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The present study evaluates the effects of 2 years of growth hormone (GH) replacement therapy on psychological well-being and cognitive performance in adults with childhood-onset growth hormone deficiency (CO-GHD). A total of 48 GHD adult men (mean age: 27 years) were randomly assigned to one of four treatment groups: placebo treatment, or GH replacement in a dose of 1, 2, or 3 IU/m2, respectively. Placebo treatment was given for 6 months. Psychological assessments were made every 6 months. Assessments included somatic and psychological complaints, depression, fatigue, vigor, tension, state/trait anxiety, iconic memory, short-term memory, long-term memory and perceptual-motor skill. GH treatment was considered physiological if the observed insulin-like growth factor-I (IGF-I) levels were within the normal range. It was considered supraphysiological if serum IGF-I rose to a value exceeding the upper normal limit. During the placebo-controlled phase of the study the changes in memory performance were positively correlated to the GH induced changes in serum IGF-I concentration and, more weakly, to the daily GH substitution dose. At 6 months memory only had improved in the group receiving supraphysiological GH treatment, but not in the group of patients who had a normalization of serum IGF-I. However, after 1 year of treatment a normalization of memory functioning was found in both groups of patients and this was preserved during the 2nd year of treatment. No changes were observed in psychological well-being and perceptual-motor skill. We conclude that GH replacement improves memory function in adults with CO-GHD. It has no effect on psychological well-being or perceptual-motor skill. Supraphysiological treatment accelerates the recovery of memory performance. However, the long-term effects are not different from those achieved with physiological GH replacement.

Objective: To assess whether growth hormone (GH) administration to adult GH-deficient men leads to increased sexual hair. The sexual hair scores are subnormal in these patients, even in the presence of normal serum androgen levels., Patients: Forty-six adult men with childhood-onset of GH deficiency of whom 25 were androgen deficient and received replacement., Design: Double-blind and placebo-controlled. Of the 46 patients, 33 started immediately with GH administration; the remaining 13 received placebo for the first 6 months followed by GH for the next 6 months. Sixty-one age-matched healthy men with normal height and serum concentrations of IGF-I served as a comparison group., Measurements: Hair scores at 13 defined body regions were assessed before, and after 6 and 12 months of the intervention. At the same time levels of IGF-I, dehydroepiandrosterone sulphate, androstenedione, dihydrotestosterone (DHT), testosterone and sex hormone binding globulin (SHBG) were measured. From the latter two, the free androgen index (FAI) was calculated., Results: Before GH administration, hair scores in the GH deficient patients were lower than in the comparison group. In the 33 men treated with GH from the beginning, there was an increase in hair scores after 6 months. The increase in hair scores was not seen during 6 months of placebo treatment. When the placebo group switched to GH administration, their hair scores had also significantly increased after 6 months of GH substitution therapy. Upon GH administration both levels of SHBG and testosterone/DHT declined while the FAI remained unchanged., Conclusion: GH substitution therapy to GH deficient men has an auxiliary effect on androgen action in the skin without an increase of the FAI.

