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Biomedical subjects

F Camanni

Publications and source records attributed to F Camanni.

At least 127 records · Page 7Linked to original sources
PubMed1994

Growth hormone-releasing activity of growth hormone-releasing peptide-6 is maintained after short-term oral pretreatment with the hexapeptide in normal aging.

The reduced activity of the growth hormone (GH)-insulin-like growth factor I (IGF-I) axis in aging may contribute to changes in body composition. As this GH insufficiency is due to hypothalamic pathogenesis, the availability of GH-releasing peptides (GHRPs), such as GHRP-6 (His-D-Trp-Ala-Trp-D-Phe-Lys-NH2) which is active even after oral administration, might be useful to restore it. The aim of our study was to verify the effectiveness of oral administration of GHRP-6 in normal elderly subjects and to investigate whether its GH-releasing activity is maintained or vanishes after short-term oral treatment. Seven normal elderly women (aged 65-82 years) were studied. The effect of oral administration of 300 micrograms/kg GHRP-6 on GH secretion was investigated before and after 4 days of treatment with the hexapeptide given twice daily. The GH response to the maximal effective dose of GHRH (1 microgram/kg i.v.) also was studied. Before treatment, oral administration of 300 micrograms/kg GHRP-6 elicited a clear GH rise (peak 10.7 +/- 3.3 micrograms/l; AUC 353.1 +/- 90.6 micrograms.l-1.h-1), which was significantly higher (p < 0.01) than that induced by intravenous GHRH (peak 5.1 +/- 1.5 micrograms/l; AUC 106.5 +/- 43.9 micrograms.l-1.h-1). After 4 days of treatment with GHRP-6, the GH response to the hexapeptide was maintained, with a trend towards an increase (peak 16.8 +/- 2.9 micrograms/l; AUC 499.8 +/- 107.2 micrograms.l-1.h-1). The IGF-I levels were not increased significantly after treatment (77.1 +/- 8.4 vs 84.1 +/- 12.2 micrograms/l).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1993

Hormonal and radiological effects of megavoltage radiotherapy in patients with growth hormone-secreting pituitary adenoma.

Nineteen acromegalic patients (12 females and 7 males, aged 24-71 yr) were studied for 1-6 yr after radiotherapy (RT), administered by X-rays (18 MeV) by linear accelerator, with parallel opposite beams (doses 45-50.4 Gy, 1.8 Gy daily). Basal GH levels gradually decreased from 6.3-76.2 micrograms/L (mean +/- SE, 27.8 +/- 4.9) to 0.3-43.4 micrograms/L (11.7 +/- 3.6 micrograms/L; p < 0.005) at the last assessment. The earliest significant decrease was observed after one yr (14.9 +/- 3.8 micrograms/L; p < 0.005). Significant changes were observed also in IGF-I values (basal values 1.93-6.85 mU/ml, 3.22 +/- 0.30; last assessment 0.55-4.57 mU/mL, 1.58 +/- 0.31; p < 0.01). The earliest significant decrease of IGF-I values was observed after 2 yr (1.61 +/- 0.16 mU/ml; p < 0.005). GH levels < 5 micrograms/L together with normal IGF-I values were observed in 9 patients, 2-4 yr after RT. No changes were observed in PRL values, either in patients with pretreatment normal or elevated PRL levels. The CT and/or MRI picture of macroadenoma disappeared after 6-12 months in 3/12 patients. Moreover, a reduction (20-55%) in the diameter of the adenoma was shown after 6-36 months in other 4 patients. After RT 5/16 (31%) patients required cortisol and 4/19 (21%) thyroid replacement therapy. In 2/3 men a gonadal impairment was shown, that did not occur in the three female patients with normal gonadal function before RT.(ABSTRACT TRUNCATED AT 250 WORDS)

Acromegaly↗
PubMed1993

Therapeutical doses of salbutamol inhibit the somatotropic responsiveness to growth hormone-releasing hormone in asthmatic children.

