PITUITARY AND GONADAL FUNCTION IN PATIENTS WITH THE LAURENCE-MOON-BIEDL SYNDROME

1977 ◽  
Vol 84 (1) ◽  
pp. 191-199 ◽  
Author(s):  
G. Pérez-Palacios ◽  
M. Uribe ◽  
H. Scaglia ◽  
R. Lisker ◽  
A. Pasapera ◽  
...  
Keyword(s):  
Adult Patient ◽  
Clomiphene Citrate ◽  
External Genitalia ◽  
Testicular Biopsy ◽  
Significant Rise ◽  
Plasma Testosterone ◽  
Sex Characteristics ◽  
Assay Sensitivity ◽  
Complete Form ◽  
Lh Rh

ABSTRACT Pituitary and gonadal functions were evaluated in two pre-pubertal male siblings and in one unrelated adult male with the complete form of the Laurence-Moon-Biedl syndrome. The adult patient (19 years old) presented lack of secondary sex characteristics, azoospermia, and sub-normal external genitalia development. Testicular biopsy showed an arrest of spermatogenesis and diminished number of Leydig cells. Low plasma testosterone levels and normal responsiveness to HCG administration were found. A significant rise of pituitary gonadotrophin after LH-RH stimulation and a lack of response to clomiphene citrate was demonstrated. The pre-pubertal siblings (9 and 11 years old) had genital hypoplasia and undetectable plasma levels of testosterone, though there was a significant rise after HCG stimulation. Plasma gonadotrophin levels were within the assay sensitivity limits and a normal pituitary responsiveness following LH-RH stimulus was noted. Slightly low excretion of urinary 17-OH-corticosteroids which increased significantly after ACTH and metyrapone was demonstrated in both patients. Elevated levels of serum lipoproteins and triglycerides were found in all cases. These results are interpreted as demonstrating the suprahypophyseal origin of the dysfunction thus producing hypogonadism observed in the adult patient, and suggesting that a similar dysfunction might account for the genital hypoplasia in the pre-pubertal boys with this inherited disorder.

SUPRAHYPOPHYSEAL DYSFUNCTION IN A PATIENT WITH ASEXUAL ATELEIOSIS

1978 ◽  
Vol 87 (3) ◽  
pp. 449-455
Author(s):  
Martha Medina ◽  
Adalberto Parra ◽  
Hugo E. Scaglia ◽  
Laura Nieto ◽  
Gregorio Pérez-Palacios
Keyword(s):  
Plasma Levels ◽  
Ovarian Function ◽  
Clomiphene Citrate ◽  
Pubertal Development ◽  
Significant Rise ◽  
Primary Amenorrhoea ◽  
Gh Secretion ◽  
Normal Limits ◽  
Undetectable Plasma ◽  
Lh Rh

ABSTRACT The neuroendocrine function of a 19 years old female dwarf with primary amenorrhoea and lack of sexual development (asexual ateleiosis) was studied. Undetectable fasting plasma levels of growth hormone (GH) and a lack of response to three different provocative stimuli was observed. Oestrogen administratin did not modify the GH response. Thyroid and adrenal function were within normal limits. Undetectable plasma levels of immunoreactive oestradiol and lack of oestrogenic activity in vaginal smears indicated absence of ovarian function. Low levels of circulating gonadotrophins with a significant rise after synthetic LH-RH administration was demonstrated, while clomiphene citrate failed to induce ovulation. Following 6 months of continuous GH administration a significant increase in the growth rate was evident, whereas no pubertal development was observed. These data are interpreted as demonstrating the suprahypophyseal origin of the sexual infantilism in a patient with inappropriate GH secretion. It is suggested that a combined deficiency of LH-RH and GH-RH may account for the aetiology of this disorder.

