Current treatment of acromegaly (surgery, radiation, and bromocriptine) is often unsatisfactory, and a sizeable proportion of patients with this disease continue to have GH hypersecretion after all therapeutic modalities have been exhausted. Fifteen patients with active acromegaly (8 previously treated and 7 newly diagnosed) were treated with the long-acting somatostatin analog SMS 201-995 (Sandoz; 50-250 micrograms, sc, every 6-8 h for up to 21 months). The mean daily plasma GH concentration was significantly suppressed in 13 patients, and it became normal in 10. Two patients, however, did not have GH suppression by SMS 201-995 treatment alone; in 1, a significant decline in mean daily GH was achieved after the addition of bromocriptine. As expected, suppression of GH secretion was associated with normalization of plasma somatomedin-C values and significant clinical improvement. Plasma GH responses to synthetic GHRH-(1-44) and TRH were either abolished or blunted by SMS 201-995. Thyroid function remained normal, and glucose tolerance did not change. Significant shrinkage of pituitary tumors occurred in 7 previously untreated and 2 previously treated patients. Side-effects were minimal. SMS 201-995 is an effective agent for the treatment of acromegaly. Further studies are necessary to establish guidelines for identification of non-responders and to examine the effect of preoperative tumor shrinkage on subsequent surgical outcome.
The gonadotropin secretory patterns of 22 sexually immature children were analyzed in detail to determine whether pulsatile secretion occurs before the onset of puberty. Eight endocrinologically normal children, 13 children with isolated GH deficiency, and 1 girl with 45X gonadal dysgenesis were divided into 2 groups according to bone age. Group A children had bone ages less than 10 yr, and group B had bone ages between 10-11.5 yr. Blood samples were drawn every 20 min for periods of 3-11 h during both the day and night; in addition, 12-h urine collections were made for gonadotropin determinations. Mean nocturnal concentrations of LH and FSH were significantly greater than daytime values in 8 of 15 and 5 of 15 children in group A and in 6 of 7 and 1 of 7 in group B, respectively. Nocturnal urinary excretion of LH and FSH was significantly greater in group A children. Eight children in group A, including 4 whose bone ages were less than 5 yr, and 4 group B children had discernible LH pulses. LH pulses were detected during the day and night in both groups. LH pulse amplitude was greater during the night in both groups, but was greatest in group B (A, 1.9 +/- 0.2 mIU/ml; B, 3.0 +/- 0.3 mIU/ml). In children who demonstrated pulsatile secretion, LH pulse frequency appeared to be similar during the day and night and was slightly faster in the older children (A, every 3 h; B, every 2 h). These studies demonstrated that LH is secreted in a pulsatile manner well before the onset of puberty. Furthermore, the gonadotropin secretory pattern characteristic of early puberty results from the amplification of an already existing circadian pattern of gonadotropin secretion.
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