Effect of adrenergic antagonism on the growth hormone, prolactin and cortisol response to a synthetic opioid agonist in man

The intravenous administration of 250 micrograms D-Ala2-MePhe4-Met-enkephalin-O-ol (DAMME) caused a marked increase in circulating growth hormone (GH) and prolactin (PRL), and a fall in cortisol, in 14 normal subjects. Neither the alpha 1-antagonist thymoxamine, nor the alpha 2-antagonist yohimbine, significantly altered the GH and PRL responses to DAMME, suggesting that in man the growth hormone- and prolactin-releasing effects of exogenous opioids are not mediated through adrenoceptor pathways. The fall in cortisol induced by DAMME was not affected by thymoxamine, but was significantly attenuated by yohimbine, indicating that opioids may lower circulating cortisol via an interaction with noradrenergic pathways.     

Lysosomal enzymes in the rat harderian gland are altered by either bromocriptine treatment or hypophysectomy and hormone replacement therapy

Four groups of adult male hypophysectomized rats were injected subcutaneously twice daily between 0800-0900 hr and 1600-1700 hr with either saline diluent, 150 micrograms sheep prolactin and/or growth hormone (GH); intact rats received either saline or 150 micrograms bromocriptine twice daily. After 4 days of treatment, lysosomal enzyme assays revealed significant elevations in both acid phosphatase and alpha-mannosidase enzyme activities in the Harderian glands of saline-injected hypophysectomized rats compared to those in intact controls. beta-Glucuronidase levels were depressed and hexosaminidase activity unaffected by hypophysectomy treatment alone compared to intact controls. Lysosomal enzyme activities in hypophysectomized animals treated with prolactin were not different from the hypophysectomized control animals. However, treatment with GH alone or in combination with prolactin had a significant inhibitory effect on beta-glucuronidase, hexosaminidase, and alpha-mannosidase enzyme activities in the Harderian gland of hypophysectomized animals. Bromocriptine treatment in intact rats only elevated acid phosphatase activity. In summary, the patterns of responses did not reveal a role for prolactin in the control of Harderian gland lysosomal enzyme activities by the pituitary. However, some of the influence on this target system may be exerted by growth hormone.     

Hormonal responses to analgesic nitrous oxide in man

Analgesic concentrations of nitrous oxide were administered to 6 healthy male subjects, and blood samples were assayed for prolactin, ACTH, follicle stimulating hormone, luteinising hormone, growth hormone, cortisol and thyroid hormones. Analgesic nitrous oxide (mean concentration = 48.8%) produced statistically significant elevation of prolactin and depression of cortisol whilst not producing statistically significant changes in the other hormones assayed. The increase in prolactin and decrease in cortisol levels are similar to the hormonal changes associated with administration of opioids in man. We have also confirmed the findings of other workers that cortisol levels may not always be correlated with ACTH levels.     

Responses of plasma adrenocorticotropin and cortisol to intravenous injection of synthetic ovine corticotropin releasing factor in the morning and early evening in normal human subjects

This study was designed to compare the responsiveness of adrenocorticotropin (ACTH) and cortisol secretion to corticotropin-releasing factor (CRF) in the morning and early evening in normal human subjects. Synthetic ovine CRF (1.0 micrograms/kg) or normal saline, was administered as an i.v. bolus injection to six normal males at 900 h and 1700 h. Blood samples were obtained before and 15, 30, 60, 90 and 120 min after CRF or saline injection. Significant increases in plasma ACTH and cortisol levels were observed in all subjects at the both time of testing after CRF injection. The net increments in the areas under the concentration curve (areas in the CRF experiment minus those in the saline control experiment) were not statistically different for both ACTH (mean +/- SEM: 41.0 +/- 10.6 pg/ml h in the morning: 51.1 +/- 8.9 pg/ml h in the evening) and cortisol (mean +/- SEM: 28.5 +/- 5.0 micrograms/dl h in the morning; 36.2 +/- 4.0 micrograms/dl h in the evening). Also no significant difference was observed in net increment, peak level and the ratio of peak level to the basal level of ACTH and cortisol after CRF injection. There were no appreciable changes in plasma concentrations of growth hormone, thyroid-stimulating hormone or prolactin, although slight but statistically significant rises in plasma levels of luteinizing hormone and follicle-stimulating hormone were observed. These results suggest that there is no significant difference in responsiveness of the pituitary-adrenal axis to CRF in the morning (900 h) and early evening (1700 h), and thus the time of day will not necessarily have to be considered when CRF is used between these times in a clinical test to evaluate pituitary ACTH reserve.     