Acceleration of puberty in boys with delayed puberty by clomiphene citrate. A clinical and laboratory study

1980 ◽  
Vol 94 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Zvi Dickerman ◽  
Ruth Prager-Lewin ◽  
Osnat Lahmy ◽  
Zvi Laron
Keyword(s):  
Peak Plasma ◽  
Clomiphene Citrate ◽  
Significant Rise ◽  
Delayed Puberty ◽  
Plasma Testosterone ◽  
Plasma Testosterone Level ◽  
Basal Plasma ◽  
The Mean ◽  
Group 2 ◽  
Group 1

Abstract. Clomiphene citrate was administered at a dose of 50 mg/day for 3 months to 29 boys with delayed puberty, 15 in a stage of early puberty (group 1) and 14 in stages of mid puberty (group 2). In both groups a significant acceleration in the advancement of pubertal signs was noted in the 6-month period following initiation of therapy as compared to a non-treated control group. A significant rise in the mean (± sd) basal plasma LH levels, from 1.0 ± 0.4 to 2.7 ± 2.2 mU/ml in group 1 (P < 0.05) and from 1.0 ± 0.6 to 2.2 ± 1.7 mU/ml in group 2 (P < 0.05) was observed following the treatment period with clomiphene. Concomitantly there was a rise of the mean basal plasma FSH level from 1.1 ± 0.4 to 2.0 ± 1.5 mU/ml in group 1 (P ± 0.05) and from 1.9 ± 1.6 to 3.4 ± 3.0 mU/ml in group 2 (P < 0.02). The mean LH peak response to an iv bolus of LRH (50 μg/m2 iv) rose from 8.3 ± 4.2 to 13.0 ± 5.3 mU/ml in group 1 (P < 0.05) and from 9.2 ± 5.8 to 12.6 ± 6.8 mU/ml in group 2 (NS). The mean peak plasma FSH response to LRH rose from 2.0 ± 0.6 to 5.9 ± 4.2 mU/ml in group 1 (P < 0.05) and from 4.3 ± 4.0 to 7.0 ± 6.8 mU/ml in group 2 (NS). Clomiphene therapy caused a rise of the basal plasma testosterone level from 68 ± 53 to 313 ± 270 ng/100 ml in group 1 (P < 0.01) and from 103 ± 67 to 392 ± 248 ng/100 ml in group 2 (P < 0.01). The plasma testosterone response to one hCG stimulation (5000 U im), tested in 4 boys immediately before and after the 3-month period of clomiphene administration revealed an increase in both the basal and the peak testosterone levels (P < 0.05 and P < 0.001, respectively). A standard clomiphene test consisting of the administration of 100–200 mg/day clomiphene citrate for 8 days was performed in 8 boys before initiation of clomiphene treatment for the 3-month period. In 4, including 2 boys in an early stage of puberty, there was a suppression of the basal level of gonadotrophins and their response to synthetic LRH. The other 4 boys, all of them in stages of mid-puberty, showed an increase in the basal and peak plasma gonadotrophin levels following LRH stimulation. In all 8 boys there was a significant rise of the basal plasma testosterone level. Despite the varying response to the short clomiphene test in these 8 boys, all gave a good response to the prolonged administration of clomiphene citrate. It was concluded that treatment with small doses of clomiphene citrate for a period of 3 months induces an acceleration of puberty in boys with delayed or slowlyprogressing puberty, once the stage of initiation of puberty has been passed.

THE EFFECT OF CLOMIPHENE ON THE PLASMA ANDROGENS OF PREPUBERTAL AND PUBERTAL BOYS

1971 ◽  
Vol 50 (3) ◽  
pp. 387-396 ◽  
Author(s):  
D. M. CATHRO ◽  
J. M. SAEZ ◽  
J. BERTRAND
Keyword(s):  
Plasma Levels ◽  
Clomiphene Citrate ◽  
Significant Rise ◽  
Plasma Testosterone ◽  
Gas Liquid Chromatography ◽  
Daily Dose ◽  
Before And After ◽  
Prepubertal Boys ◽  
Pubertal Boys ◽  
Double Isotope

