Biomedical subjects
H E Kulin
Publications and source records attributed to H E Kulin.
Hypothalamic-pituitary-gonadal axis function in pubertal male and female siblings with glucocorticoid-treated nonsalt-wasting 3 beta-hydroxysteroid dehydrogenase deficiency congenital adrenal hyperplasia.
We report pubertal maturation and dynamic studies of gonadotropin and gonadal hormone secretion in long term glucocorticoid-treated siblings with nonsalt-wasting classic adrenal and gonadal 3 beta-hydroxysteroid dehydrogenase (3 beta HSD) deficiency. The 18-yr-old female siblings spontaneously developed thelarche and menarche at 10 and 12 yr, respectively, and manifested irregular menses, hirsutism, and polycystic ovaries at 17 yr. The 16-yr-old male sibling spontaneously developed secondary sex characteristics at age 11 yr and exhibited Tanner IV-V pubic hair, a 6.5 x 3.0-cm surgically repaired penis, and enlarged nonnodular testes. Overnight (2200-0700 h) plasma gonadotropin (every 20 min) and gonadal steroid levels (every 2 h) under ACTH adrenal suppression revealed the following. In the male sibling, there were overall normal Tanner V male LH (3-21 mIU/mL) and FSH (1.2-13 mIU/mL) levels, normal peak frequency and amplitude of LH (70 +/- 62 min and 15 +/- 3 mIU/mL, respectively) and FSH (65 +/- 28 min and 13 +/- 3 mIU/mL), and low normal Tanner V testosterone (T) levels (11.4-17.9 nmol/L). In the female sibling, there were normal follicular phase range LH (10-28 mIU/mL) and FSH (5.1-17.2 mIU/mL) levels, normal peak frequency and amplitude of LH (96 +/- 17 min and 22 +/- 4.5 mIU/mL, respectively) and FSH (62 +/- 27 min, 13 +/- 4 mIU/mL), and early follicular phase estradiol (E2) levels (100-170 pmol/L). The LH-releasing hormone-stimulated LH response was in the normal adult range in the male and normal for the early follicular phase in the female. In contrast, ACTH and adrenal delta 5-steroid responses to CRH administration were elevated in each sibling. Gonadal suppression via Norlutin administration (30 mg/day for 3 days) after prolonged adrenal suppression by dexamethasone resulted in suppression of dehydroepiandrosterone (DHEA) and E2 in the female and DHEA and T in the male. Gonadal stimulation via hCG administration (5000 IU/day for 3 days, im) during continuous adrenal suppression resulted in a low E2 response in the female (200 pmol/L; control, 295-660 pmol/L) and a low T response in the male (15.3 nmol/L; control, 17-39 nmol/L), whereas delta 5-17-hydroxypregnenolone and DHEA levels rose 2- to 4.7-fold in each sibling. In conclusion, despite partial gonadal 3 beta HSD deficiency, the dynamics of gonadotropin and gonadal hormone secretion in these siblings indicate the absence of increased LH secretion, in contrast to the markedly increased ACTH secretion resulting from adrenal 3 beta HSD deficiency.(ABSTRACT TRUNCATED AT 400 WORDS)
Diminished linear growth associated with chronic salt depletion.
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Adolescent pregnancy in Africa.
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Thyroid storm. Presenting with coma and seizures. In a 3-year-old girl.
Thyroid storm is a rare occurrence in the adult population and is even more unusual in children. The current report is of a 3.5-year-old girl who had thyroid storm with unique neurologic manifestations, namely seizure and coma. Acute medical management with propylthiouracil, saturated solution of potassium iodide, hydrocortisone, and propranolol brought about complete resolution of symptoms.
The onset of sperm production in pubertal boys. Relationship to gonadotropin excretion.
