The Somogyi effect. The paediatric view.
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Adult↗
Biomedical subjects
M Silink
Publications and source records attributed to M Silink.
Transient congenital hypothyroidism due to maternal thyrotrophin binding inhibiting immunoglobulin.
Transient congenital hypothyroidism due to maternal thyrotrophin binding inhibitor immunoglobulin (TBII), a thyroid-stimulating hormone (TSH)-receptor blocking antibody, is described in three male siblings born to a mother with autoimmune thyroiditis. These cases are believed to be the first described in Australia. The first child was found to have a serum TSH of 565 mU/L and had a negative thyroid scan when presented for neonatal screening. He was treated with thyroxine but became thyrotoxic at 3 months of age when he was on a dosage of 85 micrograms/m2 of body surface area. He was euthyroid 6 months after discontinuation of therapy. Nine years later a second hypothyroid sibling was born, with a serum TSH of 709 mU/L on day 4. Both mother and child were demonstrated to be strongly positive for TBII. Again this child was able to cease therapy by the age of 9 months. A third sibling, also TBII positive, was born 12 months after the second. His TSH was 90 mU/L and his serum thyroxine (T4) was 169 nmol/L. On this occasion, thyroid stimulation-blocking antibody was found to be present in the serum of both mother and child. Thyroxine therapy was ceased at 1 month. The family present a picture of varying degrees of transient neonatal hypothyroidism due to the transplacental passage of a maternal receptor blocking antibody. The condition is self-limiting, resolving when the immunoglobulin is cleared from the infant's circulation.
Adult↗
Growth hormone hypersecretion in Sotos' syndrome?
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Adolescent↗
Growth in children with X-linked hypophosphataemic rickets.
Currently, X-linked hypophosphataemic rickets (XLHR) is most commonly treated with a combination of phosphate and vitamin D, but there is conflicting evidence about the effects of this treatment on linear growth. In all, 25 patients with XLHR (current age range, 4.1-22.1 years; median, 8.2 years) were studied to determine whether there was any improvement in height SDS during treatment. The duration of therapy was 2.9-15.0 years (median, 5.7 years). Measurements before the age of 2 years or after the onset of puberty were excluded to remove the effects of measurement difficulties in small infants and of variation in pubertal timing. The growth of these patients was compared with a similar group of untreated historical controls. Patients treated with calcitriol and phosphate for at least 2 years before the onset of puberty (n = 22) had a significantly better mean height SDS than the historical controls (-1.23 compared with -2.05 for the historical controls; p = 0.02). Among patients treated with calcitriol and phosphate for at least 2 years (n = 21), the change in height SDS had a positive correlation with the duration of therapy (r = 0.51; p = 0.02). The growth of children with XLHR treated with combination therapy was thus significantly better than that of historical controls.
Adolescent↗
Pupillary abnormalities in type I diabetes occurring during adolescence. Comparisons with cardiovascular reflexes.
OBJECTIVE: To evaluate computerized infrared pupillometry for the assessment of autonomic neuropathy in adolescents with type I diabetes. RESEARCH DESIGN AND METHODS: We measured resting pupil diameters and pupillary light reflexes in 142 adolescents with type I diabetes (72 boys and 70 girls, 10.4-19.8 yr of age, duration of diabetes 0.7-18.3 yr) and in 75 nondiabetic control subjects (29 boys, 46 girls, 11.3-19.8 yr of age). All study participants were assessed using four standard cardiovascular tests: maximum-minimum heart rate during deep breathing (mean of three cycles); heart-rate change during a Valsalva maneuver (Valsalva ratio, mean of three maneuvers); lying-to-standing heart-rate change (30:15 ratio); and lying-to-standing BP change. RESULTS: Mean resting pupil diameters were significantly smaller in the diabetic group: 6.28 +/- 0.06 vs. 6.77 +/- 0.11 mm, P < 0.0001); and significantly smaller with greater duration of diabetes (r = -0.29, P = 0.0006) and higher levels of GHb (r = -0.24, P = 0.004). Patients with retinopathy grade 30 or more (Wisconsin 191 grading) had significantly smaller resting pupil diameters: 5.9 +/- 0.16 vs. 6.4 +/- 0.12 mm, P = 0.008). The phasic light reflex as determined by reflex amplitude and maximum constriction velocity was significantly reduced in the diabetic group: 2.27 +/- 0.03 vs. 2.44 +/- 0.04 mm, P = 0.0009; and 6.68 +/- 0.12 vs. 7.24 +/- 0.16 mm/s, P = 0.007). Reduced reflex amplitude was related to a longer postpubertal duration of diabetes (r = -0.18, P = 0.04). We found no association between pupillary and cardiovascular tests. CONCLUSIONS: Infrared computerized pupillometry demonstrates subclinical diabetic autonomic neuropathy as early as adolescence. Its presence seems to be related to longer duration of diabetes and unfavorable metabolic control.
