Between-assay differences in serum growth hormone (GH) measurements: importance in the diagnosis of GH deficiency in childhood.
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Adolescent↗
Biomedical subjects
E Chaler
Publications and source records attributed to E Chaler.
Serum concentrations of follicle stimulating hormone and luteinizing hormone in normal girls and boys during prepuberty and at early puberty.
Serum luteinizing hormone (LH) and follicle stimulating hormone (FSH) morning levels were determined in 327 normal prepubertal and early pubertal children of both sexes, utilizing a highly sensitive and specific microparticle enzyme immunoassay. Female (F) and male (M) prepubertal (Tanner's stage I) subjects were divided into 4 age groups: less than 3 months (F1, M1), 3 to 12 months (F2, M2) 12 to 24 months (F3, M3) and older than 24 months (F4 and M4). F pubertal subjects were classified in Tanner's stage breast II (F5) and III F6), while M pubertal subjects belonged to Tanner's stage genitalia II (M5). Serum LH levels were relatively low in prepubertal girls and showed a significant increment in group F6. By contrast, serum LH levels were relatively high in M1 and M2, decreased to levels similar to F in M3 and M4, and increased again at puberty in M5. Serum FSH levels were relatively high in girls of all prepubertal groups, even though they decrease significantly in M4. An increase was detected in pubertal group M6. All M prepubertal groups had significantly lower FSH levels than F prepubertal groups. The high serum LH of boys during the first year of life is probably a consequence of an activation of the hypothalamic GnRH pulse generator that is not apparent in girls. On the other hand, the high serum FSH of prepubertal girls is probably a consequence of a weak restraint influence of the prepubertal ovary on pituitary FSH secretion. This sexual dimorphism in gonadotropin secretion regulates, in a sex-specific fashion, prepubertal gonadal function in the two sexes.
Adolescent↗
Thyroid function and serum thyroid binding proteins in prepubertal and pubertal children with chronic renal insufficiency receiving conservative treatment, undergoing hemodialysis, or receiving care after renal transplantation.
OBJECTIVE: The abnormalities reported in some thyroid function tests in children with renal disease could be adaptive phenomena, shared by a variety of other nonthyroidal illnesses, or could reflect hypothyroidism. STUDY DESIGN: To answer this question, we studied thyroid function and serum thyroid binding proteins in 36 prepubertal and 23 pubertal patients with renal disease receiving three different therapies: conservative treatment, hemodialysis, and care after renal transplantation. RESULTS: During prepuberty, the serum concentration thyroxine binding globulin (mean +/- SE) in the three groups of patients (294 +/- 18, 303 +/- 18, and 323 +/- 16 nmol/L, respectively) was significantly lower than in prepubertal control subjects (451 +/- 71 nmol/L). Only in prepubertal patients after renal transplantation (3583 +/- 573 nmol/L) were serum thyroxine binding prealbumin values lower than in respective control subjects (5999 +/- 908 nmol/L). The serum total thyroxine concentration in the three groups of patients (108 +/- 41.9, 121 +/- 5.7, and 123 +/- 5.5 nmol/L, respectively) was significantly lower than in prepubertal control subjects (149 +/- 10 nmol/L), whereas serum free thyroxine and serum albumin-bound thyroxine concentrations were similar to those in control subjects. The serum total triiodothyronine level in the three groups of patients (2.29 +/- 0.82, 2.13 +/- 0.13, and 2.01 +/- 0.20 nmol/L respectively) was significantly lower than in prepubertal control subjects (3.04 +/- 0.24 nmol/L), whereas serum levels of free triiodothyronine and serum albumin-bound triiodothyronine were similar to those in prepubertal control subjects. During puberty, serum thyroxine binding globulin and serum thyroxine binding prealbumin levels in the three groups of patients were not statistically different from those in pubertal control subjects (309 +/- 47 and 4950 +/- 1230 nmol/L, respectively). Serum levels of total thyroxine, free thyroxine, albumin-bound thyroxine, total triiodothyronine, free triiodothyronine, and albumin-bound triiodothyronine were similar to those in pubertal control subjects except for pubertal patients undergoing hemodialysis. In all clinical groups the basal serum thyrotropin concentration was similar to those in respective control subjects. The frequency of goiter was increased in patients undergoing hemodialysis, probably as a result of iodide washout with dialysis. CONCLUSION: Children and adolescents with chronic renal insufficiency or endstage renal disease or after renal transplantation do not have a primary abnormality of thyroid function and therefore are not candidates for thyroid hormone treatment.
Adolescent↗
Hypothalamic-pituitary-gonadal function in prepubertal boys and girls with chronic renal failure.
