Assessment of the gonadotrophin-gonadal axis in androgen insensitivity syndrome.

OBJECTIVE: To study the value of measuring serum luteinising hormone (LH), follicle stimulating hormone (FSH), testosterone, and dihydrotestosterone (DHT) in androgen insensitivity syndrome (AIS). DESIGN: Retrospective study of patients on a nationwide register of AIS. PATIENTS: Sixty one cases of AIS with androgen receptor (AR) dysfunction (abnormalities of the AR gene and/or abnormal AR binding) were divided into three age groups: infants, < 1 year old; children, 1-13 years old; and postpubertal, > 13 years old. MEASUREMENTS: Age, dose of human chorionic gonadotrophin (hCG) stimulation, pre-hCG and post-hCG serum testosterone values, serum DHT values, and serum LH and FSH values before and after LH releasing hormone (LHRH) stimulation. RESULTS: In 23 of 30 infants testosterone was within age related reference ranges; six were above this range. The median testosterone rise following variable dosage of hCG was 9.5 times the basal value. The increment was not related to the hCG dose, age, or basal concentration of testosterone. The median basal and stimulated testosterone:DHT ratios were 2.5 and 6.1, respectively. The median increment in DHT was 2.2-fold. Seventeen of 18 FSH and 11 of 19 LH measurements were within age related ranges in infants; in seven patients LH values were above the range. LHRH stimulation performed in 39 patients showed an exaggerated LH in all age groups. The FSH response was not exaggerated in children. CONCLUSION: Although a positive hCG test excludes biosynthetic defects of testosterone, an inadequate response does not exclude AIS. Basal LH and testosterone may not be raised during early infancy. An LHRH stimulation test might be useful for evaluating cases of suspected AIS presenting in mid-childhood.     

Hypothalamo-hypophyseal-testicular function in prepubertal boys with acute lymphoblastic leukemia following chemotherapy and testicular radiotherapy

Hypothalamo-hypophyseal-testicular function was studied in twenty-eight prepubertal boys with ALL in clinical and haematological remission. Eighteen were treated with combined systemic chemotherapy (24-36 months) and the other ten, who had testicular leukemic infiltrates, received chemotherapy (38-60 months) and testicular radiotherapy (2 000 rad). Plasma levels of LH and FSH were measured before and after stimulation with LHRH (100 micrograms i.v.) and plasma levels of testosterone before and after stimulation with hCG (1 500 IU/48 h/7 doses). In patients treated with chemotherapy alone, mean basal LH and FSH, mean responses to LHRH stimulation and mean testosterone levels after stimulation with hCG did not significantly differ from those of the controls. Five of these patients who had normal testosterone values after three doses of hCG had testosterone values below the normal range after seven doses. In patients treated with chemotherapy and testicular radiotherapy, mean basal FSH and mean responses to LHRH stimulation were significantly higher than those of the controls. Testosterone values after stimulation with hCG were low in three and very low in the other seven. In both groups of patients data from testicular biopsies were consistent with functional results. We conclude that chemotherapy causes slight testicular damage, but chemotherapy and testicular radiotherapy produce severe testicular damage in patients with testicular leukemic infiltrates.     

Kinetics of the steroidogenic response to single versus repeated doses of human chorionic gonadotropin in boys in prepuberty and early puberty

There is accumulating evidence that in adult men excessive amounts of gonadotropins induce testicular desensitization to further gonadotropin stimulus. We evaluated the effects of endogenous gonadotropins and of repeated doses of exogenous human chorionic gonadotropin (hCG) on steroidogenesis by studying prepubertal and pubertal boys. The boys received either two intramuscular injections of hCG 4 days apart (protocol I) or four injections at 3- to 4-day-intervals (protocol II). In protocol I, serum testosterone, 17 alpha-hydroxyprogesterone, and estradiol were measured basally and for 6 days after the second injection, and in protocol II, before each injection and 4 days after the last injection. In the prepubertal-boys, serum testosterone increased from very low basal levels to 10.3 (protocol I) and 8.3 nmol/liter (protocol II). In protocol I the increase after the first injection was 64-fold and in protocol II there was an increase after each injection to a final level 144-fold of the basal. No significant changes were seen in the estradiol levels. In the pubertal boys at genital stage G2, the serum testosterone levels increased after the first two injections, but at genital stage G3, the levels increased only after the first injection. Maximal testosterone increases were 27- and 8-fold, respectively. In pubertal boys estradiol levels increased progressively throughout the stimulation. The major testosterone response ws seen after the first dose of hCG and repeated doses, at least in the pubertal boys, increased estradiol but not testosterone levels, thus causing an estrogen-mediated 17,20-lyase block. We therefore suggest that a single-dose hCG test deserves further evaluation for diagnostic use.     