SUMMARY Plasma levels of testosterone, androst-4-ene-3,17-dione, dehydroepiandrosterone (DHA) and dehydroepiandrosterone sulphate (DHAS) were estimated both before and after administration of clomiphene citrate to endocrinologically normal boys aged from 2–16 yr and to boys with adrenocortical hypofunction or hypogonadism. A divided daily dose of 200 mg/1·7 m2 of surface area was maintained for 15 days. The unconjugated steroids were measured by means of a double isotope derivative technique and the sulphates by gas-liquid chromatography. The boys without testicular anomaly who were well established in puberty responded with a rise in plasma testosterone. In contrast, prepubertal boys showed a statistically significant decrease in plasma testosterone levels. A concomitant finding was a significant rise in the plasma levels of androstenedione, DHA and DHAS. It is concluded that clomiphene does not liberate luteinizing hormone before puberty but it may well diminish its secretion. A secondary effect of clomiphene is the stimulation of adrenal C19-steroid production.

Induction of ovulation with clomiphene citrate and LH-RH in women

1981 ◽  
Vol 14 (11) ◽  
pp. xxxvii
Author(s):  
I.C. Barbosa ◽  
H. Maia ◽  
E. Tironi ◽  
C.M. Hirsch ◽  
E.M. Coutinho
Keyword(s):  
Clomiphene Citrate ◽  
Induction Of Ovulation ◽  
Lh Rh

A STUDY OF THE FIRST EIGHT HOURS IN THE STABILIZATION OF PLASMA TESTOSTERONE CONCENTRATION IN THE HEMICASTRATED RAT

1982 ◽  
Vol 92 (2) ◽  
pp. 225-229 ◽  
Author(s):  
A. I. FRANKEL ◽  
E. J. MOCK
Keyword(s):  
Low Dose ◽  
Male Rat ◽  
Plasma Testosterone ◽  
Blood Collection ◽  
Similar Response ◽  
Luteinizing Hormone Releasing Hormone ◽  
Sham Surgery ◽  
One Step ◽  
Lh Rh ◽  
Single Testis

Plasma levels of testosterone fell within 4 h after hemicastration in the mature male rat, and recovered within 8 h, without a compensatory rise in plasma LH from 5 to 480 min after surgery. Pulsatile release of LH was not observed in any group, suggesting the possibility that its alteration was not stimulating the single testis. Luteinizing hormone releasing hormone (LH-RH) stimulated plasma LH concentration equally in both control and hemicastrated rats, rising more sharply only in sham-hemicastrated rats treated with a low dose of LH-RH. Plasma LH rose significantly at the same time (6 h after surgery) in both castrated (in one step) and hemicastrated rats which were castrated (in two steps). Bilateral denervation of the testis did not affect the response of plasma testosterone after hemicastration. There was a remarkably similar response in both plasma LH and testosterone levels to handling, blood collection, anaesthesia, sham-surgery and hemicastration separately or in combination. It was concluded that the response of testosterone to hemicastration was neither related to early changes in plasma LH levels nor to alterations in the hypothalamo-hypophysial axis.

ENDOCRINE STUDIES AND SUCCESSFUL TREATMENT IN A PATIENT WITH TRUE HERMAPHRODITISM

1979 ◽  
Vol 91 (1) ◽  
pp. 184-192
Author(s):  
Evangelina Valdés ◽  
Carlos Fernández del Castillo ◽  
Raul Gutiérrez ◽  
Fernando Larrea ◽  
Martha Medina ◽  
...  
Keyword(s):  
Chromosome Complement ◽  
Reproductive Function ◽  
External Genitalia ◽  
Serum Testosterone ◽  
Serum Levels ◽  
Normal Children ◽  
Serum Lh ◽  
Genital Ambiguity ◽  
And Gender ◽  
Lh Rh

