Search PubMed⌕ Search

Biomedical subjects

J Alcañiz

Publications and source records attributed to J Alcañiz.

10 recordsLinked to original sources

Serum growth hormone-binding protein is decreased in prepubertal children with idiopathic short stature.

The causes for growth failure in children with idiopathic short stature (ISS) are not definitely established. Peripheral GH resistance due to changes at the level of the GH receptor has been suggested as one of the most probable explanation. In this study, we have selected a group of prepubertal children with ISS to evaluate the GHBP/receptor status by measuring the GH binding protein (GHBP) activity in plasma. Thirty prepubertal children with ISS (18 boys and 12 girls; age range: 4.79 to 11.33 yr) and twenty age-matched children with normal growth (11 boys and 9 girls) were studied. The ISS group presented growth retardation of -2.3 +/- 0.43 SD score (mean +/- SD) and normal GH secretion. Plasma IGF-I levels were below or in the low normal range (mean +/- SD: 136.3 +/- 62.3 micrograms/l, a concentration that was significantly different from IGF-I levels in the normal group (mean +/- SD: 187 +/- 57.5 micrograms/l p < 0.005). Plasma GHBP activity using a GH-binding/gel chromatography assay showed significantly lower values in ISS group (mean +/- SD: 7.17 +/- 1.5%) as compared with those of the control group (mean +/- SD: 12.02 +/- 2.04%; p < 0.001). There were no significant age- or sex-related differences in GHBP values in either group. The decreased GHBP levels observed in this group of children with ISS suggest that they may present a certain degree of GH insensitivity, probably due to a defect at the GH-receptor level.

Body Height↗

Usefulness of thyrotropin-releasing hormone test, SMS 201-995, and bromocriptine in the diagnosis and treatment of gonadotropin-secreting pituitary adenomas.

Five patients with gonadotropin-secreting pituitary adenomas were studied. The utility of gonadotropin response to TRH stimulation in the diagnosis and follow-up of these tumors was evaluated, as well as the effects of somatostatin analogue SMS 201-995 and bromocriptine on gonadotropin release. Three patients had FSH and LH secreting adenomas while the other two tumors secreted FSH and alpha-subunit. Transsphenoidal resection of the pituitary adenomas were performed in all patients. Following preoperative TRH administration (400 micrograms i.v.), marked increases were observed in FSH levels in two cases, in LH levels in three and in alpha-subunit in one. The FSH and LH responses to t.his stimulus persisted in the same patients after surgery. Following acute bromocriptine administration (5 mg orally), FSH was reduced in all cases by 19% to 46%, LH in three cases by 50-67% and alpha-subunit in one by 33%. In patient no. 5, with persistent high FSH levels in the immediate postoperative period, long-term bromocriptine treatment was administered (15 mg/d orally), resulting in normalization of FSH levels 6 months later, although the size of the tumor was not reduced. After acute SMS 201-995 administration (100 micrograms sc) FSH decreased in two cases by 38% and 76%, LH in three by 30-56% and alpha-subunit in one by 20%. We conclude that gonadotropin response to TRH stimulation is useful in the diagnosis and follow-up of patients with gonadotroph adenoma. Bromocriptine and SMS 201-995 may be effective as coadjuvant treatment following surgery and radiotherapy in these patients, although long-term studies will be necessary to confirm these proposals.

Adenoma↗

Serum growth hormone-binding protein is unchanged in adult panhypopituitarism.