Adolescent↗
Mitotic activity and DNA synthesis of rat islet cells following partial pancreatectomy.
The regenerative potential of the adult rat pancreas following a 50% pancreatectomy was investigated. Blood glucose values and body weight were unchanged by the procedure. The mitotic index (MI) of alpha, beta, and exocrine cells was examined in formalin-fixed sections of the pancreas stained for hormones and 5-bromo-2'-deoxyuridine (BrDU) after treating the animals with 2.5 mg/kg colchicine and/or 50 mg/kg BrDU prior to sacrifice. The MI was unchanged within the control group. For pancreatectomized versus control animals, in beta cells after 5 days the MI was 0.84% versus 0.41% (p less than 0.05), while 7 days postoperatively it was 1.04% versus 0.57% (p less than 0.01); in alpha cells, the MI was 0.32% versus 0.17% (p less than 0.05) at 5 days and 0.47% versus 0.24% (p less than 0.05) at 7 days. The MI of exocrine cells rose transiently on day 3 postoperatively to 0.74% in the pancreatectomized group but remained low at 0.15% (p less than 0.01) in the control group. The mean ratio of BrDU + ve beta cells was 1.19% in the pancreatectomy group and 0.45% in the control group on day 5 postoperatively (p = 0.01). A highly significant (r = 0.97; p less than 0.001) correlation existed between BrDU + ve and mitotic cells. There was no difference between the two groups in the area occupied by insulin-positive cells in pancreatic sections, nor in the number of beta cells per islet.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Co-existence of coeliac disease and insulin-dependent diabetes mellitus in children: screening sera using an ELISA test for gliadin antibody.
The prevalence of coeliac disease in children with insulin-dependent diabetes mellitus was investigated using a screening test of serum for antigliadin antibody by ELISA. One hundred and eighty (180) unselected diabetic children were screened for IgA and IgG class antigliadin antibodies (AGA); children with either grossly elevated or slightly elevated AGA had small bowel biopsies. The four children with the highest IgA AGA had total villous atrophy. These four children were considered to have unsuspected coeliac disease. The prevalence of coeliac disease in this group of children was one in 45. Anti-gliadin IgA and IgG tests are suitable for screening children at high risk of having coeliac disease.
Adolescent↗
Microfollicular thyroid adenoma and congenital goitrous hypothyroidism.
Three patients with congenital goitrous hypothyroidism are reported. They were treated with adequate thyroxine replacement and developed well defined microfollicular thyroid adenomas despite being euthyroid clinically and biochemically throughout their clinical course. Patients with congenital goitrous hypothyroidism appear to be at increased risk of developing thyroid adenoma in childhood despite the use of replacement thyroxine treatment in physiological doses.
Adenoma↗
Pituitary gigantism.
A case of pituitary gigantism resulting from a pituitary adenoma which secreted growth hormone is described. The patient was successfully treated by surgery, which led to the normalisation of endogenous growth hormone secretion. An acceptable final height was achieved with high dose intramuscular testosterone treatment.
