SEARCH · PubMed Health

Results for “Steroid profiling”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 343 records · Page 19Linked to original sources

PubMed1988

In vivo and in vitro studies in a 46, XY phenotypically female infant with 17-ketosteroid reductase deficiency.

A 46, XY phenotypically female infant with 17-ketosteroid reductase (17-KSR) showed normal plasma androgens for chromosomal sex shortly after birth, but did not show the physiologic testosterone rise. One intramuscular injection with human chorionic gonadotropin resulted in high ratios between androstenedione/testosterone and dehydroepiandrosterone/delta 5-androstenediol, confirming the diagnosis. In spermatic vein plasma similarly elevated ratios were found. A urinary steroid profile revealed elevated levels of metabolites of 17-OH-progesterone and androstenedione. In vitro studies in testicular tissue showed a decreased capacity of 17-ketosteroid reductase, the reduction capacity being more affected than the oxidation capacity. The activity of 3 beta-hydroxysteroid-dehydrogenase was slightly increased. The serial analysis of plasma androgens provides more insight in the natural history of 17-ketosteroid reductase.

17-Hydroxysteroid Dehydrogenases↗

PubMed1993

Urinary cortisol metabolites in the assessment of peripheral thyroid hormone action: application for diagnosis of resistance to thyroid hormone.

Urinary cortisol metabolites are altered both quantitatively and qualitatively in thyroid dysfunction. This study was conducted to elucidate the usefulness of urinary cortisol metabolites in the assessment of peripheral thyroid hormone action, particularly in the patients with inappropriate thyrotropin secretion. Twenty-four hour urinary 17-hydroxycorticosteroid (17-OHCS) level and gas chromatographical steroid profile were studied in 25 hyperthyroid, 18 hypothyroid, and 24 euthyroid control subjects. Five patients with generalized thyroid hormone resistance and two patients with thyrotropin secreting pituitary tumor were also studied. The ratio of urinary tetrahydrocortisone to tetrahydrocortisol (THE/THF) was significantly elevated in hyperthyroidism (4.58 +/- 1.49) and depressed in hypothyroidism (1.31 +/- 0.55) compared to control (1.93 +/- 0.35). There were good correlations between THE/THF and serum thyroid hormone levels, especially in hypothyroidism. THE/THF can be a good biochemical indicator for deficiency of peripheral thyroid hormone action. Two patients with thyrotropin-secreting tumor showed high THE/THF, which reflected thyroid hormone excess. In contrast, THE/THF in the patients with generalized thyroid hormone resistance was low as compared to high serum thyroid hormone levels. Similar findings were demonstrated with 17-OHCS but discrimination of thyroid hormone resistance was insufficient. Thus, the ratio of the urinary concentrations of cortisol metabolites, THE/THF, appears to be a good marker for peripheral thyroid hormone resistance.

17-Hydroxycorticosteroids↗

PubMed1988

The effect of age on the cyclical patterns of plasma LH, FSH, oestradiol and progesterone in women with regular menstrual cycles.

Luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol and progesterone concentrations in plasma were obtained daily throughout the menstrual cycles of 94 regularly cycling women, aged between 24 and 50 years. Although mean LH concentrations changed little with advancing age, mean FSH concentrations were significantly (P less than 0.001) elevated from the age of 39 years. FSH concentrations in the oldest women studied (48-50 years) were approximately 3-fold greater than in the younger controls (women aged 23-35 years). LH concentrations rose slightly (P less than 0.05) during the last 5 years only. The increase in FSH concentration was not, however, uniform across the cycle, but was confined predominantly to the mid-follicular and post-ovulatory phases (i.e. those times in the normal menstrual cycle when circulating inhibin concentrations appear to be minimal). Despite the clear increases in FSH concentration, there was little alteration in the mean steroid profiles which remained within the normal fertile range throughout the last decade of reproductive life. The only exception to this was a small, transient, but significant (P less than 0.05) decrease in preovulatory oestradiol concentration between the ages of 36 and 38 years, which was followed by a transient increase (P less than 0.01) in oestradiol concentration between 39 and 44 years. However, no corresponding significant changes in mean progesterone concentrations were observed.

