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Biomedical subjects

S Pang

Publications and source records attributed to S Pang.

At least 109 records · Page 6Linked to original sources
PubMed1984

Recovery of adrenal function after treatment of adrenocortical carcinoma with o,p'-DDD.

The adrenolytic agent, 2,2-bis[2-chlorophenyl-4-chlorophenyl] 1,1 dichloroethane (o,p'-DDD), was used over a 20-month period following surgery in a 2 3/12-year-old girl for treatment of adrenocortical carcinoma. The child remained free of disease and was maintained on glucocorticoid and mineralo-corticoid supplements for 7 years. Hormonal evaluation was undertaken at 9 9/12 years of age to determine remaining adrenal steroidogenic capacity. Following discontinuation of both hydrocortisone and 9 alpha-fludrocortisone, she remained stable and asymptomatic. Immediately after discontinuing 9 alpha-fludrocortisone, the adrenal glomerulosa was able to respond to stimulation by the renin-angiotensin system as shown by the ability to achieve renal sodium conservation on a restricted sodium intake (less than 10 mEq/d for 5 d). The response of the adrenal fasciculata to ACTH stimulation showed a slower recovery. Baseline levels of cortisol were in the low normal range, but there was no increase in plasma cortisol or urinary 17-hydroxysteroids following stimulation with ACTH. The responses of cortisol, deoxycorticosterone, and corticosterone to ACTH stimulation gradually improved to achieve normal stimulated levels 18 months after stopping medications. Serum testosterone and delta 4-androstenedione were initially increased for level of puberty, while levels of dehydroepiandrosterone were prepubertal. Testosterone and delta 4-androstenedione did not suppress with dexamethasone (2 mg/d for 2 d; 4 mg/d for 2 d), and dehydroepiandrosterone decreased only slightly. However, administration of norethindrone (Norlutin) (10 mg orally, three times a day for 3 d) resulted in suppression while human chorionic gonadotrophin (hCG; 5000 U i.m. daily for 3 d) produced stimulation of testosterone, delta 4-androstenedione and dehydroepiandrosterone. Thus the androgens were felt be predominantly of ovarian origin. Dehydroepiandrosterone rose to low normal levels by 18 months after discontinuation of hydrocortisone. We thus demonstrate for the first time that both the adrenal glomerulosa and fasciculata have the capacity to recover normal function following treatment with o,p'-DDD. Further, we suggest that early exposure to excess adrenal androgens may result in mild alteration of gonadal function.

Adenocarcinoma↗
PubMed1984

Antepartum diagnosis of goitrous hypothyroidism by fetal ultrasonography and amniotic fluid thyrotropin concentration.

Ultrasonography of a 26-week-old fetus suggested the presence of a goiter. Amniocentesis was performed at 26 and 38 weeks gestation to evaluate thyroid function. An elevated amniotic fluid TSH level was found on both occasions, though amniotic fluid T4, T3, and rT3 levels were similar to those of euthyroid fetuses. The diagnosis of goitrous hypothyroidism was confirmed at birth. Therapy with thyroid hormone was instituted on the first day of life. Growth and development of the infant have been normal during the first year of his life. We suggest that the measurement of amniotic fluid TSH can be useful in the diagnosis of intrauterine primary hypothyroidism.

Amniotic Fluid↗
PubMed1983

Congenital adrenal hypoplasia: two new cases.

Two male adolescents with the X-linked form of congenital adrenal hypoplasia are described. Both grew slowly during childhood and adolescence and did not undergo pubertal development because of hypogonadotropic hypogonadism associated with the congenital adrenal hypoplasia. The severely delayed bone age in childhood is probably due to the adrenal androgen deficiency and suggests a role of these hormones in the prepubertal skeletal maturation. The failure of gonadotropin secretion still remains unexplained. A hypothalamic defect has been suggested, but further studies are necessary to clarify this hypothesis.

Adolescent↗
PubMed1983

Nonsalt-losing congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency with normal glomerulosa function.