In humans beta-adrenergic receptors mediate an inhibitory effect on somatotropic function, likely via stimulation of hypothalamic somatostatin release. Accordingly, salbutamol (SAL), a beta 2-agonist, given iv abolishes the GH response to GH-releasing hormone (GHRH) in adults. Taking into account that in bronchial asthma an alteration in the beta-adrenergic neural control of airways has been hypothesized, we aimed to verify whether, in asthmatic children, beta-adrenergic activation inhibits or not GH secretion. To this goal, we studied the effect of therapeutical doses of SAL on GH response to GHRH in 15 asthmatic children (12 M and 3 F, 5.9-11.1 yr, pubertal stage I-II). All children underwent a GHRH test (1 microgram/kg iv). Moreover, in 7 children (group A), SAL was administered orally (0.125 mg/kg) 1 h before GHRH, while in 8 (group B) by inhaled aerosol (2 mg) 30 min before GHRH. Oral SAL (group A) abolished the GHRH-induced GH rise (AUC, mean +/- SE 165.1 +/- 33.3 vs 959.9 +/- 158.1 micrograms/L/h; p < 0.03). In group B, the GH response to GHRH was only blunted by inhaled SAL (938.6 +/- 284.6 vs 1378.8 +/- 315.6 micrograms/L/h; p < 0.02). In conclusion, our data show that in asthmatic children, therapeutical doses of SAL exert a marked inhibitory effect on GH secretion. Further studies are needed to exclude detrimental effects of chronic treatment with beta 2-agonists on GH secretion and growth velocity in asthmatic children.

Administration, Oral↗
PubMed1993

Repetitive GHRH administration fails to increase the response to GHRH in obese subjects. Evidence for a somatotrope defect in obesity?

Spontaneous GH secretion as well as GH response to several stimuli including GHRH have been shown to be reduced in obesity. To clarify the pathogenesis underlying these alterations, in six obese patients (3 males and 3 females, age 20-44 yrs, BMI = 42.1 +/- 2.2) on unrestricted diet we studied the effect of 8 day GHRH pretreatment (1 micrograms/kg iv each day) on the acute somatotropic response to the neurohormone administered both alone and combined with arginine (ARG, 0.5 g/kg iv infused from 0 to 30 min) which likely inhibits the release of hypothalamic somatostatin. Before treatment the GH response to GHRH (AUC: 231.9 +/- 106.4 micrograms/l/h) was potentiated (p < 0.001) by ARG (932.6 +/- 166.2 micrograms/l/h). However, the GH responses to the neurohormone both alone and combined with ARG were lower (p < 0.02 and 0.002, respectively) than in normals (712.4 +/- 111.6 and 2608.3 +/- 453.2 micrograms/l/h, respectively). After repetitive GHRH administration, in obese subjects baseline GH and IGF-I levels were unchanged. Also the GH responses to GHRH both alone (217.3 +/- 68.1 micrograms/l/h) and combined with ARG (756.3 +/- 202.9 micrograms/l/h) were not modified. In conclusion, our data demonstrate the failure of GHRH pretreatment to improve the somatotrope hyporesponsiveness to GHRH both alone and combined with ARG suggesting the existence of a somatotropic defect in obesity.

Adult↗
PubMed1993

Long term therapy of patients with macroprolactinoma using repeatable injectable bromocriptine.

The efficacy and tolerability of a long term treatment (21-53 months; mean, 36) with a new injectable form of bromocriptine (Parlodel LAR, Sandoz) was assessed in 13 patients (9 males and 4 females, aged 14-68 yr) with macroprolactinoma. Parlodel LAR was administered deeply im once monthly, with 50 mg as the first dose. Depending on the patient's tolerability to the drug and the PRL levels, the dose was individually progressively increased to 100 mg (2 patients), 150 mg (3 patients), or 250 mg (4 patients). Persistently normal PRL levels were recorded in 4 patients even after the first injection and in 5 other patients treated with higher doses of Parlodel LAR (2 patients with 100 mg/month; 3 patients with 150 mg/month). The remaining 4 patients who were treated with 250 mg/month had a marked reduction of PRL levels (72-94%), but did not reach normalization. Two patients treated with 150 mg/month maintained normoprolactinemia in spite of subsequent dose reduction of Parlodel LAR to 50-100 mg/month. In 1 patient PRL plasma concentrations remained within normal range for 3 months after the transitory discontinuation of Parlodel LAR at the end of the first year of therapy. Regular menses were resumed in 1 of 3, and galactorrhea disappeared in 2 of 3 women. All male patients had a return of libido and potency; gynecomastia disappeared in both male patients, and galactorrhea disappeared in 1 of 2 male patients. Visual fields improved in all 5 patients; complete normalization occurred in 2 of them. A consistent shrinkage of the macroadenoma (23-100%) at different times after therapy was shown by magnetic resonance imaging and/or computed tomography in 12 of 13 patients. Six patients reported mild/moderate side-effects (nausea, vomiting, orthostatic hypotension, or dizziness) within 24 h after the first injection. In 2 of these patients, mild side-effects persisted for 1-2 days after the first 3-6 injections, and in one patient, mild nausea was reported after each injection. In conclusion, in patients with macroprolactinoma, Parlodel LAR is an effective and well tolerated preparation of bromocriptine when administered once a month.