To determine the relationship of gonadotropin excretion to spermarche, 26 boys ranging in age from 10.3 to 17.5 years each provided ten overnight urine samples. Microscopic observation of sperm was found in 33 (13%) of the 260 samples, with 50% of the boys exhibiting sperm in at least one specimen. No further cumulative gain in detecting spermaturia occurred after the seventh urine collection. The median age of spermarche was computed by logistic regression analysis to be 14 years. Three urine collections from each boy were assessed for gonadotropin levels. At age 14 years mean follicule-stimulating hormone and luteinizing hormone excretion were, respectively, 857 and 503 mIU/h, into the reported adult daytime range. Spermarche is a midpubertal event associated with age-appropriate gonadotropin production.
Adolescent pregnancy in Africa: a programmatic focus.
An increasing age of marriage coupled with high rates of premarital sexual activity have caused notable changes in the incidence of out-of-wedlock pregnancies in much of the developing world. In Africa, local policy makers are beginning to perceive the medical implications of these changes as the youth component of illicit abortion, maternal mortality, and sexually transmitted disease becomes more visible. Other social issues, which include school leaving, unemployment, violence and drug abuse, are emerging among the young people of Africa as elsewhere. A successful approach to these problems will require a multi-disciplinary perspective of the adolescent with professional contributions from the arenas of health, behavior, education and sociology. This report stresses the thesis that adolescents constitute a unique sub-population whose special needs must be recognized in Africa; strong institutional facilities are required, backed by committed advocates and leadership for the youth sector. Programs initiated in Kenya and Zimbabwe serve as useful models for other African locales.
The endocrine control of growth in children with chronic renal failure.
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The assessment of diminished testicular function in boys of pubertal age.
Nine boys with anorchia and 9 individuals with diminished testicular function were followed between ages 10 and 18 with serial determinations of urine gonadotrophins and serum testosterone. Ten hCG stimulation tests were performed in eight of these patients. Adult levels of LH (greater than 500 mIU/h) and low measurements of serum testosterone (less than 54 ng/dl) confirmed the anorchic state. Boys with diminished testicular reserve exhibited urinary gonadotrophin changes similar to peripubertal anorchic patients but testosterone levels increased progressively with age (90-715 ng/dl). FSH attained adult castrate levels (greater than 1700 mIU/h) by age 13 in these boys and served to distinguish them from normal controls. The longitudinal assessment of basal hormone levels can separate anorchia from diminished testicular reserve in boys of pubertal age and testing with hCG is not required for evaluation.
46,XY gonadal dysgenesis: is oncogenesis related to H-Y phenotype or breast development?
Among women with 46,XY gonadal dysgenesis, there is a high incidence of gonadal tumors. Because of evidence of a connection between occurrence of those tumors, H-Y phenotype, and breast development, we surveyed 55 cases of 46,XY gonadal dysgenesis and 12 related cases involving chromosomal and/or skeletal abnormalities. Our survey, including three new cases presented here, indicates that H-Y phenotype but not breast development may be related to the development of the gonadoblastoma-dysgerminoma. Thus among women with 46,XY gonadal dysgenesis, there are H-Y- and H-Y+ classes, but gonadal tumors are found almost exclusively in the H-Y+ class. Yet one of our patients may represent an exception to the association of H-Y+ phenotype and gonadal tumors in this syndrome.
Response of the prepubertal ovary to acute chorionic gonadotropin administration: absence of modulation by growth hormone.
Twenty-five short term hCG stimulation tests were performed in seven prepubertal girls, aged 3-11 yr, who were being evaluated for short stature. Provocative testing revealed GH deficiency in all patients, but reevaluation of one girl at a later date showed normal somatotropin levels. The study protocol lasted 18 months and included testing before, during, and after 1 yr of GH therapy. Delta 4-Androstenedione, testosterone, estrone, and estradiol were determined 0, 24, 48, and 72 h after initiation of a two-injection course of CG. Significant responses (approximately 2-fold over baseline) to the stimulation tests occurred for all steroids except testosterone, though no augmented effects were found in the presence of human GH. The results indicate functional capability of the prepubertal ovary when exposed acutely to a LH-like material, but no role for somatotropin in gonadal steroid production in the prepubertal female.