We investigated the effects of GH on bone structure and turnover by histomorphometry in GH-deficient adults. Therefore, transiliac bone biopsies were obtained before and after 1 yr of treatment in 36 GH-deficient men (mean age, 28 +/- 4 yr). Thirteen patients had isolated GH deficiency and 23 patients had multiple pituitary hormone deficiencies. Patients were randomly assigned to four treatment groups. Groups 1, 2, and 3 received 1, 2, and 3 IU/m2/day (0.35, 0.69, and 1.3 mg/m2/day) [corrected] GH, respectively, and the fourth group received placebo for the first 6 months and 2 IU/m2/day (5.8 mg/m2/day) GH for the subsequent 6 months. GH treatment resulted in an increase of cortical thickness from 0.98 +/- 0.27 to 1.20 +/- 0.35 mm (P = 0.005), but trabecular bone volume did not change. Bone formation variables increased significantly: osteoid surface increased from 8.5 +/- 5.3 to 15.5 +/- 6.1% (P = 0.0002), mineralizing surface increased from 6.7 +/- 2.5 to 10.8 +/- 4.4% (P = 0.0002), and bone formation rate increased from 0.04 +/- 0.02 to 0.08 +/- 0.04 mm3/mm2/day (P = 0.0001). Eroded surface did not change, but osteoclast number increased from 0.6 +/- 0.5 to 1.25 +/- 0.5 Oc/mm2 (P = 0.0001). The relative formation period increased significantly (P = 0.001), whereas the resorption period, including reversal phase, decreased from 65 to 40 days (P = 0.02). Activation frequency increased from 0.39 +/- 0.17 to 0.74 +/- 0.34 y(-1) (P = 0.0001). These data indicate a stimulated bone turnover as a result of GH treatment and a shorter resorption and reversal time. The increased turnover did not result in an increased trabecular bone volume, but the cortical thickness increased significantly.

To minimize the rate of side-effects, a retrospective analysis of 28 studies of GH replacement therapy in adults indicates that the maintenance dose should usually not exceed 1.0 IU/m2/day (about 1.5-2.0 IU/day) in GHD patients 40-60 years old, or 1.5 IU/m2/day (about 2.5-3.0 IU/day) in GHD patients 20-40 years old. GHD women may tolerate, and in fact may need, higher replacement doses, though this issue requires further investigation. GH treatment should be started at a low dose, i.e. about 1.0 IU/day, and increased gradually, by about 0.5 IU per month, until the target dose is reached. In the absence of side-effects, the GH dose may be either too low, adequate, or too high. Measurement of GH-dependent serum markers provides the most promising approach to detect both GH depletion and excess, with serum IGF-I concentration the current method of choice. Clinical awareness of symptoms of GH excess remains important, however, particularly in patients with IGF-I levels in the high normal range.

Objectives: To assess the degree of subcutaneous and intraabdominal fat accumulation in growth hormone (GH) deficient adult men, and to evaluate the lipolytic effects of GH replacement therapy., Design: Placebo-controlled, double-blind, dose-response study. All patients, including those initially starting on placebo, received GH for a period of one year., Subjects: 46 adult men (mean age 28.0 +/- 4.5 y) with childhood-onset GH deficiency (GHD)., Measurements: Subcutaneous fat mass and fat distribution was assessed by measurement of skinfold thicknesses at seven different sites. Intraabdominal fat mass was assessed by computerized tomography (CT). Reference values were obtained from age- and sex-matched controls with a normal body mass index., Results: The sum of skinfolds (SKFs) was 75% (95% CI: 52-98%) higher, and intraabdominal fat area was 84% (95% CI: 45-122%) greater in GHD patients than in age- and sex-matched controls. Patients with multiple pituitary hormone deficiencies (MPHD, n = 30), who were all receiving conventional hormone replacement therapy, were more obese than patients with isolated GHD (IGHD, n = 16). This difference was attributed to a more severe impairment in GH secretion, as well as to the lower androgen levels in patients with MPHD. GH treatment was associated with a gradual decline in subcutaneous fat that continued for approximately six months. Thereafter, a new steady-state was reached. The GH-induced decline in subcutaneous and intraabdominal fat was dose-dependent (r = 0.84, p < 0.001 and r = 0.52, p < 0.001, respectively). The efficacy of GH treatment was similar to IGHD and MPHD patients. Optimal GH replacement, defined as treatment resulting in normalization of serum insulin-like growth factor-I (IGF-I) concentration, was achieved in 25 patients. In this subgroup the sum of SKFs decreased by 27% (95% CI: 22-32%) and intraabdominal fat was reduced by 47% (95% CI: 38-57%)., Conclusion: We conclude that subcutaneous as well as intraabdominal fat mass are abnormally high in GHD men, and that GH treatment with doses within the physiological range profoundly reduces the sizes of both fat compartments. In addition, GH replacement therapy was found to be equally effective in men with IGHD as in those with MPHD.

