M. A. Preece

Critically ill patients have high basal growth hormone levels with attenuated oscillatory activity associated with low levels of insulin–like growth factor-I

Summary. objective The aim was to study the relationship between growth hormone (GH) and insulin‐like growth factor‐I (IGF‐I) in critically ill patients.

Laron-type dwarfism with apparently normal high affinity serum growth hormone-binding protein

Summary. objective Normal serum contains a high affinity GH‐binding protein, which appears to be Identical with the extracellular domain of the GH receptor. It Is normally absent from the serum of patients with Laron‐type dwarf‐ism. We wished in this study to define the serum GH‐binding protein status of a family with Laron‐type dwarf‐ism.

GONADOTROPHIN, GROWTH HORMONE AND PROLACTIN SECRETION IN CHILDREN WITH PRIMARY HYPOTHYROIDISM

We have studied eight children with primary hypothyroidism (6F, 2M) aged 6–7 to 14–2 years. The girls were prepubertal and the boys had early normal pubertal development. Overnight secretion of LH, FSH, TSH, PRL and GH, and ovarian ultrasound morphology were assessed before and up to 9 months after commencing thyroxine treatment. Serum FSH concentrations in all the girls were increased above LH levels and severe hypothyroidism was associated with reduced GH secretion. These abnormalities reversed with thyroxine treatment. The boys had less severe hypothyroidism and did not demonstrate abnormal gonadotrophin or GH secretion. We conclude that primary hypothyroidism in childhood is associated with widespread disturbance of pituitary function, including increased FSH secretion often without signs of early sexual maturation.

PHYSIOLOGICAL GROWTH HORMONE (GH) SECRETION DURING THE RECOVERY FROM PSYCHOSOCIAL DWARFISM: A CASE REPORT

We describe a 6.4 year old boy who had reversible GH insufficiency secondary to psychosocial dwarfism. On removal to a more favourable environment we observed the recovery of physiological GH secretion by progressive increase in GH pulse amplitude. These observations are relevant to our understanding of the control of GH secretion in that GH pulse frequency appears invariable and alteration in GH secretion is by pulse amplitude modulation.

PHYSIOLOGICAL GROWTH HORMONE SECRETION DURING SLOW‐WAVE SLEEP IN SHORT PREPUBERTAL CHILDREN

The usefulness of a limited nocturnal GH profile has been evaluated for the assessment of physiological GH secretion. We have analysed the complete overnight GH and sleep profiles of 20 short prepubertal children, sampled at 15‐min intervals. The mean age was 9.1 years (range 4.3‐11.7 years) and mean height velocity standard deviation score (SDS) ‐ 1 0 (range ‐ 2.4 to + 0.4). The sleep stage in which the maximal GH value was reached varied considerably between the patients. Only 55% achieved the maximal GH value during the first slow‐wave sleep period, and 65% in the first 2 h of sleep. The maximal values during the first slow‐wave period correlated weakly with the sum of the nocturnal peak values and the total area under the curve of the complete GH profile. None of these parameters correlated with height velocity. We conclude that at present there is no substitute for complete overnight or 24 h GH profiles for the assessment of physiological GH secretion, but the clinical significance of the variations seen remains unclear.

Antigenicity and efficacy of authentic sequence recombinant human growth hormone (somatropin): first-year experience in the United Kingdom.

Twenty‐one children were treated for GH deficiency with authentic sequence biosynthetic human GH (somatropin), 60 μg/kg body weight, subcutaneously, three times weekly for 1 year or longer. The magnitude of growth response and rise in serum insulin‐like growth factor I levels were similar to those expected from experience with pituitary GH and somatrem. Three patients developed serum antibodies to GH with a binding capacity < 0.02 μg/l, but in only one patient was the GH binding capacity < 10 μg/l and he showed no attenuation of growth response. Eschericliia coli polypeptide antibodies did not rise significantly and no clinically important side‐effects occurred. Somatropin is safe, effective and of low immunogenicity in the treatment of GH deficiency.

Growth, insulin-like growth factor I (IGF-I), and igf-binding proteins 1 and 3 in children with severe liver disease before and after liver transplantation : A longitudinal and cross-sectional study

We aimed to study the growth and growth factors of children with liver disease before and after liver transplantation (LT). Three observation intervals: 1) before LT (preLT), 2) after LT on daily prednisone treatment (dP), and 3) on alternate day prednisone (adP). A longitudinal study (LS) involved 17 infants (9 male) aged 0.73-2.38 y at LT; mean (±SD) height (Ht) SD score (SDS) at LT was -2.02 (± 1.25). In a cross-sectional study, there were 123 children (73 male) aged 0.16-14.88 y (mean 3.72 y). IGF-I and IGF binding proteins (BP) 1 and 3 were measured at the same intervals. The results were, for LS, preLT height velocity (HV) SDS(-X ± SD -0.8 ± 1.4) lower (p < 0.01) than adP-HV SDS (3.1 ± 1.8) but not different from dp-HV SDS(-1.0 ± 1.9). For the cross-sectional study, dP-Ht SDS(-X ± SD -1.94 ± 1.31) lower (p < 0.001) than preLT-Ht SDS (-1.03 ± 1.06) and adP-Ht SDS (-0.98 ± 1.20). Parental target SDS was not different from adP-Ht SDS. (Similar observations were made in the LS.) The dP- sitting height (SH) and subischial leg length (SLL) SDS were significantly lower than both preLT- and adP-SH SDS and SLL SDS (p = 0.02 and 0.002, respectively). There was a significant improvement of head circumference SDS and arm circumference SDS from preLT to adP. The dP and adP IGF-I and IGF-BP3 levels were greater than preLT levels (p < 0.001); no differences were found between preLT, dP, and adP IGF-BP1 levels. We conclude that growth in children with liver disease does not improve after LT on dP, but catch-up growth is shown on adP, appearing to depend mainly on the clinical course and corticosteroid regimen. IGF-I and IGF-BP3 increment on dP (and sustained on adP) is possibly due to liver regeneration, in contrast with inhibition of body growth on dP, possibly due to central and peripheral effects of corticosteroid.

