To evaluate the dynamics of GH-secretion after infusion of growth hormone releasing factor, human pancreatic growth hormone releasing factor (hpGRF1-44) was infused over 2 and 5 h at a dosage of 100 \ g=m\ ghpGRF1-44/h into 11 healthy subjects. The infusion was started and terminated with a 50 \g=m\ghpGRF1-44 bolus injection. In 5 subjects 200 \ g=m\ g TRH was given 4 h after starting the infusion. In addition, 4 healthy subjects received 50 \g=m\ghpGRF1-44 bolus injection every 2 h. GRF, somatostatin, GH, Prl, and TSH were measured by radioimmunoassay. The initial 50 \ g=m\ g GRF bolus increased GH-levels in all 11 subjects with a maximum at 30 min (24.1 \ m=+-\5.1 ng/ml \ m=+-\ SE). However, though hpGRF1-44 was continuously infused and GFR-levels remained elevated, GH decreased to a minimum 270 min after start of infusion (2.6 \m=+-\0.6 ng/ml). The GH-response to the second bolus at the end of the infusion was lower compared to the first response (14.6 \ m=+-\ 3.4 ng/ml after 2 h and 7.6 \ m=+-\ 2.5 ng/ml after 5 h). TRH did not lead to a GH-increase during hpGRF1-44 infusion though Prl and TSH rose normally. The intermittent bolus injection of 50 \g=m\ghpGRF1-44 led to continuously decreasing GH-responses to the same GRF\x=req-\ dosage (I. bolus: 16.5 \ m=+-\1.6 ng/ml; II. bolus: 4.2 \ m=+-\ 0.8 ng/ml; III. bolus: 3.4 \m=+-\0.5 ng/ml). No change in somatostatin levels was observed.These findings show that GRF infusion or bolus injection in short intervals does not sustain elevated GH-levels.Pituitary GH is either not readily available for continuous GRF-stimulation or GH-secretion may be antagonized by increasing portal somatostatin levels which are not reflected in the peripheral circulation.

We have investigated the function of the hypothalamic-pituitary-gonadal (H-P-G)-axis in patients with severe, untreated Graves' disease. We studied 7 male and 6 female healthy volunteers, and 7 male and 7 female patients with Graves' disease. Hormone profiles were developed by blood sampling every 10 min for an 8 hour period. In women this was done in the early follicular phase of menstrual cycle. LH-, FSH-, and PRL levels were measured using immunoradiometric assays and testosterone (T), estradiol (E2), sex-hormone binding globulin (SHBG), and progesterone (P) were measured with standard assays. The pulsatility of LH, FSH and PRL was calculated using the programmes Pulsar, Cluster and Desade. The temporal relationship of plasma LH, FSH, and PRL pulses was also investigated using specific concordance analysis. Data were evaluated by means of non-parametric statistics. LH-secretion was increased in all hyperthyroid patients, while FSH-secretion was increased in hyperthyroid men only. Pulsatile characteristics of LH- and FSH-secretion (frequency, peak shape) in patients were not different from controls. No change in PRL-secretion was shown. Significant copulsatility occurred between LH and FSH, and LH and PRL. This was more pronounced in hyperthyroid than in healthy study subjects. Plasma levels of steroid hormones and sex-hormone-binding globulin were significantly (p<0.005) increased in hyperthyroid men. Free Androgen Index was significantly (p<0.005) decreased in hyperthyroid males. No other auto immune diseases were noticed. Our results indicate that the function of the H-P-G axis is not impaired in hyperthyroid patients, but gonadotropin levels are increased. Hyperthyroid men show relative primary gonadal insufficiency that may be due to exaggerated SHBG levels. The copulsatility of LH and FSH, and of LH and PRL was confirmed both in patients and controls.

Abstract. The biological activity of ovine (o) and human (h) corticotrophin releasing factor (CRF) in normal volunteers was investigated. Nine subjects received an iv bolus injection of 50, 100 and 200 μg oCRF. There was no dose-response relationship between the injected oCRF dosage and stimulated ACTH, β-endorphin, and cortisol secretion. The addition of glycine as a stabilizer to 50 and 100 μg oCRF had no effect on stimulated ACTH and cortisol secretion. When 50 and 100 μg hCRF were injected into the same subjects no significant difference compared to the oCRF induced ACTH-response was observed. In contrast to the lacking relationship between the CRF dosage and the biological response there was a clearcut dose-response relationship between the amount of oCRF injected and CRF-immunoreactivity 15 min after injection measured with a specific oCRF radioimmunoassay. Though there was only 10% cross-reactivity with synthetic hCRF, endogenous CRF-immunoreactivity could be detected in 53 of 55 pregnant females and in placental extracts. The fact that endogenous CRF immunoreactivity in humans measured by the oCRF-system may be due to the CRF molecule could be supported by identical elution profiles of synthetic and endogenous hCRF which eluted less retarded than oCRF from the Sephadex column. Our data suggest that the already established stimulation-test with oCRF can be replaced in the future by a test using human material in an identical dosage. In addition determination of endogenous CRF seems to be feasible, particularly with the homologous human system and may be of use in evaluation of patients with pituitary adrenal diseases.

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Here we present a pragmatic multistep approach for the treatment of transsexual patients. The importance of an individually designed cross-gender hormone replacement therapy embedded in a multidisciplinary treatment concept, provided by psychiatrists, endocrinologists and surgeons, is demonstrated. Following this concept outcome of therapy has been improved in the last years. Over the last 5 years we have gained substantial experience in the cross-gender hormone treatment of transsexual patients. By continuous follow-up examinations and therapy adjustment the risk of side effects accompanying this therapy has been significantly minimized. This report is designed as a guideline to the clinical endocrinologist for the handling and treatment of transsexual patients.