In order to establish whether reported psychological complaints in hypopituitary adults are related to growth hormone (GH) deficiency or other pituitary hormone deficiencies, emotional well-being and cognitive performance were evaluated in 31 men with multiple pituitary hormone deficiencies (MPHD) and in 17 men with isolated growth hormone deficiency (IGHD). Assessments included evaluation of somatic and psychological complaints, depression, fatigue, vigor, tension, state and trait anxiety, iconic memory, short-term memory, long-term memory and perceptual-motor skill. The control group consisted of 41 healthy men, matched for age. Growth hormone secretion was more severely impaired in MPHD than in IGHD patients. Despite oral replacement therapy, MPHD patients also had lower serum testosterone levels than IGHD subjects. The MPHD patients were found to have lower vigor scores, higher state anxiety scores, worse perceptual-motor skill and worse memory performance than controls. In contrast, IGHD patients only showed subnormal memory performance. It was concluded, therefore, that the cognitive impairment in both MPHD and IGHD was related to GH deficiency. The subnormal vigor scores in MPHD patients were attributed to the reduced testosterone levels. The worse perceptual-motor skill in MPHD patients might be related specifically to ACTH deficiency. Finally, the higher state anxiety in MPHD was attributed to a low self-esteem, which may be the psychological consequence of the hypogonadal appearance these patients have. We conclude that, from a psychological point of view, MPHD and IGHD adult patients are quite distinct groups.

The optimal dose for GH replacement therapy in GH-deficient (GHD) adults is not known, nor is there a consensus as to which method is the most appropriate for the monitoring of treatment. To establish a general guideline for GH replacement therapy in adults, we evaluated the relationship between the administered GH dose and the achieved serum levels of three GH-dependent serum markers. Serum levels of insulin-like growth factor I (IGF-I), IGF-binding protein-3 (IGFBP-3), and the acid-labile subunit (ALS) were measured in 46 GHD men participating in a 1-yr, double blind, and placebo-controlled dose-response study. The doses of recombinant human GH ranged from 0.33-3.0 IU/m(2)-day. During GH treatment, dose reduction was necessary because of side-effects in 18 of 46 patients, i.e. in 18% of the patients receiving a maintenance dose of 1 IU/M(2)-day, in 35% of the patients receiving a dose of 2 IU/m(2)-day, and in 67% of the patients receiving a dose of 3 IU/M(2)-day. In the untreated state, serum levels of all three markers were below the normal range in 90% of the patients. The rise in serum marker concentrations during the first month of treatment was dose dependent. Significant increases in IGF-I, IGFBP-3, and ALS levels were observed with a dose as low as 0.33 IU/M(2)-day. The minimal GH dose required for normalization of the serum IGF-I concentration was 0.66 IU/M(2)-day, and it was 1.0 IU/M(2)-day for ALS and IGFBP-3. In patients receiving 2.0 IU/M(2)-day, the mean serum IGF-I concentration rose to an abnormally high level, whereas at this dose, the mean IGFBP-3 and ALS levels were not different from normal. The lower sensitivity of IGFBP-3 and ALS to GH doses in the high range was also apparent during long term treatment. The number of patients who developed IGFBP-3 or ALS levels that exceeded the upper normal limit was substantially smaller than the number of patients with elevated IGF-I concentrations (2, 8, and 19 of 46 patients, respectively). In conclusion, serum IGF-I appears to be the preferred biochemical marker for the detection of GH excess in adults receiving GH replacement therapy, because it is more sensitive than IGFBP-3 and ALS to GH doses in the high range. If normalization of the serum IGF-I concentration is taken as the criterion for optimal GH replacement therapy, the predicted optimal GH dose for GHD men 20 - 40 yr old is 1.4 IU/M(2)-day, and the 95% confidence interval is 1.2-1.6 IU/M(2)-day.