Menstrual disturbances in chronic renal failure.

Twelve female patients undergoing intermittent hemodialysis (HD) and 5 females posttransplantation (PT) were studied. All the HD patients had menstrual disturbances and 5 had galactorrhea. The mean basal LH level was significantly elevated (p less than .05) in patients on HD compared to normal controls, but the mean LH response to luteinizing hormone releasing hormone (LRH) was not significantly different from the control group. Mean basal FSH and the FSH response to LRH was normal. In the PT pateints the LH response to LRH was significantly greater at 120 min when compared to normal females. In the HD group the serum 17B estradiol, progesterone and testosterone levels were significantly lower than in the controls but in the PT group only testosterone levels were significantly lower. These results differ from those previously found in uremic males. Elevated prolactin levels were found in the patients on hemodialysis and correlated well with the presence of galactorrhea. These was no correlation between the elevated prolactin levels and amenorrhea in the patients on hemodialysis but one PT patient with amenorrhea had elevated prolactin levels.     

Different effects of aging on the opioid mechanisms controlling gonadotropin and cortisol secretion in man

The present study was undertaken in order to assess the influence of aging on the endogenous opioid control of gonadotropin and adrenocorticotropin/cortisol secretion in man. For this purpose, the capability of the opioid antagonist naloxone to increase circulating levels of luteinizing hormone (LH), follicle-stimulating hormone (FSH) and cortisol was tested in male subjects of different ages. Thirty normal men were randomly chosen and divided into 3 groups by age: group I = 22-40 years (n = 10); group II = 41-59 years (n = 10); group III = 62-80 years (n = 10). Since the men of group III showed higher basal serum gonadotropin concentrations than the subjects of group I and group II, we selected from a large population a fourth group of elderly men with normal basal LH and FSH levels: group IV = 61-82 years (n = 7). All subjects were tested for 120 min during the intravenous administration of naloxone (4 mg given in an intravenous bolus at time 0, plus 10 mg infused for 2 h). Control tests with normal saline instead of naloxone were performed in all groups. All subjects had similar blood testosterone and cortisol levels, whereas LH and FSH concentrations were significantly higher in group III than in groups I, II and IV. Naloxone increased plasma cortisol concentrations by 50% in all groups. The cortisol secretory response followed a similar pattern regardless of age.(ABSTRACT TRUNCATED AT 250 WORDS)     

A 24-Hour Study of the Hypothalamo-Pituitary Axes in Huntington’s Disease

BackgroundHuntington’s disease is an inherited neurodegenerative disorder characterised by motor, cognitive and psychiatric disturbances. Patients exhibit other symptoms including sleep and mood disturbances, muscle atrophy and weight loss which may be linked to hypothalamic pathology and dysfunction of hypothalamo-pituitary axes.MethodsWe studied neuroendocrine profiles of corticotropic, somatotropic and gonadotropic hypothalamo-pituitary axes hormones over a 24-hour period in controlled environment in 15 healthy controls, 14 premanifest and 13 stage II/III Huntington’s disease subjects. We also quantified fasting levels of vasopressin, oestradiol, testosterone, dehydroepiandrosterone sulphate, thyroid stimulating hormone, free triiodothyronine, free total thyroxine, prolactin, adrenaline and noradrenaline. Somatotropic axis hormones, growth hormone releasing hormone, insulin-like growth factor-1 and insulin-like factor binding protein-3 were quantified at 06:00 (fasting), 15:00 and 23:00. A battery of clinical tests, including neurological rating and function scales were performed.Results24-hour concentrations of adrenocorticotropic hormone, cortisol, luteinizing hormone and follicle-stimulating hormone did not differ significantly between the Huntington’s disease group and controls. Daytime growth hormone secretion was similar in control and Huntington’s disease subjects. Stage II/III Huntington’s disease subjects had lower concentration of post-sleep growth hormone pulse and higher insulin-like growth factor-1:growth hormone ratio which did not reach significance. In Huntington’s disease subjects, baseline levels of hypothalamo-pituitary axis hormones measured did not significantly differ from those of healthy controls.ConclusionsThe relatively small subject group means that the study may not detect subtle perturbations in hormone concentrations. A targeted study of the somatotropic axis in larger cohorts may be warranted. However, the lack of significant results despite many variables being tested does imply that the majority of them do not differ substantially between HD and controls.     