Adolescent↗
PubMed1993

Somatotropic function in short stature: evaluation by integrated auxological and hormonal indices in 214 children. The Italian Collaborative Group of Neuroendocrinology.

GH secretion was evaluated in 214 children and adolescents (age, 5-16 yr; 160 males and 54 females) with short stature (height, < or = 5th percentile) by assessing mean spontaneous overnight GH concentration (normal values, > or = 3 and 3.9 micrograms/L for prepubertal and pubertal subjects, respectively) and responsiveness to stimulation with GH-releasing hormone combined with pyridostigmine (normal peak values, > or = 20 micrograms/L). Plasma insulin-like growth factor-I (IGF-I) was also measured. According to their GH secretory status, children were grouped as follows: group I, 154 subjects with normal spontaneous and stimulated GH (43 slow-growing and 111 normally growing); group II, 39 subjects with low spontaneous, but normal stimulated, GH (27 slow-growing and 12 normally growing); group III, 18 slow-growing subjects with low spontaneous and stimulated GH; and group IV, 3 subjects with normal spontaneous, but low stimulated, GH. The following conclusions were drawn. 1) Forty-five slow-growing subjects (21% of the total sample) had GH deficiency; 27 (12.6%) belonged to group II (with a preserved GH pituitary reserve, denoting a hypothalamic dysfunction) and 18 (8.4%) to group III (with a reduced GH pituitary reserve). 2) Forty-three slow-growing children in group I had normal GH secretion but low mean IGF-I, which may indicate nutritional problems or a biologically hypoactive GH molecule. 3) The remaining 111 subjects in group I (52%), with normal growth rate, but low mean parental height, were considered as having familial and/or constitutional short stature. GH responses after pyridostigmine plus GH-releasing hormone were normal in all children with a normal growth rate. These findings show that besides clinical evaluation, the assessment of spontaneous GH secretion, GH pituitary reserve, and IGF-I concentration allows proper pathophysiological characterization of short stature. By this approach, the frequency of GH deficiency in our sample was higher than commonly thought.

Adolescent↗
PubMed1993

Comparison of the potentiating effect of pyridostigmine, arginine and propranolol on the GHRH-induced GH release in short children.

The effect of pyridostigmine (60 mg orally), arginine (0.5 g/kg iv) and propranolol (PROP, 40 mg orally) on GHRH (1 microgram/kg iv)-induced GH release was studied in seven short children. Pyridostigmine and arginine induced a similar potentiating effect on GHRH-induced GH rise (Peak, mean +/- SEM: 56.9 +/- 12.8 and 48.6 +/- 8.5 micrograms/L, respectively vs 12.3 +/- 1.6 micrograms/L; p < 0.05). Combination of GHRH with propranolol induced an increase of GH that was significant only with regard to peak (28.9 +/- 8.4 micrograms/L) but not to AUC. However, GH rises observed after GHRH combined with PD or ARG did not significantly differ from that recorded after coadministration of GHRH and PROP both for peak and AUC. Our results confirm that pyridostigmine and arginine have a striking potentiating effect on the GHRH-induced GH rise in children and show that the tests with GHRH + PD and GH + H + ARG are ore reliable than that with GHRH + PROP to explore the secretory capacity of somatotroph cells.

Adolescent↗
PubMed1992

Arginine abolishes the inhibitory effect of glucose on the growth hormone response to growth hormone-releasing hormone in man.