The prevalence of clinical signs and symptoms related to fluid retention is high in most studies evaluating the efficacy of GH treatment in GH-deficient (GHD) adults. This may be a consequence of supraphysiological GH replacement. To examine whether fluid retention is a dose-related phenomenon, we evaluated the impact of various GH substitution doses on body fluid status in 46 GHD men participating in a 1-yr, double blind, and placebo-controlled study. The patients were randomized to receive either placebo (n = 13) or GH in a dose of 1 (n = 11), 2 (n = 10), or 3 (n = 12) IU/m2.day, respectively. Treatment was started at one third of the predetermined dose and was subsequently increased by another third every month until the maintenance dose was reached. Tissue hydration was assessed by means of electrical impedance measurements. Normal values were obtained from 128 age- and sex-matched controls. In the untreated GHD state, whole body resistance was abnormally high (observed, 642 +/- 82 omega; predicted, 550 +/- 31 omega; P < 0.001). This was mainly caused by an increase in specific resistance of the lean body as a consequence of a reduction in extracellular water (ECW). The first month of GH treatment was associated with a sharp decline in electrical resistance that was attributed to an increase in ECW. Whole body resistance reached its nadir after 3 months of treatment (517 +/- 72 omega, i.e. 19.6 +/- 6.5% lower than before treatment; P < 0.001) and did not change significantly thereafter. The GH-induced changes in body resistance were dose dependent. A significant decrease was observed with a dose as low as 0.33 IU/m2.day (P < 0.005). However, whole body resistance remained higher than normal in patients receiving less than 0.67 IU/m2.day (P = 0.05). Abnormally low resistance values, indicative of overhydration, were observed in patients receiving doses equal to or higher than 2 IU/m2.day (P < 0.005). Regression analysis of the pooled data showed that GH replacement in a dose of 1.10 IU/m2.day (95% confidence interval, 0.85-1.45 IU/m2.day) resulted in a normalization of whole body resistance. In conclusion, GH replacement therapy in adults rapidly corrects the preexisting deficit in ECW. This rehydration process is dose dependent and may result in a substantial weight gain.(ABSTRACT TRUNCATED AT 400 WORDS)

Objectives: To study the effects of growth hormone administration on insulin-like growth factor I concentration, nitrogen balance, and fuel utilization, and to study its safety in critically ill nonseptic patients., Design: Prospective, randomized, placebo-controlled trial., Setting: Medical intensive care unit of a university hospital., Patients: Eighteen critically ill nonseptic patients were studied for 8 days after admission., Interventions: Growth hormone (0.1 mg/kg/day) or placebo was administered as a continuous intravenous infusion on the second, third, and fourth days after admission. The study period was 8 days., Measurements and Main Results: Plasma hormone concentrations were measured every 6 hrs and average daily values were calculated. The 24-hr urinary nitrogen and 3-methylhistidine excretion were measured. Indirect calorimetry was used to calculate fuel utilization. Insulin-like growth factor I concentrations increased in the treatment group from subnormal to normal values and remained increased despite discontinuation of growth hormone treatment (p = .02). Nitrogen balance differed between the groups upon admission: growth hormone group (3.9 +/- 4.1 g/day) vs. controls (13.8 +/- 5.4 g/day), but improved with growth hormone. This finding appeared independent of the imbalance between the groups. The 3-methylhistidine excretion was not different between the groups and did not change during growth hormone administration. Free fatty acids and glycerol concentrations increased during growth hormone treatment, but calculated fuel utilization did not change. During growth hormone treatment, insulin concentrations increased, due to the increased administration of insulin necessary for glycemic control. Side effects other than hyperglycemia were not observed., Conclusions: Growth hormone administration in a heterogeneous group of critically ill nonseptic patients resulted in normalization of insulin-like growth factor I levels, even after cessation of growth hormone treatment. Nitrogen balance improved, but this change was transient. Hence, growth hormone affects nitrogen balance, probably partly independent of insulin-like growth factor I.

