Growth hormone response to TRH in families multiply affected with schizophrenia.
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Adult↗
Biomedical subjects
Z Laron
Publications and source records attributed to Z Laron.
Effects of insulin-like growth factor on linear growth, head circumference, and body fat in patients with Laron-type dwarfism.
Patients with Laron-type dwarfism are clinically indistinguishable from those with isolated growth hormone (GH) deficiency, yet have high circulating GH concentrations associated with an inability to generate endogenous insulin-like growth factor I (IGF-I). Biosynthetic IGF-I was administered subcutaneously once daily for 3 to 10 months to 5 children with Laron-type dwarfism aged 3.3 to 14.5 years. There was a rapid stimulation of linear growth in body limbs, with a striking increase in head circumference, increased body weight, and a reduction in subcutaneous fat. Administration of IGF-I to patients with Laron-type dwarfism seems to have a beneficial effect on growth similar to that observed with long-term administration of GH in children with GH deficiency.
Adipose Tissue↗
Growth hormone therapy in normal short children induces a transitory decrease in plasma growth hormone releasing hormone levels and in human growth hormone responsiveness to exogenous growth hormone releasing hormone.
A three-month study of the effect of growth hormone (hGH) therapy (0.1 U/kg/day sc) on plasma levels of GH releasing hormone (GHRH), somatostatin and insulin-like growth factor I (IGF-I) and on the hGH responsiveness to exogenous GHRH was carried out in 32 prepubertal short-stature children with normal GH secretion. Blood samples were collected prior to initiation of therapy, and at 5, 30 and 90 days of onset of therapy, as well as 2 and 90 days after termination of therapy. The nonconventional hGH therapy induced an increase in serum IGF-I levels which lasted as long as therapy was continued. Plasma GHRH levels showed an early transitory decrease after five days of therapy, whereas plasma somatostatin levels were unaltered. A slight suppression in hGH responsiveness to exogenous GHRH was found at 2 but not at 90 days after termination of hGH therapy. It is concluded that nonconventional hGH treatment does not cause permanent changes in physiological hGH secretion.
Adolescent↗
Effect of sodium valproate on the secretion of prolactin, cortisol and growth hormone in migraine patients.
A single oral dose of 500 mg sodium valproate had no effect on prolactin, growth hormone and cortisol secretion in 10 migraine patients when compared with five healthy controls and four migraine patients receiving placebo. Basal values of prolactin (PRL), cortisol and growth hormone (GH) were within the normal range, though PRL basal levels were lower in three patients (21.5%) in the migraine group.
Adult↗
Neuroendocrine response to trihexyphenidyl in depressed patients.
The effect of a single dose (10 mg P.O.) of trihexyphenidyl (THP) on plasma cortisol, growth hormone (GH), and immunoreactive beta-endorphin (ir-beta-EP) was studied in seven major depressed patients and seven controls. GH secretion was suppressed (34-41%) by THP in both groups. THP did not affect cortisol secretion in depressed patients and controls. An increase (18%; p less than 0.05) in plasma ir-beta-EP levels was detected in the healthy subjects only. The results of this study do not support the hypothesized altered responsiveness to anticholinergic provocation in major depression. The inhibitory activity of THP on GH secretion indicates the involvement of the cholinergic system in the regulation of GH release in humans.
Adult↗
IGF binding protein 3 in patients with Laron type dwarfism: effect of exogenous rIGF-I.
OBJECTIVE: The aim of the study was to investigate the serum levels of IGFBP-3, the major IGF-I binding protein, in patients with Laron type dwarfism (LTD) before and after IGF-I treatment. DESIGN AND PATIENTS: Eight Laron type dwarfism patients (four children and four adults) were treated for 7 days by one daily s.c. injection of biosynthetic IGF-I in doses of 120 or 150 micrograms/kg/day. MEASUREMENTS: Blood was sampled in the fasting state before and 1 and 7 days after the last injection. RESULTS: It was found that IGF-I administration significantly reduced plasma hGH levels with recovery after one week of no treatment. Serum IGFBP-3 was abnormally low (0.70 +/- 0.37 mg/l) and decreased significantly further during IGF-I treatment (to 0.48 +/- 0.28 mg/l) (P less than 0.065). CONCLUSIONS: The finding that serum IGFBP-3 is low in Laron type dwarfism, a disease due to molecular defects in the GH receptor, is compatible with the hypothesis that this IGF binding protein is GH-dependent. On the other hand the decrease during IGF-I administration and concomitant suppression of GH secretion may denote either that GH activity is not completely blocked in this syndrome or that there are additional mechanisms regulating IGFBP-3 synthesis.
