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.     

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.
     

Endocrine studies in Blackfan-diamond anemia: Evidence for hypothalamic-pituitary dysfunction under frequent transfusion therapy

A 13 year old boy with Blackfan-Diamond anemia treated with frequent transfusions was investigated for endocrine abnormalities. Prepubertal plasma LH and FSH values, lack of sleep-related hormone rhythms of the gonadotropins, as well as prepubertal responses of LH and FSH to acute stimulation with LHRH strongly suggests that a hypothalamic-pituitary abnormality is the cause of the hypogonadotropic hypogonadism observed in this patient. As a result of impaired stimulation of the gonads plasma testosterone was prepubertal. A three-to fourfold increase of basal plasma PRL values was found without any signs of a typical sleep-dependent increase. Values obtained ranged between 21 ng/ml and 24 ng/ml (normal range 5–8 ng/ml). A normal response to TRH stimulation was found.These results suggest that hemosiderosis may responsible for the hyperprolactinemia as a result of hypothalamic-pituitary dysfunction. Furthermore, dysfunction is demonstrated by prepubertal responses of LH and FSH to LHRH stimulation.Abbreviations LH luteinizing hormone - FSH follicle-stimulating hormone - PRL prolactin - LHRH luteinizing-hormone-releasing hormone - TRH thyrotropin releasing hormone - PIF prolactin inhibiting factor     

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.     

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.     

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.     

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.     

Primary gonadal failure and precocious adrenarche in a boy with Prader-Labhart-Willi syndrome

A 7-year-old boy with Prader-Labhart-Willi syndrome who had precocious adrenarche was found to have primary gonadal failure, as evidenced by appropriate laboratory investigations: elevated basal levels of plasma FSH and LH with exaggerated responses to LH-RH stimulation and unresponsiveness of plasma testosterone to repeated hCG stimulations. The elevated values of plasma DHEA which were found indicate an early activation of the adrenal gland. This patient demonstrates the varibility of pubertal development in the Prader-Labhart-Willi syndrome, with the unusual association of primary gonadal failure and precocious adrenarche.     

Molecular analysis of the AR and SRD5A2 genes in patients with 46,XY disorders of sex development

The aim of this study was to assess the clinical and endocrinological features, and to analyze AR and SRD5A2 genes in patients with 46,XY disorders of sex development (DSD). This study included 20 patients from 19 families showing clinical features of 46,XY DSD. Molecular analysis was performed of the AR and SRD5A2 genes, as well as endocrinological evaluations, such as 17a-hydroxyprogesterone, plasma renin activity, aldosterone, adrenocorticotropic hormone and hCG stimulation test. Out of 20 patients with 46,XY DSD, only one (5%) displayed androgen insensitivity syndrome (AIS), and four (20%) were 5alpha-reductase deficient by mutation analysis. The patient with AIS revealed significant elevation of serum testosterone following hCG stimulation. The patient with 5alpha-reductase deficiency with a homozygous p.R246Q mutation had a low basal dihydrotestosterone level. The patient with p.Q6X/p.R246Q mutations showed a moderately elevated testosterone/dihydrotestosterone ratio following hCG stimulation. Endocrinological tests are not reliable for the etiological diagnosis of AIS and 5alpha-reductase deficiency due to variable reference ranges of hormonal profiles according to the age and the severity of the enzyme defect. DNA analysis may be employed as a tool for the early and precise diagnosis of patients with 46,XY DSD, and genetic counseling can be used for families at risk.     

The effect of synthetic androgens on the hypothalamic-pituitary-gonadal axis in boys with constitutionally delayed growth.

Serial concentrations of basal serum LH, FSH, testosterone, and LH and FSH responses to intravenous gonadotropin-releasing hormone were measured before and during six months of administration of fluoxymesterone or oxandrolone in 14 boys with constitutionally delayed growth and adolescence, in order to assess the effects of these androgens on maturation of the hypothalamic-pituitary-gonadal axis. Before therapy all boys had normal hormonal responses based on bone age. At the end of six months therapy 10 of the 14 boys had lower LH responses (34 to 89% reduction) to GnRH without consistent changes in FSH responses. With both androgens, there there was significant suppression of both basal serum FSH and testosterone. Eleven boys were restudied six months after completion of therapy; basal serum LH, FSH, and testosterone and responses to GnRH were equal to or greater than pretreatment levels, indicating recovery or progressive maturation of the HPGA. All boys had increased growth velocity and imporved weight gain without excessive bone age advancement; all had improved psychosocial adjustment.     