Purpose: The effects of recombinant human growth hormone (GH) on fuel utilization, mineral and fluid balance in critically ill patients were studied., Methods: Twenty patients requiring mechanical ventilation and receiving standard parenteral nutrition were studied. GH 0.1 mg/kg/day (n = 10) or placebo (n = 10) was administered as continuous intravenous infusion for 3 days. Plasma mineral levels, urinary nitrogen, and mineral excretion were measured. Indirect calorimetry was used to calculate energy production rate and fuel utilization., Results: Insulin-like growth factor I concentrations increased: day 4 GH, 18.9 +/- 7.0 ng/mL; controls 11.6 +/- 3.2 ng/mL (P < .05). During GH administration, the nitrogen balance became zero, whereas it remained negative in controls (P = .03). Fuel utilization did not differ between the groups. Neither did oxygen consumption, carbon dioxide production, or the respiratory quotient (RQ). Nonprotein RQ showed a tendency to decrease in the GH group, whereas an increase was present in controls. Mineral balance improved in both groups. Phosphate balance improved by 250% in the GH group (P = .054)., Conclusions: GH administration in critically ill patients reduces nitrogen loss and improves phosphate retention but does not have an important effect on fuel utilization.

To assess the implications of prolonged growth hormone deficiency (GHD) for the acquisition and maintenance of bone mass, bone mineral density (BMD) was measured in 70 adult males (mean age 26.7 +/- 4.5 years) with childhood-onset GHD, 7.4 +/- 4.2 years after discontinuation of previous GH therapy. Because most of these patients were short (mean height 165.8 +/- 6.6 cm), the influence of body height on standard BMD measurements, conventionally reported as the areal density (BMDarea, expressed in g/cm2), was analyzed in a group of age-matched healthy males. In GHD patients, BMDarea was significantly reduced at the lumbar spine (Z score -1.59 +/- 1.08, p < 0.001) as well as at the nondominant hip (Z score -1.18 +/- 0.95, p < 0.001). The reduction in BMDarea was similar for patients with isolated GHD (N = 25) and those with combined deficiencies of GH and luteinizing hormone (N = 40). In patients and controls, BMDarea was positively correlated with body height, a relation that was attributed to skeletal size. Bone dimensions were significantly smaller in patients than in controls, and therefore it was hypothesized that the difference in areal density between patients and controls might be confounded by differences in bone size. Measured bone mineral content corrected for the estimated bone volume (BMDvolume, expressed in g/cm3) remained significantly reduced (Z score: lumbar spine, -0.90 +/- 1.08, p < 0.001; femoral neck, -0.74 +/- 1.00, p < 0.001), but the differences between GHD patients and controls were less than indicated by BMDarea (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the impact of growth hormone deficiency (GHD) on lipid metabolism, serum lipid and apolipoprotein concentrations were measured in 64 GHD adult males (mean age, 27.1 +/- 4.7 years). Results were compared with those obtained from an age- and sex-matched control group. Total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein (apo) B levels were significantly higher in GHD patients (P < .001). In 14 patients (23%), total cholesterol concentration exceeded the 95th percentile for healthy adults. Total and LDL cholesterol were inversely related to plasma insulin-like growth factor-I (IGF-I). Apo B also tended to be negatively correlated with IGF-I; however, statistical significance was not reached (P = .054). High-density lipoprotein (HDL) cholesterol and plasma triglyceride concentrations were within normal limits, whereas apo A-1 and A-2 levels were only slightly different from normal. We conclude that GHD in adulthood is associated with mild hypercholesterolemia due to an increased LDL cholesterol level. An inverse relationship was established between LDL cholesterol concentration and GH secretory status.

