Effect of growth hormone replacement therapy on pituitary hormone secretion and hormone replacement therapies in GHD adults

OBJECTIVE: We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes. METHODS: 22 GHD patients were investigated in a double-blind randomized study and 90 GHD patients in an open study at baseline and after 6 and 12 months of GH replacement therapy. RESULTS: In the placebo-controlled trial, the FT(3) levels increased after 6 months in the GH-treated group, and in the open study the FT(3) levels tended to increase. Other hormone concentrations did not change in either part of the study. Four patients required an increase in thyroxine dose, while 2 patients needed dose reduction. One originally euthyroid patient required thyroxine replacement. Two patients with originally conserved pituitary-adrenal function developed ACTH insufficiency. The hydrocortisone dose was increased in 1 and decreased in 1 of the 66 patients with secondary hypocortisolism. None of the females required any adjustment of sex hormone replacement therapy. Two of 37 males needed dose increase of testosterone, while 1 needed dose reduction. CONCLUSION: GH replacement therapy required dose adjustments regarding other hormone replacement therapies in 12.2% (n = 11), while initiation of new hormone replacement was performed in 3.3% (n = 3) of the 90 patients during the 1-year follow-up. Monitoring of pituitary hormone axes is advisable after commencement of GH replacement therapy, since changes of hormone replacement therapy was observed in a small but clinically significant number of patients.     

The effects of growth hormone deficiency and growth hormone replacement therapy on bone. A meeting report

Recently, several reports have described the effects of growth hormone (GH) deficiency (GHD) on bone and the associated potential benefits of GH therapy. Not all of these reports have, however, been consistent and the results are debated. Some of the contention surrounding this issue reflects disagreement about which bone parameters are the best indicators of bone strength and fracture risk. In November 1999, a meeting was held in Taormina, Italy, to discuss the assessment of bone in patients with GHD and the effects of GH therapy on the skeleton. The participants included endocrinologists, orthopaedists and biophysicists from around the world. During the meeting, the advantages and disadvantages of the various indicators of bone strength were defined. In considering GH therapy, the delegates agreed that it had beneficial effects on bone in adults with GHD, but that further studies were needed in GH-deficient children. Finally, the participants stressed the need for more data to clarify which indicator of bone strength is the most appropriate to use in adults and children with GHD, and to define fully the role of GH therapy in bone metabolism. It was recognized that pharmacoepidemiological surveys, such as KIGS (Pharmacia International Growth Database) and KIMS (Pharmacia International Metabolic Database), are valuable sources of such data, and are, therefore, important in the development of evidence-based medicine.     

Partial growth hormone deficiency with pituitary stalk transection.

Partial growth hormone deficiency was found in a 13-year-old Japanese boy who was born by breech delivery. Magnetic resonance imaging showed transection of the pituitary stalk and the presence of an ectopic posterior lobe located at the proximal stump of the transected stalk.     

Human pituitary growth hormone. Intrinsic lipolytic activity on rabbit fat cells.

The stimulation of lipolysis in isolated rabbit fat cells by human growth hormone was investigated in detail. The action of the hormone on rabbit adipocytes is very similar to that of adrenocorticotropin and the melanotropins. The effect is rapid, requires Ca²⁺, appears to be mediated by cyclic AMP, and is not blocked by inhibitors of protein synthesis. The lipolytic action of human growth hormone was neutralized by antisera to itself and to human chorionic somatomammotropin. Several lines of evidence indicate that the rapid lipolytic activity of the growth hormone in rabbit fat cells in an intrinsic property of the hormone, although the physiological significance of this activity remains obscure.     

Equilibrium denaturation of buffalo pituitary growth hormone

To understand the structural properties of buffalo growth hormone (buGH), the equilibrium denaturation using guanidinium chloride (GdmCl) was carried out and was monitored by ultraviolet absorption spectroscopy, intrinsic fluorescence spectroscopy, far UV-circular dichroism and size-exclusion chromatography. The normalized denaturation transition curves for each of the above methods were not coincident, showing that buGH does not follow a simple two state folding mechanism. Further, size-exclusion chromatography also showed the presence of an associated intermediate during the unfolding of buGH. It was observed that in buGH, denaturation resulted in an initial disruption of the tertiary structure, whereas the secondary structure and the degree of compactness were disrupted at a higher concentration of the denaturant. This suggests that buGH follows the hierarchical model of protein folding.