Acute hyperglycemia inhibits the growth hormone (GH) response to several stimuli including growth hormone-releasing hormone (GHRH), likely acting by stimulation of endogenous somatostatin release. The aim of our study was to verify whether arginine ([Arg] 30 g intravenously [IV] in 30 minutes), a well-known GH secretagogue likely acting via inhibition of hypothalamic somatostatin release, counteracts the inhibitory effect of oral glucose (OG) administration (100 mg orally) on the GH response to GHRH (1 micrograms/kg IV bolus) in seven normal subjects (aged 20 to 30 years). The GH response to GHRH (peak, 11.6 +/- 1.8 micrograms/L) was inhibited by previous OG load (peak, 7.4 +/- 0.8 micrograms/L; P less than .02 v GHRH alone) and potentiated by Arg coadministration (peak, 36.2 +/- 8.8 micrograms/L; P less than .03 v GHRH alone). The potentiating effect of Arg on the GHRH-induced GH increase was unaffected by previous OG load (peak, 30.4 +/- 6.9 micrograms/L). In conclusion, our results show that Arg abolishes the inhibitory effect of OG administration on the GHRH-induced GH response in man. These data, although indirect, suggest that both acute hyperglycemia and Arg act at the hypothalamic level, stimulating and inhibiting, respectively, the release of somatostatin.

Administration, Oral↗
PubMed1992

Interactions of galanin and arginine on growth hormone, prolactin, and insulin secretion in man.

Galanin (GAL), a 29 amino acid neuropeptide, is known to increase both basal and growth hormone-releasing hormone (GHRH)-induced growth hormone (GH) secretion while not significantly increasing prolactin (PRL) secretion in man. GAL is also endowed with an inhibiting effect on glucose-stimulated insulin release in animals, but not in man. We studied the effect of GAL (80 pmol/kg/min infused over 60 minutes) on the arginine- (ARG, 30 g infused over 30 minutes) stimulated GH, PRL, insulin, and C-peptide secretion in eight healthy volunteers (age, 20 to 30 years). GAL induced an increase of GH (GAL v saline, area under curve [AUC], mean +/- SEM: 316.5 +/- 73.9 v 93.2 +/- 20.9 micrograms/L/h, P less than .05), but failed to modify both PRL and insulin secretion. GAL enhanced the ARG-induced stimulation of both GH (1,634.1 +/- 293.1 v 566.9 +/- 144.0 micrograms/L/h, P less than .02) and PRL secretion (1,541.9 +/- 248.8 v 1,023.8 +/- 158.7 micrograms/L/h, P less than .02). On the contrary, GAL blunted the ARG-stimulated insulin (816.3 +/- 87.7 v 1,322.7 +/- 240.9 mU/L/h, P less than .05), as well as C-peptide secretion (105.1 +/- 9.8 v 132.8 +/- 17.3 micrograms/L/h, P less than .02). ARG administration induced a transient increase of glucose levels (P less than .01 v baseline) followed by a significant decrease (P less than .05 v baseline). This latter effect was prevented by the coadministration of GAL. In conclusion, these results show that in man GAL potentiates the GH response to ARG, suggesting that these drugs act at the hypothalamic level, at least in part, via different mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Arginine potentiates but does not restore the blunted growth hormone response to growth hormone-releasing hormone in obesity.

A blunted growth hormone (GH) response to several stimuli, including growth hormone-releasing hormone (GHRH), has been shown in obesity. Arginine (ARG) has been demonstrated to potentiate the GHRH-induced GH increase in normal subjects, likely acting via inhibition of hypothalamic somatostatin release. To shed further light onto the mechanisms underlying the blunted GH secretion in obesity, we studied the effect of ARG (0.5 g/kg infused intravenously [IV] over 30 minutes) on both basal and GHRH (1 micron/kg IV)-stimulated GH secretion. Eight obese subjects (aged 26.4 +/- 3.9 years; body mass index, 39.0 +/- 1.9 kg/m2) and eight normal control volunteers (aged 27.0 +/- 1.7 years; body mass index, 22.3 +/- 0.5 kg/m2) were studied. In obese subjects, the GH response to both GHRH and ARG was lower (P less than .01 and P less than .002, respectively) than in controls. ARG potentiated the GH response to GHRH in obese patients (P less than .0003). However, in these patients, the GH secretion elicited by GHRH, even when coadministered with ARG, persisted at reduced levels (P less than .005) when compared with controls. Basal insulin-like growth factor-1 (IGF-1) levels did not significantly differ in obese subjects and in normal subjects (161.1 +/- 37.0 v 181.0 +/- 12.8 micrograms/L). In conclusion, ARG enhances the blunted GHRH-induced GH increase in obese patients, but the GH responses to ARG alone and to ARG + GHRH persist at lower levels than in normals. Thus, our results suggest the existence of a reduced pituitary GH pool in obesity.