ABSTRACT A 12-year old, 46 XX true hermaphrodite born with genital ambiguity was studied and successfully treated. The serum LH and FSH profile resembled that of a pubertal normal individual, and LH-RH administration induced a normal LH response. Baseline testosterone serum levels were within the range for normal children. Exogenous HCG stimulation induced a significant serum testosterone increase up to values similar to those observed in normal post-pubertal males. Surgical examination disclosed the presence of bilateral ovotestis, normal Mullerian derivatives, epididymis, and vas deferens. A complete ovotestis with testicular predominance and the testicular portion of the contralateral ovotestis as well as the Wolffian derivatives, were removed. A further HCG stimulation 3 months after surgery, failed to induce serum testosterone increase. Spontaneous menarche was observed 6 months after surgery and ovulation was well documented. At present the patient has several characteristics of female sex including those of chromosome complement, gonad, internal and external genitalia, hormone levels and gender identity, thus demonstrating that treatment was successful and that reproductive function could be obtained. The finding of spontaneous ovulation following removal of the testicular portion suggests normal cyclic gonadotrophic release implying a difference between animal models and man in regard to hypothalamic virilization.

Endocrine and immunogenetic evaluation of an XX male infant with perineoscrotal hypospadias

1985 ◽  
Vol 108 (3) ◽  
pp. 421-427 ◽  
Author(s):  
S. Kofman-Alfaro ◽  
E. Valdés ◽  
J. Terá ◽  
S. S. Wachtel ◽  
B. Chávez ◽  
...  
Keyword(s):  
Specific Binding ◽  
Chromosome Complement ◽  
External Genitalia ◽  
Male Infant ◽  
Serum Testosterone ◽  
Normal Activity ◽  
Significant Rise ◽  
Cultured Fibroblasts ◽  
Genital Ambiguity ◽  
Xx Male

Abstract. To clarify the origin of the genital ambiguity occasionally associated with the XX male syndrome, a series of endocrinological studies were undertaken in an affected 6 months old infant with perineoscrotal hypospadias. The patient fulfilled all the diagnostic criteria of the syndrome: the testes were descended bilaterally, the Mullerian derivatives were absent, the 46,XX chromosome complement was ascertained in different cell lines, and male levels of H-Y antigen were detected in cultured skin fibroblasts. Circulating gonadotrophin levels and pituitary LRH responsiveness were within normal limits for the age group. Serum testosterone (T) levels were normal, and gonadal stimulation with hCG caused a significant rise on serum T. Incubations of [3H]T with fibroblasts from genital skin revealed normal activity of steroid 5α-reductase. Moreover, normal concentrations of thermostable cytosol androgen receptors were revealed in cultured fibroblasts. Altogether the results indicated that ambiguity of the external genitalia in this patient was the result of neither abnormal T biosynthesis, peripheral A-ring T reduction, nor androgen intracellular specific binding, and suggested that the nature of the imcomplete virilization could be a non-endocrine independent event associated to this disorder. The data are also consistent with the notion that testicular impairment observed in adult XX males develops later in life.

HERMAPHRODITISM: CLASSIFICATION, DIAGNOSIS, SELECTION OF SEX AND TREATMENT

PEDIATRICS ◽  
1955 ◽  
Vol 16 (3) ◽  
pp. 287-302
Author(s):  
Lawson Wilkins ◽  
Melvin M. Grumbach ◽  
Judson J. Van Wyk ◽  
Thomas H. Shepard ◽  
Constantine Papadatos
Keyword(s):  
External Genitalia ◽  
Exploratory Laparotomy ◽  
Ambiguous Genitalia ◽  
Urogenital Sinus ◽  
Sex Characteristics ◽  
Normal Female ◽  
Anatomic Structure ◽  
Before School ◽  
And Behavior ◽  
Made In