Hypothalamo-Hypophyseal-Testicular Function in Prepubertal Boys with Acute Lymphoblastic Leukemia following Chemotherapy and Testicular Radiotherapy

ABSTRACT. Hypothalamo-hypophyseal-testicular function was studied in twenty-eight prepubertal boys with ALL in clinical and haematological remission. Eighteen were treated with combined systemic chemotherapy (24–36 months) and the other ten, who had testicular leukemic infiltrates, received chemotherapy (38–60 months) and testicular radiotherapy (2000 rad). Plasma levels of LH and FSH were measured before and after stimulation with LHRH (100 μg i.v.) and plasma levels of testosterone before and after stimulation with hCG (1500 IU/48 h/7 doses). In patients treated with chemotherapy alone, mean basal LH and FSH, mean responses to LHRH stimulation and mean testosterone levels after stimulation with hCG did not significantly differ from those of the controls. Five of these patients who had normal testosterone values after three doses of hCG had testosterone values below the normal range after seven doses. In patients treated with chemotherapy and testicular radiotherapy, mean basal FSH and mean responses to LHRH stimulation were significantly higher than those of the controls. Testosterone values after stimulation with hCG were low in three and very low in the other seven. In both groups of patients data from testicular biopsies were consistent with functional results. We conclude that chemotherapy causes slight testicular damage, but chemotherapy and testicular radiotherapy produce severe testicular damage in patients with testicular leukemic infiltrates.     

ENDOCRINOLOGICAL STUDIES IN UNDESCENDED TESTES

Abstract. A cross-sectional study was carried out on 168 boys aged 2.5–16.8 years with unilateral or bilateral testicular maldescent. Urinary excretion of testosterone, Δ₄-androstenedione, LH and FSH was investigated. The results were related to chronological age, bone age and sexual maturation stage. Urinary testosterone excretion was elevated in unilateral and bilateral cases of undescended testis under 9 years of age. The pubertal increase of testosterone excretion seemed to be moderately delayed in the patients. In pubertal stage V the testosterone excretion was normal. The mean testosterone/androstenedione relationship was normal in all age groups up to 14.9 years and increased in patients above this age. After HCG stimulation, the testosterone excretion increased at all ages studied whereas the androstenedione excretion increased only in bilateral cases under 11 years of age. Urinary LH excretion was diminished in bilateral cases aged 6.0–7.9 years and elevated in unilateral cases in pubertal stage V. Urinary FSH excretion was normal below 8 years of age, moderately elevated in bilateral cases aged 8.0–11.9 years and increased in unilateral cases in pubertal stage V. Patients with bilateral anorchia in pubertal stage I, had normal basal testosterone and androstenedione excretion while the LH and FSH levels were increased. The findings in this study indicated that disturbances in the pituitary-gonadal function of cryptorchids might be operative from early childhood and throughout pubertal years.     

Endocrinological studies in undescended testes.