Adolescent↗
PubMed1992

Normal development of lymphokine activated killing (LAK) in peripheral blood lymphocytes from hyperprolactinemic patients.

The effect of prolactin on the interleukin 2 (IL2)-driven development of Lymphokine Activated Killing (LAK) by normal PBL and by PBL from hyperprolactinemic patients was investigated. Concentrations of PRL corresponding to the physiological serum levels of the hormone and to the Kd of the PRL receptors on NK cells (6-20 ng/ml, 0.3-1 nM) had no effect on the generation of LAK activity by normal PBL, whereas 100-200 ng/ml were slightly, although significantly, inhibitory. By contrast, PBL from 16 hyperprolactinemic patients developed levels of LAK activity comparable with those generated by PBL from age- and sex-matched normoprolactinemic donors.

Adolescent↗
PubMed1992

Inhibition by salbutamol of GHRH-induced GH release in type 1 diabetes mellitus.

Patients with type 1 diabetes mellitus (IDDM) show augmented GH secretion, which is implicated in the pathogenesis of microvascular complications. On the other hand, it is well known that beta-adrenergic receptors have inhibitory influence on GH secretion, likely via stimulation of hypothalamic somatostatin. Since the possibility of pharmacological suppression of GH secretion would be of value in IDDM, we investigated the effect of salbutamol (SAL, 4 mg orally at -60 min) on the GH response to GHRH (1 micrograms/kg iv at 0 min) in 6 well-controlled (mean HbA1c +/- SEM: 7.3 +/- 0.5%) patients with IDDM. Salbutamol was able to inhibit basal GH levels (p < 0.05) as well as to abolish the GHRH-induced GH rise. After SAL administration, a significant (p < 0.05) reduction of glucagon levels was also found. Our data show that the enhancement of beta 2 adrenergic activity by oral therapeutical doses of SAL inhibits basal and GHRH-stimulated GH secretion in patients with IDDM.

Adult↗
PubMed1992

Galanin reinstates the growth hormone response to repeated growth hormone-releasing hormone administration in man.

OBJECTIVE: To clarify the mechanism by which galanin, a 29-amino-acid peptide, increases GH secretion in man. DESIGN: We studied the GH-releasing effect of this neurohormone (galanin, 15 micrograms/kg) infused over 60 minutes after 120 minutes of saline, following a previous GHRH bolus (GHRH 1 microgram/kg i.v. at 0 minutes, galanin infused from 120 to 180 minutes) and coadministered with the second of two consecutive GHRH boluses (GHRH every 120 minutes, galanin infused from 120 to 180 minutes). PATIENTS: Fourteen healthy male subjects, aged 20-34 years, in two groups (group A, 20-31 years (n = 8); group B, 25-34 years (n = 6)) were studied. MEASUREMENT: Blood samples were drawn every 15 minutes of 255 minutes. Serum GH was measured in duplicate by IRMA. Statistical analysis of the data was carried out by non-parametric ANOVA test. RESULTS: The GH response to galanin infused 120 minutes after saline overlapped with that induced by the neuropeptide infused following previous GHRH bolus (AUC, mean +/- SEM: 317.3 +/- 73.2 vs 326.8 +/- 54.2 micrograms/l/h). The GH-releasing effect of the second GHRH bolus (126.9 +/- 32.3 micrograms/l/h) was lower than that of the first one (503.4 +/- 41.3 micrograms/l/h; P = 0.0002). Galanin markedly enhanced the GH responses to the second GHRH bolus (1118.0 +/- 212.7 micrograms/l/h; P = 0.0002 vs second GHRH bolus alone) so that it did not significantly differ from the first one (710.9 +/- 107.8 micrograms/l/h). CONCLUSIONS: Our results show that the GH-releasing effect of galanin is not modified by GHRH pretreatment and that the neuropeptide reinstates the GH response to the repeated GHRH stimulation in man. They suggest that these effects are due to the inhibition of hypothalamic somatostatin release.

