Action of growth hormone on erythropoiesis: changes in red blood cell enzyme activities in growth-retarded patients with and without growth hormone deficiency

Fifteen red cell enzyme activities of growth-retarded patients with and without growth hormone (GH) deficiency were investigated before and after GH administration. The 15 enzymes were Hexokinase, phosphoglucomutase, glucose phosphate, isomerase, phosphofructokinase, fructose diphosphate aldolase, glyceraldehyde-3-phosphae dehydrogenase, triosephosphate isomerase, 2,3-diphosphoglycerate mutase, 3-phosphoglycerate kinase, 3-phosphoglycerate mutase, enolase, pyruvate kinase, glycose-6-phosphate dehydrogenase, 6-phosphogluconic dehydrogenase, glutathione reducase. Sixty-six subjects were studied: 30 normal control subjects (group N) and 36 patients (aged 5-23 years) with short stature. Complete endocrine evaluation showed 21 (group I) to have GH deficiency (10 patients with isolated GH deficiency) and 15 (group II) to have normal hypothalamic and pituitary function except for two patients with a moderate hypothyroidism. Both had been receiving thyroid hormone treatment for a long time before our studies. All 36 patients were treated with 2 mg human growth hormone intramuscularly for 7 days. Before GH treatment no significant difference was observed between hematologic data in group I (GH deficiency) and group II (no GH deficiency). After GH therapy there was a significant increase in reticulocyte count in both groups of patients with short stature. The mean pretreatment value in group I was 1.294% +/- 0.084 (SEM); the mean post-treatment value was 2.081% +/- 0.287 (SEM)< P less than 0.005. The mean pretreatment value in group II was 1.0% 0.184 (SEM); the mean post-treatment value was 1.407% +/- 0.193 (SEM), P less than 0.01. In group II (no GH deficiency) mean pretreatment erythrocyte enzyme activities were not significantly different from those activities observed in normal control subjects (group N). However, in patients who lacked GH, the pretreatment activities of five red cell enzymes (glucose phosphate isomerase, triosephosphate isomerase, glyceraldehyde-3-phosphate dehydrogenase, 2,3-diphosphoglycerate mutase, 3-phosphoglycerate kinase) were significantly decreased before GH administration compared with the values in normal control subjects...     

Strength and its relationship to changes in fat-free mass, total body potassium, total body water and IGF-1 in adults with growth hormone deficiency: effect of treatment with growth hormone

The present investigation examined changes in strength in growth hormone deficient (GHD) adults following treatment with recombinant human growth hormone (rhGH), and assessed their relationship to changes in fat-free mass (FFM), total body potassium (TBK), total body water (TBW), the concentration of TBK and TBW per kg FFM, and insulin like growth factor-1 (IGF-1). The investigation was double-blind and placebo-controlled for a period of 6 months; this was followed by a period of open treatment for a further 6 months. Patients were assigned randomly to experimental (E) and control (C) groups. In the first 6 months group E received rhGH and group C placebo; in the second 6 months both groups received rhGH. Serial data were analysed for 23 males (11 group E, 12 group C) and 20 females (10 group E, 10 group C). Body composition was assessed by dual energy X-ray absorptiometry, TBK and TBW. Muscle strength was recorded for arm flexion, leg extension and hand grip. Significant increases in FFM occurred in the first 6 months in group E (2.3 kg males, 1.4 kg females) and in the second 6 months in group C (2.4 kg males, 1.4 kg females). There was a modest increase in absolute strength with time, although only three increments were significant (knee extension in group E males and arm flexion in groups E and C females), all of which occurred during the 6-12 month period. Allometric scaling did not improve the identification of significant increments of strength. The mean concentrations of TBK (males 57.0-58.6, females 51.4-53.9 mmol) and TBW (males 0.65-0.69, females 0.65-0.68 l) per kg FFM, were significantly smaller at all stages of the trial than the reference values, suggesting that treatment had not fully normalized these variables. Likewise, the relationship between most of the increments of regional and total strength, and the corresponding increments of FFM, were generally poor and not significant. It was concluded that the reduced concentrations of TBK and TBW per kg FFM, which may be the effect of an inappropriate dose regime or mode of delivery, may, in part, contribute to the anomaly between increases in strength and FFM.     