A cross-sectional study was carried out on 168 boys aged 2.5-16.8 years with unilateral or bilateral testicular maldescent. Urinary excretion of testosterone, delta4-androstenedione, LH and FSH was investigated. The results were related to chronological age, bone age and sexual maturation stage. Urinary testosterone excretion was elevated in unilateral and bilateral cases of undescended testis under 9 years of age. The pubertal increase of testosterone excretion seemed to be moderately delayed in the patients. In pubertal stage V the testosterone excretion was normal. The mean testosterone/androstenedione relationship was normal in all age groups up to 14.9 years and increased in patients above this age. After HCG stimulation, the testosterone excretion increased at all ages studied whereas the androstenedione excretion increased only in bilateral cases under 11 years of age. Urinary LH excretion was diminished in bilateral cases aged 6.0-7.9 years and elevated in unilateral cases in pubertal stage V. Urinary FSH excretion was normal below 8 years of age, moderately elevated in bilateral cases aged 8.0-11.9 years and increased in unilateral cases in pubertal stage V. Patients with bilateral anorchia in pubertal stage I, had normal basal testosterone and androstenedione excretion while the LH and FSH levels were increased. The findings in this study indicated that disturbances in the pituitary-gonadal function of cryptorchids might be operative from early childhood and throughout pubertal years.     

Pituitary-gonadal axis in male undermasculinisation.

AIMS: To study the value of assessing serum concentrations of luteinising hormone (LH), follicle stimulating hormone (FSH), testosterone, and dihydrotestosterone (DHT) in patients with male undermasculinisation not caused by androgen insensitivity. METHODS: A retrospective study of a register of cases of male undermasculinisation (20 with abnormal testes, eight with 5alpha-reductase deficiency, three with testosterone biosynthetic defects, seven with Drash syndrome, and 210 undiagnosed). RESULTS: A human chorionic gonadotropin (hCG) stimulation test was performed in 66 of 185 children with male undermasculinisation. In 41 of 66 patients the dose of hCG was either 1000 U or 1500 U on three consecutive days. The rise in testosterone was related to basal serum testosterone and was not significantly different between the two groups. Testosterone:DHT ratio in patients with 5alpha-reductase deficiency was 12.5-72.8. During early infancy, baseline concentrations of LH and FSH were often within normal reference ranges. In patients with abnormal testes, median pre-LHRH (luteinising hormone releasing hormone) concentrations of LH and FSH were 2 and 6.4 U/l, respectively, and post-LHRH concentrations were 21 and 28 U/l. An exaggerated response to LHRH stimulation was observed during mid-childhood in children where the diagnosis was not clear and in all children with abnormal testes. CONCLUSIONS: The testosterone:DHT ratio following hCG stimulation is more reliable than the basal testosterone:DHT ratio in identifying 5alpha-reductase deficiency. During infancy, the LHRH stimulation test may be more reliable in identifying cases of male undermasculinisation due to abnormal testes than basal gonadotrophin concentrations.     

The relationship of adrenal androgens to the secretory patterns for cortisol, prolactin, and growth hormone during early puberty.

Serum concentrations of dehydroepiandrosterone (DHA), dehydroepiandrosterone sulfate (DHA-sulfate), cortisol, prolactin, and growth hormone were measured at half-hour intervals for 24 hr in five healthy children aged 8--13 yr. Their adolescent development was assessed by clinical staging, plus determinations of serum FSH, LH, testosterone and estradiol during both wakefulness and sleep. Correlative analysis indicates that there was synchronous secretion of DHA and cortisol, implying regulation of both by ACTH. With advancing age and sexual maturation, there was a progressive rise in mean serum DHA and DHA-sulfate levels, but no similar change in serum cortisol concentrations. There was evidence for enhanced secretion of both growth hormone and prolactin during sleep in all subjects (including one who was hyperprolactinemic), but there was no obvious relationship between levels of these pituitary hormones and the early pubertal rise in adrenal androgens.     