The role of GH in regulating GH-binding protein (GHBP) and GH receptor concentrations in humans is not clear. Studies performed mostly in children and on a minor scale in adults are somewhat controversial. The key question as to whether GHBP levels are altered in hypopituitarism before GH treatment is instituted remains unanswered. In this study, we have selected a severely GH-deficient group of adult patients with panhypopituitarism, acquired as a result of surgery and irradiation of hypothalamic-pituitary tumors, to evaluate the GHBP/receptor status by measuring GHBP activity in plasma. Twenty panhypopituitary patients (8 males and 12 females; age range, 20-74 yr) and 20 age (22-68 yr)- and sex-matched normal subjects were studied. GH deficiency was confirmed by insulin-induced hypoglycemia and arginine infusion tests; the peak GH response was less than 2 micrograms/L. Plasma insulin-like growth factor-I levels were below or in the low normal range (mean +/- SD, 88.3 +/- 53.6 micrograms/L) and were significantly different from insulin-like growth factor-I (IGF-I) levels in the normal group (mean +/- SD, 189 +/- 49.8 micrograms/L; P < 0.01). Plasma GHBP activity, measured using a GH-binding/gel chromatography assay, showed similar values in the GH-deficient group (mean +/- SD, 14.1 +/- 3.83%) and the control group (mean +/- SD, 13.7 +/- 3.79%), with no statistically significant difference. Neither the intra- nor intergroup comparison of GHBP levels according to age and sex showed statistically significant differences or age trends. In the light of these data and considering that GHBP activity in plasma probably reflects the GH receptor status in tissues, we may assume that the GH receptor was unaffected by chronic GH deficiency. These findings also support the previously reported concept that the GHBP/receptor level is a relatively fixed determinant of growth, established individually and independently of GH secretory status in early life, perhaps on a genetic basis.

Adult↗

Treatment of invasive growth hormone pituitary adenomas with long-acting somatostatin analog SMS 201-995 before transsphenoidal surgery.

The purpose of this study was to determine whether the long-acting somatostatin analog SMS 201-995 (octreotide) shrinks growth hormone (GH)-secreting adenomas and improves the results of subsequent transsphenoidal surgery. Ten previously untreated active acromegalic patients (nine women and one man) with invasive tumors were treated with SMS 201-995 (100 micrograms subcutaneously every 8 hours) for 6 weeks prior to transsphenoidal surgery. The clinical activity, mean GH secretion, insulin-like growth factor (IGF)-I concentration, and tumor volume were measured under basal conditions and on Days 14, 28, and 42 of treatment. The SMS 201-995 improved the symptoms of acromegaly in all patients. Mean levels of both GH and IGF-I (+/- standard deviation) were significantly decreased by Day 14 (from 92.9 +/- 30.5 to 44.9 +/- 20.3 micrograms/liter and from 10.6 +/- 7.4 to 5.9 +/- 2.6 U/ml, respectively), after which there were only slight further decreases. Six (60%) of the 10 patients experienced tumor shrinkage ranging from 9% to 78% (mean 30%). When it occurred, tumor shrinkage was significant by Day 14 (7.9 +/- 6.3 to 6.5 +/- 5.1 cu cm) and no further shrinkage was achieved by longer administration. Transsphenoidal surgery reduced postoperative GH levels to less than 2 micrograms/liter and IGF-I to less than 1.5 U/ml in six patients (60%). This percentage of cure is higher than expected from the literature and the authors' previous experience. However, an investigation of the influence of this drug on several parameters, such as reduction of tumor size or GH and IGF-I concentrations, has failed to prove any relationship. Only pretreatment size of the tumor was of predictive value with respect to the surgical outcome.

Acromegaly↗

Prolactin and deficient luteal function.

The possibility of prolactin-dependent subfertility was investigated in a group of 8 women, with luteal insufficiency exhibiting moderately elevated plasma prolactin (PRL) levels and/or galactorrhea. Another group of 10 normal women volunteers served as the control group. A "luteal index" was elaborated by integration of the area below the curve of plasma progesterone (P) values recorded throughout the postovulatory period. The calculated index for normal women was 177 +/- 35 (SD) expressed as [(ng/ml) x time], and the value of 107 (--2 SD) was adopted as the lower limit of normality (97.5% confidence limit). All 8 patients had luteal indexes (range 20--105) below the established limit. Therapy with bromocriptine (CB 154), 5 mg/day, suppressed PRL to normal levels and prolonged the postovulatory hyperthermic phase in 6 out of 8 women. This was accompanied by an improvement in the luteal index, and 5 women conceived. It is concluded that prolactin may interfere with normal progesterone synthesis by the corpus luteum, as demonstrated by the prompt restoration of fertility by bromocriptine treatment in women with regular cycles and inadequate luteal function.

Adult↗