Intense sympathetic nerve activity in adults with hypopituitarism and untreated growth hormone deficiency

Perturbations in the sympathetic nervous system may be anticipated in adults with hypopituitarism and untreated GH deficiency, because the syndrome is associated with both peripheral and central factors known to modulate sympathetic traffic. The higher prevalence of hypertension and increased cardiovascular morbidity/mortality reported in GH-deficient patients may suggest increased activity of the sympathetic nervous system. We recorded muscle sympathetic nerve activity (MSNA) in 10 hypopituitary adults with adequate hormonal replacement therapy except GH and in 10 healthy controls matched for age, gender, and body mass index to test whether hormonal aberrations in hypopituitarism and untreated GH deficiency are associated with an increase in sympathetic nerve traffic. Blood samples for insulin-like growth factor I, free T4, and TSH were taken after an overnight fast, followed by an oral glucose tolerance test. Direct intraneural recordings of MSNA were performed with a tungsten microelectrode from the peroneal nerve. The hypopituitary subjects had markedly increased MSNA (54 +/- 4 bursts/min vs. 34 +/- 4 in controls; P < 0.002), which was not related to abdominal obesity or altered glucose metabolism. When assessed for the whole study group, MSNA was inversely correlated to serum insulin-like growth factor I (r = -0.59; P < 0.006) and TSH (r = -0.46; P < 0.04). MSNA was positively correlated to diastolic blood pressure (r = 0.80; P < 0.0005) in patients, but not in controls. The intense sympathetic discharge is suggested to be of central origin and may be an important underlying mechanism for the secondary hypertension and increased cardiovascular morbidity/mortality in this patient group.     

Contractile properties and fiber type distribution of quadriceps muscles in adults with childhood-onset growth hormone deficiency

Adults with GH deficiency (GHD) report weakness and fatigability. The origin of such symptoms is still debated. This work aimed to clarify whether weakness and fatigability depend on impairment of skeletal muscle contractile capacity. Five males with childhood-onset GHD (age +/- SE, 29.6 +/- 1.9) and 13 age- and sex-matched controls were enrolled in the study. Quadriceps muscle cross-sectional area (CSA), strength, twitch characteristics, and fatigue index of voluntary and electrically evoked contractions were determined in vivo in all subjects. Fiber type distribution and CSA of identified types of skeletal fibers were determined on needle biopsy samples of the vastus lateralis muscle of all subjects. Fiber type distribution was assessed on the basis of myosin heavy chain (MHC) isoform composition determined by electrophoresis on polyacrylamide gels. Fiber CSA was determined on cross-cryosections of fiber bundles immunostained by monoclonal antibodies against MHC isoforms. Absolute values of strength and fiber CSA of quadriceps were significantly lower in patients affected by GHD than in controls. However, once strength and fiber CSA were normalized for quadriceps CSA and subject height, respectively, differences disappeared. No difference was found between GHD patients and controls for quadriceps muscle twitch characteristics, fatigue index, and fiber type distribution. The results reported here suggest that weakness and fatigability in childhood-onset GHD do not have a skeletal muscle origin.     

Diurnal variations in twenty-four-hour energy expenditure during growth hormone treatment of adults with pituitary deficiency

The effects of growth hormone (GH) treatment on 24-h energy expenditure (EE) were studied in a open trial over a period of 4 weeks. Five subjects, four men and one woman, with a history of complete GH deficiency were included. All the subjects were examined on 2 consecutive days on baseline and, thereafter, at six occasions during a period of 1 month (days 1, 2, 5, 8, 15, and 30). The dose of GH was 0.25 U/kg.week, administered sc once a day in the evening. EE was determined in a chamber for indirect calorimetry. Body composition was determined with dual-energy x-ray absorptiometry and computed tomography using a four-scan technique. Blood samples were examined using well-established RIAs. During the first 2 weeks, 24-h EE increased by 6 +/- 3% (range 1-8%) from 40.9 +/- 4.8 to 42.9 +/- 4.8 kcal/24 h.kg (P < 0.05), sleeping metabolic rate by 14 +/- 3% (range 10-18%) from 28.4 +/- 1.9 to 32.9 +/- 2.2 kcal/24h.kg (P < 0.001), and basal metabolic rate by 11 +/- 7% (range 0-18%) from 29.6 +/- 2.4 to 33.3 +/- 2.6 kcal/24h.kg (P < 0.05). No change was found in daytime EE. The increase in EE covaried with changes in insulin-like growth factor 1, the free T3/free T4 ratio, insulin-like growth factor-binding protein-3, and the aminoterminal procollagen III peptide but not with changes in body composition. It is suggested that the stimulating effect of GH on EE occurs gradually during a 2-week period and is only detectable during night and morning hours, when significant levels of GH occur.     