Hypergonadotropic Hypogonadism in Newborn Males with Primary Testicular Failure

ABSTRACT. Four infants with genital ambiguity but with apparent testes were given a gonadotropin-releasing hormone (GnRH) test and a human chorionic gonadotropin (hCG) test at age 3–12 days. The results were compared with those from 16 newborn males (aged 2 to 6 days) with minor genital anomalies; 9 with unilateral and 3 with bilateral incomplete testicular descent, 2 with surgically insignificant glandular hypospadias and 2 with penis length <(-2 SD) for gestational age. Treatment with testosterone resulted in clear phallus growth in all four patients. All four patients had elevated basal luteinizing hormone (LH) concentrations as well as an exaggerated LH response to GnRH; three of them also had an exaggerated follicle stimulating hormone (FSH) response. Thus in all patients the etiology of genital ambiguity was considered to be testicular. The testosterone response to hCG was normal in two of the patients but impaired in the other two. The steroidogenic response did not show any specific enzyme defect. We conclude that 1) newborn boys with Leydig cell failure are clearly hypergonadotropic, 2) the GnRH test is a more sensitive indicator of Leydig cell failure neonatally than the hCG test and 3) normal testes greatly inhibit the secretion of both LH and FSH during the first week of life.     

Pituitary-gonadal axis in male undermasculinisation

AIMS—To study the value of assessing serum concentrations of luteinising hormone (LH), follicle stimulating hormone (FSH), testosterone, and dihydrotestosterone (DHT) in patients with male undermasculinisation not caused by androgen insensitivity.
METHODS—A retrospective study of a register of cases of male undermasculinisation (20 with abnormal testes, eight with 5α-reductase deficiency, three with testosterone biosynthetic defects, seven with Drash syndrome, and 210undiagnosed).
RESULTS—A human chorionic gonadotropin (hCG) stimulation test was performed in 66 of 185 children with male undermasculinisation. In 41 of 66 patients the dose of hCG was either 1000 U or 1500U on three consecutive days. The rise in testosterone was related to basal serum testosterone and was not significantly different between the two groups. Testosterone:DHT ratio in patients with 5α-reductase deficiency was 12.5-72.8. During early infancy, baseline concentrations of LH and FSH were often within normal reference ranges. In patients with abnormal testes, median pre-LHRH (luteinising hormone releasing hormone) concentrations of LH and FSH were 2and 6.4 U/l, respectively, and post-LHRH concentrations were 21and 28 U/l. An exaggerated response to LHRH stimulation was observed during mid-childhood in children where the diagnosis was not clear and in all children with abnormal testes.
CONCLUSIONS—The testosterone:DHT ratio following hCG stimulation is more reliable than the basal testosterone:DHT ratio in identifying 5α-reductase deficiency. During infancy, the LHRH stimulation test may be more reliable in identifying cases of male undermasculinisation due to abnormal testes than basal gonadotrophin concentrations.
     

Pituitary deficiency and lack of gonads in an XY pseudohermaphrodite with beta 39/lepore haemoglobinopathy

We describe the occurrence of hypothyroidism and hypogonadotropic hypogonadism in an XY pseudohermaphrodite subject affected by beta-thalassemia. The patient, reared as female, diagnosed at 14 months of age as having a beta 39/Lepore hemoglobinopathy, treated with multiple transfusion therapy, was referred at age of 15 years because of delayed puberty. Complete endocrine evaluation showed low levels, both basal and after combined LHRH-TRH and hCG stimuli, of FSH, LH, TSH, estradiol (E2), testosterone (T), progesterone (P), androstenedione (A), and FT4 levels, and normal PRL, cortisol, 17OHP and ACTH levels. Imaging studies (ultrasound, magnetic resonance, radioisotope scanning and gonadal vessels phlebography) did not show internal genitalia and gonads. Karyotype resulted 46,XY. PCR amplification of the SRY gene confirmed the presence of the Y chromosome. Female genitalia without uterus in a subject with Y chromosome SRY gene, and no detectable testes indicate a condition of male pseudohermaphroditism associated with testicular regression. Low gonadotropin and sex steroid levels are suggestive of combined acquired hypothalamic-pituitary and gonadal impairment, due to iron deposition in both organs. We cannot exclude congenital failure of testosterone synthesis and action in this case, because lack of gonads is an unusual finding in thalassemic hypogonadic subjects.     