Adult↗

PubMed1993

How does daily treatment with human chorionic gonadotropin induce superovulation in the cyclic hamster?

Daily s.c. injection of 2.0 IU hCG per day, begun on Day 1 of the cycle (estrus), results in hamsters ovulating 20.7 +/- 0.7 eggs instead of the normal number of 13.3 +/- 0.5 (SEM). This is associated with a reduced rate of follicular atresia so that more of the 10 developing follicles per ovary (large preantral stages) normally recruited on Day 1 of the cycle mature and go on to ovulate. The hCG-treated follicles were larger than control follicles, but contained similar amounts of DNA/follicle; increased size of the antral cavity accounted for their greater size. Moreover, DNA synthesis was significantly reduced in the hCG follicles on Days 2 and 4. Thecal vascularity as judged by the number of red blood cells retained in the theca or microsphere uptake by follicles indicates that on Day 2, thecal blood flow was significantly lower in the hCG-treated animals than in controls. On the other hand, after hCG treatment begun on Day 1, serum levels and in vitro incubation of individual follicles revealed that on Day 2 and beyond, androstenedione (A) and estradiol (E2) levels were elevated. After hCG treatment, the elevated serum E2 correlated with reduced serum LH on Days 3 and 4 whereas FSH was unaffected. To study in vitro steroid accumulation, the 10 largest follicles (the developing follicles) were dissected from alternate left and right ovaries from control and hCG-treated animals and incubated individually, and their histology was then compared with the steroid profiles. Accumulation of A and E2 was significantly greater in the hCG-treated follicles than in controls in a 1-h basal incubation and after the addition of 50 ng LH. Progesterone accumulation usually did not differ between the control and hCG-treated follicles. Early stage 1 atretic follicles (judged by histology) were still capable of producing A and E2 in vitro, comparable to control follicles; but, as atresia progressed, the follicles synthesized only progesterone. This is consistent with the temporal pattern previously observed in a model of induced follicular atresia in the hamster [Greenwald, Biol Reprod 1989; 40:175-181]. It is concluded that superovulation resulting from hCG injections is due to thecal production of androgens from follicles normally destined for atresia. For the untreated cyclic hamster, the critical time for thecal androgen production is the first 2 days of the cycle. The aromatizable androgens are then converted into estrogens, which in turn may maintain the microenvironment of the antral cavity, which is essential for viability of the granulosa cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1996

Role of estrogen and prostaglandin F2 alpha in premature luteal regression in monovulatory and superovulated red deer (Cervus elaphus).

The superovulation of red deer hinds with eCG is commonly associated with premature luteal regression. This study was an investigation of the endocrine mechanisms regulating luteal function after superovulation. Four groups of hinds (n = 7-8 per group) were treated with progesterone-impregnated intravaginal controlled internal drug-releasing (CIDR) devices for 12 days to synchronize estrus (CIDR device withdrawal = Day 0). Group 1 served as controls; group 2 received an i.m. injection of 0.25 mg estradiol benzoate (EDB) at 72, 84, 96, and 108 h after removal of the device; group 3 received an i.m. injection of 1200 IU eCG at -72 h; group 4 received both EDB and eCG treatments. Oxytocin-induced prostaglandin F2 alpha (PGF2 alpha) release was assessed on Day 4 by oxytocin challenge. Ovarian response was determined by laparoscopy on Day 14. Plasma steroid profiles were determined from thrice-weekly plasma samples collected from Day -13 to Day 35 (progesterone) and Days 0 to 14 (estradiol). EDB increased the incidence of premature luteal regression in monovulatory and eCG-treated animals (p < 0.05) and reduced the number of CL (p < 0.05) in eCG-treated animals. EDB and eCG each elevated plasma concentrations of estradiol and increased the incidence of significant oxytocin-induced PGF2 alpha release. These results support the hypothesis that eCG causes premature luteal regression by inducing prolonged estrogen secretion that sensitizes the endometrium to oxytocin, thereby eliciting PGF2 alpha release during the early luteal phase.