The role of plasma growth hormone, prolactin, triiodothyronine and tetraiodothyronine in the regulation of growth and sex differences in body weight of turkeys

An attempt was made to alter male:female (M:F) body weight ratios in two strains (S12 and S72) of turkeys by selective matings; to study their post-hatching growth patterns and to relate growth patterns to plasma growth hormone (GH), prolactin (Prl), tetraiodothyronine (T4), and triiodothyronine (T3) concentrations. Selection for high and low M:F body weight ratio (HR and LR) was essentially ineffective in both strains. Sex differences in body weight were first significant in S12 at day of age and in S72 at 6 wk. Plasma GH and Prl rose during the first 2 wk of age and fell thereafter while T3 levels decreased and T4 levels increased over time. Differences in plasma hormones between lines and sexes within strains were noted, but showed no consistent patterns. Correlations between GH and growth were mostly negative. When significant, regressions between body weight and GH or gain and GH were generally negative. Significant correlations between Prl and body weight in males were negative whereas they were of mixed sign in females. Correlations between T3 levels from 2 to 8 wk of age and body weight over this same period were mostly positive in males whereas those at later ages and in females were mostly negative. Few significant correlations between T4 and weight were found. These findings suggest that the regulation of growth in turkeys is quite different than that of mammals and that hormones known to regulate growth in some species may not do so in others.     

Possible role of plasma neurotensin on growth hormone regulation in neonates

The multimedia portrayals of dentists and dentistry have expanded in scope. Prevention and esthetics have replaced drilling and extraction in the public perception of dental practice. According to the author, dentists themselves are no longer treated exclusively as buffoons or sadists. Instead, he writes, they are more apt to be seen as solid citizens, occasionally as romantic figures and even as complex, realistic human beings.     

Growth hormone deficiency and its treatment in adults

Deficiency of growth hormone produced in the pituitary is manifested not only in children by impaired growth but also in adults. It is encountered most frequently in adults after surgery or irradiation in the hypothalamo-pituitary area, less frequently in idiopathic disorders of growth hormone production and secretion, either isolated or in conjunction with other trophic pituitary hormones. The diagnosis of growth hormone deficiency must be assessed by dynamic stimulation tests: most frequently the insulin stimulation test is used. Growth hormone deficiency in adult age is manifested by various non-specific symptoms which resemble symptoms (manifestations) of ageing: increase of adipose tissue, deterioration of lipid metabolism, osteopenia, impaired cardiac output and others; the symptoms recede partly if growth hormone is administered for a prolonged period. Clinical trials which are under way should define not only suitable indications but also ways of administration of this expensive treatment.     

Microcytosis, anisocytosis and the red cell indices in iron deficiency

Red cell volume distribution curves have been used to measure microcytosis and anisocytosis in normal subjects, blood donors and patients with iron deficiency anaemia. These measurements were more sensitive than the conventional red cell indices for detecting blood donors with a low transferrin saturation. Three stages are suggested as iron deficiency progressively interferes with haemopoietic function. Anisocytosis and an increased percentage of microcytic cells are the first haematological abnormalities to occur and at this stage haemoglobin concentration is usually normal and trasferrin saturation less than 32%. At the second stage the MCV and MCH decline, haemoglobin concentration is generally sub-normal, though not below 9 g/dl, and transferrin saturation is usually below 16%. The final stage of iron deficiency is associated with a low MCHC, a haemoglobin concentration below 9 g/dl and a transferrin saturation of less than 16%.     

Decreased plasma and extracellular volume in growth hormone deficient adults and the acute and prolonged effects of GH administration: a controlled experimental study

