Bei 16 Patienten mit Nebennierenrindeninsuffizienz und nach bilateraler Adrenalektomie wurde Prednisolon im Serum und im Urin nach peroraler und intravenöser Gabe von Prednison und Prednisolon gemessen. Dabei sollten pharmakokinetische Daten über das Verhalten von Prednisolon gewonnen werden und die Frage geklärt werden, wie lange die Substanz nachweisbar ist. Da sich Prednisolon ähnlich wie Cortisol an Transcortin und Albumin bindet, konnte wegen des Fehlens endogener Corticosteroide eine einfache Proteinbindungsmethode zum Nachweis angewendet werden. Die Ergebnisse zeigen keinen signifikanten Unterschied in den Serumspiegeln nach oraler Gabe von Prednison oder Prednisolon. Die höchsten Konzentrationen wurden nach 2–3 h erreicht und betrugen nach 5, 7,5 und 10 mg Prednison 11,9±2,2 bzw. 15,9±3,4 und 21,5±5,9 µg/dl. Die Serumhalbwertszeit von ca 5 1/2 h läßt nach Gabe von entsprechend höheren Dosen noch auf das Vorkommen meßbarer Serumkonzentrationen nach 2 Tagen schließen. Da Prednisolon die meisten Meßmethoden für Cortisol beeinflußt, empfehlen wir, 2 Tage vor einer Cortisolbestimmung die Prednisontherapie abzusetzen. Die bei nebennierenrindeninsuffizienten Patienten ermittelte erniedrigte metabolische Clearancerate (56,0±7,2 1/24 h/m2) führen wir auf Alterationen im Corticoidstoffwechsel, möglicherweise bedingt durch eine erhöhte Transcortinproduktion, zurück.

Ten euthyroid and 9 hypothyroid volunteers were orally administered 2 mg L-thyroxine (T4) to study the interaction between substitutive and suppressive effects of a single high T4 dose. After a significant rise in the serum T4 concentration for 5 days in euthyroid and for 11 days in hypothyroid patients an inhibition of basal and of TRH stimulated TSH release was observed. Maximal inhibition of the TSH response in hypothyroid patients occurred 1 to 7 days after the individual T4 peak. This interval was significantly correlated to the extent of the respective T4 rise. In euthyroid subjects TSH response was significantly inhibited for 8, in hypothyroid patients for 22 days. In all but 3 of the euthyroid patients there was a significant inhibition of the thyroidal 132I uptake on day 8. Normalization of thyroidal 132I uptake and of pituitary TSH secretion generally coincided.

UNLABELLED:The MCR of constantly infused synthetic GnRH (1.53 micrograms/min) was studied in relation to age, sex, and male sexual maturation. GnRH was determined by a radioimmunoassay using a specific GnRH antiserum and 125I-GnRH, prepared by the chloramine T technique and purified on Sephadex G 25. Serum LH and FSH were measured by RIA. The results (mean values +/- SEM) of MCR expressed here as ml/min/1.86 m2 showed a statistically significant difference: infants (6-13 yrs) 1170 +/- 79, sexually mature males (22-29 yrs) 639 +/- 28, elderly men (64-79 yrs) 520 +/- 38, sexually mature females (20-24 yrs) follicular phases: 1354 +/- 90, luteal phases: 1736 +/- 242, postmenopausal women (53-74 yrs) 598 +/- 45. We found a linear negative correlation between serum LH and MCR of GnRH in both sexes. During male puberty the MCRLH-RH decreased simultaneously to the stages of pubic hair development.IN CONCLUSION:1) The MCR of GnRH is a function of age, sex, and sexual maturation, 2) its negative linear correlation with LH in both sexes indicates that the MCR presumably reflects endogenous GnRH levels, 3) the MCRGnRH seem to be subject to endocrine regulation.

Beim hypothalamisch-hypophysären Cushing-Syndrom galt lange Zeit die bilaterale Adrenalektomie mit anschließender lebenslänglicher Corticosteroidsubstitution als Therapie der Wahl. Trotz der postoperativen Erfolge ist die Therapie umstritten, weil die Langzeitprognose durch das mögliche Auftreten von Nelson-Tumoren und NNR-Regeneraten eingeschränkt wird. Wir haben deshalb im Hinblick auf den therapeutischen Erfolg sowie die möglichen Komplikationen 27 Patienten durchschnittlich 6 Jahre (1-18) nach bilateraler Adrenalektomie nachuntersucht. Ihr Durchschnittsalter betrug zum Zeitpunkt der Diagnosestellung 35 Jahre (19-53). Sie standen unter einer Substitutionstherapie von durchschnittlich 37,5 mg Cortison und 0,1 mg Fludorcortison. Die Glucocorticoidsubstitution wurde für die Nachuntersuchung für wenigstens 20 Std unterbrochen. Zum Vergleich wurden drei Patientinnen kontrolliert, welche wegen eines Nebennierenrindenadenoms unilateral adrenalektomiert worden waren. Diese bedurften nach einer postoperativen Übergangsphase von durchschnittlich 2 Jahren keiner weiteren Substitution.