In studies of a 6-yr-old boy and his non-HLA identical 8-yr-old sister, we demonstrated 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency in the biosynthetic pathways of glucocorticoids and androgens, but not mineralocorticoids. The sister did not manifest abnormal genital development at birth, but developed premature adrenarche at the age of 4 yr, with clitoromegaly and advanced bone age. The brother had perineal hypospadias at birth and developed premature adrenarche at the age of 6 yr. In both siblings, baseline and ACTH-stimulated delta 5 steroids were markedly elevated. The baseline and ACTH-stimulated ratios of delta 5 to delta 4 steroids remained extremely high, and all steroids promptly suppressed with dexamethasone (DEX). Normal baseline PRA and serum and urinary aldosterone (Aldo) levels increased after stimulation with a low Na+ diet. Renal Na+ conservation was normal after dietary Na+ deprivation with and without DEX administration. The PRA to pH 1 Aldo ratio remained normal with normal and low Na+ diets, regardless of DEX administration, indicating normal glomerulosa function with renin stimulation. In both siblings, ACTH increased PRA and Aldo levels, maintaining the PRA to pH 1 Aldo ratio unchanged from the baseline value. In contrast, in control children, PRA was suppressed, while Aldo increased, resulting in a fall of the PRA to pH 1 Aldo ratio. The increase in PRA with exogenous ACTH in these siblings suggests there may be an ACTH-stimulable mineralocorticoid antagonist. During prolonged DEX administration, hCG administration caused a slight increase in 17-hydroxypregnenolone and dehydroepiandrosterone in both the siblings, while testosterone (T) rose poorly in the brother, and estradiol did not rise at all in the sister. These results suggest the possibility of a deficiency of 3 beta-HSD in the gonads as well as the adrenals. After [3H]dehydroepiandrosterone iv infusion, there was normal conversion to [3H]-conjugated testosterone glucuronide, suggesting the presence of normal peripheral 3 beta-HSD activity. We propose that in these siblings, there is a deficiency of 3 beta-HSD in the adrenal zona fasciculata and zona reticularis, whereas 3 beta-HSD activity is intact in the zona glomerulosa. In addition, in these siblings, 3 beta-HSD deficiency was present in the gonads, while peripheral 3 beta-HSD activity appeared to be intact. These cases demonstrate further the heterogeneity of congenital adrenal hyperplasia due to 3 beta-HSD deficiency.

3-Hydroxysteroid Dehydrogenases↗
PubMed1983

Genotyping steroid 21-hydroxylase deficiency: hormonal reference data.

Hormonal reference data, in the form of nomograms relating baseline and stimulated levels of adrenal hormones, provide a means of genotyping steroid 21-hydroxylase (21-OH) deficiency in congenital adrenal hyperplasia. Data from both 360- and 60-min ACTH stimulation tests are given. The serum hormone concentrations that have proven most useful in classifying 21-OH deficiency are 17-hydroxyprogesterone and delta 4-androstenedione. These nomograms clearly distinguish the patient with classical 21-OH deficiency from those with the milder symptomatic and asymptomatic nonclassical forms of 21-OH deficiency (previously referred to as late onset and cryptic forms) as well as heterozygotes for all of the forms and those subjects predicted by HLA genotyping to be unaffected. The nomograms also can identify individuals heterozygous for 21-OH deficiency in the general population who have a characteristic heterozygote response. These nomograms provide a powerful tool by which to assign the 21-OH deficiency genotype. Patients whose hormonal values fall on the regression line within a defined group are assigned to that group. In view of the strong correlation between the 60- and 360-min ACTH stimulation tests, the less cumbersome and shorter 60-min test can be used with the same confidence as the longer test.

Adrenal Hyperplasia, Congenital↗
PubMed1982

Late-onset steroid 21-hydroxylase deficiency: a variant of classical congenital adrenal hyperplasia.

Hormonal studies and human leukocyte antigen (HLA) genotyping were performed in 5 males and 13 females who were demonstrated to have 21-hydroxylase deficiency. The enzymatic deficiency of steroidogenesis was detected by family studies of 10 females who presented with varying symptoms of androgen excess. The 10 index cases had normal genitalia at birth, but virilized to varying degrees postnatally. The additional 8 affected family members had not sought medical care, but some were found to have signs of virilization on physical examination, while others were normal. Thus both late-onset (symptomatic) and cryptic asymptomatic) 21-hydroxylase deficiency occurred in the same pedigree. The hormonal and genetic linkage studies indicate that the late-onset (symptomatic) form of 21-hydroxylase deficiency, like the cryptic (asymptomatic) and classical forms of 21-hydroxylase deficiency, is transmitted by an autosomal recessive gene which is linked to HLA-B. Furthermore, the classical form of 21-hydroxylase deficiency associated with prenatal virilization is transmitted by an allelic variant for steroid 21-hydroxylase different from that of the nonclassical forms, late-onset (symptomatic) and cryptic (asymptomatic) 21-hydroxylase deficiency. Although these latter 2 disorders have different clinical manifestations, they demonstrate a similar degree of steroid 21-hydroxylase deficiency that is less severe than that observed in classical 21-hydroxylase deficiency. The hormonal and genetic linkage data indicate that cryptic (asymptomatic) and late-onset (symptomatic) 21-hydroxylase deficiency result from the same allelic variant at the steroid 21-hydroxylase locus. A glossary of terms is presented to describe the various allelic forms of 21-hydroxylase deficiency with consistency.