Adenoma↗
Effects of therapy in X-linked hypophosphatemic rickets.
BACKGROUND: Patients with X-linked hypophosphatemic rickets, which is clinically manifested by growth failure and bowing of the legs, are usually treated with phosphate and a vitamin D preparation. However, the efficacy of this treatment has been disputed, and nephrocalcinosis is a recognized complication of therapy. METHODS: We studied 24 patients with X-linked hypophosphatemic rickets (9 boys and 15 girls) ranging in age from 1 to 16 years (median, 5.3). The duration of combination therapy ranged from 0.3 to 11.8 years (median, 3.0). We measured height as a standard-deviation (SD) score (the number of SDs from the mean height for chronologic age). Measurements made before the age of two years or after the onset of puberty were excluded. We compared the results with those reported in 1971 for 16 untreated prepubertal Australian patients. We also determined the severity of nephrocalcinosis (on a scale of 0 to 4, with 0 indicating no abnormalities and 4 stone formation) with renal ultrasonography and whether it could be related to the dosage of phosphate or vitamin D or to other factors. RESULTS: Patients treated for at least two years before the onset of puberty (n = 19) had a mean height SD score of -1.08, as compared with -2.05 in the untreated historical controls. The 13 patients who had been treated with calcitriol and phosphate for at least two years had an increase in the mean height SD score of 0.33, from -1.58 to -1.25 (95 percent confidence interval, 0 to 0.67; P = 0.05). Nineteen of the 24 patients (79 percent) had nephrocalcinosis detected on renal ultrasonography. The grade of nephrocalcinosis was significantly correlated with the mean phosphate dose (r = 0.60, P = 0.002), but not with the dose of vitamin D or the duration of therapy. All patients had normal serum creatinine concentrations. CONCLUSIONS: Therapy with calcitriol and phosphate may increase the growth of children with X-linked hypophosphatemic rickets. Nephrocalcinosis in these children represents a complication of therapy and is associated with the dose of phosphate received.
Body Height↗
Effect of obesity on endogenous secretion of growth hormone in Turner's syndrome.
Nocturnal growth hormone secretion over a 12 hour period was assessed at 20 minute intervals in 25 prepubertal subjects with Turner's syndrome and 11 normal prepubertal girls of short stature to try and elucidate the relationship between body weight and endogenous secretion of growth hormone in Turner's syndrome. There were no differences in mean growth hormone concentration, age, height, or growth velocity between the two groups. There was an age related decline in mean growth hormone concentration in patient's with Turner's syndrome in contrast to the age related increase in controls. Mean percentage of ideal body weight was significantly higher in the Turner's syndrome group than among controls and it increased with age. There was a strong inverse relationship between mean growth hormone concentration and percentage of ideal body weight in those with Turner's syndrome. Covariate analysis of the multiple linear regression of mean growth hormone concentration on age and percentage of ideal body weight in Turner's syndrome indicated that percentage of ideal body weight had a significant effect on endogenous secretion of growth hormone when age was held constant, but not the other way round. We conclude that the age related decline in endogenous secretion of growth hormone in Turner's syndrome is partly the result of increasing body weight with age. The significant influences of biological variables such as age and body weight in the interpretation of measurements of endogenous secretion of growth hormone in Turner's syndrome should be emphasised.
Adolescent↗
Luteinizing hormone-releasing hormone analogue (Buserelin) treatment for central precocious puberty: a multi-centre trial.
A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty.
Administration, Inhalation↗
Patterns of hospitalisation in a paediatric diabetes clinic in Sydney.