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.     

Normoprolactinemia in boys with marked gynecomastia

Pubertal gynecomastia normally occurs as a transient phenomenon of several months duration, whereas marked pubertal gynecomastia (more than 6 cm in diameter) may persist into aduldhood. In the present study the possible involvement of prolactin (PRL) secretion in the development of marked pubertal gynecomastia was investigated. The diurnal variations of PRL, luteinizing hormone (LH), follicle-stimulating hormone (FSH), as well as the basal values of testosterone (T) and estradiol (E₂) were determined in 5 pubertal boys with marked gynecomastia and in 5 age-matched controls. Mean age of all patients was 14.4 years. The pubertal development was classified as P 3–4.In comparison to controls, boys with marked gynecomastia revealed no differences in basal values of PRL, LH and FSH, as well as in peak values of all hormones during sleep. The response of PRL, LH and FSH to LHRH/TRH stimulation was normal for pubertal age in both groups. In comparison to controls, decreased mean plasma T levels (P<0.05) and slightly increased E₂ levels (P<0.05) were found in boys with marked gynecomastia. The E₂/T ratio was also higher in boys with gynecomastia (P<0.005).These data suggest that prolactin, a hormone which may be increased in galactorrhea, is not involved in the development of marked pubertal gynecomastia in boys. The above findings suggest that slightly elevated day-time E₂ levels may be involved in the development of female-appearing breasts in pubertal boys.     

Anorexia nervosa in male adolescents. II. Psychoneuroendocrinologic findings

Female patients with anorexia nervosa (a.n.) are characterized by distinct endocrine features probably due to hypothalamic pituitary dysfunctions. There is only a limited number of case reports available on patients with a.n.; mostly with few data on hormones. In six male patients with a.n. we examined basal and stimulation values of several hormones performing three pituitary function tests. Basal and stimulated values of luteinizing hormone (LH) and of follicle stimulating hormone (FSH) after LHRH were low comparable to results in prepuberal boys. Similarly, testosterone levels in serum were also markedly reduced. By exploring the pituitary-thyroidal axis total T4 was diminished in one patient and at the lower limit in two patients; concentration of free T4 was in the normal range, while five of six subjects had reduced total T3 concentration and two of six patients showed increased reversed T3 levels; TBG concentration was always in the normal range. Basal TSH was normal, while in two patients the TSH stimulation levels after TRH were diminished; in all patients the TSH stimulation levels were found to be delayed. The basal levels of growth hormone were normal, but the growth hormone response after insulin was diminished in four patients. In all six patients basal prolactin (PRL) and PRL concentration after TRH stimulation was in the normal range. The neuroendocrine results in the six patients with a.n. confirm in males a similar hypothalamic-pituitary dysfunction as it is already known for female patients.     

血清促性腺激素基础值在性早熟女童诊断中的价值

目的：探讨血清促性腺激素基础值在性早熟女童诊断中的价值。方法：以促性腺激素释放激素（GnRH）激发试验结果作为性早熟诊断的金标准,将77例性早熟女童分为中枢性性早熟（CPP,n=45）和单纯性乳房早发育（IPT,n=32）两组,分别比较两组黄体生成素（LH）、卵泡刺激素（FSH）基础值及LH/FSH比值的差异;并采用受试者工作特征（ROC）曲线分析LH、FSH基础值及LH/FSH比值诊断性早熟的准确性。结果：CPP组患儿血清基础LH、FSH水平及LH/FSH比值均高于IPT组（P<0.01）;两组患儿LH基础值与GnRH激发试验中LH峰值存在正相关;LH、FSH和LH/FSH比值诊断CPP的曲线下面积（AUC）进行比较,AUCLH大于AUCFSH和AUCLH/FSH（均P＜0.05）,而AUCFSH和AUCLH/FSH之间比较差异无统计学意义。当血清LH基础值为0.62 IU/L时,敏感度为0.778,特异度为0.906,Youden指数最大（0.684）;当切割值为1.5 IU/L时,诊断敏感度下降为0.311,但特异度为1.0。结论：血清LH基础值诊断CPP的价值优于LH/FSH比值及FSH基础值,可用于性早熟女童门诊的初步诊断,但存在一定的误诊和漏诊率;对于LH基础值大于1.5 IU/L的患儿,结合临床表现可明确诊断,无需另行GnRH激发试验。     