Animals↗

PubMed1988

Measurement of progesterone in saliva: assessment of the normal fertile range using spontaneous conception cycles.

The concentration of progesterone in saliva can be used as an alternative to the measurement of the hormone in plasma because the steroid profiles are qualitatively, although not quantitatively, similar. Reference values for concentrations of the hormone during the luteal phase have been established using data derived from selected, apparently normal women, some of whom conceived in the study cycle. Six to eight days after the LH surge salivary progesterone values of 300-800 pmol/l can be regarded as 'normal' and can therefore be used as a reference for the clinical assessment of infertile women. Moreover, since there is a significant within-subject, between-cycle correlation (P less than 0.001) in salivary progesterone index values, the clinical information derived from one cycle is likely to be representative for that individual.

Female↗

PubMed1995

Extra-adrenal effects of metyrapone include inhibition of the 11-oxoreductase activity of 11 beta-hydroxysteroid dehydrogenase: a model for 11-HSD I deficiency.

BACKGROUND AND OBJECTIVE: Previous studies suggesting effects of metyrapone on extra-adrenal corticosteroid metabolism have involved significant alterations in plasma cortisol. We have therefore studied effects of metyrapone on urinary excretion of steroids in a group of patients treated concurrently with hydrocortisone so that changes in plasma cortisol were minimized. DESIGN: Replacement doses of hydrocortisone (30 mg/day) were given concurrently with metyrapone (2-4 g/day) for 2 weeks. Blood samples were taken and 24-hour urinary steroid collections were made at baseline and after 1 and 2 weeks of treatment. PATIENTS: Subjects were 6 female patients with major depression from a trial of metyrapone as an antidepressant. MEASUREMENTS: Urinary steroid profiles were measured by gas chromatography; plasma cortisol and urinary free cortisol were measured by fluorescence immunoassay. RESULTS: Plasma cortisol levels were not significantly decreased by treatment, while excretion of 11-deoxycortisol metabolites increased eightfold after 2 weeks indicating that concurrent hydrocortisone administration had not suppressed the adrenal. Ratios reflecting 11 beta-hydroxy/11-oxo metabolites of cortisol were significantly decreased, consistent with inhibition of the 11-oxoreductase activity of 11 beta-hydroxysteroid dehydrogenase (11-HSD). Other changes included significant decreases in the rates of 5 alpha vs 5 beta and of 20 alpha vs 20 beta reduction of corticosteroids. CONCLUSIONS: Metyrapone has multiple effects on extra-adrenal corticosteroid metabolism and is the only agent we know of which selectively inhibits 11-oxoreductase. Metyrapone thus provides a model for 11-HSD I deficiency and a tool for in-vitro studies of cortisol-cortisone interconversion. The results also suggest mechanisms whereby corticosteroid effects can be regulated separately from corticosteroid synthesis.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2005

Clinical evidence that hyperinsulinaemia independent of gonadotropins stimulates ovarian growth.

OBJECTIVE: Ovarian enlargement is a constant feature of syndromes of extreme insulin resistance. The objective of this study is to show the role of insulin on ovarian growth in the presence of low gonadotropin levels. PATIENTS: Seven young patients with syndromes of extreme insulin resistance (five with lipodystrophy, one with Type B syndrome and one with Rabson-Mendenhall syndrome) were studied. MEASUREMENTS: Baseline LH concentrations and luteinizing hormone releasing hormone (LHRH) tests were performed. Total testosterone, insulin and C-peptide values were measured. Pelvic ultrasounds were performed. RESULTS: Four patients were prepubertal (age range 7-10 years old) and had prepubertal gonadotropin levels, and 2 of the 4 who were tested did not respond to LHRH (NIH 10 and RM-PAL). Three patients were Tanner stage 4 (age range 13-17 years old) and had low gonadotropins that did not respond to LHRH stimulation test. All seven patients had marked hyperinsulinaemia and 6 of 7 had at least one enlarged ovary. Testosterone values were increased in 4 of 7 patients. CONCLUSION: This represents the first example of the pathologic role of insulin to stimulate ovarian growth with low circulating gonadotropins. Thus, while ovarian growth and steroidogenesis are normally stimulated by gonadotropins at puberty, hyperinsulinaemia stimulates pathologic growth of the ovary and an androgenic steroid profile that is active at all ages. We suggest that these patients constitute a model to separate the effect of insulin from gonadotropin in stimulating ovarian growth and/or steroidogenesis.