Adolescent↗
Social, educational and vocational status of 48 young adult females with gonadal dysgenesis.
OBJECTIVE: The purpose of this study was to evaluate the educational, vocational and social function of young adults with gonadal dysgenesis. DESIGN: Forty-eight female patients with gonadal dysgenesis (17, 45XO; 26, 45XO/46XX or other mosaics; and five pure gonadal dysgenesis) followed by our multidisciplinary team from childhood, were re-evaluated in adult age. RESULTS: Mean age +/- SD at diagnosis was 11.4 +/- 5.0 years and mean age at the time of survey was 29.6 +/- 6.3 years. The mean final height for the patients was 145.5 +/- 8.3 cm (range 134-170 cm). Mean verbal IQ (WISC-R) for the 39 subjects tested was 101.4 +/- 20.7 and mean performance IQ was 86.8 +/- 17.7. No difference in verbal IQ levels was found between the various karyotype groups. Twenty-five had an academic education. All were employed except for one housewife; 37 work in white collar professions. A significant correlation was found between verbal IQ and education (P = 0.005) and between verbal IQ and profession (P = 0.005). Twenty-three served in the army. Fourteen are married: three have an adopted child and two a child born after in vitro fertilization (IVF); others are waiting for IVF or adoption. Five patients had some form of psychiatric problem that required psychiatric or psychological treatment in the past (two had transitory anorexia nervosa and three behavioural problems). Sixty-three per cent reported having wide and satisfactory social relations but limited to female friends. CONCLUSION: Positive adjustment in the professional area and fair adjustment in the social area were not related to physical stigmata or to any other independent variable tested, but rather to intellectual ability and a high degree of achievement motivation.
Adult↗
Growth in patients with isolated gonadotrophin deficiency.
The growth pattern of 66 patients (50 males, 16 females) with isolated gonadotrophin deficiency (IGnD), who had reached their final height with epiphyseal closure, was evaluated. For the purpose of analysis the males were divided into two groups according to age at referral: group 1 less than 16 years (n = 23) and group 2 greater than or equal to 16 years (n = 27). Sex hormone treatment was initiated at a mean (SD) chronological age of 15.8 (1.3) and 18.6 (1.2) years in groups 1 and 2 in the males and at 15.3 (1.3) years in the females. The duration of treatment (until epiphyseal closure) in the males was 3.9 (1.5) years in group 1 and 2.1 (1.0) years in group 2 and 2.8 (1.3) years in the females. There was no significant difference between the mean final height in groups 1 and 2, but it was significantly higher than the mean parental height (mean height SD score (HtSDS): 0.1 (1.1) v -0.8 (0.9)) and they were significantly correlated. For females the mean HtSDS compared with parental height was 0.4 (1.5) v -0.6 (1.2). It is concluded that the timing of induction of puberty by sex hormones in males and females with IGnD has no significant effect on final height provided that moderate doses are used. Furthermore final height was significantly correlated to mid-parental height.
Adolescent↗
Serum prolactin in patients with Laron-type dwarfism: effect of insulin-like growth factor I.
Prolactin (PRL) secretion was studied in Laron-type dwarfism (LTD) patients (8 children and 9 adults) in basal condition, after acute insulin-like growth factor (IGF-I) or TRH injections and during 2 months of daily IGF-I treatment. Basal PRL was repeatedly higher (12.6 +/- 1.6 micrograms/l) than that in control subjects (7.6 +/- 1.2 micrograms/l, p < 0.05). Acute IGF-I injection caused an immediate slight decrease in serum PRL and growth hormone (GH), followed by a progressive rise to mean peak levels of 33.3 +/- 4.5 micrograms/l again parallel to serum hGH which rose to 86 +/- 20 micrograms/l--a response to the IGF-I-induced hypoglycemia. Intravenous TRH in LTD children induced a marked response in serum PRL, similar to that registered in estrogenized adult females. Serum PRL did not show consistent changes during chronic IGF-I treatment. It is suggested that the higher-than-normal PRL levels and release in LTD patients are due to a drift phenomenon of the mammosomatotropes which produce large amounts of hGH.
Adult↗
Growth hormone and insulin-like growth factor regulate insulin-like growth factor-binding protein-1 in Laron type dwarfism, growth hormone deficiency and constitutional short stature.
