Effects of sumatriptan on growth hormone releasing hormone-stimulated growth hormone secretion in acromegaly.

Sumatriptan (SU), a specific 5-HT1D receptor agonist, was recently shown to be able to increase growth hormone (GH) levels in normals, but not in acromegalics, while no effect was seen on prolactine (PRL). SU is also able to produce an increase in GH response to growth hormone releasing hormone (GHRH) in prepubertal children. In this study we investigated whether SU administration influences GHRH-induced GH secretion in 8 acromegalics, and 6 age-matched normal volunteers, as a control group. We evaluated the effects of SU (6 mg s.c.) or placebo (PL) administration on GHRH (1 microgram/kg bw i.v.)-induced GH and PRL secretion. After SU priming the GH response to GHRH did not changed in acromegalics, but significantly decreased in controls, in comparison with that observed after PL plus GHRH. In acromegalics, no difference in GH peak was seen after SU plus GHRH and PL plus GHRH, nor was any difference seen in AUC between tests. In controls, no difference was seen in GH peaks, while SU priming significantly (P < 0.03) decreased the AUC 90-120 min of GH after GHRH administration. In acromegalics, SU did not change the slight GHRH-induced increase in PRL levels. Our study documents that 5-HT1 D receptors do not interfere with GHRH-stimulated GH secretion in acromegalic subjects. In normals, SU is able to decrease GH response to GHRH, thus confirming that 5-HT1D receptors are able to modulate GH secretion in normals.

Hexarelin is a stronger GH-releasing peptide than GHRH in normal cycling women but not in anorexia nervosa.

Anorexia nervosa (AN) is a chronic disease in which an enhanced GH response to GHRH, a paradoxic increase after TRH and LHRH, and low IGF1 levels may be present according to the patient's clinical state. It is well known that the GH hypersecretory state commonly found in the "acute phase" of AN is restored with weight gain. The new synthetic hexapeptide, Hexarelin (HEX), which is chemically similar to GH-releasing peptide 6, has recently been shown to possess a stronger GH-releasing activity than GHRH in humans and to share a synergistic effect with GHRH when administered intravenously. Indeed, HEX shows a slight cortisol and PRL-releasing activity. The aim of the study was to evaluate the effect of i.v. administration of old (GHRH) and new (HEX) GH-releasing peptides on GH, PRL and cortisol secretion in 9 AN patients in the "recovery phase" of the disease, after partial but significant weight gain. For controls we studied 7 normal cycling women. No significant difference in GH secretion after GHRH was found between AN and controls. GHRH was not able to release cortisol or PRL either in AN or controls. HEX produced a significantly (p < 0.05) higher GH peak in controls than in AN, while GH AUC was slightly but not significantly higher. Indeed, only in controls, HEX was a stronger GH-releasing peptide than GHRH. These findings could be explained by the fact that, in AN, GH secretion is already stimulated both by reduced IGF1 levels and by increased GHRH/somatostatin ratio. As reported in the literature, the action of HEX action is only slightly influenced by variations in somatostatin tone. It therefore appears likely that the absolute or relative GHRH increase present in AN could partially mimic the unknown hypothalamic factor necessary for HEX action on the hypophisis and that, following a structural modification of pituitary HEX receptors, GHRH would become able to bind to HEX receptors on somatotropic cells. Consequently, the pituitary cells would already be over-activated and so unable to respond maximally to HEX stimulation. Indeed, in AN, GHRH might play a role of negative modulation in the control of HEX action. Finally, in our study HEX was able to produce a persistent PRL release in controls but not in AN, thus suggesting that its action could be partially dependent on the estrogen milieu, while it stimulated cortisol secretion only transiently in the patients studied.

Lack of effect of desmopressin on ACTH and cortisol responses to ovine corticotropin-releasing hormone in anorexia nervosa.

Both arginine vasopressin (AVP) and corticotropin-releasing hormone (CRH) are involved in the release of ACTH in man. Desmopressin (DDAVP), a synthetic analogue of AVP, has been shown to have a CRH-like action (able to promote ACTH and cortisol release) in animals but not in normal man. Nevertheless, DDAVP is able to release ACTH and cortisol in ACTH-dependent Cushing's disease. We studied eight anorexia nervosa (AN) patients [as AN is a condition in which chronic activation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly reported] in a refeeding phase of the disease, to evaluate whether, after weight gain, ACTH and cortisol response to ovine corticotropin-releasing hormone (oCRH) [1 microgram i.v. DDAVP alone and as pretreatment to oCRH (1 microgram kg-1 BW i.v.)-induced secretion of ACTH and cortisol. We studied six normal women as control subjects. No significant differences in ACTH and cortisol responses to oCRH were found between AN patients and control subjects. DDAVP was not able to stimulate ACTH or cortisol release in AN patients or in control subjects, but in the latter it was able to significantly enhance (P < 0.05) ACTH [area under curve (AUC): 590.0 +/- 104.4 pmol L-1 120 min-1] and cortisol (AUC: 28899.0 +/- 6935.2 nmol L-1 120 min-1) responses to oCRH (ACTH AUC: 325.7 +/- 101.7 pmol L-1 120 min-1, cortisol AUC: 14197.4 +/- 2930.0 nmol L-1 120 min-1). The present data show that DDAVP does not stimulate ACTH and cortisol in AN patients or, as previously reported, in normal subjects. However, DDAVP is able to enhance ACTH and cortisol release after oCRH administration in normal subjects but not in AN patients. This finding could be due to a down-regulation of hypophyseal DDAVP V3 receptors in AN as a direct consequence of the hypercortisolaemic status usually present.

