Abstract: Objective  1) To analyze the predictors of GH suppression after standard glucose load (oGTT) in the healthy population and 2) to establish the 97(th) percentile of GH nadir post-oGTT according with these variables. Design  Analytical, retrospective. Measurements  GH nadir after oGTT. Subjects  231 healthy subjects (113 women, 118 men 15-80 yrs) were studied. Results  The GH nadir after glucose load ranged from 0.01 (<assay detection limit) to 0.65 μg/l, was higher in women and was inversely correlated with age, BMI, waist circumference, waist/hip, total cholesterol, triglycerides, basal and maximal glucose and basal insulin levels and directly correlated with basal GH levels, IGF-I SDS, and HDL-cholesterol (p values ranging 0.004-<0.0001). On multistep regression analysis, the best predictors of nadir GH levels were waist circumference (t=-9.64, p<0.0001), gender (t=-3.86, p=0.0001) and age (t=-3.63, p=0.0003). The results of comparative analysis among subjects grouped according with these variable showed different results in GH nadir in premenopausal women with waist circumference ≤88 cm (97(th) percentile 0.65 μg/l), in premenopausal women with waist circumference ≤88 cm and in men of any age with waist circumference ≤102 cm (97(th) percentile 0.33 μg/l) and in subjects of either gender and any age with waist circumference > 88 cm in women and 102 cm in men (97(th) percentile 0.16 μg/l). Conclusions  The results of this study show that GH nadir after oGTT should be analyzed according with gender, menopausal status and waist circumference. The GH cutoff should be limited to the assay used.
Abstract: IGF-I and PTH have synergistic actions on bone and some effects of the anabolic actions of PTH are mediated by local production of IGF-I, as has been shown in vitro and in vivo studies both in animals and humans. PTH can induce skeletal IGF-I expression both in vitro and in vivo. In chondrocytes, IGF-I synthesis is under GH control, whereas in osteoblasts its synthesis is fundamentally under the control of PTH. PTH stimulates the synthesis of IGF-I via a cAMP-dependent mechanism, and this factor has pro-differentiating and prosurvival effects on osteoblasts. In in vitro studies, IGF-I and PTH have shown a synergistic action on the osteoblasts of bone marrow. Human clinical data confirm the interactions between PTH and GH-IGF-I axis on bone. PTH is involved in the development of osteoporosis in adult patients with GH deficiency (GHD). In fact, patients with GHD show renal, skeletal, and intestinal cell insensitivity to PTH, leading to a mild state of PTH resistance and increased serum PTH levels. In addition, GH replacement in these patients restores PTH secretory rhythm, increases bone turnover markers, 1,25-dihydroxy vitamin D concentration, and Ca absorption/reabsorption, thus contributing to the positive effects of GH on bone. On the other hand, in post-menopausal women with primary hyperparathyroidism a reduced secretion of GH is observed, in association with a greater impairment of bone mass. GH administration resulted in increased IGF-I concentration, decreased PTH concentration, and increased nephrogenous cAMP. In conclusion, the anabolic action of PTH requires paracrine and autocrine effects of IGF-I.
Abstract: Somatostatin analogs (SA) are widely used in acromegaly, either as first-line or adjuvant treatment after surgery. First-line treatment with these drugs is generally used in the patients with macroadenomas or in those with clinical conditions so severe as to prevent unsafe reactions during anesthesia. Generally, the response to SA takes into account both control of GH and IGF-I excess, with consequent improvement of clinical symptoms directly related to GH and IGF-I excess, and tumor shrinkage. This latter effect is more prominent in the patients treated first-line and bearing large macroadenomas, but it is also observed in patients with microadenomas, even with little clinical implication. Predictors of response are patients' gender, age, initial GH and IGF-I levels, and tumor mass, as well as adequate expression of somatostatin receptor types 2 and 5, those with the highest affinity for octreotide and lanreotide. Only sporadic cases of somatostatin receptor gene mutation or impaired signaling pathways have been described in GH-secreting tumors so far. The response to SA also depends on treatment duration and dosage of the drug used, so that a definition of resistance based on short-term treatments using low doses of long-acting SA is limited. Current data suggest that response to these drugs is better analyzed taking together biochemical and tumoral effects because only the absence of both responses might be considered as a poor response or resistance. This latter evidence seems to occur in 25% of treated patients after 12 months of currently available long-acting SA.