Effect of opiates on growth hormone secretion in acromegaly.

Morphine at doses of 5 mg and 10 mg does not stimulate growth hormone (GH) secretion in normal subjects, and its effect on GH secretion in acromegaly is not widely documented. We investigated the effect of 15 mg intravenous morphine on growth hormone in patients with active acromegaly compared to normal subjects (7 acromegalics and 5 controls). Their mean (+/- SEM) age was 30.5 +/- 7.6 years and 29.5 +/- 0.5 years, respectively. Basal and peak response of growth hormone after morphine was measured with simultaneous assay of cortisol to exclude the effect of stress. Mean (+/- SEM) basal growth hormone was 103.16 +/- 28.04 ng/ml in acromegalics compared to 4.51 +/- 1.43 ng/ml in controls. Morphine caused an elevation of growth hormone in both acromegalics and normal subjects (p < 0.05). However, the Delta (peak minus basal) response of growth hormone was comparable between the two groups. A concurrent fall in cortisol was noted after morphine in both the groups, excluding the effect of stress on growth hormone. We conclude that higher doses (15 mg) of morphine are required to stimulate GH secretion in normal subjects, and that opioids exert a positive modulating effect on growth hormone secretion in patients with active acromegaly suggesting partial autonomy of the pituitary tumor.     

Effect of synthetic ovine corticotropin-releasing factor on growth hormone secretion in patients with acromegaly

In a significant proportion of patients with acromegaly, a non-specific increase in plasma growth hormone (GH) has been recognized following administration of thyrotropin-releasing hormone (TRH) or luteinizing hormone-releasing hormone (LH-RH), probably due to the lack of the specificity of the receptor in their tumor cells. In this study, the effects of corticotropin-releasing factor (CRF), a newly isolated hypothalamic hormone, in addition to TRH and LH-RH, on plasma levels of GH and the other anterior pituitary hormones were evaluated in 6 patients with acromegaly. Synthetic ovine CRF (1.0 microgram/kg), TRH (500 micrograms) or LH-RH (100 micrograms) was given as an iv bolus injection, in the morning after an overnight fast. Blood specimens were taken before and after injection at intervals up to 120 min, and plasma GH, adrenocorticotropin (ACTH), thyrotropin, prolactin, luteinizing hormone, follicle-stimulating hormone and cortisol were assayed by radioimmunoassays. A non-specific rise in plasma GH was demonstrated following injection of TRH and LH-RH, in 5 of 6 and 2 of 5 patients, respectively. In all subjects, rapid rises were observed in both plasma ACTH (34.3 +/- 6.2 pg/ml at 0 min to 79.5 +/- 9.5 pg/ml at 30 min, mean +/- SEM) and cortisol level (9.1 +/- 1.3 micrograms/dl at 0 min to 23.4 +/- 1.2 micrograms/dl at 90 min). However, plasma levels of GH and the other anterior pituitary hormones did not change significantly after CRF injection. These results indicate that CRF specifically stimulates ACTH secretion and any non-specific response of GH to CRF appears to be an infrequent phenomenon in this disorder.     

Hormonal adaptation determines the increase in muscle mass and strength during low-intensity strength training without relaxation

The study was designed to test the hypothesis that, during strength training, a restricted blood supply to the working muscles stimulates the secretion of anabolic hormones and an increase in the muscle mass and strength can be achieved with significantly lower training loads. During eight weeks, three times a week, 18 young, physically active males trained their leg extensor muscles. Nine subjects (group I) worked at 80% of the maximal voluntary contraction (MVC), whereas the rest (group II) performed their exercise without relaxation and at a lower load (50% MVC). The total training load in group II was significantly lower than in group I (77 ± 5 vs. 157 ± 7 kJ, respectively). The eight-week training of both groups significantly increased the mean maximum strength (by 35 and 21% in groups I and II, respectively) and volume (by 17 and 9%, respectively) of the muscles trained (however, the differences between the groups with respect to these changes were nonsignificant). Group I displayed a higher increase in the blood level of creatine phosphokinase than group II, while group II showed a greater increase in the blood concentration of lactate. In contrast to group I, group II displayed a significant increase in the blood concentrations of growth hormone, insulin-like growth factor 1 (IGF-1), and cortisol. Hence, the suggestion that the secretion of metabolic hormones is triggered by a metabolic, rather than mechanical, stimulus from working muscles seems plausible.     