Adolescent↗
PubMed1981

HLA genotypes and HLA-linked genetic markers in Italian patients with classical 21-hydroxylase deficiency.

HLA genotype and HLA-linked marker data for 40 unrelated patients from central Italy and 2 unrelated patients from Sardinia with congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH-def) were analyzed. The results confirm that the HLA-linked 21-OH-def gene is associated with several different HLA determinants and complete HLA haplotypes, although the only determinant with significantly increased frequency was the complement C2 allele C2B. The HLA antigens B8 and DR3 were found in significantly decreased frequencies. The haplotype A3, Cw6, Bw47, BfF, DR7, which is exceptionally rare in the general population but which has been found in many other 21-OH-def patients from diverse geographical origins, was also found in one of the Italian patients. This and other HLA haplotype associations found among the Italian patients may represent mutations that have occurred on HLA haplotypes with genetic linkage disequilibrium or, alternatively, may represent mutations that have not yet had time to become randomly associated with different HLA complex determinants. The marked negative associations with B8 and DR3 could, however, result from an interaction between the gene products of the HLA complex and the 21-OH-def phenotype.

Adrenal Hyperplasia, Congenital↗
PubMed1981

The variable bone scan appearances of nonosteogenic fibroma of bone.

Ten radiographically diagnosed fibrous defects of bone were assessed by three-phase bone scanning. Normal scans are obtained when the lesion is quiescent of has fully heated. Mild hyperemia and moderate bone uptake is present during the healing phase and is not significant. More intense hyperemia and a markedly positive bone scan suggest that a more active process, such as fracture or tumor, may be present.

Adolescent↗
PubMed1981

The 21-hydroxylase activity in the glomerulosa and fasciculata of the adrenal cortex in congenital adrenal hyperplasia.

In the two clinical syndromes of congenital adrenal hyperplasia due to a 21-hydroxylation defect of adrenal steroidogenesis, the simple virilizing and the salt-wasting forms, the 21-hydroxylase activity was studied considering the zona fasciculata and the zona glomerulosa of the adrenal cortex as two separate glands under different regulation. To test this hypothesis, we stimulated adrenal steroidogenesis by ACTH infusion or dietary sodium restriction in eight patients with congenital adrenal hyperplasia (four patients with the simple virilizing form and four with the salt-wasting form of congenital adrenal hyperplasia) and in six normal children. Both the 17-hydroxy and 17-deoxy pathways of adrenocortical steroid biosynthesis were examined by measuring serum concentrations of 17-hydroxyprogesterone, cortisol, progesterone, deoxycorticosterone, corticosterone, and aldosterone and the excretion of free deoxycorticosterone, 18-hydroxydeoxycorticosterone, corticosterone, 18-hydroxycorticosterone, cortisol, and aldosterone. We considered the steroids 18-hydroxycorticosterone and aldosterone to be primarily of zona glomerulosa origin. These studies indicated that the zona fasciculata of both the salt-wasting and the simple virilizing forms is defective in 21-hydroxylation of 17-hydroxy and 17-deoxy steroids. The zona glomerulosa demonstrated deficient 21-hydroxylation only in the salt-wasting form, whereas in the simple virilizing form, the glomerulosa was spared this defect.

Adrenal Cortex↗
PubMed1981

Genetic and hormonal characterization of cryptic 21-hydroxylase deficiency.