Gonadotropin excretion during puberty in malnourished children.
p6nadotropins were measured by radioimmunoassay of urine samples from 285 privileged Nairobi adolescents and from 238 rural peripubertal Kenyan boys and girls who had had moderate malnutrition during childhood. Gonadotropins were reduced at all ages in the rural adolescents, but pubertal stage-matched comparisons showed no differences between children of the two study areas in middle or late phases of sexual maturity. These results document the pattern of gonadotropin changes in an environment of reduced caloric intake and confirm the presumed hypothalamic-pituitary origin of the delayed adolescence that occurs under such circumstances.
Transient thyroid binding globulin deficiency with classic galactosemia.
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Clomiphene in the treatment of adolescent gynecomastia. Clinical and endocrine studies.
Twelve boys, aged 12 to 19 years, with persistent gynecomastia were treated with the antiestrogen, clomiphene citrate, at a dose of 50 mg/day by mouth for one to three months. The mean breast size decreased by 0% to 36%, with only five boys experiencing a reduction of greater than 20%. Five boys subsequently required reduction mammoplasty. Levels of urinary gonadotropins, serum testosterone, and estradiol increased significantly during therapy. Since the ratio of testosterone to estradiol remained unchanged during treatment, the antiestrogen effects were achieved primarily at the level of breast tissue. Clomiphene citrate in a dose of 50 mg/day resulted in only small decreases in persistent pubertal gynecomastia and was not a satisfactory medical therapy for the condition.
Detection of isolated aldosterone deficiency in the neonate.
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Perturbations of negative feedback sensitivity in agonadal patients undergoing estrogen replacement therapy.
UNLABELLED: Urinary gonadotropin excretion was measured in 30 patients with gonadal dysgenesis, aged 2 months to 17 yr. Between bone ages 3-8 yr, mean FSH excretion (575 mIU/h) was elevated 8-fold in agonadal individuals compared to levels in intact prepubertal girls; mean urinary LH (49 mIU/h) in agonadal patients during this time period was increased nearly 2-fold over results from normal prepubertal females. Nine of 10 patients given 0.3 to 0.6 mg conjugated estrogen (Premarin) daily to initiate puberty exhibited prompt suppression of urinary gonadotropin levels from markedly elevated levels to within or very close to the normal prepubertal range. Such a response was found in only two of seven patients given 0.15 mg of the same drug. All instances of suppression were followed by escape from low levels of gonadotropin excretion as treatment was continued. Prior exposure to exogenous or endogenous estrogen markedly reduced the suppressive potential of treatment with 0.3 or 0.6 mg Premarin. A favorable advance of bone maturation in relation to chronological age was achieved by the administration of 0.15 mg Premarin daily, a dose which caused a satisfactory onset of secondary sex characteristics. IN CONCLUSION: 1) a component of gonadotropin restraint in midchildhood is supplied by the ovary; 2) adult castrate levels of gonadotropins are achieved in the agonadal patient of peripubertal age in the presence of a highly sensitive negative feedback axis between sex hormones and gonadotropins; 3) sex steroids themselves may modify the gonadotropin-gonadal negative feedback axis in patients with gonadal dysgenesis; and 4) puberty may be initiated favorably with conjugated estrogens in an oral dose of 0.15 mg daily.
The effect of chronic childhood malnutrition on pubertal growth and development.
Pubertal growth and development were compared in 342 privileged, urban children and 347 impoverished rural adolescents from Kenya. Measurements of height, weight, upper arm circumference, and triceps skinfolds revealed marked differences between the two study groups just before the onset of sexual maturation. These differences were also found in the early stages of puberty but notable catch-up was evident throughout the later period of the maturational process. Early stages of sexual maturity were delayed by 3 yr in malnourished boys with a 2.1-yr lag in the age of onset of menarche in rural girls. Derived estimates of body fat as well as direct anthropometry revealed that the onset of puberty is not size related under the circumstances of chronic childhood malnutrition.