Adolescent↗

PubMed1996

Diagnosis and treatment of a child with the syndrome of apparent mineralocorticoid excess type 1.

We report the case of a 16-month-old boy who presented with chronic vomiting, failure to thrive, arterial hypertension and medullary nephrocalcinosis. Laboratory results revealed hypokalaemia, metabolic alkalosis, increased urinary potassium excretion and a hyporeninaemic hypoaldosteronism. Chromatographic determination of urinary steroid metabolites showed an abnormal elevation of tetrahydrocortisol and allo-tetrahydrocortisol compared to tetrahydrocortisone; this pattern of urinary steroid excretion is essential for the diagnosis of the syndrome of apparent mineralocorticoid excess type 1 and believed to be a result of the underlying metabolic defect, a decreased activity of the 11 beta-hydroxysteroid dehydrogenase. A second variant, called syndrome of apparent mineralocorticoid excess type 2, has similar clinical features but lacks the typical urinary steroid profile. Therapy with spironolactone resulted in growth, weight gain and blood pressure control.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1981

Short-term fluctuations in the concentration of cortisol and progesterone in fetal plasma, maternal plasma, and amniotic and allantoic fluids from sheep during late pregnancy.

Fluctuations in the concentrations of cortisol and progesterone in fetal plasma, maternal plasma, and amniotic and allantoic fluids were measured in samples taken at 10-min intervals over a 90-min period from three groups of sheep sampled at different times during late pregnancy. During the last 30 days of gestation there was a significant rise in the mean concentration of cortisol in fetal plasma and amniotic fluid and a significant correlation between the cortisol concentration in these two fluids. The concentration of cortisol in allantoic fluid exceeded that in amniotic fluid. The concentration of cortisol in fetal plasma varied in a pulsatile manner, however the coefficient of variation (CV) within animals was greater (36%) on days -11 to -20, relative to the day of parturition (day 0), than on days -21 to -30 or days -5 to 0(15-19%). The CV values for cortisol in amniotic fluid and maternal plasma during the last 30 days of pregnancy were 20-50% and two at five times greater than the intraassay CV. The concentration of progesterone in amniotic fluid increased after day -20 but was not correlated with that in maternal plasma or fetal plasma. The concentrations of progesterone in paired samples of amniotic fluid and allantoic fluid were similar. The CV values for progesterone (18-34%) were similar in fetal and maternal plasma and amniotic fluid and did not change significantly during late pregnancy. Changes in the concentration of progesterone were unrelated to changes in cortisol. Interpretation of steroid profiles in fetal plasma and fluids through late pregnancy should take into account these short-term fluctuations in hormone concentrations.

Allantois↗

PubMed1999

Genetic, biochemical, and clinical studies of patients with A328V or R213C mutations in 11betaHSD2 causing apparent mineralocorticoid excess.

Apparent mineralocorticoid excess is a recessively inherited hypertensive syndrome caused by mutations in the 11beta-hydroxysteroid dehydrogenase type 2 gene, which encodes the enzyme normally responsible for converting cortisol to inactive cortisone. Failure to convert cortisol to cortisone in mineralocorticoid-sensitive tissues permits cortisol to bind to and activate mineralocorticoid receptors, causing hypervolemic hypertension. Typically, these patients have increased ratios of cortisol to cortisone and of 5alpha- to 5beta-cortisol metabolites in serum and urine. We have studied 3 patients in 2 families with severe, apparent mineralocorticoid excess and other family members in terms of their genetic, biochemical, and clinical parameters, as well as normal controls. Two brothers were homozygous for an A328V mutation and the third patient was homozygous for an R213C mutation in the 11beta-hydroxysteroid dehydrogenase type 2 gene; both mutations caused a marked reduction in the activity of the encoded enzymes in transfection assays. The steroid profiles of the 7 heterozygotes and 2 other family members studied were completely normal. The results of a novel assay used to distinguish 5alpha- and 5beta-tetrahydrometabolites suggest that 5beta-reductase activity is reduced or inhibited in apparent mineralocorticoid excess. In 1 patient undergoing renal dialysis for chronic renal insufficiency, direct control of salt and water balance completely corrected the hypertension, emphasizing the importance of mineralocorticoid action in this syndrome.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed1992