Cryptic 21-hydroxylase deficiency has been previously described in asymptomatic family members of patients with classical congenital adrenal hyperplasia (CAH). These family members were detected by high baseline 17-hydroxyprogesterone levels found in the course of family studies. The hormonal responses to ACTH of the family members with cryptic 21-hydroxylase deficiency were determined and compared to the responses of patients with CAH, patients with acquired adrenal hyperplasia, family members predicted to be heterozygous for CAH, family members predicted to be unaffected, and the general population. The ACTH-stimulated levels of 17-hydroxyprogesterone and delta 4-androstenedione in the cryptic family members were elevated above the level of the general population or family members heterozygous for classical CAH, but below that of patients with CAH. The hormonal profile of patients with cryptic 21-hydroxylase deficiency is similar to that of patients with acquired adrenal hyperplasia. The response of family members heterozygous for the cryptic gene (21-OH CRYPTIC/21-OH NORMAL) was indistinguishable from that of family members heterozygous for the classical CAH gene (21-OH CAH/21-OH NORMAL). These studies support our previous proposal that patients with cryptic 21-hydroxylase deficiency are genetic compounds, having one gene for a severe enzyme deficiency and one gene for a mild 21-hydroxylase deficiency. Thus, the 21-hydroxylase genotype in cryptic 21-hydroxylase deficiency is 21-OH CAH/21-OH CRYPTIC.

Adolescent↗
PubMed1981

Adrenocortical tumor in a patient with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

An adrenal cortical tissue tumor developed in a patient with poorly controlled salt-losing congenital adrenal hyperplasia. A 16-year-old girl became progressively virilized from 13 to 16 years of age. Base line serum progesterone, 17-hydroxyprogesterone, and testosterone levels were high and there was a diurnal pattern of the hormones. Initially elevated urinary 17-ketosteroid and serum steroid levels were decreased by high dose dexamethasone therapy, and at laparotomy an adenoma was found in the cortex of the hyperplastic left adrenal gland. It is inferred that persistent adrenocorticotrophic hormone stimulation may result in neoplastic transformation of hyperplastic adrenal cortical tissue in patients with congenital adrenal hyperplasia.

Adenoma↗
PubMed1981

HLA linkage and B14, DR1, BfS haplotype association with the genes for late onset and cryptic 21-hydroxylase deficiency.

Classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21-OH-def) has been established to be an HLA-linked, recessive monogenetic disease. However, two nonclassical forms of 21-OH-def have also been described: "cryptic" 21-OH-def, which has been shown to be HLA-linked, and "late onset" 21-OH-def, for which the status of linkage to HLA has been less certain. We now describe studies of eight additional unrelated probands with symptomatic, "late onset" 21-OH-def, and conclude that this form is also HLA-linked. Both "late onset" and "cryptic" 21-OH-def are highly associated with the same HLA antigens and markers (HLA-B14, HLA-DR1, and Bf type S) in individuals from different ethnic and geographical backgrounds. Since both "late onset" and "cryptic" 21-OH-def appear to occur in individuals with one classical 21-OH-def (21-OHCAH) allele who in addition have another 21-OH-def allele, as well as in individuals who appear to be homozygous for variant 21-PH-def alleles, and since both late onset and cryptic 21-OH-def appear to occur in the same families, our data suggest that these syndromes may represent different clinical expressions of similar or identical nonclassical 21-OH-def alleles.

Adolescent↗
PubMed1980

Delayed puberty in males with chronic renal failure.

The effects of chronic renal failure on the pituitary-testicular axis of 31 males, aged 11.7 to 20.0 yr (mean, 16.0 yr) were studied. Nine patients not on hemodialysis (group I) had serum creatinines between 2.5 and 8.0 mg/dl, 10 patients were on hemodialysis (group II) and 12 patients had received a renal transplant (group III). The Tanner stage of pubertal development was delayed relative to chronologic age. Testosterone (T), delta 4-androstenedione (delta 4), and urinary 17-keto steroids were normal when related to pubertal stage in groups I and II; and dehydroepiandrosterone (DHEA) and DHEA sulfate (DS) were in the low normal range. In group III, adrenal androgens (delta 4, DHEA, DS) were decreased as a consequence of prednisone therapy whereas T was normal. Luteinizing hormone levels were normal in all. Follicle-stimulating hormone levels were normal in all. Follicle-stimulating hormone (FSH) was significantly increased in groups I and II. In group III, FSH was normal in 6 of 9 patients with serum creatinine concentrations < 2 mg/dl. FSH levels were uniformly elevated in Tanner I-V patients with creatinines > 2 mg/dl. The data shows that FSH is elevated in patients with chronic renal failure even in prepuberty and early adolescence. This may reflect damage to germinal epithelium prior to the advent of spermatogenesis, whereas Leydig cell function appears to remain intact.

Adolescent↗