Adult↗
PubMed1991

Arginine reinstates the somatotrope responsiveness to intermittent growth hormone-releasing hormone administration in normal adults.

It is well known that in normal adults the growth hormone (GH) response to GH-releasing hormone (GHRH) is inhibited by previous administration of the neurohormone. In 7 healthy volunteers (age 20-34 years) we studied the GH responses to two consecutive GHRH boluses (1 microgram/kg i.v. every 120 min) alone or coadministered with arginine (30 g i.v. over 30 min). The GH response to the first GHRH bolus (area under the curve, mean +/- SEM: 506.3 +/- 35.1 micrograms/l/h) was higher (p = 0.0001) than that to the second one (87.1 +/- 14.6 micrograms/l/h). The latter response was clearly increased (p = 0.0001) by coadministering arginine (980.5 +/- 257.5 micrograms/l/h). When every GHRH bolus was combined with arginine a marked potentiation of GH response to both boluses was found. However, the second combined administration of arginine and GHRH induced a GH increase which was lower compared to the first one (p = 0.016). In conclusion, our results show that arginine potentiates the GHRH-induced GH secretion preventing the lessening of somatotrope responsiveness to the neurohormone alone. As there is evidence that this phenomenon is due to an enhanced somatostatin release, these findings give further evidence of a somatostatin-suppressing effect of arginine.

Adult↗
PubMed1991

Intranasal administration of neostigmine potentiates both intravenous and intranasal growth hormone (GH)-releasing hormone-induced GH release in short children.

Administration of cholinergic agonists increases both basal and GH-releasing hormone (GHRH)-induced GH secretion, probably acting via inhibition of endogenous somatostatin release. The aim of our study was to verify in two groups of children with idiopathic short stature the effect of intranasal administration of neostigmine (inNS; 3 mg), a cholinesterase inhibitor, on basal GH levels as well as on the somatotroph response to GHRH when the peptide was administered either iv (ivGHRH; 1 microgram/kg) or intranasally (inGHRH; 10 micrograms/kg). In group A (n = 6; age, 10.6-16.0 yr) inNS induced a significant GH increase [inNS vs. saline, area under the curve (AUC; mean +/- SEM), 263.7 +/- 60.2 vs. 73.8 +/- 3.1 micrograms/L.h; P less than 0.03] and potentiated the somatotroph response to ivGHRH (inNS with ivGHRH vs. ivGHRH, 1316 +/- 183.0 vs. 644.9 +/- 154.5 micrograms/L.h; P less than 0.03). In group B (n = 6; age, 11.5-15.9 yr) ivGHRH induced a GH rise clearly higher than that induced by inGHRH (604.2 +/- 154.3 vs. 137.1 +/- 28.2 micrograms/L.h; P less than 0.03). Administration of inNS induced a GH rise similar to that occurring after inGHRH (AUC, 239.2 +/- 69.5 micrograms/L.h) and markedly increased the inGHRH-induced GH response (482.4 +/- 103.6 micrograms/L.h; P less than 0.05 and 0.03 vs. inNS and inGHRH, respectively), so that it overlapped with that induced by ivGHRH alone. In conclusion, cholinergic agonists such as neostigmine are able to increase both basal and GHRH-induced GH secretion in short children even when given intranasally. Combined intranasal administration of neostigmine and GHRH (10 micrograms/kg) is able to induce a GH rise similar to that induced by ivGHRH alone (1 microgram/kg), suggesting the potential usefulness of this combination cocktail and route of administration for the treatment of short stature.

Administration, Intranasal↗
PubMed1991

Involvement of brain catecholamines and acetylcholine in growth hormone deficiency states. Pathophysiological, diagnostic and therapeutic implications.