The objective of this study was to evaluate the safety and the effect of recombinant exogenous growth hormone (GH) on nitrogen production in patients with severe sepsis. It was designed as a prospective, randomized, placebo-controlled trial, and performed in the medical intensive care unit of a university hospital. Twenty patients admitted with septic shock and receiving standard parenteral nutrition served as subjects. Treatment consisted of GH 0.1 mg/kg/day or placebo administered as continuous intravenous infusion on the second, third, and fourth days after admission. The study period was eight days. During GH administration, nitrogen production decreased significantly in the GH group and increased in controls (p < 0.01). Nitrogen balance became slightly positive in the GH group during treatment: 1.2 +/- 6.4 versus controls -3.7 +/- 3.8 g/day (day 3) (p < 0.05). Within 24 hours after cessation of treatment, differences between GH and controls disappeared. 3-Methylhistidine excretion as a measure of absolute muscle breakdown declined during the study period, but did not differ between groups. The levels of insulin, insulinlike growth factor 1, glycerol, free fatty acids, and beta-hydroxybutyrate increased during treatment. Despite continuous intravenous administration, GH levels gradually declined during the 3 treatment days, indicating increased metabolic clearance. Side effects other than insulin resistance were not observed. Growth hormone administration reduces nitrogen production and improves nitrogen balance in patients with severe sepsis. These effects are not sustained after cessation of treatment.

Critical illness, surgery and hypocaloric feeding are accompanied by a high rate of total body nitrogen loss. Loss of body protein, occurring despite adequate nutrition, results in increased incidence of infection, poor wound healing, skeletal muscle weakness and increased mortality. Growth hormone (GH) administration together with nutritional support attenuates protein catabolism. This review focuses on normal GH physiology and the administration of GH in adult catabolic patients.

Anthropometry and bioimpedance analysis (BIA) were used to assess body composition in 42 GH-deficient (GHD) adult males (mean age, 27.2 +/- 4.7 yr). During childhood, all patients had received GH treatment for a mean period of 8.4 +/- 3.8 yr. At the start of this study, GH therapy had been discontinued for a mean period of 7.5 +/- 4.5 yr. Eighteen patients had isolated GH deficiency (I-GHD). Twenty-four patients had multiple pituitary hormone deficiencies (M-PHD), substituted adequately. Compared to age- and sex-matched controls, the sum of skinfolds measured at 7 different sites was significantly higher in I-GHD and M-PHD patients [controls, 73.1 +/- 25.4 mm; I-GHD patients, 102.1 +/- 37.7 mm (P less than 0.001); M-PHD patients, 126.8 +/- 35.4 mm (P less than 0.001)]. The increase in sc fat deposition was most pronounced on the trunk, particularly in the breast and abdominal area. Total body muscle mass was significantly lower in GHD patients (P less than 0.001). In patients, body muscle mass and plasma somatomedin-C level were positively correlated (r = 0.43; P less than 0.005). Total body resistance measured by whole body BIA was significantly higher in the patient group and was negatively correlated with plasma somatomedin-C (r = -0.53; P less than 0.001). The high resistance values observed in GHD patients could only in part be explained by their lower lean body mass. The most important cause, however, was an increase in specific electrical resistance of the lean body mass (LBM), reflecting relative dehydration. We conclude that GH deficiency in adult males is associated with an increase in sc fat and a decrease in body muscle mass. In addition, there is a qualitative change in LBM. The BIA data indicate that in these patients, the hydration state of the LBM is lower than normal, due to a decrease in extracellular water.