Contractile protein synthesis rates in vivo in the rat jejunum: modulating role of adrenalectomy and thyroidectomy on ethanol-induced changes

Abstract Acute ethanol toxicity has many deleterious effects on the gastrointestinal tract and, in particular, inhibits small intestinal protein synthesis. The mechanism(s) of the ethanol‐induced inhibition of protein synthesis are unknown. This study was designed to investigate the role of adrenal and thyroid hormones on the ethanol‐induced inhibition of whole jejunal protein synthesis in adrenalectomised and thyroidectomised male Wistar rats. Acute ethanol dosage significantly reduced protein synthesis in all subcellular protein fractions of the whole jejunum, in sham‐thyroidectomized, thyroidectomized, sham‐ardrenalectomized and adrenalectomized rats. Synthesis rates relative to RNA and DNA were also highly significantly reduced in all treatment groups in ethanol‐dosed rats. However in most protein fractions the inhibition of protein synthesis was greater in thyroidectomized compared to sham‐thyroidectomized rats, whereas the reverse was true in adrenalectomized rats. Neither adrenalectomy or thyroidectomy completely abolished ethanol‐induced inhibition in protein synthesis, suggesting that ethanol or its metabolites, e.g. acetaldehyde, acts directly on the tissue. However, the ethanol‐induced inhibition of protein synthesis was greater in thyroidectomized rats demonstrating that contractile and non‐contractile proteins synthesis in the jejunum is under control of complex regulatory processes.

GONADOTROPHIN, GROWTH HORMONE AND PROLACTIN SECRETORY DYSFUNCTION IN PRIMARY HYPOTHYROIDISM

We have studied 5 prepubertal girls (age 6.7 - 12.3 yr) and 2 boys (age 13.3 and 14.2 yr) in early puberty (stage 2 genitalia) with primary hypothyroidism. Overnight serum hormone profiles (15-minute sampling) were performed at diagnosis and after 3 and 6 months of replacement therapy (Thyroxine 100μg/m2/day).Pre-treatment, the girls had peak TSH levels 850-4800 mU/l with FSH concentrations raised (peak 3.9-19.5 U/l) above the LH levels (peak 1.8-3.7 U/l) which were non-pulsatile. Pelvic ultrasound showed small numbers of ovarian cysts without a multicystic morphology. Prolactin concentrations were elevated and pulsatile (peaks 800-4600 mU/l). Progressive falls in TSH, prolactin and FSH occurred during treatment. LH levels were unchanged in 3 girls but increased, becoming pulsatile in the 2 older girls, who also progressed to breast stage 2 by 3 months. GH pulse amplitude increased during treatment.In contrast, the boys had less severe hypothyroidism. Pretreatment TSH levels were 210 and 1400 mU/l; prolactin levels were elevated to 1200 and 1700 mU/l. Gonadotrophin profiles showed pulsatile patterns appropriate for early puberty with LH predominating over FSH.Raised FSH secretion occurs as a spectrum in children with primary hypothyrodism, even in those without abnormal sexual development.

PHYSIOLOGICAL GH SECRETION IN CHILDREN WITH SHORT STATURE DUE TO LOW BIRTHWEIGHT/RUSSELL-SILVER SYNDROME

We have studied 24 prepubertal children (7F, 17M) with short stature, mean height SDS -2.8 (range, -5.2 to -1.7) as a consequence of intrauterine growth retardation. Mean age at assessment was 6.3 yrs (range, 1.6-9.6). Mean birthweight SDS, allowing for gestational age, was -2.9 (range, -5.0 to -2.0). Mean height velocity SDS was -0.9 (range, -2.6 to + 1.0). Mean bone age delay was 0.6 “yrs”. Patients were divided into 2 groups; 11(3F, 8M) had dysmorphic features of the Russell-Silver syndrome (RSS group) and 13 (4F, 9M) did not (non RSS group).All children had an overnight serum GH profile from 1900-0800 hrs via an indwelling intravenous cannula with blood drawn at 15 minute intervals. A PULSAR computer programme was used for GH pulse analysis. GH pulse frequency, area under the GH pulses and sum of the GH peaks were calculated. All children had a maximum GH peak >20 mU/l except one boy who only attained a peak GH of 14mU/l. One boy in the non RSS group had high frequency “neurosecretory dysfunction”. The most pronounced abnormality in 6 of the 11 children with RSS was that only one large GH pulse during the night was observed with a mean value of 37 mU/l (range, 27-65). GH secretion remained detectable between pulses in 6 of the children in the non RSS group.It is probable that more than one endogenous GH pulse during the night is required for normal growth. Although growth failure in RSS is multi-factoral and end-organ insensitivity is probably important, abnormal GH secretion may be contributory.