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Turner syndrome (TS) has been included for several years among the indications for GH treatment, generally with satisfactory outcomes. Nevertheless, the long-term effects of this treatment in non-GH deficient patients are not fully known. The incidence of thyroid carcinoma is rare in patients during childhood, it is unusual to find this neoplasia in children under sixteen years old. This article reports the cases of two Spanish patients with papillary thyroid carcinoma after GH treatment for TS. Recent studies have indicated a possible relationship between the GH-IGF axis and the pathogenesis of neoplasias, questioning the chance association of these two pathologies. In line with this, we detected GH receptor expression in the papillary carcinoma cells. Long-term prospective studies are required to clarify the possible effects of GH treatment on the risk of neoplasia.

Elevated glucocorticoid (GC) levels produce a marked impairment in somatic growth in both rodents and primates. In addition, GC play an important role in the regulation of growth hormone (GH) synthesis and secretion. Blunted GH response to stimulation tests in conditions of chronic exposure to excessive cortisol secretion or administration are well documented. In contrast, acute administration of GC to normal human subjects induces a transient increase in plasma GH levels. This dual action of GC on GH secretion is probably due to the fact that they act at different loci; i.e. in the regulation of GH transcription and GHRH and somatostatin receptors at the pituitary level as well as GHRH, somatostatin and GH receptor gene expression at the hypothalamic level.

GH-releasing peptide (GHRP-6; His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) is a synthetic compound that releases GH in a specific and dose-related manner through mechanisms and a point of action that are mostly unknown, but different from those of GHRH. In man, GHRP-6 is more efficacious than GHRH, and a striking synergistic action occurs when both compounds are administered together. To explain such a synergistic effect, it has been postulated, but not proven, that GHRP-6 acts through a double mechanism, with actions exerted at the pituitary and the hypothalamic level. On the other hand, patients with the syndrome of GH deficiency due to perinatal pituitary stalk transection have any hypothalamic factor nonoperandi. The aim of the present study was 3-fold: 1) to further understand how relevant, if at all, the hypothalamic action of GHRP-6 is for GH regulation; 2) to evaluate whether GHRP-6 plus GHRH could be a suitable diagnostic tool in children with pituitary stalk transection; and 3) to compare these results with similar published studies performed in patients with hypothalamo-pituitary disconnection, who developed the disease as adults. Seven patients with GH deficiency and different degrees of panhypopituitarism due to perinatal pituitary stalk transection and 7 age- and sex-matched normal controls were studied. The subjects underwent 3 different tests on separate occasions, being challenged with GHRH (1 microgram/kg, iv), GHRP-6 (1 microgram/kg, iv), or GHRH plus GHRP-6. GH was analyzed as the area under the curve (mean +/- SE; micrograms per L/90 min). In normal subjects, GH secretion was 1029 +/- 202 after GHRH treatment, 1221 +/- 345 after GHRP-6, and 3542 +/- 650 after GHRH plus GHRP-6; the latter value was significantly (P < 0.05) higher than the secretion elicited by GHRH or GHRP-6 alone. In the group of patients with perinatal pituitary stalk transection, the level of GH after GHRH treatment was 116 +/- 22 and was even more reduced (P < 0.05) after GHRP-6 treatment (37 +/- 8). After GHRH plus GHRP-6, GH secretion in those patients was 177 +/- 27, significantly higher (P < 0.05) than the secretion induced by either GHRH or GHRP-6 alone. Individually examined, none of the patients tested with the most potent stimulus known to date (GHRH plus GHRP-6) exhibited GH secretion greater than 5 micrograms/L.(ABSTRACT TRUNCATED AT 400 WORDS)

Eighteen children with short stature were evaluated for growth hormone (GH) reserve after pharmacological tests and a single iv injection of GH-RP-6. These children were divided into two groups: 10 were diagnosed as having idiopathic GH deficiency by classical stimulation tests (group A) and the remaining 8 (group B) were considered growth-retarded children with normal GH secretion, following conventional stimulation, but reduced endogenous GH secretion. The results were compared with a group of 12 normal children. As a group, patients in group A showed a lower GH response to GH-RP-6, while patients in group B had a similar response as normal controls. However, on an individual basis, a considerable degree of overlapping in responses among the three groups was evident. These data indicate that, on an individual basis, GH-RP-6 testing is not of diagnostic value in children suspected of having idiopathic GH deficiency.