Differential contributions of ovarian and extraovarian factors to age-related reductions in plasma estradiol and progesterone during the estrous cycle of C57BL/6J mice.

The relative contributions of ovarian and extra-ovarian factors to the altered ovarian steroidal profiles of middle-aged mice were assessed by reciprocal, heterochronic ovarian grafting. Ovaries from cycling, young (2 months), and middle-aged (12 months) mice were exchanged by grafting under the renal capsules. Blood samples were obtained daily at midday throughout the estrous cycle for measurement of estradiol (E2) and 3-4 h after lights-out on proestrus to measure the preovulatory elevation of progesterone (P4). Middle-aged intact mice had lower mean concentrations of E2 during the cycle, no detectable midday preovulatory elevation of E2, and an attenuated preovulatory increase of P4 compared to young mice. Ovarian grafts from young donors failed to increase mean E2 levels of middle-aged mice, but did restore the preovulatory elevation of E2 and preovulatory P4 to levels of young controls. Reciprocal grafting confirmed these findings: ovaries from middle-aged donors in young hosts produced mean E2 levels equivalent to those of young mice but were unable to support a preovulatory increase of E2 or a preovulatory P4 level equivalent to that of young controls. These results reveal differential contributions of ovarian and extra-ovarian factors to age changes in E2 and P4. They indicate that ovarian aging plays an important role in attenuating the preovulatory increase of E2 and P4, but extra-ovarian, presumably neuroendocrine, age changes underlie the mean reduction of E2 levels across the estrous cycle.

Aging↗

PubMed1986

Biochemical diagnosis and management of corticosterone methyl oxidase type II deficiency.

Corticosterone methyl oxidase deficiency type II (CMO type II deficiency) is an autosomal recessive disorder characterized by a defect in the terminal step of aldosterone biosynthesis. Previous reports emphasized the diagnostic utility of elevated urinary ratios of 18-hydroxytetrahydro-compound A to tetrahydro-aldosterone, which are primary metabolites of 18-hydroxycorticosterone (18-OHB) and aldosterone, respectively. Limited data suggest that plasma ratios of 18-OHB to aldosterone are also abnormal in affected individuals. We report serum steroid profiles in two siblings with CMO type II deficiency. Serum levels of aldosterone precursors were elevated in both patients before treatment. In particular, the serum ratios of 18-OHB to aldosterone were greatly elevated and declined to normal levels during mineralocorticoid replacement. The possibility of heterozygote detection using this ratio is suggested. We also confirm previous reports of a detrimental effect on linear growth rate after cessation of mineralocorticoid therapy despite maintenance of normal serum electrolytes. This effect is associated with biochemical evidence of chronic salt depletion. Based on our observations, we recommend that serum 18-OHB to aldosterone ratios be routinely measured for the diagnosis and management of patients with CMO type II deficiency.

Adrenal Cortex Hormones↗

PubMed1986

The dependency of folliculogenesis and corpus luteum function on pulsatile gonadotropin secretion in cycling women using a gonadotropin-releasing hormone antagonist as a probe.