Synergistic effect of cortisol and thyrotrophin releasing hormone on lung maturation in the fetal sheep entails connective tissue maturation.

Pressure-volume relationships and collagen and elastin contents were measured in the lungs of fetal sheep infused either with saline (n = 4), thyrotrophin-releasing hormone (TRH; n = 6), cortisol (n = 9) or TRH plus cortisol (n = 10) at 128 days of gestation (term = 149 days) for 7 days. Lung distensibility (V40 = 1.8 +/- 0.1 ml/g wet wt; mean +/- SD) and stability (V5 = 0.6 +/- 0.1) increased along with collagen (C) (10.1 +/- 2.7 micrograms/mg) and elastin (E) contents (128 +/- 35 ng/mg) in the animals infused with TRH plus cortisol and were significantly higher (p < 0.05) than those observed in TRH (V40 0.62 +/- 0.07; V5 0.32 +/- 0.04; C 3.53 +/- 1.3; E 38.2 +/- 8.3), cortisol (V4 0.66 +/- 0.6; V5 0.27 +/- 0.03; C 4.27 +/- 0.8; E 41.02 +/- 12.7) or saline infused fetuses (V40 0.40 +/- 0.1; V5 0.20 +/- 0.06; C 3.28 +/- 0.9; E 31.5 +/- 9.2). Plasma concentrations of prolactin (PRL), triiodothyronine (T3) and cortisol (F) were also higher in the group of fetuses infused with both hormones in comparison with the other groups. In fetuses treated with TRH plus cortisol, PRL (32 +/- 8.3 ng/ml) and T3 (308.3 +/- 36 micrograms/dl) were significantly higher than in those infused with cortisol alone (PRL 3.7 +/- 2.3; T3 128 +/- 30) or with saline (PRL 4.2 +/- 1.6; T3 < 5 micrograms/dl). In the group treated with TRH alone, PRL also increased significantly (37 +/- 6.4), but T3 increased only slightly (18 +/- 3.4).(ABSTRACT TRUNCATED AT 250 WORDS)     

Influence of melatonin on mammary gland growth: in vivo and in vitro studies

Our objective was to determine whether melatonin influenced mammary growth in response to mammogenic hormones. Prepubertal female BALB/c mice were injected for 9 days with 1 microgram of 17 beta-estradiol and 1 mg of progesterone or 17 beta-estradiol/progesterone plus 50, 100, or 200 micrograms of melatonin. Area of the parenchyma and total DNA content of the second thoracic gland were similar between controls and melatonin-injected mice. However, micrograms of DNA/100 mg of mammary tissue were lower in animals treated with 17 beta-estradiol/progesterone plus 200 micrograms of melatonin than in controls. Triglyceride content of mammary glands from animals treated with 100 or 200 micrograms of melatonin/day increased relative to controls. In an in vitro experiment, thoracic mammary glands of 21-day-old mice were cultured for 6 days in a mammogenic milieu of hormones (17 beta-estradiol/progesterone, aldosterone, bovine prolactin, growth hormone, and insulin) with 0 (control), 10(-6), 10(-9), or 10(-12) M melatonin. Relative to controls, 10(-12) M melatonin increased and 10(-6) M melatonin decreased mammary DNA and uptake of [methyl-3H]thymidine. We conclude that high doses of melatonin reduce mammary development in normal mice and that some of this effect may be mediated directly at the mammary tissue.     

Control of mammary gland fibroblast growth by insulin, growth hormone and prolactin

Fibroblasts isolated from guinea pig mammary glands were cultured in 96 well culture plates in the presence of various concentrations of insulin, growth hormone and prolactin. Insulin (30 micrograms/ml increased uptake of tritiated thymidine by 30%. Higher concentrations of insulin did not result in any further increase in thymidine uptake. Growth hormone alone did not alter thymidine uptake in concentrations of 0 to 250 ng/ml. 300 ng/ml gave thymidine uptake of 136% of controls. In the presence of 20 g/ml insulin, growth hormone (250 ng/ml) increased thymidine uptake to approximately double that of controls. Prolactin alone (300 ng/ml decreased thymidine uptake by 19%. Insulin increased thymidine uptake, but the negative effect of prolactin was still evident above 150 ng/ml.     

