The effects of human growth hormone (GH) administration in GH-deficient adults: a 20-day metabolic ward study.

The early effects of human GH administration in GH-deficient (GHD) adults on protein, electrolyte homeostasis, and body composition were investigated in a metabolic ward study. Four patients were studied. In addition to a constant caloric and nitrogen (N)-sufficient diet, the patients received GH for 15 days in dosages of 12.5-25 micrograms/kg.day, with a maximum of 1.48 mg (4 IU)/day. GH replacement therapy was well tolerated by all patients. There was a slowly increasing effect on IGF-I levels, which reached a maximum after 8-12 days. The lowered IGFBP-3 levels normalized quicker, reaching maximum circulating concentrations 3 days after the start of GH treatment. Insulin concentrations maximally increased after 5 days, after which they leveled off. Insulin-like growth factor-binding protein-1 levels were maximally suppressed after 2 days of treatment. N balance became positive in all patients (mean, +2.8 +/- 0.2 g/day). Maximal N retention occurred after 2-5 days of GH administration, after which adaptation occurred. This degree of N retention represents a formation of 20 g muscle/day, which would mean an increase of 3.6 kg muscle over a period of 6 months of GH replacement therapy. A rapidly occurring positive sodium balance was observed within 24-72 h. Maximal sodium retention amounted to 61 mmol/day. It slowly decreased spontaneously over the subsequent 12 days. In parallel, rapid changes in bioelectrical impedance analysis (BIA) were observed. There was a close parallel between the net cumulative sodium retention and the decrease in BIA in these patients during the first 15 days of GH therapy. This suggests that the calculation of body composition compartments on the basis of BIA measurements during the initial phase of GH replacement does not represent actual changes in fat mass. This was substantiated with measurements of body composition using dual energy x-ray absorptiometry. In conclusion, measurements of early metabolic changes in GHD adults during the first 15 days after the start of GH replacement indicate that IGF-I values reach maximal levels only after 8-12 days, that the measurements of changes in IGFBP-1 and IGFBP-3 levels probably do not contribute to a determination of the optimal GH replacement dose, that maximal N-retaining effects occur within 2-5 days, after which adaptation occurs, that massive sodium retention occurs during this period, which spontaneously levels off, and that cumulative sodium retention closely correlates during this period with changes in BIA.(ABSTRACT TRUNCATED AT 400 WORDS)

Current tools in the diagnosis of pituitary tumours.

Pituitary tumours result in hypersecretion of different hormones which can be used in diagnosis. Prolactinomas can be diagnosed by measurement of prolactin serum concentration. Prolactin concentrations of > 150 to 200 micrograms/l are invariably due to macroprolactinoma. Lower levels may indicate microprolactinoma or a peripituitary tumour. Computed tomography scans visualize (micro)prolactinomas of 3 mm. Diagnosis of acromegaly is now based on measurement of serum IGF-I concentration. IGF-I levels correlate with the old test which measured insufficient suppression of GH levels to < 2 micrograms/l in response to oral glucose load. Most endocrine tumours have somatostatin receptors, allowing visualization with radiolabelled somatostatin analogues. 111In-diethylenetriaminopentaacetic acid-octreotide allows normal pituitary and somatostatin positive tumours to be visualized. A positive scan is predictive of good response to octreotide therapy. Cushing's syndrome is diagnosed by ecchymoses, myopathy, hypertension, and by measurement of the overnight 1 mg dexamethasone suppression test, urine cortisol levels and the diurnal cortisol rhythm. Clinically nonfunctioning macroadenomas in post-menopausal women often do not immunostain for gonadotropins. Serum gonadotropin levels are not elevated, although they do release gonadotropins or subunits in vitro. Diagnosis is assisted by TRH administration which increases serum gonadotropins or subunits, especially LH-beta.

Long-term in-vitro treatment of human growth hormone (GH)-secreting pituitary adenoma cells with octreotide causes accumulation of intracellular GH and GH mRNA levels.

OBJECTIVE: We studied the effects of long-term in-vitro exposure of human GH secreting pituitary adenoma cells to octreotide on GH release, intracellular GH concentrations and GH messenger ribonucleic acid (mRNA) levels. DESIGN: Human GH-secreting pituitary adenoma cells were cultured for periods from 4 days up to 3 weeks without or with octreotide (10 nM) and/or bromocriptine (10 nM). The effects of these drugs were measured on GH release, intracellular GH concentrations and intracellular GH mRNA levels. PATIENTS: Thirteen patients with GH-secreting pituitary adenomas were studied. Twelve patients were untreated, one had been pretreated with octreotide (12 weeks, 3 x 100 micrograms daily). MEASUREMENTS: GH, PRL, alpha-subunit and IGF-I concentrations in plasma, media and cell extracts were determined by immunoradiometric or radioimmuno-assays. GH mRNA levels were determined by automatic quantification of grain numbers in individual adenoma cells. RESULTS: Incubation of the adenoma cells for 4 days with 10 nM octreotide induced a dose-dependent inhibition of GH release and a parallel increase (increase varying between 124 and 617% of control) in the intracellular GH levels was observed in six of seven adenomas. In addition, bromocriptine, when effective in inhibiting GH release by the adenomas, also induced an increase in intracellular GH levels. Even after 3 weeks of exposure to 10 nM octreotide in vitro there was a statistically significant increase in intracellular GH levels (between 191 and 923% of control). Withdrawal of octreotide after 6 days of incubation resulted in a lowering of intracellular GH levels to control values, showing that the octreotide-induced increase in intracellular GH is reversible. In a 96-hour incubation with 10 nM octreotide, GH mRNA levels were increased in two, and slightly decreased in one of the three adenomas tested. This effect was time dependent in that there was no significant effect of 10 nM octreotide on GH mRNA levels in a 24-hour incubation. CONCLUSIONS: (1) Long-term in-vitro exposure of GH-adenoma cells to octreotide causes an increase in intracellular GH levels in the majority of the adenomas, probably because of an increase in GH mRNA levels in the adenoma cells; and (2) this considerable increase in intracellular GH levels may be one of the explanations for the relatively poor effect of octreotide on tumour shrinkage in patients with GH-secreting pituitary adenomas.

Change of serum calcitonin in patients receiving glucocorticoids: an acute phase study.

The basal and calcium-stimulated calcitonin response was measured in 10 patients with giant cell arteritis before and 1, 3 and 6 wk after the start of daily treatment with 60 mg of prednisone. The study shows that plasma calcitonin level in response to a calcium injection is increased after 1 wk treatment with prednisone. Later on the calcitonin secretion capacity diminishes significantly compared to the initial level. The phylogenetic old calcitonin system first tries to prevent the occurrence of the process of osteoporosis. Moreover, exhaustion of this system later contributes to the process of steroid osteoporosis.