A potent GnRH antagonist, [Ac-delta 3-Pro1,p-F-D-Phe2,D-Trp3,6]GnRH (4F-Antag), was used as a probe to determine the relative dependency of ovarian cyclicity on pulsatile gonadotropin secretion. 4F-Antag was administered in a dose of 80 micrograms/kg sc twice a day for 3 consecutive days during different phases of the menstrual cycle. This treatment resulted in a prompt attenuation of pulsatile gonadotropin secretion in all women studied. Maximal suppression of gonadotropin levels, expressed as percent change from baseline, averaged 48% for LH and 22% for FSH. The reduced pulsatile gonadotropin release induced by 4F-Antag administration during the early follicular phase resulted in a significant decrease in serum estradiol levels during the period of treatment and was followed by a prolongation of follicular phase (2.4 days) and cycle length (3.5 days), but no alteration of subsequent cyclic ovarian steroid profiles compared to control cycles. Treatment initiated during the midfollicular phase 4-6 days before the expected LH surge resulted in a more dramatic decline in serum estradiol levels and prolongation of follicular phase length by 5-6 days compared to control cycles. Normal luteal function was preserved. These alterations were compatible with induction of the demise of the dominant follicle followed by the reinitiation of follicular recruitment. Administration of 4F-Antag during the midluteal phase resulted in rapid falls in serum estradiol and progesterone levels and the onset of menstrual bleeding in all women. The luteolytic effect of 4F-Antag was completely negated by the administration of hCG. These data indicate that 4F-Antag interferes with ongoing cyclic ovarian function by reducing pulsatile gonadotropin stimulation, which disrupts folliculogenic processes and induces the demise of the corpus luteum. From these findings we infer that the functional integrity of ovarian cyclicity is remarkably sensitive to brief (3 days) and partial reduction in pulsatile gonadotropin secretion.

Adult↗

PubMed1992

Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1.

In multiple endocrine neoplasia type 1 (MEN-1), benign enlargement of the adrenal cortex has been found in about one third of necropsy cases. To elucidate the clinical and genetic characteristics of the MEN-1 adrenal lesion, we have investigated 33 MEN-1 patients. Twelve individuals (37%) demonstrated adrenal enlargement, which was bilateral in 7 of them. Histopathology revealed diffuse and nodular cortical hyperplasia, adenomas, and a single case of adrenocortical carcinoma. The apparently benign adrenal enlargements were not associated with presently ascertainable biochemical disturbances in the hypothalamic-pituitary-adrenocortical axis, and they were without radiological signs of progression during follow-up. The individual developing unilateral adrenocortical carcinoma showed rapid adrenal expansion, feminization, and an abnormal urinary steroid profile after 4 yr of observation for bilateral minor adrenal enlargements. Pancreatic endocrine tumors were significantly overrepresented and present in all MEN-1 individuals with adrenal involvement. In agreement with findings in sporadic cases, the MEN-1 adrenocortical carcinoma genome showed loss of constitutional heterozygosity for alleles at 17p, 13q, 11p, and 11q. The benign adrenal lesions retained heterozygosity for the MEN-1 locus at chromosome 11 q 13. Despite its prevalence and malignant potential, the pituitary-independent adrenocortical proliferation does not appear to be a primary lesion in MEN-1, but might represent a secondary phenomenon, perhaps related to the pancreatic endocrine tumor.

Adrenal Cortex↗

PubMed1994

Clinical and hormonal effects of the 5 alpha-reductase inhibitor finasteride in idiopathic hirsutism.

Hyperactivity of 5 alpha-reductase in the skin is considered a major mechanism of excessive hair growth in hirsute women with normal levels of serum androgens (idiopathic hirsutism). Preventing the conversion of testosterone to dihydrotestosterone by inhibiting 5 alpha-reductase activity could thus be the most rational and effective treatment in this condition. The present study evaluated the effects of the oral administration of finasteride (5 mg once daily) for 6 months in 17 young women with idiopathic hirsutism, 5 of whom were also given an oral contraceptive. The degree of hirsutism (graded by a modified Ferriman-Gallwey score), serum sex hormone levels, and serum and urinary 5 alpha-metabolism steroid profiles were determined basally and periodically during the treatment period. The modified Ferriman-Gallwey score showed a remarkable reduction after 6 months of finasteride treatment (5.9 +/- 0.6 vs. 11.7 +/- 1.3; P < 0.01). Serum 5 alpha-dihydrotestosterone and 3 alpha-androstanediol glucuronide levels were decreased, and urinary C19 and C21 5 beta/5 alpha metabolite ratios were increased compared with pretreatment values. No significant adverse effect was reported. In women treated with finasteride and oral contraceptive, clinical efficacy was slightly more pronounced. In conclusion, the 5 alpha-reductase inhibitor finasteride is well tolerated and seems to be a useful tool in the treatment of idiopathic hirsutism.

