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.     

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.     

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.
     

Hypergonadotropic hypogonadism,SHBG deficiency and hyperprolactinaemia: A transient phenomenon during induction chemotherapy in leukemic children

Five pubertal boys (puberty stage Iv–V) and four prepubertal girls with acute lymphoblastic leukemia were treated with a combination of prednisone, vincristine, daunorubicin and l-asparaginase for remission induction. The hypothalamopituitary-gonadal axis was investigated by measuring basal plasma levels of LH, FSH, and PRL in both groups as well as the response to LHRH/TRH stimulation in pubertal boys before, on day 10, 21, and 28 during induction therapy and 23 days after the induction phase (day 51). Furthermore, the binding capacity of sex-hormone-binding globulin (SHBG), plasma levels of testosterone (T) and estradiol (E₂) were monitored as well as the testicular volumes of the boys.Within three weeks of induction chemotherapy, plasma T, E₂ and the binding capacity of SHBG decreased in both groups, together with a reduction of testicular volumes in the boys. Concommitantly, basal LH, FSH, and PRL values doubled with a normal gonadotrophin response to LHRH. The PRL response to TRH increased at the end of the induction phase, when chemotherapy with vincristine, daunorubicin and l-asparaginase was terminated, but prednisone treatment was continued for 7 another days.During the subsequent prophylactic irradiation of the central nervous system combined with other antileukemic drugs, all hormonal values including testicular volumes in pubertal boys became normal within a period of 3 weeks. Our data clearly demonstrate that an induction chemotherapy regimen such as that employed by the Berlin protocol leads to a transient castrating effect at the gonadal level and to a transient failure of synthesis of SHBG at the hepatic level. Increased prolactin values as well as an increased response to TRH may be related to a decrease in T indicating the existence of a negative feed-back-loop mechanism between T and PRL.Presented in part at the 20th Meeting of the European Society for Paediatric Endocrinology, September 7–11th, 1981, Genf, Switzerland     

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.     

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.     

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     

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.     

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.     

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.     

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.     

Male Gonadal Function After Chemotherapy in Survivors of Childhood Malignancy

Investigations of adult patients have shown that chemotherapy causes gonadal damage, but much less information is available about the impact of chemotherapy on gonadal function in children with malignant disease. At one time, being prepubertal during therapy was thought to confer some protection against chemotherapy induced gonadal damage. However, recent studies have indicated otherwise. We designed this study to assess gonadal function in 15 postpubertal males who had received polychemotherapy for a malignant disease during childhood and we compared them with 13 control adults males. The mean age of the patients at the time of the study was 18.2 ± 3.6 years (range 13.8–29.0), and when given chemotherapy treatment was 10.2 ± 3.0 years (range 6–16). At that time 12 were prepubertal and at the time of the study all were Tanner V. The mean interval from the completion of treatment until the study was 6.42 years (range 2.0–16.5). All patients had received polychemotherapy. We evaluated testicular size, sperm counts, LH and FSH after GnRH test, and testosterone levels. Puberty had progressed normally in all patients. We found no significant differences in testosterone and basal LH levels between patients and controls. However, we detected an appreciable difference in peak LH levels (P < 0.05) and in basal and peak FSH levels (P < 0.001). Seven patients had exaggerated LH response to GnRH, indicating dysfunction of the Leydig cells. The results of semen analyses were: 8 patients had azoospermia, 3 oligospermia, and 1 patient had a normal semen analysis. All patients with semen abnormalities presented a basal and peak FSH higher than the mean +2 SD of the control group. In summary, we found no evidence of gonadal protection in prepubertal patients. We found a high incidence of germinal cell damage, whereas Leydig cell abnormalities were found less often. An endocrine study of patients that have received chemotherapy is warranted. © 1995 Wi1ey-Liss, Inc.     