Longitudinal study of calcium metabolism in male puberty. II. Relationship between mineralization and serum testosterone

Height velocity, bone mineral content (BMC), serum concentrations of alkaline phosphatase (AP), testosterone, dehydroepiandrosterone (DHEA) and androstenedione (A-dione) were determined as a part of a longitudinal study of calcium metabolism in normal male puberty. The time of maximal increase (Tm) in concentrations was calculated for 20 boys from a curve-fitting analysis program. Highly significant correlations were found between Tm testosterone and Tm BMC (r = 0.73, p less than 0.001); Tm AP and Tm BMC (r = 0.68, p less than 0.001). The mean difference in time between Tm testosterone and Tm BMC was 4.7 months and between Tm AP and Tm testosterone 0.7 month. Our data indicate a very close relationship between testosterone, osteoblastic activity, and mineralization in normal male puberty, whereas the adrenal androgens do not seem to have a major influence on the mineralization at the male puberty growth spurt phase.     

Hypergonadotropic hypogonadism in newborn males with primary testicular failure

Four infants with genital ambiguity but with apparent testes were given a gonadotropin-releasing hormone (GnRH) test and a human chorionic gonadotropin (hCG) test at age 3-12 days. The results were compared with those from 16 newborn males (aged 2 to 6 days) with minor genital anomalies; 9 with unilateral and 3 with bilateral incomplete testicular descent, 2 with surgically insignificant glandular hypospadias and 2 with penis length less than (means-2 SD) for gestational age. Treatment with testosterone resulted in clear phallus growth in all four patients. All four patients had elevated basal luteinizing hormone (LH) concentrations as well as an exaggerated LH response to GnRH; three of them also had an exaggerated follicle stimulating hormone (FSH) response. Thus in all patients the etiology of genital ambiguity was considered to be testicular. The testosterone response to hCG was normal in two of the patients but impaired in the other two. The steroidogenic response did not show any specific enzyme defect. We conclude that newborn boys with Leydig cell failure are clearly hypergonadotropic, the GnRH test is a more sensitive indicator of Leydig cell failure neonatally than the hCG test and normal testes greatly inhibit the secretion of both LH and FSH during the first week of life.     

17 beta-hydroxysteroid dehydrogenase 3 deficiency in the Mediterranean population

Eighty-five males with 17 beta-HSD3 were identified among a highly inbred Arab population in Israel and 57 studied over a period of 25 years. The founders of this defect originated in the mountainous regions of present Lebanon and Syria, but most of the families now live in Jerusalem, Hebron, the Tel-Aviv area and, in particular, in Gaza, where the frequency of affected males is estimated at 1 in 100 to 150. Affected individuals are born with ambiguity of the external genitalia and reared as females until puberty. Thereafter marked virilization occurs, leading in many cases to the spontaneous adoption of a male gender identity and role. Adults develop a male habitus with abundant body hair and beard and the phallus and testes enlarge to adult proportions. Gender reassignment in infancy was only possible when enough erectile tissue was present at birth and developed into a normal size penis with testosterone. 17 beta-HSD3 deficiency can be reliably diagnosed by endocrine evaluation and mutation analysis. In adults the defect is characterized by markedly increased concentrations of androstenedione (A) with borderline low to normal testosterone (T) levels and a high A/T ratio. 5a-dihydrotestosterone (DHT) concentrations are moderately decreased, normal or high and dehydroepiandrosterone (DHEA) levels are high. The estrogen pathway is also impaired, even though both estrone (E-1) and estradiol-17 beta (E-2) levels are high. Children have low basal levels of all androgens, but the defect may be demonstrated after prolonged stimulation with human chorionic gonadotropin (HCG). LH and FSH levels are very high after puberty and normal in childhood. 17 beta-HSD3 isozyme is encoded by the chromosome 9q22 17 beta-HSD3 gene and expressed exclusively in testes. A point mutation in exon 3, codon 80 of the 17 beta-HSD3 gene, R80Q, caused by a single base substitution from CGG ( arginine) to CAG ( glutamine) was identified in both alleles of 24 individuals from 9 extended Arab families from Gaza, Jerusalem and Lod-Ramle. Twenty-one homozygote males (46,XY) were MPH with testicular 17 beta-HSD3 deficiency whereas the three homozygote females (46,XX) were asymptomatic, had normal internal and external genitalia, normal sexual development and revealed no biochemical evidence of 17 beta-HSD3 deficiency. The molecular pattern is compatible with an autosomal recessive mode of inheritance, sex dependent.     