The gonadotrophins response to GnRH test is not a predictor of neurological lesion in girls with central precocious puberty

OBJECTIVES: To assess the value of gonadotrophin releasing hormone (GnRH) stimulation test in identifying intracranial abnormality in girls with central precocious puberty (CPP). PATIENTS AND METHODS: A study of 67 girls diagnosed with CPP who underwent cranial MRI scans. Patients were not receiving any therapy and there were no neurological signs or symptoms at presentation. Patients underwent evaluation of GnRH stimulation test and plasma oestradiol levels at presentation. RESULTS: Mean age at onset of puberty was 6.2 years (range 2.0 to 8.0 years). Intracranial abnormalities were present in 10 (15%) patients, while 57 girls (85%) had no abnormalities. No significant difference was shown between girls with intracranial abnormality and girls without intracranial abnormality in basal LH or FSH values, peak LH or FSH values, LH/FSH peak ratios, peak LH/basal LH ratios, peak FSH/ basal FSH ratios at presentation. CONCLUSION: GnRH stimulation test does not identify those with underlying intracranial abnormality at presentation. MRI imaging remains necessary in all cases of central precocious puberty in girls.     

Testicular function after combination chemotherapy in childhood for acute lymphoblastic leukaemia.

We have assessed testicular function with luteinising hormone-releasing hormone (LH-RH) and human chorionic gonadotrophin stimulation tests in 44 boys previously treated with, or currently receiving, chemotherapy for acute lymphoblastic leukaemia (ALL). At the same time a testicular biopsy was performed in each boy and the morphology was studied. Histologically the chemotherapy appeared to damage the tubular system in particular, and the degree of damage was assessed by estimating the tubular fertility (TF) index which is defined as the percentage of seminiferous tubules containing identifiable spermatogonia. The mean TF index in all 44 biopsies was 51%. Only 2 of the 44 boys showed an absent or blunted testosterone response to human chorionic gonadotrophin. This suggests that Leydig cell function is rarely impaired by such chemotherapy and that most of the boys, similarly treat for ALL, will undergo normal pubertal maturation. Apart from the basal luteinising hormone (LH) levels in the prepubertal group which could not be compared, the median basal serum follicle-stimulating hormone (FSH), LH, and testosterone concentrations, the median peak FSH and LH responses to LH-RH, and the mean plasma testosterone responses to human chorionic gonadotrophin stimulation did not differ between the prepubertal, early pubertal, and late pubertal groups compared with normal boys of similar pubertal maturation. Three of 32 prepubertal ALL boys, and 5 of 12 pubertal ALL boys showed abnormalities of gonadotrophin secretion. The increased frequency of abnormalities of FSH secretion in the pubertal ALL boys compared with the prepubertal ALL boys could not be explained by more severe tubular damage in the former group. We conclude that moderately severe damage to the tubular system of the testis unassociated with Leydig cell impairment may not be detected in the prepubertal boy with current tests of testicular function.     

Diagnosis of 5alpha-reductase type 2 deficiency: contribution of anti-Müllerian hormone evaluation

AIM: To evaluate anti-Müllerian hormone (AMH) levels in patients with clinical and molecular diagnosis of 5alpha-reductase 2 deficiency. PATIENTS AND METHODS: Data from 14 patients whose age ranged from 21 days to 29 years were analyzed according to age and pubertal stage. Sexual ambiguity was rated as Prader III in 11 patients. LH, FSH, testosterone (T), dihydrotestosterone (DHT) and AMH serum levels were measured in all but two patients, who had been previously submitted to gonadectomy; T and DHT were also measured in 20 age-matched controls. RESULTS: Gonadotropin levels were normal in all but one patient who retained gonads (six of whom had reached puberty) and T/DHT ratio was elevated in all patients when compared to controls. All prepubertal patients had AMH levels < -1 SD for age, while most pubertal patients had AMH levels compatible with pubertal stage. CONCLUSIONS: Prepubertal patients with 5alpha-reductase 2 deficiency have AMH values in the lower part of the normal range. These data indicate that T does not need to be converted to DHT to inhibit AMH secretion by Sertoli cells.     