A cohort of brain neurotransmitters, especially catecholamines and acetylcholine, play a crucial role in the control of neurosecretory growth hormone-releasing hormone (GH-RH)- and somatostatin (SS)-producing neurons, and hence growth hormone (GH) secretion. Stimulation of alpha 2-adrenoceptors or of muscarinic cholinergic receptors in the hypothalamus stimulates GH release, probably via stimulation of GH-RH and inhibition of somatostatin release, respectively. Additionally, stimulation of dopamine receptors is stimulatory to GH release, while activation of beta-receptors inhibits GH release via stimulation of hypothalamic somatostatin function. As a corollary, in GH deficiency states drugs affecting catecholaminergic and cholinergic functions may be exploited for diagnostic and/or therapeutic purposes, and may be useful for a better understanding of the underlying pathophysiology. Levodopa (L-dopa) [125 to 500mg orally], the physiological precursor of the catecholamines, administered either alone or in combination with carbidopa (50mg orally), to prevent its peripheral decarboxylation to dopamine, and/or the beta-adrenoceptor antagonist propranolol (0.75 mg/kg orally), and the alpha 2-adrenoceptor agonist clonidine (0.15 mg/m2 orally), are a fairly reliable stimulus of GH release. In normal subjects, however, false-negative GH responses and wide inter-individual variability may occur with these drugs. Additionally, the GH secretory response to these provocation tests is a poor predictor of endogenous 24-hour GH secretion, since levodopa or clonidine may elicit a response within normal limits in children of short stature with reduced 24-hour GH secretion and good responsiveness to GH therapy. The availability of GH-RH, a direct probe of pituitary somatotrophs, held out promise of unravelling the hypothalamic or pituitary origin of GH secretory disturbance. It soon became apparent, however, that this was not the case, because of the wide inter- and intraindividual variation in the GH response. However, the coadministration of GH-RH and muscarinic cholinergic agonists, for example pyridostigmine (which deprive the pituitary of hypothalamic SS inhibitory influences), is a useful diagnostic probe. In a large group of normal children and adolescents who received an intravenous injection of GH-RH, preceded by oral administration of pyridostigmine (60mg orally), none gave a false-negative response; this was also true for a group of short children with different forms of GH disturbances, in whom 8-hour nocturnal GH secretion was within normal limits. However, some false-negative responses occurred in children following testing with GH-RH, clonidine or pyridostigmine alone. Interestingly, the cut-off point for normality following pyridostigmine + GH-RH was as high as 20 ng/ml, while for the other provocation tests it is only 5 to 10 ng/ml. Responses lower than 20 ng/ml were present in all children with organic and most of the children with idiopathic GH deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetylcholine↗
PubMed1990

Long-term follow-up of 'cured' prolactinoma patients after successful adenomectomy.

The long-term follow-up (greater than or equal to 4 years) of clinical, hormonal and radiological aspects in 22 'cured' prolactinoma patients after adenomectomy was studied. Dynamic secretion of PRL and TSH was also evaluated, in order to identify the persistence of any underlying abnormality of hypothalamic pituitary control and to predict relapses. A relapse into hyperprolactinaemia was shown in 36% of patients 5-90 months (mean 46) after surgery. This was accompanied by reappearance of clinical symptoms but not by the radiological demonstration of the adenoma in any patients. A significant PRL rise after domperidone, a dopaminergic antagonist drug, was shown in cured patients after surgery (mean +/- SEM peak, 2977 +/- 645 mU/l) but this was markedly lower than that observed in control subjects (5732 +/- 440 mU/l). In fact, normal PRL increments were shown in only 6/16 (37%) patients. TSH hyper-responsiveness to domperidone normalized in only 46% of patients. Similar PRL responses to those obtained with domperidone were shown when a TRH test was given. A relapse into hyperprolactinaemia was observed in six of ten (60%) non-responders to domperidone and in four of seven (57%) non-responders to TRH, whereas six normal responders to domperidone and TRH had not relapsed at that time. Plasma PRL levels during pregnancy showed increments lower than those observed in normal pregnant women only in domperidone and TRH non-responder patients. These results indicate that a relapse into hyperprolactinaemia and a blunted PRL rise during pregnancy were present only in patients with persistently reduced PRL response to dynamic tests.

Adenoma↗