At present, four main types of serotonin (5-HT) receptors have been identified in the brain (5-HT1, 5-HT2, 5-HT3, and 5-HT4). In addition, the 5-HT1 have been further subclassified. We have taken advantage of a new selective 5-HT1D receptor agonist 3-[2-(dimethylamino)ethyl]-N-methyl-1H-indole-5-methanesulfonamide succinate, Sumatriptan, to evaluate the role of 5-HT1D receptors on GH secretion. To this end, several tests with or without sumatriptan were undertaken in normal prepubertal children. Furthermore, we assessed the effect of Sumatriptan on basal GH secretion and the GH response to GHRH in obese children. In normal children, Sumatriptan administration (3 mg, sc) resulted in an increase in basal GH levels at 30 min (7.7 +/- 1.5 micrograms/L; P < 0.05) and increased GH responses to GHRH (47.3 +/- 6.4 vs. 29.6 +/- 9.7 micrograms/L; P < 0.05). The Sumatriptan-induced increase in GH responses to GHRH was dependent on the stimulus tested. Pretreatment with Sumatriptan did not modify the GH response to clonidine or pyridostigmine, as assessed by the peak GH response and the area under the curve. In contrast, it increased the GH response to arginine. In the obese subjects, the GH response to GHRH was reduced (7.3 +/- 1.0 vs. 29.6 +/- 9.7 micrograms/L at 30 min) compared to that in control children (P < 0.05). Sumatriptan administration did not alter the basal GH value (peak GH, 1.7 +/- 0.3 micrograms/L at 30 min). However, Sumatriptan administration clearly increased the effect of GHRH, resulting in a GH peak of 14.6 +/- 3.1 micrograms/L at 30 min (P < 0.01). To assess the specificity of Sumatriptan on anterior pituitary hormone secretion, we studied its effect on TSH and PRL responses to TRH as well as LH-releasing hormone-induced LH and FSH secretion. Administration of Sumatriptan did not alter the response of any of these hormones. Our results indicate that 5-HT1D receptors have a stimulatory effect on GH secretion, possibly by inhibiting hypothalamic somatostatin release.

Pharmacological tests are essential for the diagnosis of growth hormone (GH) insufficiency. Obesity is a pathological state associated with blunted GH response to all the classical stimuli tested. In the present study, three new pharmacological stimuli for GH reserve were evaluated in three groups of subjects: Normal, GH-insufficient and normal growing obese children. Dexamethasone provokes a clear GH-response in normal children, whereas the response in the other 2 groups of patients is significantly diminished. Galanin-induced GH-secretion is significantly higher in normal than in obese children. GHRP-6 causes a potent GH release in normal children, higher than in GH-insufficiency or obesity. The overlap shown between GH-insufficient patients and normal children reduces the usefulness of the tests. Similar to the classical stimuli, the response to these new tests is also decreased in obesity.

Objective: His-dTrp-Ala-Trp-dPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species including man. To further characterize the effects of GHRP-6 on GH secretion in normal human subjects, we assessed plasma GH levels following GHRP-6 administration in normal male adult subjects, normal female adult subjects at different stages of their menstrual cycle and in normal prepubertal male and female children. We also studied the influence of adrenergic pathways on GHRP-6 induced GH secretion in normal adult male subjects., Design: In a group of eight volunteers the following tests were carried out: GHRP-6 alone (1 microgram/kg i.v. at 0 minutes); propranolol (40 mg p.o. at -30 minutes) plus GHRP-6; and prazosin (3 mg p.o. at -120 minutes) plus GHRP-6. Another group of eight volunteers were studied with GHRP-6 as above; clonidine alone (300 mg p.o. at -60 minutes); and clonidine plus GHRP-6. A group of nine women were studied with 1 microgram/kg i.v. of GHRP-6 at 0 minutes, at different stages of their menstrual cycle. Finally, 12 children were studied with GHRP-6 using the same dose and methods as above., Patients: Twenty-five normal adult subjects (16 male and nine female) and 12 normal prepubertal children (six male and six female) wer studied after giving informed consent., Measurements: Plasma GH levels were measured by radioimmunoassay., Results: No differences in GH responses to GHRP-6 were found between children and normal adult male or female subjects at different stages of their menstrual cycle. Administration of propranolol and clonidine did not modify the GH responses to GHRP-6 in male adults. In contrast, prazosin administration induced an increase in plasma GH levels that was statistically different from that of GHRP-6 alone (. < 0.05 between area under curve)., Conclusions: GHRP-6 exerts a potent stimulatory effect on GH secretion in adults and children. Its effects, at least at the dose studied, are independent of sex and age. Noradrenergic pathways through alpha 2 adrenergic receptors are unlikely to influence this response.