Insulin-like growth factors (IGFs) mediate the effects of growth hormone (GH), and the insulin-like growth factor-binding proteins (IGFBPs) modulate the actions of IGFs in tissues. We studied the circulating levels of IGFBP-1 in 6 children and 9 adults with Laron type dwarfism (LTD), in 11 children and 21 adults with growth hormone deficiency (GHD), and in 8 children with constitutional short stature. Compared with the situation in healthy children, the basal serum IGFBP-1 concentration was 5.4-fold higher in LTD children, 4.1-fold higher in GHD children, and 3.8-fold higher in children with short stature (p < 0.02 vs controls in all groups). In adult patients with multiple pituitary hormone deficiency (MPHD), the IGFBP-1 concentration was 2-fold elevated, but it was normal in adult LTD patients. Intravenous (N = 10) or subcutaneous (N = 9) administration of IGF-I (75 micrograms.kg-1 and 150 micrograms.kg-1, respectively) in LTD children resulted in a rapid 50-60% fall in serum insulin (p < 0.02), a decline in blood glucose and a concomitant 40-60% rise of IGFBP-1 levels (p < 0.05). Treatment for seven days with IGF-I (150 micrograms.kg-1 x d-1) resulted in a decrease by 34% and 44% of serum IGFBP-1 level in two out of three children with LTD. After prolonged GH therapy, the IGFBP-1 level fell in GHD children by 29% (p < 0.05), in GHD adults by 52% (p < 0.02) and in children with constitutional short stature by 17% (p < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Effect of insulin-like growth factor I on the thyroid axis in patients with Laron-type dwarfism and healthy subjects.
We have evaluated the effect of exogenous administration of IGF-I on the thyroid axis in four separate studies: (1) iv bolus injection; (2) single sc injection; (3) seven days' sc treatment, and (4) four months' treatment. Thirteen patients with Laron-type dwarfism (LTD) participated in the investigations. In studies 1 and 2, 10 healthy subjects were also included. Before and during long-term treatment (study 4) six LTD patients underwent a TRH test. IGF-I was administered in a dose of 75 micrograms.kg-1 iv or 120-150 micrograms.kg-1 sc. Single injections of IGF-I caused significant decreases of serum TSH in LTD patients (iv: 1.7 +/- 0.2 to 1.1 +/- 0.1 mU/l; sc: from 2.1 +/- 0.4 to 1.1 +/- 0.2; p < 0.0005). In controls the decrease was for iv from 1.2 +/- 0.2 to 0.8 +/- 0.2 mU/l (p < 0.02) and for sc from 2.0 +/- 0.5 to 0.8 +/- 0.2 mU/l (p < 0.05). Long-term administration of IGF-I induces a transitory decrease of both serum TSH and fT4, followed by a spontaneous rise to pretreatment or even higher values. No changes in T3 were observed. TSH stimulation by TRH was significantly augmented after four months of IGF-I treatment (p < 0.005). The effects of IGF-I can be explained by an early stimulation of somatostatin release causing a decrease in TSH and followed by the development of compensatory mechanisms. All changes were within the normal ranges, not causing abnormal thyroid function.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Picture of the month. Laron-type dwarfism.
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Child, Preschool↗
Myopathy associated with ketoconazole treatment.
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Adolescent↗
Mortality in Israeli Jewish patients with type 1 (insulin-dependent) diabetes mellitus diagnosed prior to 18 years of age: a population based study.
A total of 614 Jewish patients under the age of 18 with Type 1 (insulin-dependent) diabetes mellitus, diagnosed in Israel during the period 1 January 1965 to 31 December 1979, were identified by exhaustive screening of all possible sources. Mortality experience of this cohort was updated to 31 March 1988 through the Central Population Registry and 14 deaths were identified. The ascertainment rate for diagnosed cases as well as for deaths is estimated at about 95%. There was a significantly higher (p less than 0.001) by 3.2-fold excess mortality relative to the age and sex-adjusted mortality as expected the general Jewish population in Israel. This excess was due to three cause-of-death categories: diabetic ketoacidosis (n = 3; p less than 0.001), cardiovascular diseases (n = 3; p less than 0.001) and infections (n = 2; p = 0.03). The rate of malignancies (n = 2), external causes (n = 3) and other general causes (n = 1) did not differ significantly from that expected. During the first 15 years of the disease cumulative mortality resembled that of the general population, with a subsequent steep increase so that by 20 years disease duration, the rate was four-fold higher than expected. This mortality pattern was similar irrespective of age at onset, sex and ethnic group (Ashkenazi vs non-Ashkenazi Jews). A factor contributing to the lack of increase in mortality rate in the first 15 years of Type 1 diabetes may be the comprehensive multidisciplinary treatment approach employed for most juvenile diabetic patients in Israel leading to early referral and an overall better metabolic control.