HCG stimulation in children with cryptorchidism

Fifty-eight children with cryptorchidism have been given hCG stimulation testing, 31 with bilateral cryptorchidism, 22 with unilateral, and 5 with prior unsuccessful orchiopexy. Hormonal studies were carried out prior to and following stimulation. In bilateral cryptorchidism, bilateral descent was observed in 32 percent of cases and in unilateral, the success rate was 55 percent. From their data, the authors concluded that hCG is not indicated if patients present elevated LH and FSH levels or if the basal T levels are in the pubertal range. In the other subjects, the hCG test will permit the determination of the presence or absence of testosterone production and in some cases it results in testicular descent. Finally, in cases of failure that require surgery, the hCG will stimulate tissue growth enhancing the success of orchiopexy.     

Puberty in 24 patients with Klinefelter syndrome

Twenty four boys with Klinefelter syndrome, 18 of whom were diagnosed prepubertally, were observed until adulthood. Onset of puberty, as judged from testicular enlargement and pubic hair development, occurred between 11 to 14 years in the above 18 patients. By the age of 17 pubic hair, penile length and height had reached the adult stage in all patients, but arrest of testicular growth was noted at midpuberty, 13 years, with maximal mean (±SD) volume attained being 3.5±1.5 ml. The first conscious ejaculation was reported to have occurred between 13 to 16 years in 10 patients and in the remaining 4 between 17 to 18 years of age. Sperm counts obtained after the age of 18 revealed azospermia or severe oligospermia in all patients except one, who had a sperm count of 30×10⁶/ml. The hypothalamic-pituitary-gonadal axis, assessed by LH-RH and hCG stimulation tests, was found to be normal in prepuberty and during early pubertal stages. From mid-puberty the basal levels of plasma FSH and the response to LH-RH showed a gradual increase above the normal. Towards late puberty (>15 years) basal and peak levels of LH were above normal with a concomitant decrease in the basal level of testosterone and its response to hCG.These findings indicate that during childhood and early puberty function of the hypothalamic-pituitary-gonadal axis is normal in Klinefelter syndrome, allowing the onset of pubertal signs at the appropriate age, and that until late puberty there is a relative preservation of function in the testicular Leydig cells, permitting the normal sequential development of the androgen-dependent pubertal signs. The measurement of testicular testosterone reserve by means of hCG stimulation constitutes a useful aid in determining when and if testosterone replacement therapy should be instituted.     

Kinetics of the testicular steroidogenic response to stimulation by placental gonadotropin hormone. VI. Enzyme deficiencies of testicular biosynthesis

The kinetics of the responses of plasma testosterone (T) its precursors and estrogens to a single injection of human chorionic gonadotropin (hCG) was studied in 9 46 XY subjects affected with one of 4 inborn errors of testicular biosynthesis. In the adults (n = 4), the kinetics and profile of the hormonal responses to hCG were qualitatively comparable to those previously described in normal adult men, and the profile of response characteristic of the hCG-induced steroidogenic desensitization was observed, suggesting that the 17,20 desmolase blockade induced by hCG is superimposed to the inborn enzymatic defect. In the prepubertal patients (n = 5), testicular desensitization was not observed, as in prepubertal controls. However, T precursors, each marker of a given enzymatic blockade, significantly rose several fold 2-5 days after the hCG injection, while they do not in normal children. The results also show that an hCG test is necessary for a clear-cut diagnosis of a given enzymatic block in children, but is not in adults. The single hCG injection protocol used in this study offers a sophisticated way of a qualitative analysis of the testicular secretory products, but is not a must.     