Effect of bombesin on basal and stimulated secretion of some pituitary hormones in humans

The effect of bombesin (5 ng/kg/min X 2.5 h) on basal pituitary secretion as well as on the response to thyrotropin releasing hormone (TRH; 200 micrograms) plus luteinizing hormone releasing hormone (LHRH; 100 micrograms) was studied in healthy male volunteers. The peptide did not change the basal level of growth hormone (GH), prolactin, thyroid-stimulating hormone (TSH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH). On the contrary, the pituitary response to releasing hormones was modified by bombesin administration. When compared with control (saline) values, prolactin and TSH levels after TRH were lower during bombesin infusion, whereas LH and FSH levels after LHRH were higher. Thus bombesin affects in man, as in experimental animals, the secretion of some pituitary hormones.     

Pyridostigmine enhances even if it does not normalize the growth hormone responses to growth hormone-releasing hormone in patients with Cushing's disease.

Subjects with Cushing's disease have diminished growth hormone (GH) response to growth hormone-releasing hormone (GHRH). The aim of our study was to investigate the underlying mechanism of this diminished GH response in these patients using pyridostigmine (PD), an acetylcholinesterase inhibitor, which is reported to increase GH secretion by reducing somatostatin tone. Eight subjects with untreated Cushing's disease (caused by a pituitary adenoma) and 6 control subjects received GHRH 100 micrograms in 1 ml of saline, as intravenous bolus injection 60 min after (1) placebo (2 tablets, p.o.) or (2) PD (120 mg, p.o.). After GHRH plus placebo, the GH peak (mean +/- SEM) was significantly lower in subjects with Cushing's disease (2.4 +/- 0.5 micrograms/l) compared to control subjects (25.1 +/- 1.8 micrograms/l, p less than 0.05). After GHRH plus PD, the GH peak was significantly enhanced both in subjects with Cushing's disease (7.1 +/- 2.3 micrograms/l, p less than 0.05) and in control subjects (42.3 +/- 4.3 micrograms/l, p less than 0.05). In patients with Cushing's disease, the GH response to GHRH plus PD was lower with respect to the GH response to GHRH alone in normal subjects. We conclude that hypercortisolism may cause a decrease in central cholinergic tone which is in turn hypothesized to be responsible of an enhanced somatostatin release from the hypothalamus. However, other metabolic or central nervous system alterations may act synergistically with hypercortisolism in causing GH inhibition in patients with Cushing's disease.     

Lower 24-hour growth hormone levels in type I diabetics responding to thyrotropin-releasing hormone (TRH).

The aim of the study was the evaluation of growth hormone secretion under physiologic conditions in two groups of type I diabetics: responding and nonresponding to TRH stimulation. Both groups matched for age and metabolic control of diabetes were studied during 24-hours and after GHRH stimulation. The whole diabetic group (n = 18) showed circadian rhythm of GH secretion with mesor value of 4.03 micrograms/l. TRH-responders had lower mesor GH value than TRH-nonresponders: 3.53 vs. 5.32, p < 0.05. GH response to GHRH was almost identical in both groups. C-peptide level was lower in TRH-responders: 0.16 vs. 0.56 microgram/l, p < 0.05. No correlation was found between growth hormone response and HbA1 and C-peptide levels. It is concluded that type I diabetics responding to TRH stimulation are characterized by lower mean 24-hour GH levels and lower C-peptide values.     

Hormonal regulation of the synthesis of casein and alpha-lactalbumin in a primary mammary cell culture system