Adolescent↗
Ectopic thyroid in siblings.
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Choristoma↗
TRH stimulation test in obsessive-compulsive patients.
Serum thyroid stimulating hormone (TSH), prolactin (PRL), and growth hormone (GH) levels were measured before and after stimulation with 200 micrograms of thyrotropin releasing hormone (TRH) in 10 patients with obsessive-compulsive disorder (OCD) and in 10 control subjects. There were significantly more blunted TSH responses among OCD patients than control subjects. PRL and GH responses to TRH challenge did not differ between OCD patients and controls. These results may indicate dysregulation of the hypothalamic-pituitary-thyroid axis in OCD.
Adult↗
Biochemical and hormonal changes induced by one week of administration of rIGF-I to patients with Laron type dwarfism.
OBJECTIVE: The purpose of this investigation was to evaluate the effectiveness of short-term administration of recombinant biosynthetic IGF-I on patients with an hereditary inability to generate this hormone. DESIGN AND PATIENTS: Ten patients with Laron type dwarfism (LTD) (4 males, six females) aged 3 1/2 to 37 3/4 years were submitted to seven daily s.c. injections of recombinant IGF-I in doses of 120 or 150 micrograms/kg/day. MEASUREMENTS: Blood samples were drawn before, after three and seven injections, and one week after stopping the trial. RESULTS: The main biochemical and hormonal changes registered were (mean +/- SD): a marked rise in serum type III procollagen (PIIINP) from 4.2 +/- 0.9 to 7.3 +/- 2 micrograms/l (P less than 0.0003) and decrease in the following blood components: plasma hGH from 32.51 +/- 43.77 to 4.02 +/- 2.48 mU/l (P less than 0.001), serum cholesterol from 5.9 +/- 1 to 5.7 +/- 0.8 mmol/l (P less than 0.04), serum SGOT from 28.9 +/- 11.6 to 15.5 +/- 7.6 U/l (P less than 0.01) and serum LDH from 286 +/- 88 to 222 +/- 37 U/l (P less than 0.0005). The response of plasma insulin was variable, decreasing in seven of ten and increasing in three. Some of these effects were transitory, and were found after 3 days therapy but afterwards decreased (insulin, cholesterol and liver tests), others persisted throughout the whole treatment period (hGH, PIINP). CONCLUSIONS: IGF-I mimics the biochemical and hormonal changes described after administration of hGH. The administration of IGF-I in patients with Laron type dwarfism is devoid of side-effects and warrants assessment in long-term studies.
Adolescent↗
Effect of octreotide on 24-hour growth hormone and prolactin secretory patterns in acromegalics.
Four adult patients with active acromegaly underwent studies of their 24-hour secretory pattern of hGH and Prl prior to and at the end of 3 months of treatment with the octreotide (somatostatin analog SMS 201-995) 100 micrograms s.c. every 8 h. Blood was withdrawn at 30-min intervals with the aid of a constant withdrawal pump. The best fit cosinor method was used to define the following rhythm parameters: mesor, amplitude, acrophase and periodicity. Prior to treatment, hGH secretion was increased in all patients. The mean 24-hour ranged from 9-47 ng/ml with amplitude 5.2-23 and observed maximal pulse 41-95 ng/ml. Computed rhythms were circadian in 3 patients and ultradian in 1; in 2 patients the acrophases were shifted to daytime. hPrl secretion was altered in 3 of the patients. Two had elevated mean 24-hour of 17.7 and 22.2 ng/ml, while computed rhythms showed semicircadian periodicity in 1 of them and circadian periodicity with a shift of acrophase to daytime in the other. The third patient who had normal hPrl levels, showed ultradian 8-hour periodicity. At the end of treatment there was a marked reduction in hGH secretion in 1 patient and a lesser reduction in the other 3. The rhythm was influenced by the masking effect of the drug, to yield an 8-hour period with acrophases related to injection clock time having equal amplitudes.(ABSTRACT TRUNCATED AT 250 WORDS)
Acromegaly↗