HYPOPHYSO-GONADAL FUNCTION IN THE DIABETIC CHILD

ABSTRACT. 14 diabetic boys (five with a family history of diabetes and nine without) and 29 "short normal" boys were studied. A gonadal function test (2.000 IU of hCG i.m. for 3 days and plasma testosterone assay before and after the hCG administration) as well as an LH-RH test (50 μg i.v.) were carried out. While basal testosterone level turned out to be similar in the two groups of children, it was significantly lower ( p <0.01) after hCG than the mean value of the control group. This difference was mainly observed in those patients with a family history of diabetes. In the diabetic children, basal LH level was normal and the pituitary LH reserve was lower than in the control group. Both basal FSH level and FSH pituitary reserve were lower than in normal children. These data show that an alteration in the hypothalamus-pituitary-gonadal function is already evident in the diabetic child.     

Hypophyso-gonadal function in the diabetic child.

14 diabetic boys (five with a family history of diabetes and nine without) and 29 "short normal" boys were studied. A gonadal function test (2.000 IU of hCG i.m. for 3 days and plasma testosterone assay before and after the hCG administration) as well as an LH-RH test (50 microgram i.v.) were carried out. While basal testosterone level turned out to be similar in the two groups of children, it was significantly lower (p less than 0.01) after hCG than the mean value of the control group. This difference was mainly observed in those patients with a family history of diabetes. In the diabetic children, basal LH level was normal and the pituitary LH reserve was lower than in the control group. Both basal FSH level and FSH pituitary reserve were lower than in normal children. These data show that an alteration in the hypothalamus-pituitary-gonadal function is already evident in the diabetic child.     

Testicular descent: when to interfere?

Spontaneous descent of testes after birth can occur in up to 70% of cases, yet the factors contributing to it are still controversial. This study aims to evaluate factors contributing to spontaneous descent of palpable undescended testes. Eighty-four newborns with 126 palpable undescended testes (42 unilateral and 42 bilateral) were followed up for a period of one year to study the occurrence and time of testicular descent and its relation to gestational age, birth weight, uni- or bilaterality and levels of FSH, LH and testosterone. A total of 58 testes (46%) descended between 3 and 6 months. Spontaneous descent occurred in 10 premature patients (14 testes 63%) compared to 44 testes of full-term patients (43%). Descent occurred in 14 unilateral undescended testes (33%) compared to 44 (52%) in bilateral cases. In patients with spontaneous testicular descent there was postnatal peak of LH and testosterone at 2 to 3 months of age which returned to basal level at 6 months of age. In patients with permanent undescended testes the peak of LH and testosterone was very low and almost absent in some of them; no significant difference was found between the mean values of FSH in both groups. No spontaneous testicular descent occurred after the 4th month in the full-term group, whereas in the pre-term group spontaneous descent occurred up to 6 months of age. This study concluded that spontaneous descent of palpable undescended testes is closely related to the presence of LH and testosterone surge. Therapy of undescended testes should start at 4 months of age in a full-term baby and at 6 months of age in a pre-term baby.     

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.     

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.     

MALE PSEUDOHERMAPHRODITISM DUE TO DEFICIENCY OF TESTICULAR 17-KETOSTEROID REDUCTASE

ABSTRACT. A 12.9 year-old girl, genotypically 46, XY, and considered to have a testicular feminization syndrome, developed signs of virilization and gynaecomastia. Very high androstenedione concentrations (10-fold the mean of the reference interval in boys) in relation to low normal testosterone in peripheral serum indicated a 17-ketosteroid reductase deficiency. In addition to androstenedione, the basal peripheral levels of 17-hydroxyprogesterone and estrone were increased, being 5- and 3-fold the mean of the reference interval, respectively, whereas pregnenolone, progesterone, dehydroepiandrosterone, 5α-dihydrotestosterone and estradiol concentrations were within pubertal stage-appropriate reference intervals. The total spermatic vein serum steroid concentrations were about 5-fold the mean in old men, and androstenedione, estrone and dehydroepiandrosterone were particularly elevated, whereas estradiol was normal and testosterone subnormal by a factor of 1/8. In the testis tissue, the concentration of androstenedione was extremely high, whereas that of testosterone tended to be relatively low. Our patient was obviously producing testicular steroids at her maximal rate, because no response to hCG administration was observed. This state was assiociated with a high-normal circulating LH concentration. The concentration of testicular LH/hCG receptors was only one-fifth of that seen in old men, which may have resulted from receptor down-regulation associated with a high degree of stimulation.