Kh Voigt

Somatostatin: a potent inhibitor of ACTH-hypersecretion in adrenal insufficiency.

ZusammenfassungSomatostatin (250 µg als Bolus i.v. und 250 µg als Dauerinfusion über eine Stunde) wurde 5 Patienten mit Nebennierenrindeninsuffizienz verschiedener Ätiologie gegeben. Bei jedem Patienten wurde ein anhaltender, kontinuierlicher Abfall des Plasma-ACTH während der Infusionsperiode beobachtet. Die durchschnittliche maximale Verminderung des Plasma-ACTH betrug 43,8±5,9%. Nach Beendigung der Somatostatininfusion stieg das Plasma-ACTH innerhalb einer halben Stunde wieder auf den Ausgangswert an. Diese Ergebnisse zeigen, daß Somatostatin ein potenter Inhibitor der ACTH-Sekretion ist, jedoch nur bei einem bestehenden Mangel an Glucokortikoiden.SummarySomatostatin (250 µg as a bolus i.v. and 250 µg as a 1-hr infusion) was administered to 5 patients with adrenal insufficiency of different origin. In each patient a sustained, progressive fall in plasma ACTH was observed during the infusion period. The mean maximal reduction in plasma ACTH was 43.8±5.9%. After cessation of the somatostatin infusion there was a rise of plasma ACTH to starting levels within 1/2 hour. These findings suggest that somatostatin is a potent inhibitor of ACTH secretion, however, only in a condition in which glucocorticoids are lacking.

Differential and Integral Corticosteroid Feedback Effects on ACTH Secretion in Hypoadrenocorticism

Recent work suggests the existence of a dual corticosteroid feedback mechanism of stress-induced ACTH secretion in the rat. This possibility led us to study the kinetics of suppression of ACTH levels by corticosteroid administration in patients with nonstress ACTH hypersecretion secondary to hypoadrenocorticism. Cortisol was administered according to different protocols, which were chosen to provide extreme variations of the input signal. By this means, two phases of suppression of ACTH levels could be differentiated. A first decrease occurred without latency whenever, and as long as, plasma cortisol levels were rising. There was a linear regression between the logarithm of the increments in cortisol concentrations and the decrease in ACTH levels per minute (r = 0.951) (differential or rate-sensitive feedback mechanism). Neither the absolute doses of cortisol, nor plasma cortisol concentrations were closely correlated with the degree of suppression of ACTH by this rapid mechanism. A second decrease in ACTH levels began congruent with30 min after corticosteroid administration. In this case there was a significant linear regression between the degree of inhibition of ACTH levels and the cortisol doses (r = 0.997) (integral or dose-sensitive feedback mechanism). The dose-sensitive feedback effects of dexamethasone were less than might have been predicted from its relative anti-inflammatory potency. No rate-sensitive effects were seen with dexamethasone doses of 1.0 or 1.25 mg.

Localization of corticotropin-releasing activity in the rat hypothalamus.

Hypothalamic nuclei were removed from frozen sections of rat brain and examined for their corticotropin-releasing activity. The highest concentration was measured in the median eminence. In addition there was significantly more activity detected in the nuclei paraventricularis, supraopticus, suprachiasmaticus and arcuatus than in the other nuclei.

Spontaneous and stimulated secretion of QUSO-extractable immunoassayable ACTH in man

SummaryA factor is present in the plasma which “binds” ACTH thus disturbing the radioimmunologic system. Therefore, ACTH was extracted for radioimmunological measurement. A simple method is described to extract a representative part of the ACTH from plasma utilizing the high capacity of silicates (QUSO G-32) to adsorb free, intact ACTH.Basal values of QUSO-extractable, immunoassayable ACTH in normal persons at 8 a.m. amounted from 0 to 120 pg/ml (

Influence of plasma on ACTH stimulated corticosterone production of isolated adrenal cells

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The Involvement of the Thyroid and Adrenal in the Regulation of Enzyme Activities of Hepatic and Renal Steroid Metabolism in the Rat

=30.3 pg/ml). In most patients with Cushings disease basal values were clearly elevated. The highest ACTH levels (up to 6000 pg/ml) were found in untreated Addisons disease. Under normal clinical conditions there were marked fluctuations of the ACTH level during 24 hours in normal persons as well as in patients with Cushings disease. However, a peak value during the early morning hours was not constantly recovered. Lysin-vasopressin infusion (5 I.U. LVP/60 min) induced a rapid increase in ACTH concentrations, which began to fall after the 30th minute while infusion of LVP continued. The rise in plasma ACTH following oral administration of metyrapone (750 mg every 4 hours during 24 hours) was delayed for about 12 hours from the first administration and elevated levels were demonstrable up to 12 hours after the last administration. There were remarkable differences in the temporal pattern of the ACTH levels after administration of metyrapone.ZusammenfassungEin in Plasma vorhandener Faktor „bindet“ ACTH und stört so das radioimmunologische System. Deswegen wurde ACTH zur radioimmunologischen Messung extrahiert. Eine einfache Methode zur Extraktion eines representativen Teils des Plasma-ACTH wird beschrieben, die die hohe Kapazität von Silicaten (QUSO-G32) nützt, freies, intaktes ACTH zu adsorbieren.Die basalen Werte des QUSO extrahierbaren, immunologisch meßbaren ACTH bei Normalpersonen um 800 lagen zwischen 0 und 120 pg/ml (

DISSOCIATION OF IN VIVO AND IN VITRO "AUTONOMY" IN A HUMAN ADRENOCORTICAL TUMOUR

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