Diagnosis of X-recessive Kallmann syndrome in early infancy

A 3-month-old infant presented with hypogonadism, a small penis and bilateral cryptorchidism. He showed an insufficient response of luteotropic hormone (LH) and follicle stimulating hormone (FSH) to luteotropic hormone releasing hormone (LHRH) and of testosterone to human chorionic gonadotrophin. The maternal uncle had hypogonadism and anosmia and also showed an impaired LH and FSH response to LHRH. MRI examination showed hypoplasia of the rhinencephalon in both cases. These findings in the son and brother of the clinically unaffected mother suggest X-linked recessive inheritance.     

Two-year results of treatment with depot leuprolide acetate for central precocious puberty.

We report results from 2 years of therapy with the long-acting form of the gonadotropin-releasing hormone (GnRH) analog leuprolide acetate, which was previously reported in short-term trials to be efficacious in the treatment of central precocious puberty. Thirteen girls and two boys, aged 1.9 to 9.7 years, who satisfied clinical criteria including GnRH-stimulated luteinizing hormone (LH) greater than 10 IU/L (mean radioimmunoassay LH, 29.1 +/- 5.54 IU/L), received depot leuprolide, 6 to 15 mg intramuscularly every 4 weeks. Estradiol (or testosterone), insulin-like growth factor I, and GnRH-stimulated gonadotropins were obtained at baseline, at 2 months, and at 6-month intervals with bone age determinations. Pubertal progression ceased in all patients, and menses did not occur. Mean increase in height during therapy was 5.77 +/- 2.0 cm/yr. Predicted adult height increased over baseline by 5.52 +/- 1.16 cm at 18 months. Mean estradiol values in the girls declined from 3.3 +/- 0.6 to 0.60 +/- 0.03 ng/dl, with no overlap of baseline and treatment values. The mean basal LH value was unchanged by therapy; mean basal and peak LH values for all follow-up GnRH stimulation tests were 4.05 +/- 0.57 and 4.95 +/- 0.70 IU/L, respectively. Basal and peak follicle-stimulating hormone (FSH) values were suppressed from 4.10 +/- 0.62 and 10.06 +/- 1.34 IU/L, respectively, to generally undetectable levels (< 1). Comparison with untreated control patients suggested that basal LH did not completely return to prepubertal levels, whereas FSH levels were suppressed below prepubertal levels. Estradiol, FSH, and LH levels reached their nadir by 2 months; in contrast, mean serum levels of insulin-like growth factor I progressively declined from +0.57 +/- 0.19 SD score to -0.06 +/- 0.22 SD score at 24 months. Two girls were withdrawn from the study because of reactions at injection sites, with apparent sterile abscess formation in one patient. This study provides evidence that (1) long-term treatment with depot leuprolide is characterized by immediate and sustained laboratory and clinical suppression, (2) GnRH-stimulated LH and random FSH and estradiol concentrations are useful laboratory measures of efficacy, and (3) the progressive increase in predicted adult height is temporally associated with decreased serum levels of insulin-like growth factor I and striking deceleration of bone age advancement.     

Inverse relationship between serum inhibin B and FSH levels in prepubertal boys with cryptorchidism.

To investigate the gonadal control of FSH secretion in prepuberty, we studied the relationship between circulating inhibin B and FSH levels in 16 prepubertal boys with cryptorchidism (age range, 1-8 y). The effect of Leydig cell stimulation on the secretion of inhibin B, sex steroids, and FSH was investigated in nine boys who were given human chorionic gonadotropin (hCG) treatment. In these boys, serum inhibin B, testosterone, estradiol, and gonadotropin levels were measured before and on the fourth day of the last (third) hCG injection, given at 1-wk intervals. Except for one boy with both high inhibin B and FSH concentrations, basal serum levels of these hormones correlated negatively (r(s) = -0.79, n = 15, p < 0.005). This inverse relationship remained significant in the subgroup of boys younger than 2 y of age (r(s) = -0.84, n = 11, p = 0.008) who also had greater variance of serum FSH concentrations than 14 control boys of similar age with normally located testes (p < 0.01). hCG stimulation increased serum testosterone and suppressed serum FSH concentrations in each boy (n = 9, p < 0.005). In the four oldest subjects, the serum inhibin B level increased from the mean of 91 to 135 pg/mL (p < 0.05). These findings suggest that inhibin B regulates FSH secretion in early childhood. Moreover, the hCG-induced suppression of FSH secretion was probably mediated by sex steroids rather than by inhibin B. Finally, the increase in serum inhibin B concentration during the hCG treatment was likely to be indirect via Leydig cell-Sertoli cell or Sertoli cell-germ cell interaction(s).