[Anorexia nervosa: a follow-up of nutritional, hormonal and psychiatric parameters]. / Anoressia nervosa: follow-up di parametri nutrizionali, ormonali e psichiatrici.

Well known is the need to treat "acute onset" Anorexia Nervosa in care units. Nevertheless even the "successfully treated" patients show a very high percentage of relapse. The aim of our study has been to revalue different clinical, nutritional (hemoglobin, transferrin, IGF1), hormonal (thyroid function, gonadotropins) and psychiatric (EDI: Eating Disorder Inventory Test) parameters in a group of nineteen women aged 20-34 years (median 27 years) admitted to our department 1-11 years (median 6 years) before for anorexia nervosa treatment. On admission their weight loss was -33% +/- 10% according to Ideal Body Weight (IBW); a "low T3 syndrome" was present and all the patients not treated with estro-progestins were amenorrhoic. After a long hospitalization (median 51 days) the patients showed a significant decrease in weight loss (25% +/- 6%; p < 0.01). At follow-up seventeen patients had a weight better than at discharge (13% +/- 12%; p < 0.01) and 9/17 patients non treated with estro-progestins had spontaneous menses. Nutritional (hemoglobin*: 13 +/- 0.2 g%, transferrin*: 313 +/- 57 mg%, IGF-1: 187 +/- 15 ng/ml) and hormonal (LH*: 9.4 +/- 1 mUI/ml, FSH*: 15 +/- 1.3 mUI/ml, T3: 1 +/- 1 ng/ml) parameters were significantly improved (*p < 0.01, p < 0.05) compared to those at admission (hemoglobin: 12 +/- 0.2 g%, transferrin: 218 +/- 58 mg%, IGF-1: 154 +/- 21 ng/ml, LH: 5.6 +/- 0.8 mUI/ml, FSH: 9.5 +/- 1 mUI/ml, T3: 0.8 +/- 1 ng/ml). The EDI test has shown a persistence of anorexic condition ("overt" or latent) in 2/3 of patients. This study confirms the endocrine and nutritional modifications of anorexia nervosa and underlines the persistence of psychiatric ones in a great number of patients including the "clinically cured", justifying long-term follow-up and the high percentage of disease relapse.

The effect of non-steroidal antiandrogen flutamide on luteinizing hormone pulsatile secretion in male-to-female transsexual subjects.

We evaluated LH pulsatile patterns before and 4 weeks after the oral administration of flutamide (750 mg/day) in 9 male-to-female transsexuals (age range 17-28 yr) requesting gender reassignment. Flutamide was given to explore the feedback role of androgens on the LHRH-LH unit in LH pulsatility in transsexuals. Seven normal age-matched men served as a control group, without receiving flutamide, due to ethical considerations. LH pulsatility was evaluated on samples collected every 15 min for 360 min. FSH, PRL, cortisol, SHBG and sex steroids were evaluated on pooled samples. LH pulses were analyzed by the Santen and Bardin algorithm, slightly modified. No differences in FSH, PRL, total- or free-testosterone, estradiol and SHBG levels were noted between transsexuals and controls. Normal circadian cortisol decline was observed in all subjects. Mean LH levels (p < 0.05) and LH pulses (p < 0.01) were significantly lower in transsexuals. Flutamide induced an increase in mean LH and testosterone levels (p < 0.01). After flutamide administration there was an increase in LH pulse frequency (P < 0.01) and the frequency and amplitude of LH pulses in transsexuals were restored to levels observed in controls. No differences in FSH, PRL or estradiol levels were found after flutamide. These data suggest that a decrease in LH pulse frequency could be an endocrine marker in male-to-female transsexuals. An increase in endogenous androgen negative feed-back could be speculated in these subjects. However, normal testosterone levels indirectly suggest that a normal that a normal qualitative LH secretion is maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Sumatriptan does not stimulate PRL and GH secretion in acromegaly.

OBJECTIVE: Serotoninergic receptors are involved in the regulation of PRL and GH secretion. We studied the effects of sumatriptan, a new 5-HT1D receptor agonist, on PRL and GH secretion in active acromegaly. EXPERIMENTAL DESIGN: After their informed consent, all subjects were submitted to sumatriptan or placebo administration in single blind and in a random order. The time interval between the tests was of 7 days. ENVIRONMENT: We examined all patients in the morning, after 12 hours of fasting. All subjects were in recumbent position during the tests. Pulse rate and blood pressure were monitored during the test. SUBJECTS: Eight acromegalics (42-65 years) and 10 age-matched (33-63 years) normal subjects. PROTOCOL: Blood samples were taken after needle insertion kept patent by slow saline solution infusion. PRL and GH secretion were evaluated after sumatriptan (6 mg sc) and placebo. Blood samples were taken before (45, 15 and 0 minutes) and every 15 minutes for 2 hours after sumatriptan or placebo administration. RESULTS: No significant changes in PRL secretion were observed after sumatriptan in both groups of subjects. A significant increase in GH levels after sumatriptan was observed in controls but not in acromegalics. An age-related negative trend in GH response to sumatriptan was observed in controls. CONCLUSIONS: Our study indicated that 5-HT1D receptors are not involved in PRL and GH secretion in middle-aged acromegalics.