Developmental processes in early adolescence: relationships between adolescent adjustment problems and chronologic age, pubertal stage, and puberty-related serum hormone levels

Relations between adolescent psychosocial adjustment problems and markers of biologic development, including chronologic age, pubertal status, and serum hormone levels, were examined in 56 normal boys and 52 normal girls, ages 9 to 14 years. Adolescent psychosocial adjustment was assessed by adolescent self-ratings of various aspects of self-image (Offer Self-Image Questionnaire for Adolescents) and parent ratings of adolescent behavior problems (Child Behavior Checklist). The pubertal status measure used in the analyses was Tanner genital stage for boys and Tanner breast stage for girls. The hormone measures, determined by radioimmunoassay, were serum levels of gonadotropins (luteinizing hormone and follicle stimulating hormone), sex steroids (testosterone and estradiol), and adrenal androgens (dehydroepiandrosterone and its sulfate, and androstenedione). The testosterone/estradiol ratio also was computed. Overall, findings were stronger, more consistent, and more generalized for boys than for girls. For boys, adjustment problems typically were associated with a multivariate profile that may be characteristic for later maturers: relatively low sex steroid levels, or lower pubertal stage, and relatively high adrenal androgen (androstenedione) levels, frequently in conjunction with higher chronologic age. Univariate relations predominated for girls; that is, associated with adjustment problems for girls were relatively high levels of gonadotropins, relatively low levels of dehydroepiandrosterone sulfate, and relatively high levels of androstenedione on their own or in conjunction with lower pubertal stage. Higher levels of androstenedione, a steroid particularly responsive to stress, were associated with adjustment problems in both boys and girls. This relation may reflect the stress of later maturation, which could result from environmental factors, such as adolescent self-comparisons with same-age peers, or endogenous effects of hormones.     

Hormonal profile of puberty in South Australian children I

Serum follicle stimulating hormone (FSH), luteinising hormone (LH) and testosterone (T) concentrations in 118 boys aged 8 to 17.9 years were related to chronological age (CA), bone age (BA), genital development (G1–5+), pubic hair development (PH1–5 +) and mean testicular volume (MTV). A progressive rise in serum FSH, LH and T was noted in relation to CA, BA and all pubertal parameters studied. FSH showed an approximate twofold increase, LH an eight to tenfold increase and T a fourfold increase from pre-puberty through to full adult maturity. The FSH/LH ratio decreased with advancing CA, BA and pubertal development.     

Smith-Lemli-Opitz syndrome: in vivo and in vitro study of testicular function in a prepubertal patient with ambiguous genitalia

The pathogenesis of the development of ambiguous genitalia reported in some 46,XY patients with Smith-Lemli-Opitz syndrome is not understood. Presumably, it is related to the 7-dehydrocholesterol reductase deficiency present in these patients. In this study we have evaluated testicular function, both in vivo and in vitro, in a 46,XY patient with ambiguous genitalia, reared as a girl. The diagnosis was based on clinical features, low serum cholesterol and high serum 7-dehydrocholesterol levels. Serum hormone values, determined during the first month of age, showed normal basal testosterone (1.95 ng/ml), LH (0.91 U/l) and FSH (2.51 U/l). However, serum testosterone did not increase after hCG administration (1.98 ng/ml). On the other hand, the patient had a positive biological response to exogenous testosterone (decrease in sex hormone-binding globulin serum levels). She was orchidectomized at the age of 33 mo. Testicular cells were dispersed and maintained in culture for 6 d. These cells showed a very good capacity to secrete testosterone into the culture medium (X +/- SD, 26.1 +/- 11.7 vs. 4.36 +/- 1.70 pmol/10(6) cells/24 h in a control group of testicular cells prepared from testes collected at necropsy). The patient's cells failed to respond to LH stimulation (18.6 +/- 4.0 pmol/10(6) cells/24 h), although they did respond to other stimuli. It is concluded that the severe cholesterol deficiency of this patient did not impair the capacity of the testes to synthesize testosterone. However, the LH/hCG receptor or its subsequent message was activated neither in vivo nor in vitro. This finding suggests that the foetal testes might have failed to respond to placental hCG at the time of male external genital differentiation. This failure could have been responsible for the ambiguous genitalia present in this patient.