The hospital notes of all children with diabetes admitted to the Children's Hospital (both newly diagnosed and subsequent admissions) for the period 1985-1987 were examined. The information collected included basic demographic data, number of bed-days per admission, and reasons for admission. The direct cost of a bed-day and an admission for diabetes in this hospital were calculated. The median duration of an admission at diagnosis was 12 days, and of a subsequent admission 7 days. The proportion of total admissions to the Children's Hospital in 1987 which were due to diabetes (post diagnosis) was eight times the prevalence of IDDM in the 0-14-year population. In 1987, 5.5% of the diabetic patients (excluding new cases) aged 0-19 years and registered with this Diabetes Unit were admitted to hospital. Most of these admissions were for poor control, and were thus potentially preventable. The age group most at risk for admission due to ketoacidosis was the 10-14-year group. The cost of a diabetic bed-day was $Aust 295, average cost of an admission at diagnosis $Aust 3660, and of a post-diagnosis admission $Aust 2680. Thus, even in this young age group there is considerable morbidity due to diabetes, most of which can probably be prevented.
Adolescent↗
Normal or early development of puberty despite gonadal damage in children treated for acute lymphoblastic leukemia.
To determine the timing of pubertal development and the frequency of gonadal dysfunction in children who survive acute lymphoblastic leukemia, we assessed pubertal status and the plasma levels of sex steroids, gonadotropin, and inhibin in 45 children (20 girls and 25 boys) who had received combination chemotherapy along with 24 Gy of irradiation to the cranium (modified LSA2L2 protocol). We also reexamined testicular biopsy specimens, obtained at the time of the cessation of chemotherapy, for the presence of germ cells. Germ-cell damage, indicated by marked elevations in the plasma level of follicle-stimulating hormone (P less than 0.001 for the comparison with normal children), was evident in both sexes and was confirmed in the boys by the absence of germ cells in the testicular biopsy specimens and by the small size of the testes for pubic-hair stage. Only 44 percent of the pubertal girls had measurable plasma inhibin levels, as compared with more than 93 percent of normal pubertal girls. Although plasma sex-steroid levels were normal, the secretion of luteinizing hormone in response to stimulation with gonadotropin-releasing hormone was elevated in the pubertal children (P less than 0.01 for the comparison with normal controls)--a finding that suggests compensation for decreased gonadal function. Despite clear evidence of gonadal damage, girls had early menarche at a mean age (+/- SD) of 11.95 +/- 0.91 years, as compared with the Australian standard of 12.98 +/- 1.11 years (P less than 0.01). Thus, in girls, puberty was early despite primary gonadal damage. Thirteen of 23 boys reached puberty at a mean age of 12.36 +/- 0.73 years. We conclude that treatment for acute lymphoblastic leukemia may lead to primary gonadal damage in both sexes, regardless of the age at treatment, but that the secondary characteristics of puberty develop at a normal age or, in girls, relatively early.
Adolescent↗
Carbohydrate metabolism on high dose growth hormone therapy in children treated for leukaemia.
The effect on carbohydrate metabolism of a high dose growth hormone (GH) regimen (1.2 U/kg per week) was assessed on 24 children who had previously been treated for leukaemia. Sixteen patients received high dose GH and eight patients received a conventional dose of GH (0.6 U/kg per week). Oral glucose tolerance tests (OGTT) were performed at baseline and after 3 months of treatment with GH. For the entire group between 0 and 3 months, there was a significant increase in mean (and standard deviation) fasting plasma glucose (0.3 +/- 0.6 mmol/L), fasting insulin level (11 +/- 26 mU/L), and 2 h insulin level (20 +/- 40 mU/L). One patient, who received a conventional dose of GH, developed substantial carbohydrate intolerance. For the entire group, there was no change in response to a carbohydrate load at 3 months as measured by the area under the plasma glucose or insulin curve. There was no significant difference between conventional and high dose groups at 3 months as assessed by these parameters. This study demonstrates that a higher dose of GH may be used in these children in an attempt to improve their final height, without increased risk of carbohydrate intolerance in the short term.
Blood Glucose↗
Congenital adrenal hyperplasia family studies using the short ACTH test.