His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GHRP-6) is a synthetic compound that releases GH in a dose-related and specific manner in several species, including man. To further characterize the effects and mechanism of action of GHRP-6 on GH secretion, we assessed in normal man plasma GH responses to that hexapeptide 1) alone and in combination with exogenous GH-releasing hormone (GHRH) administration, 2) in a state of high endogenous somatostatinergic tone after atropine administration, and 3) in a state of low endogenous somatostatinergic tone induced by the cholinergic receptor agonist drug pyridostigmine or after insulin-induced hypoglycemia. We found a similar increase in plasma GH levels after the administration of either GHRP-6 (1 microgram/kg) or GHRH (1 microgram/kg); the areas under the curve (AUC) were (mean +/- SEM) 973 +/- 181 and 821 +/- 139, respectively. After combined GHRP-6 and GHRH administration, GH responses were considerably greater than those after either compound alone (4412 +/- 842; P < 0.01). Administration of the cholinergic receptor antagonist atropine (1 mg, im) completely prevented the GH responses to GHRP-6 (area under the curve, 103 +/- 14 vs. 815 +/- 156, respectively). On the other hand, pyridostigmine, a cholinergic agonist, slightly increased GH responses to GHRP-6 (P < 0.01 when comparing the AUC after pyridostigmine administration of 1571 +/- 151 and the AUC after administration of GHRP-6 alone of 815 +/- 156). Finally, combined GHRP-6 and insulin administration induced a much greater increase in plasma GH levels (AUC, 4047 +/- 327) than insulin alone (1747 +/- 229; P < 0.05) or GHRP-6 alone (1248 +/- 376; P < 0.05). Our results lend support to the view that GHRP-6-induced GH secretion is exerted through a non-GHRH-dependent mechanism. Furthermore, the fact that enhancement of somatostatinergic tone with atropine completely prevented the GH responses to GHRP-6, while pyridostigmine and insulin-induced hypoglycemia, which increased plasma GH levels by inhibiting hypothalamic somatostatin release, increased the same response suggest that although GHRP-6-induced GH secretion is dependent on the endogenous somatostatinergic tone, the stimulatory effect of GHRP-6 on plasma GH levels is not mediated by a change in hypothalamic somatostatinergic tone.

The efficacy and safety of a 12-month treatment with recombinant human growth hormone from mammalian cells (r-hGH, Saizen) in growth hormone neurosecretory dysfunction (GHND) are evaluated in this study. r-hGH was administered subcutaneously, at a dosage of 0.5 IU/kg/week divided into 6 equal daily doses. A total of 16 (12 M and 4 F) poorly growing patients, height -2.3 SD or more below the mean for chronological age and sex, were included in the study. r-hGH therapy significantly increased the growth velocity; from 3.57 +/- 0.85 cm/year, before therapy, to 7.09 +/- 2.29 cm/year after 12 months (p less than 0.001). Patients' height SD score rose from -3.40 +/- 0.84 SDS to -2.98 +/- 0.69 SDS (p less than 0.01). Somatomedin C increased significantly from a baseline value of 0.59 +/- 0.32 U/ml to 1.26 +/- 0.66 U/ml after therapy (p less than 0.01). Finally, r-hGH therapy improved the pretreatment adult height prediction; from an initial prognosis of -2.66 +/- 0.79 SDS to -2.17 +/- 0.81 SDS after treatment (p less than 0.01). No side effects or adverse reactions were observed during treatment. Anti-r-hGH antibody formation was not found in any of the patients included in the study.