OBJECTIVE: There are few data on the endocrine mechanisms underlying the body fluid changes in GH deficiency and their subsequent alteration following GH replacement. We have therefore investigated the time effects of GH on body fluid distribution and fluid regulating hormones in GH deficient adults. DESIGN: The patients underwent in random order four study periods: (1) saline, a 42-hour infusion following 3 weeks without GH, (2) acute GH, a 42-hour GH infusion following 3 weeks without GH, (3) 3 days GH, a 42-hour GH infusion preceded by 3 weeks without GH and 3 days pretreatment with subcutaneous GH injections, (4) 3 weeks GH, a 42-hour GH infusion after at least 3 weeks GH therapy. SUBJECTS: Seven GH deficient adult males and 8 healthy control subjects. MEASUREMENTS: During each infusion period 24-hour blood pressure was recorded, bioimpedance was repeatedly measured and blood samples were obtained every 6 hours. After 41 hours extracellular and plasma volumes were determined isotopically. Extracellular volume, plasma volume and bioimpedance were measured in the control group. RESULTS: GH increased extracellular volume (saline 16.45 +/- 0.79 vs acute GH 16.83 +/- 0.87; vs 3 days GH 17.58 +/- 0.71; vs 3 weeks GH 17.92 +/- 0.88 l, P = 0.01). After 3 weeks of GH, extracellular volumes in the patients and in the control group were identical (control 17.94 +/- 0.32). Plasma volume was increased only after 3 weeks GH treatment (saline 2.93 +/- 0.16 vs acute GH 3.04 +/- 0.22; vs 3 days GH 3.06 +/- 0.07; vs 3 weeks GH 3.37 +/- 0.18 l, P = 0.03), and was decreased compared to the control group (control 3.56 +/- 0.03 l, P < 0.01). Bioimpedance decreased significantly in all treatment periods and was significantly increased compared to the control group. Plasma renin increased during GH administration (saline 16.2 +/- 1.9 vs acute 19.0 +/- 1.9; vs 3 days GH 30.8 +/- 3.0; vs 3 weeks GH 27.0 +/- 3.0 mU/l, P = 0.03), whereas aldosterone and atrial natriuretic factor (ANF) levels remained unaffected by GH. GH caused an increase in systolic blood pressure (BP) and heart rate, whereas diastolic BP remained unaffected. CONCLUSIONS: The present data show that GH deficiency is associated with decreased plasma volume and extracellular volume. GH exposure acutely increases extracellular volume, whereas substitution for a longer time was required to normalize both extracellular and plasma volumes. Renin seems to be involved in these fluid volume regulating effects of GH.     

Disturbed release of growth hormone in mature dogs: a comparison with congenital growth hormone deficiency

An acquired defect in growth hormone secretion in mature dogs has been associated with some forms of generalised alopecia. In an attempt to elucidate the pathogenesis of the disturbance in growth hormone release, the plasma concentrations of growth hormone and insulin-like growth factor I (IGF-I) were measured in two seven-year-old poodles with alopecia and, for comparison, in two young German sheperd dogs with congenital hyposomatotropism (pituitary dwarfism). In the poodles the basal concentrations of growth hormone were low, although often above the detection limit of the assay. The concentrations of IGF-I were in the reference range for healthy poodles. No growth hormone could be detected in the plasma of the German sheperd dogs and the concentrations of IGF-I were very low. Stimulation with clonidine and growth hormone releasing hormone (GHRH) before and after repeated injections of GHRH did not result in significant increases in growth hormone concentrations in plasma. The concentrations of growth hormone in the poodles fluctuated at low levels during the test period. In the German sheperd dogs the levels of growth hormone remained unmeasurable during the stimulation tests. It was concluded that in the two poodles the basal concentrations of growth hormone were sufficient to maintain normal IGF-I concentrations, and thus the release of growth hormone was considered appropriate. Based upon measurements of urinary corticoids and a review of the literature it is suggested that the lack of a growth hormone response to stimulation was due to the enhanced release of somatostatin as a result of mild and fluctuating hyperadrenocorticism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Use of insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 in the diagnosis of acromegaly and growth hormone deficiency in adults

The goal of our study was to compare the clinical usefulness of plasma insulin-like growth factor-I (IGF-I) (with and without binding protein extraction) and IGF binding protein-3 (IGFBP-3) measurements in the diagnosis of growth hormone (GH) disorders in adults. IGF-I and IGFBP-3 concentrations were measured in 25 acromegalic and 25 GH-deficient adult (GHDA) subjects (20-76 years) by comparison to a control population (n = 81) after age and sex stratification. In untreated acromegaly, IGF-I and IGFBP-3 were clearly increased (10 times the mean of controls for unextracted IGF-I, 4 times for extracted IGF-I and 2 times for IGFBP-3). Using the mean + 2SD of the control population as the cut-off point, the sensitivity of IGF-I for the diagnosis of acromegaly was higher than that of IGFBP-3 (unextracted IGF-I: 96% and extracted IGF-I: 100% vs IGFBP-3: 76%). In GHDAs, IGF-I and IGFBP-3 were decreased (34% of the mean of controls for unextracted IGF-I, 37% for extracted IGF-I and 70% for IGFBP-3). Using the mean - 2SD of the control population as the cut-off point, the sensitivity of IGF-I measurement for the diagnosis of GHDA was relatively low, but better for unextracted (68%) than for extracted IGF-I (52%). The sensitivity of IGFBP-3 was much lower (36%), thus invalidating this parameter for the diagnosis of GHDA. Our observations demonstrate that IGF-I measurement is a more powerful tool than IGFBP-3 measurement for the diagnosis of GH disorders in adults. Both IGF-I and IGFBP-3 are very useful for the diagnosis of acromegaly, but they are less reliable for diagnosing GHDA, as normal IGF-I or IGFBP-3 values do not rule out GH deficiency.     