Because of the increasing use of 17-hydroxyprogesterone (17OHP) levels with the short adrenocorticotrophic hormone (ACTH) test in the detection of 21-hydroxylase deficiency, the diagnostic efficiency of the test was evaluated in patient and family studies of congenital adrenal hyperplasia due to 21-hydroxylase deficiency and of congenital adrenal hyperplasia due to 11-hydroxylase (11OH) deficiency (the latter disorder now overlaps basally with the milder non-classical 21-hydroxylase deficiency [NC-CAH]). Stimulated 17-hydroxyprogesterone level (17OHP30), 17-hydroxyprogesterone increase (delta 17 OHP) and the ratio 17-hydroxyprogesterone increase to cortisol increase (delta 17OHP/delta cortisol) were the parameters from the short ACTH test derived for assessment. 17-OHP30 provided complete differentiation of NC-CAH from the controls and heterozygotes, but overlap between NC-CAH and 11-OH occurred. Complete differentiation of NC-CAH from 11-OH was achieved using delta 17OHP. The heterozygotes showed best differentiation from the controls using delta 17OHP/delta cortisol with a diagnostic accuracy of 70%, however marked overlap of heterozygotes and NC-CAH with 11-OH was found. The short ACTH test proved to be a valuable technique with the further detection of homozygotes (n = 3) and heterozygotes (n = 5) in the 13 families studied. However, when interpreting the short ACTH test a careful choice of parameters should be made. It should be kept in mind that mild NC-CAH patients can only be differentiated from 11OH patients by using delta 17OHP.
17-alpha-Hydroxyprogesterone↗
Insulin and variation in glucose levels modify the secretion rates of the growth hormone-independent insulin-like growth factor binding protein-1 in the human hepatoblastoma cell line Hep G2.
The plasma level of the GH-independent insulin-like growth factor binding-protein-1 (IGFBP-1) is regulated inversely by insulin. In this study the effect of insulin and changes in the glucose concentration on in-vitro IGFBP-1 secretion by the Hep G2 cell line was studied. Media from confluent cells in 12 replicates were collected for consecutive periods: initial control (20 h), study (6 h) and recovery (20 h). Insulin suppressed IGFBP-1 secretion maximally at 100 mU/l (-32%) within 6 h. The secretion of IGFBP-1 was stimulated by a decrease in the glucose concentration in the medium, maximally (+25%) with a decrease from 24 to 6 mmol/l. Stimulation by varying glucose levels and suppression by insulin of IGFBP-1 secretion persisted on return to control conditions after the removal of physiological concentrations of glucose (4-12 mmol/l) and insulin (50-500 mU/l). The findings in the Hep G2 cell line that a variation in the physiological concentrations of glucose and insulin each independently regulate IGFBP-1 secretion suggest that this cell line may be a suitable model for further in-vitro studies of the regulation of secretion of IGFBP-1.
Carcinoma, Hepatocellular↗
Growth and growth hormone therapy of children treated for leukaemia.
A total of 37 children (24 male, 13 female) who had been treated for leukaemia with chemotherapy and 24 Gy cranial irradiation, and who were disease free for at least 18 months, were commenced on somatrem at a mean of 7.6 years (range, 4.8-12.1 years) after leukaemia diagnosis because of growth rate below the 25th centile for bone age. Peak GH response to provocation (exercise, arginine, insulin hypoglycaemia) was less than 20 milliunits/litre in 27 children (deficient group) and 20 milliunits/litre or more in 10 children (non-deficient group). The mean height SD decrease from diagnosis of leukaemia to commencement of somatrem was 1.98, 86% of the children decreasing by more than 1 SD. Those who were tall for age at leukaemia diagnosis and females were more severely affected. Mean (+/- SD) height velocity increased on somatrem from 2.7 +/- 1.1 to 6.6 +/- 2.2 cm/year during the first 6 months (n = 25), and to 6.0 +/- 1.7 cm/year during the first 12 months (n = 19). No difference in growth response was seen between the sexes or between the deficient and non-deficient groups. Catch-up growth occurred for the first 6 months only. It is concluded that children with a low growth rate after treatment of leukaemia should be considered for GH therapy irrespective of the results of GH provocative tests.
Adolescent↗