The metabolic response to sepsis is dependent on the hormonal status. However, reported plasma hormone levels vary widely among studies. The persistence of pulsatile secretion, as occurs normally, may explain the observed variability. To study whether pulsatile hormone secretion persists during sepsis and how it affects assessment of the hormonal status from single measurements, we measured growth hormone (GH), prolactin, cortisol, insulin, and C-peptide at 20-minute intervals for 24 hours in eight consecutive patients with severe sepsis. Twenty-four-hour averages (mean +/- SD) were 3.3 +/- 2.5 ng/mL for GH, 640 +/- 461 nmol/L for cortisol, 18.2 +/- 4.8 mU/L for insulin, and 3.4 +/- 2.9 U/L for C-peptide, at a pulse frequency between 3.3 +/- 2.7 for C-peptide and 10.2 +/- 3.4 for insulin, and an increase of the maximal value in a pulse above the preceding nadir of 131% +/- 13% for cortisol and 376% +/- 386% for GH, as assessed with Cluster analysis. Prolactin levels were below the detection limit in all but one patient, probably due to the administration of dopamine. To determine the accuracy of less frequent blood sampling regimens, we simulated different sampling strategies and compared them with the 24-hour averages. The accuracy of single samples proved inadequate for all hormones. Sampling every 20 minutes for periods of 4, 8, or 12 hours improved accuracy, but intermittent sampling every 1, 2, 4, or 6 hours during a 24-hour period yielded even more accurate results.(ABSTRACT TRUNCATED AT 250 WORDS)

The pulsatile release of GH was investigated in eight active acromegalic patients before and during a subcutaneous infusion of 300 micrograms octreotide/24 h for 4 weeks. The number of GH pulses increased from a basal value of 14.4/24h to 16.3/24h during octreotide therapy. At the same time the mean GH concentration, valley concentration, peak height and amplitude decreased significantly. The inhibitory effect of octreotide on pulse characteristics did not depend on the time of day. IGF-I levels also decreased significantly; in five patients normal levels were reached. IGF-I levels correlated significantly with the mean GH level (r = 0.714, P less than 0.001), mean valley concentration (r = 0.697, P less than 0.001) and, to a lesser extent, area under the curve (r = 0.436, P = 0.033), but not the number of pulses. Plasma octreotide levels did not correlate with pulse parameters. In all but one patient a circadian rhythm was present during both the basal study and octreotide therapy. Compared with surgically treated acromegalics, the number of GH pulses was higher in untreated and octreotide-treated patients. This study demonstrates the pulsatile release of GH in active acromegaly both before and during octreotide therapy. This result suggests that endogenous GHRH is important for the generation of GH pulses in this disease.

cDNAs prepared using poly(A)mRNA from pituitaries and containing the coding sequences for bovine and porcine growth hormones (bGH and pGH) were cloned in bacteria. The primary structures of the peptide hormones derived from the nucleotide sequences of the respective cDNAs show approximately 90% homology. The cloned cDNAs were modified using synthetic DNA to construct expression vectors for efficient bacterial production of the mature animal growth hormones.

The plasma growth hormone profiles and sleep patterns of 13 treated male acromegalic patients, aged 29-67 years, were studied. All patients had undergone selective pituitary transsphenoidal surgery 4-9 years previously; five patients had also undergone supplemental pituitary irradiation. Blood samples were taken at 20-min intervals; the sleep patterns were obtained by EEG. GH reserve was assessed after insulin-induced hypoglycaemia and GHRH (1-44) with and without pyridostigmine. The profiles were analysed with the aid of the Pulsar program. Seven out of eight non-irradiated patients had 1-3 nocturnal GH peaks; in the irradiated group only one patient had a normal profile. The GH reserve after insulin-induced hypoglycaemia was normal in seven out of eight non-irradiated patients, and subnormal in all five irradiated patients. In the latter group the GH reserve was diminished when tested with GHRH. One patient from each group had a severe apnoea syndrome; in both cases there was no nocturnal GH increase. The percentage sleep stage 1 was lower for irradiated patients when compared with non-irradiated patients, but the 14 other sleep parameters did not differ. From this study we conclude that the physiological regulation of GH secretion is restored in surgically treated patients. Radiation therapy may lead to pituitary and hypothalamic damage, which could affect spontaneous GH secretion.