Short and long-term cardiovascular effects of growth hormone therapy in growth hormone deficient adults

OBJECTIVE: Since GH substitution therapy is now available for adult GH deficient patients, information on the cardiovascular effects of GH substitution has assumed major clinical interest. We have therefore assessed cardiovascular effects of short and long-term growth hormone substitution therapy in these patients. PATIENTS AND MEASUREMENTS: Doppler echocardiography was performed in 21 GH deficient patients after 4 months placebo and 4 months GH therapy, in a double blind cross-over study. In an open design study, 13 patients were reinvestigated following 16 months and 9 patients following 38 months of GH therapy. Twenty-one age and sex-matched normal control subjects were also investigated. RESULTS: Heart rate was increased in placebo treated patients as compared to controls. After 4 months of GH treatment, heart rate showed a further increase (10%, P < 0.01) and seemed to remain elevated after 16 months of GH therapy. Systolic and diastolic blood pressures were significantly lower in placebo treated patients than in controls, and did not change significantly after GH treatment. The left ventricular diastolic diameter was reduced in patients as compared to controls, but increased after 4 months GH therapy (P > 0.05) and seemed to increase further during prolonged GH treatment. Cardiac index was at the same level in controls and in placebo-treated patients, but increased by 20% following GH therapy and remained elevated after 16 and 38 months (P < 0.05) of GH substitution. CONCLUSION: Following GH substitution in GH deficient adult patients, left ventricular diastolic dimensions increased and seemed to normalize, while heart rate and cardiac output were found to be increased to supranormal levels.     

Vitamin A deficiency and growth hormone in children

Proliferating trichilemmal tumors are benign epitheliomas that may show malignant transformation. We present a trichilemmal tumor 15 x 15 x 10 cm in size and emphasize malignant transformation criteria.     

Dental maturity in children of short stature, with or without growth hormone deficiency

Macrophages are important constituents of the immune system by exerting phagocytosis on invading pathogens as well as secreting various immunoregulatory factors. Generation of human macrophage hybridoma has not been possible so far due to the lack of an appropriate fusion partner cell line. In the present study, an 8'-azaguanine resistant cell line, termed HL-60R, was established by drug selection of the promyelocytic cell line HL-60. This novel cell line showed resistance to high concentrations of 8'-azaguanine and was sensitive to aminopterin. These characteristics make it suitable for serving as a potential fusion partner cell line in the development of macrophage hybridoma. Cell-surface analysis by FACS revealed that HL-60R cells per se do not express MHC-class II molecules or the macrophage marker, CD11b. PEG-mediated fusion of HL-60R was performed with PBMC-derived human macrophages. Fluorescence labelling of ex vivo isolated macrophages prior to fusion and subsequent FACS analysis showed that PEG-4000 is a more effective fusion agent than PEG-1500. The generation of this novel fusion partner cell line opens the possibility for development of human macrophage hybridoma or other cell lines from myelocytic origin. Such hybridoma clones will not only enable a more convenient study of these cell but will also provide an excellent host site for the proper production and expression of various recombinant proteins from myelocytic origin in vitro.     

Combined deficiency of thyroid stimulating hormone and growth hormone in a diabetic patient with Hashimoto thyroiditis

We report the case of a 36-year-old female patient with insulin dependent diabetes who developed hypothyroidism of pituitary origin after giving birth. She had low levels of free T4 and TSH with no response to i.v. TRH. Antimicrosome antibodies were increased (1/25000), suggesting Hashimoto's thyroiditis. The other hormones were normal except for a low level of growth hormone and insulin growth factor 1. There were no antibodies against the pituitary. MRI of the pituitary was normal. We suspect a vascular origin for this partial pituitary deficiency.     

The regulation of cell volume: the mechanisms, coupled cellular reactions and pathophysiological significance

A review contemplates as a whole the problem of regulation of the cellular volume. The first part of the review considers the influences inducing alterations in the cells volume on account of changes in the tonicity of extracellular milieu and cytoplasm. The review elucidates the ways of implementing the fast and slow regulatory volume increase as well as decrease (RVI, RVD). The volume increase seems to enhance cells' proliferative ability due to activation of ions transport. The volume decrease needs further investigations. The last chapter of the review considers pathophysiological significance of the volume regulation in hyponatremia, diabetes, neutrophil activation.