rapidly decomposed to nitrite (NO2-) and nitrate (NO3-). Since these metabolites are stable, they are good indices of NO production under various conditions. In the present study, we measured NO2- and NO3- concentrations in the urine collected from 62 hospital controls and 504 healthy subjects by means of a new HPLC system combined with Griess reaction. NOx was the sum of NO2- and NO3-. There was no considerable inter-day variation in urinary NO metabolite levels, and there was close correlation between NO2-, NO3- and NOx values in spot urine obtained in the early morning and those in 24-h stored urine in hospital controls. Urinary NO metabolite levels, which were corrected by creatinine (Cr) excretion and expressed on a logarithmic scale, showed normal distribution and were independent of sex and age in healthy subjects. The normal ranges of urinary NO2-, NO3- and NOx levels were estimated as 17-72 micromol/g Cr, 1,023-2,818 pmol/g Cr, and 1,071-2,951 micromol/g Cr, respectively. We also found that urinary NO metabolite levels were lower than normal range in patients with various diseases.

[Urinary catecholamine excretion and blood serotonin content in juvenile hypothalamic syndrome]. / Ekskretsiia katekholaminov s mochoi i soderzhanie serotonina v krovi pri iunosheskom gipotalamicheskom sindrome.

Daily urinary adrenalin, noradrenaline, dopamine excretion and blood levels of serotonin were measured over the course of the cycle in 8 healthy girls and in 52 patients with the juvenile hypothalamic syndrome in the acute and chronic stages. These parameters were found virtually the same in healthy girls and in those suffering from the hypothalamic syndrome in the course of the cycle or in patients during the acute and chronic stages of the condition. Urinary catecholamine excretion and blood serotonin levels were increased by 1.5-2 times in the acute stage of the syndrome and somewhat reduced in the chronic stage; this appears to be due to reduced activity of the sympathoadrenal system in the course of disease progress.

The assessment of the functional capacity of the hypothalamic-pituitary-adrenal axis by measurement of basal plasma and urinary cortisol in comparison with insulin-induced hypoglycaemia and metyrapone tests.

In 58 patients with a pituitary adenoma or hypothalamic-pituitary disease an insulin-induced hypoglycaemia test and a metyrapone test were performed. The results of these tests were compared with morning plasma cortisol levels and daily urinary cortisol excretion as indicators of insufficiency of the pituitary-adrenal axis. Basal unstressed urinary cortisol excretion was insufficient in 20 cases. These patients, needing life-long glucocorticoid substitution therapy, were excellently detected by both tests and daily urinary cortisol excretion. The predictive value of the morning plasma cortisol level was inferior to these. Five cases with sufficient basal cortisol excretion showed a defective adrenal response to hypoglycaemia. These patients were not discriminated by the metyrapone test, urinary cortisol excretion or plasma cortisol levels. It is concluded that urinary cortisol excretion can safely replace the hypoglycaemia and metyrapone test for the detection of insufficient basal cortisol production in patients with hypothalamic and/or pituitary disorders.

Recurrent pregnancy-induced polyuria and thirst due to hypothalamic diabetes insipidus: an investigation into possible mechanisms responsible for polyuria.

A young patient developed hypothalamic diabetes insipidus due to histiocytosis in infancy and was satisfactorily treated with Pitressin. As a teenager she no longer had thirst or polyuria after treatment was stopped. These symptoms only returned during her two pregnancies. When non-pregnant her urine output was 1.7-2.0 1/24 h, basal plasma osmolality 288-290 mOsm/kg, and during pregnancy 24 h urine volume was 4.5-5.21, plasma osmolality 278-280 mOsm/kg. Studies on osmoregulation of thirst and AVP release, and on renal sensitivity to the V2 agonist desmopressin and endogenous vasopressin were performed in pregnant and non-pregnant states. She had no circulating antibodies to AVP, and the effect of pregnancy-associated vasopressinase was eliminated. Results showed lowered basal plasma osmolality and osmolar thirst threshold in pregnancy but no failure of the renal concentrating mechanism. Plasma AVP concentrations after osmotic stimulation were lower in pregnancy. We propose that she developed thirst and polyuria during pregnancy because of lowering of her osmolar thirst threshold to plasma osmolalities which caused her to drink sufficient quantities of fluid to further reduce AVP secretion. We cannot exclude, however, the possibility that there was increased clearance of circulating AVP.

[Urinary excretion of testosterone and androstenedione in hypogonadism in men]. / Vydelenie s mochoi testosterona i androstendiona pri gipogonadizme u muzhchin.

The authors present the results of determination of the testosterone and androstendion excretion in the patients with various forms of hypogonadism and in healthy men. Testosterone excretion was decreased in the patients with hypogonadism, against the background of normal or increased androstendion excretion whereas the degree of deviations of the testosterone/androstendion ratio depended on the clinical variant of hypogonadism. Thus, retarded or decreased accumulation of the enzymes in the testes responsible for the change from the "child" to the "mature" type of steroid biosynthesis could serve as a mechanism of hypogonadism occurrence, which should be taken into consideration in the elaboration of the methods of syndrome therapy of this type of pathology.