Hypothalamic-pituitary-gonadal function was evaluated in 24 prepubertal children with chronic renal failure (CRF). Among the 17 boys, 5 were receiving conservative treatment and four long-term dialysis. Another eight boys were studied 6 months to 3.3 years after renal transplantation; their ages ranged from 5 years 8 months to 15 1/2 years. Among the girls, two patients were receiving conservative treatment and five long-term dialysis; their ages ranged from 3 1/2 years to 11 years 2 months. In boys with CRF, but not in those after transplantation, mean serum follicle-stimulating hormone 60 minutes after administration of gonadotropin releasing hormone (GnRH) was lower than in 18 control prepubertal boys (mean +/- SD: 2.53 +/- 1.34 vs 6.25 +/- 2.84 IU/L, respectively; p < 0.01). Testosterone steroidogenic capacity after 1 week of stimulation with human chorionic gonadotropin and androgen sensitivity (percentage of decrease of serum sex hormone-binding globulin 1 week after intramuscular administration of testosterone enanthate) were normal. In girls, no difference between those with CRF and a control group of 19 girls was found after intravenous administration of GnRH. However, after intramuscular administration of GnRH agonist, serum follicle-stimulating hormone concentration was lower in girls with CRF than in control girls (p < 0.02); six of seven control girls had an increase of serum estradiol to more than 55 pmol/L, whereas three of seven girls with CRF had no response, and serum follicle-stimulating hormone failed to increase after GnRH agonist therapy in two of these patients. We conclude that hypothalamic-pituitary function is not normal in some prepubertal boys and girls with CRF, particularly in those with low serum albumin concentrations. On the other hand, testicular and ovarian steroidogenic capacity is not impaired, and the biologic response to androgens in boys is preserved.
Adolescent↗
High serum sex hormone-binding globulin (SHBG) in premature thelarche.
OBJECTIVE: We determined serum sex hormone-binding globulin (SHBG), serum dehydroepiandrosterone sulphate, serum oestradiol and serum testosterone and its fractions in girls with premature thelarche. DESIGN: Blood was drawn from girls with recently diagnosed (3-12 weeks) premature thelarche. Serum was kept frozen for at least one year before hormonal determination to exclude precocious puberty by clinical evaluation. PATIENTS: Seventeen girls with premature thelarche aged 0.83-7.16 years were studied, and compared with a group of 22 normal prepubertal girls. MEASUREMENTS: SHBG was measured by saturation analysis and serum dehydroepiandrosterone sulphate, serum total oestradiol and serum total testosterone were determined by radioimmunoassay. Non-SHBG-bound testosterone and free testosterone were calculated from an equation derived from the law of mass action. RESULTS: Median serum SHBG in premature thelarche was 137 nmol/l (range 64-221), significantly higher than in normal controls, 93.7 (32-172) (P < 0.05) non-parametric test of medians. Serum SHBG decreased significantly with age in controls but not in premature thelarche. No difference was found in serum dehydroepiandrosterone sulphate. Median serum total testosterone (0.34 nmol/l, 0.17-0.97), median serum non-SHBG-bound testosterone (0.04 nmol/l, 0.02-0.10) and median free testosterone (2.2 pmol/l, 1.0-4.5) were significantly lower in premature thelarche than in control (P < 0.001). CONCLUSIONS: Serum SHBG is high and bioavailable T is low in girls with premature thelarche. This might alter the oestrogen/androgen ratio in the breast.
Breast↗
Endocrine disorders in 66 suprasellar and pineal tumors of patients with prepubertal and pubertal ages.
Tumor oncotypes, initial symptoms and endocrine disturbances before and/or 1 month after surgery were studied in 66 patients with prepubertal and pubertal ages having suprasellar or pineal intracranial tumors. Neoplasms found in patients of prepubertal age were: 15 craniopharyngiomas (CRA), 24 neuroepithelial-cell-derived tumors (NEC), 5 germ cell tumors (GERM) and 4 other lesions (OTHER). In patients of pubertal age, there were 7 CRA, 7 pituitary tumors (PIT), 2 NEC, 1 GERM and 1 OTHER. Approximately 90% of patients had visual abnormalities as one of the initial signs and symptoms, while 59% had increased intracranial pressure. Short stature was observed in only 10% of patients. Before surgery, somatotropic function was found to be deficient (by 2 pharmacological tests) in 90-100% of patients with CRA, PIT or GERM and in 40% of patients with NEC. Overt hypothyroidism was found in 5-25% of CRA, NEC or GERM but in 40% of PIT. Abnormal TSH responses to TRH were observed in 64% of CRA and in 29% of NEC. Low basal serum cortisol was found in 21 or 6% of patients with CRA or NEC, but in 100 or 60% of patients with PIT or GERM, respectively. Diabetes insipidus was diagnosed in 13.6% of all patients. Surgery produced few additional disturbances in endocrine function, except for the incidence of diabetes insipidus which was doubled. Gonadotropic deficiency was found in most patients of pubertal age with CRA and PIT. They were readily differentiated by the high prolactin or growth hormone (GH) levels of the latter.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Variations in soluble and particulate ABP of rat testis during sexual development.