The addition of 5 micrograms/ml of both insulin and prolactin, 3 microM cortisol and 5% fetal bovine serum stimulated casein synthesis during a 5 day culture of mammary epithelium from lactating mice using a floating collagen gel as a culture substratum. Omission of any of the three hormones or serum decreased casein synthesis substantially. The use of 10% serum or the attached gel culture system also decreased casein synthesis. Cells cultured with the combination of the three hormones and 5% serum contained a low level of casein mRNA on day 2, but it increased to much higher levels on day 4 and 5, amounting to over 30% of total mRNA on day 5. In contrast to casein synthesis, the maximal increase in alpha-lactalbumin synthesis required the presence of 0.03 microM cortisol. The combination of insulin, prolactin and 3 microM cortisol or insulin and prolactin elicited smaller increases. The translatable mRNA for alpha-lactalbumin in cells cultured with insulin, cortisol and prolactin for 5 days was detected, but not in cells with insulin and cortisol. Both a high and low concentration of cortisol in combination with insulin increased prolactin binding capacity of cultured cells to the same extent, whereas cells cultured with insulin alone contained much lower levels of prolactin binding. The difference in the capacity of prolactin binding between cells cultured with insulin alone and those cultured with insulin and cortisol correlated well with their ability to synthesize casein in response to prolactin.     

Final height after growth hormone therapy in peripubertal boys with a subnormal integrated concentration of growth hormone.

The aim of this study was to test the effect of growth hormone (GH) therapy on final height in peripubertal boys with idiopathic short stature in whom a subnormal integrated concentration of GH (< 3.2 micrograms/l) was found. Twenty-eight peripubertal children were studied. Height was below 2 SD for age, growth velocity was < 4.5 cm/year, bone age was more than 2 SD below mean for age and GH response to provocative tests was more than 10 micrograms/l. Eleven subjects (group B) were treated with recombinant GH 0.75 unit/kg/week, divided into 3 weekly doses for 2 years, and then the same weekly dose divided into daily injections was administered until final height was attained. Seventeen untreated children (group A) who were followed until cessation of growth served as controls. The GH-treated patients reached their target heights (-2.1 +/- 0.5, mean +/- SD in SDS) and predicted heights (-1.8 +/- 0.8) determined by the Bayley and Pinneau method, while the final heights of the untreated patients were significantly lower than their target heights and their predicted final heights (-2.7 +/- 0.7, -1.8 +/- 1.0 and -2.7 +/- 0.7, respectively). The main effect of GH was observed during the 1st year of treatment when height velocity was significantly higher in the GH-treated group than in the untreated one (9.3 +/- 2.1 vs. 5.3 +/- 1.1, respectively, p < 0.001). The high cost of the treatment in this specific age group should be weighed against the results.     

Plasma hormone profliles and fertility in ewe lambs given progestagen supplementation after mating

Clun Forest ewe lambs (n = 124) were used to investigate the effects of post-mating progestagen supplementation on fertility. The animals were assigned to 1 of 3 three treatments: Group A (n = 41) served as the controls, Group B (n = 42) received 3 weekly injections of 6 mg of medroxyprogesterone acetate (MAP), while Group C (n = 41) was treated with intravaginal sponge containing 60 mg of MAP; all treatments were administered from Day 5 to Day 26 post mating. Supplementation did not increase the percentage of animals pregnant or those lambing: Group A, 72.2 and 66.6%; Group B, 57.5 and 50.0%; and Group C, 67.5 and 60.0%, respectively. Furthermore, there was no effect of supplementation on plasma progesterone, prolactin, cortisol, growth hormone, insulin, or glucose concentrations (P>0.05). However, pre- and post- mating hormone profiles differed significantly between the animals that lambed or aborted and the animals which were found to be barren at lambing. In the barren animals, progesterone concentrations were lower 4 days before and 9 to 33 days after mating (P<0.01), while overall prolactin concentrations were higher throughout the trial (P<0.01). But there was no difference between barren and fertile lambs in cortisol, growth hormone, insulin or glucose concentrations (P>0.05). These results indicate that progestagen supplementation does not increase the reproductive performance of ewe lambs. However, infertility is associated with reduced luteal function and increased prolactin concentration before and after mating.     

Effects of methyldopa on prolactin and growth hormone.

The effects of administration of methyldopa on serum prolactin and growth hormone (GH) concentrations in hypertensive patients were studied. Single doses of methyldopa (750 or 1000 mg) significantly increased serum prolactin levels, peak concentrations occurring four to six hours after drug administrations. Long-term methyldopa treatment was associated with threefold to fourfold increases in basal prolactin levels compared with those in normal subjects. In patients treated with methyldopa for two to three weeks the GH response to insulin hypoglycaemia was significantly greater than in normal subjects and untreated hypertensive patients. In contrast, patients treated for prolonged periods (mean 13-4 months) had a GH reponse indistinguishable from normal.