Sera of 7 patients with active acromegaly were fractionated by Sephadex G-100 chromatography and the effects of bromocriptine on the concentrations of total growth hormone (hGH) and its different molecular forms studied. Three immunoreactive peaks were observed, corresponding to molecular weights of about 20,000 ('little hGH'), 40,000 ('big hGH'), and more than 100,000 ('big big hGH') Following bromocriptine administration, there was significantly more reduction of 'little hGH' than of 'big big hGH'. Careful interpretation of these changes is required in view of the possible influences of sample storage and handling on hGH heterogeneity. We suggest that either bromocriptine acts differentially on the release of 'little' and 'big big hGH', or that these components differ in their metabolic half-life. However, even the suppression of 'little hGH' is insufficient to explain the clinical response of the disease to bromocriptine.

SUMMARYSerum somatomedin B was measured by radioimmunoassay in forty‐seven normal subjects, twenty‐nine patients with acromegaly before and twenty‐four after treatment, and eighteen patients with Turner's syndrome. Somatomedin B levels were significantly elevated in untreated acromegaly and in Turner's syndrome compared with the control group; they decreased following treatment of acromegaly. Because of the overlap between the groups, little information could be obtained from single somatomedin B estimations, which could, therefore, not replace dynamic tests of growth hormone secretion. No correlation between growth hormone and somatomedin B in acromegaly was detected; however, somatomedin B appeared to be related to the insulin response during the oral glucose tolerance test. In Turner's syndrome, no relationship between somatomedin B and insulin production, urinary oestrogen excretion, growth hormone secretion, gonadotrophin levels, age or height was found. The reason for the raised somatomedin B levels in Turner's syndrome remains at present unknown.

Die Bindung von Steroidhormonen an Proteine des Serums unterdrückt temporär die biologische Wirkung. Andererseits schützt die Proteinbindung das Steroidhormon vor chemischem und enzymatischem Angriff, vor nicht adäquater intracellulär Aufnahme, Metabolisierung und Ausscheidung.

Binding of 125I-LH-RH and its analogue, 125I-6-D-Leu-10-Des-Gly-Ethylamide-LH-RH (6-D-LH-RH) in male serum was studied in 10 healthy males and in 11 patients with idiopathic gonadotropin deficiency (IGD) before and during treatment with 6-D-LH-RH. Using either equilibrium dialysis (A) or ethanol precipitation (B) 13.57 +/- 0.69% (A) or 19.32 +/- 1.73% (B) of LH-RH and 7.12 +/- 0.86% (A) or 14.56 +/- 1.06% (B) of the analogue were in the bound form, without difference between normal subjects and IGD. Capacity of this binding was high (greater than 9 less than 18 mu-Mol LH-RH/0.06 mMol of protein), affinity very low, and the binding almost completely disappeared following removal of albumins by affinity chromatography. Chronic treatment with 6-D-LH-RH did not alter these binding characteristics. These observations suggest non specific albumin binding of LH-RH in male serum and stress the role of this decapeptide as a rapid modulating regulator of gonadotropin secreting system.

The effect of a single dose of 2 mg L-thyroxine on central and peripheral parameters of the hypophyseal-thyroid axis was studied on ten euthyroid and ten hypothyroid patients, and ten with euthyroid goitre. Without the occurrence of hyperthyroid symptoms, the T4 serum level was raised for five days in the euthyroid group, for 11 days in the hypothyroid ones. During this time the T3 serum level did not alter. Suppression of iodine uptake by the thyroid and TSH secretion of the hypophysis persisted longer, both for basal and TRH-stimulated liberation, than the substitution effect. Even when the T4 bolus has to be at a higher total T4 dose for the same therapeutic effect than with daily small single doses, it is a comparable alternative to present-day forms of treatment. It is of particular advantage where there are medical reasons for widely spaced drug intake or rapid normalisation of the T4 serum level is deemed desirable.

Die Bedeutung normaler Prolaktin (PRL)-Spiegel beim Mann, und außerhalb der Laktationsphase auch bei der Frau ist unklar. Bisher wurden mehr als 80 Funktionen des Prolaktins beschrieben [l, 2].

Prednison und Prednisolon stellen heute günstige Präparate für die systemische Glucocorticoidtherapie dar. Ziel dieser Arbeit ist, die Frage nach der Verteilung und Ausscheidung dieser Steroide nach Applikation pharmakologischer Dosen exakt zu beantworten. Ferner sollte geklärt werden, wie lange Prednisolon nachweisbar ist, da es in den meisten Verfahren zur Cortisolbestimmung die Funktionsdiagnostik der NNR und der adrenocorticotropen Partialfunktionen des HVL störend beeinflußt.