Androgen binding activity (ABP) was determined in two different fractions of developing rat testicular homogenates: in cytosol (cABP) and in a particulate fraction isolated by differential centrifugation (pABP). Homogenates were prepared under stabilization conditions by adding 350 nM testosterone to the homogenization buffer. cABP and pABP concentrations were maximal in 22- to 32-day-old animals, to decrease thereafter during sexual maturation. However, both cABP and pABP increased with age when results were expressed on a per organ basis. pABP could be solubilized under conditions in which it could retain its binding activity. It was then photoaffinity labeled and chromatographed on a Sephadex G 200 column using cytosolic epididymal ABP as a control. Similarities between cABP and pABP include not only the same androgen binding characteristics but also the same exclusion volume after Sephadex G 200 chromatography. Since pABP is only present in Sertoli cells, it might represent ABP before being secreted. Because of its intracellular localization, it could play a role in the compartmentalization of androgens within the testis.
Androgen-Binding Protein↗
Photoaffinity labeling of extracellular and intracellular androgen binding proteins.
A method is described for the photoaffinity labeling of human and rabbit serum sex hormone binding globulin (SHBG) in ammonium sulphate precipitates utilizing 3H-delta 6-testosterone as affinity label. The precipitation step diminished albumin contamination and at the same time concentrated the binding globulin. Photolysis was conveniently carried out with an electronic flash. Unbound and non-covalently bound steroids were adsorbed by prolonged dextran-coated charcoal treatment. Sephadex G-200 gel filtration column chromatography showed a single peak of covalently bound radioactivity with the elution volume of SHBG. With some modifications, the method was applied to the affinity labeling of the prostate androgen receptor utilizing 3H-methyltrienolone (R 1881) as affinity label. The receptor was also precipitated from prostate cytosol with ammonium sulphate. After labeling, photolysis and heating at 50 degrees C, non covalently bound 3H-R 1881 was removed by dextran coated charcoal treatment. Sephadex G-25 microcolumn chromatography after heating showed a peak of radioactivity eluting with macromolecules if photolysis had been carried out, while it disappeared in the absence of previous photolysis. However, the photolabeled receptor had a sedimentation coefficient different from the non-irradiated receptor, suggesting that photolysis induced a change in the configuration of the complex.
Affinity Labels↗
Acute effect of hCG on testicular and epididymal levels of androgen binding protein (ABP) in the immature rat.
We have studied the acute effect of hOG and testosterone administration to immature rats, on testicular (particulate fraction and cytosol) and epididymal (cytosol) ABP levels. One and four hours after a single dose of 10 IU hCG/rat, ABP concentration decreased slightly in testicular membranes and cytosol, but increased markedly in epididymal cytosol (169 +/- 5 and 182 +/- 5 at 1 and 4 h respectively, compared to 113 +/- 13 fmoles/mg protein in control animals, mean +/- SEM). Since testicular and epididymal concentrations of testosterone increased after hCG, as expected, the effect might have been mediated by gonadotrophin stimulated testosterone production in Leydig cells. To test this hypothesis, the hCG effect was studied in rats that previously had received aminoglutethimide to block steroidogenesis. Under these conditions, hCG failed to increase epididymal ABP. Finally, administration of testosterone propionate was also able to stimulate epididymal ABP, but with delayed response: the increase was observed 4 h after injection (212 +/- 18 compared to 127 +/- 28 fmoles/mg protein in control animals, mean +/- SEM). It is concluded that the hCG-induced increase of intratesticular androgen levels results in rapid passage of ABP from testis to epididymis.
Androgen-Binding Protein↗
Evaluation of serum total thyroxine and triiodothyronine and their serum fractions in nonthyroidal illness secondary to congenital heart disease. Studies before and after surgery.
Serum thyroid hormones, serum thyroxine-binding proteins and serum thyroid hormone fractions have been measured in children with congenital heart disease before and after open cardiac surgery. Twenty prepubertal patients, mean (+/- SD) age 3.6 +/- 3.7 yr, were studied before, immediately after, and 24 and 48 h after surgery. A control group of 6 normal prepubertal children was also studied in basal conditions. Serum TSH was normal in all samples collected. Significantly low mean levels of serum TBG (261 +/- 57 vs 456 +/- 71 nmol/L in normals), serum TBPA (2692 +/- 1119 vs 5999 +/- 2226 nmol/L), serum TBG-bound T4, serum TBPA-bound T4, serum TT3, serum TBG-bound T3 and free T3 were found before cardiac surgery in the patients. While serum binding proteins did not change after surgery, significant decrements in serum TT4, serum TBG-bound T4, serum TT3, serum TBG-bound T3, serum albumin-bound T3 and free T3 were observed after surgery. Free T4 and albumin-bound T4 remained normal. Our study shows that many features of nonthyroidal illness were present in our patients before surgery. In this context, the stress of surgery induced further alterations in several parameters of thyroid metabolism. It is concluded that the changes occurring in this model of chronic, as well as acute, nonthyroidal illness reflect adaptative changes, rather than altered thyroid function, as shown by normal serum free T4, serum albumin-bound T4 and serum TSH.
Child↗