Adult↗

PubMed2000

A novel A10E homozygous mutation in the HSD3B2 gene causing severe salt-wasting 3beta-hydroxysteroid dehydrogenase deficiency in 46,XX and 46,XY French-Canadians: evaluation of gonadal function after puberty.

Severe 3beta-hydroxysteroid dehydrogenase (3betaHSD) deficiency is a rare form of congenital adrenal hyperplasia resulting from mutations in the HSD3B2 gene that impair steroidogenesis in both the adrenals and gonads and cause salt-wasting in both sexes and incomplete masculinization of the external genitalia in genetic males. About two thirds of the reported patients are 46,XY. We describe two French-Canadian patients from two families without a known relationship who presented with severe salt-wasting 3betaHSD deficiency in infancy. Although the diagnosis was considered clinically, plasma steroid profiles were confusing. We have thus directly sequenced DNA fragments generated by PCR amplification of the four exons, exon-intron boundaries, and the 5'-flanking regions of the HSD3B2 gene. Sequencing of exon II revealed the presence of a C to A transversion in both alleles of these two cases, thus converting codon 10 (GCA), which codes for Ala, into GAA, encoding Glu. This Ala is highly conserved in the vertebrate 3betaHSD gene family and is located in the putative NAD-binding domain of the enzyme. The mutant type II 3betaHSD enzyme carrying an A10E substitution exhibited no detectable activity in intact transfected Ad293 cells. Both homozygous patients share the same haplotype, spanning approximately 3.3 centimorgans surrounding the HSD3B2 locus, which is consistent with a founder effect for this missense mutation. The 46,XY patient presented with ambiguous genitalia at birth and underwent normal masculinization at puberty, but was azoospermic at 18.5 yr of age. The 46,XX patient presented progressive breast development, menarche, and evidence of progesterone secretion. The only previously reported cases with pubertal follow-up revealed paternity in one male and hypogonadism in one female. These findings demonstrate the complex relationships between the genotype and the gonadal phenotype in severe 3betaHSD deficiency and the difficulty in predicting fertility.

3-Hydroxysteroid Dehydrogenases↗

PubMed2002

Cortisol and 17-hydroxyprogesterone kinetics in saliva after oral administration of hydrocortisone in children and young adolescents with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.

We have analyzed the kinetics of salivary cortisol (F) and 17-hydoxyprogesterone (17OHP) after a single oral administration of hydrocortisone (HC; 10 mg; 0700 h) in healthy male volunteers (n = 10; 18-29 yr) and in patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (males, n = 7; females, n = 3; 8.5-20.4 yr). The HC doses, related to body surface area, ranged from 6.3-9.2 mg/m(2) in controls and from 4.2-10.7 mg/m(2) in CAH patients. Saliva was collected over 5 h (at intervals of 15-30 min), and the steroids were measured with adapted RIAs. In healthy controls, maximal cortisol values (250.3 +/- 35.9 nmol/liter) were reached after 30 min. Values showed a monophasic decrease. A t(1/2) of 94.5 min was calculated. The proportion of the HC dose in the total area under the curve was 71.2 +/- 3.2%. For 17OHP, a monophasic decrease was found, with a minimum level of 48 +/- 27 pmol/liter after 300 min. In CAH patients the salivary steroid profiles showed individual kinetics (maximal cortisol values ranged from 107-726 nmol/liter). Here a monophasic decrease was found with a shorter t(1/2) of 56.4 min. The HC dose proportion in the area under the curve was 88.3 +/- 6%. 17OHP showed biphasic courses with a decrease to the minimum 17OHP level after 210 min at the latest and a subsequent gradual increase. Our findings of limited normalization of the adrenal cortex by oral HC administration underlines the necessity of optimizing therapy control and indicates the usefulness of kinetic studies for the judgement of therapy in CAH patients.

17-alpha-Hydroxyprogesterone↗