The different types of ambisexual development have been described. It is most important in earliest infancy to differentiate, on the basis of the 17-ketosteroid excretion, female pseudohermaphroditism due to congenital adrenal hyperplasia from other forms of ambisexual development. The female pseudohermaphrodites should be reared as girls and treated with cortisone according to the methods described. Surgical exploration is not indicated. If the clitoris is enlarged it should be removed before school age and the urogenital sinus corrected to form a separate vagina. With cortisone therapy continued normal female development can be assured. When the adreno-genital syndrome has been excluded, all patients with ambiguous genitalia should be submitted to careful urethroscopic study and exploratory laparotomy. This applies also to individuals who appear to be cryptorchid males with hypospadias and those resembling females with gonads in the groins or labia. These procedures should be carried out in the earliest months of life and a definite decision made as to the sex in which the child is to be reared. Abundant evidence has been accumulated that an individual's gender role and erotic orientation are established through the cumulative experiences of years of living as a boy or a girl. Irrespective of chromosomes, gonads or hormones, the child who from earliest infancy has been steadfastly accepted as a girl or as a boy, particularly if the external genitals have been altered to conform to this sex, will not question his own gender and will conform to the habits and behavior of the sex of rearing. When there is prolonged doubt and uncertainty on the part of the parents or when a change of sex is imposed after an early age and before late adolescence the child will be confused and perplexed and psychologic difficulties result. Accordingly, every effort should be made in early infancy to decide the sex of rearing and the parents should be given support, guidance and reassurance. Necessary corrective operations should be undertaken as early in life as possible. No change from the original decision should be made in later childhood. It is advisable to select the sex of rearing according to the anatomic structure of the external genitalia rather than the type of gonads or the sex chromosomal pattern. To attempt to make a boy of an individual who does not have a fairly well-developed phallus is unwise and condemns the patient to a life of misery. Male pseudohermaphrodites who have external genitalia of female configuration invariably feminize at puberty, so that orchidectomy is not necessary to prevent masculinization. Its only indication might be to avoid the possible risk of testicular malignancy. Male pseudohermaphrodites whose genitalia resemble the male or are ambiguous may either masculinize or feminize at puberty. If it is decided to raise such a child as a female because of the small size of the phallus, orchidectomy may be performed in infancy to avoid the risk of masculinization or it may be postponed until masculinization begins. The former course often seems preferable. At puberty estrogen should be given in doses adequate to develop female sex characteristics. In these cases gonadectomy cannot be considered a mutilating operation or one which deprives the patient of fertility. On the contrary it is one which enables the patient to continue as a reasonably normal individual in the sex in which he has been reared and prevents the disastrous psychologic upheaval of a sex reversal.

The role of oestrogens on gonadotrophin secretion in the testicular feminization syndrome1

1980 ◽  
Vol 95 (3) ◽  
pp. 314-318 ◽  
Author(s):  
Martha Medina ◽  
Alfredo Ulloa-Aguirre ◽  
Maria A. Fernández ◽  
Gregorio Pérez-palacios
Keyword(s):  
Clomiphene Citrate ◽  
Poor Response ◽  
Testicular Feminization ◽  
Normal Response ◽  
Serum Lh ◽  
Gonadotrophin Secretion ◽  
Before And After ◽  
Complete Form ◽  
Lh Secretion

Abstract. The role of oestrogens on gonadotrophin secretion was assessed in three related patients with the complete form of testicular feminization syndrome. Serum LH and FSH levels were measured before and after I.RH stimulation as well as before, during and after chronic clomiphene citrate administration. Moderately elevated LH basal levels with a significant LH rise following I.RH were observed. Normal or even low FSH level with poor response to LRH were found in all subjects. Administration of clomiphene citrate resulted in a significant serum LH increase without any change of FSH. Following castration both LH and FSH rose and a normal response to LRH was observed. These results were interpreted as demonstrating that, while endogenous oestrogens modulate LH secretion in patients with androgen unresponsiveness, it plays no role in regulating FSH secretion and suggested that a factor of testicular origin without androgenic or oestrogenic activity is responsible for FSH regulation.

THE HEMICASTRATED RAT: DEFINITION OF A MODEL FOR THE STUDY OF THE REGULATION OF TESTICULAR STEROIDOGENESIS

1982 ◽  
Vol 92 (2) ◽  
pp. 213-223 ◽  
Author(s):  
A. I. FRANKEL ◽  
W. W. WRIGHT
Keyword(s):  
Group Analysis ◽  
Age Groups ◽  
Basic Mechanism ◽  
Compensatory Hypertrophy ◽  
Significant Rise ◽  
Plasma Testosterone ◽  
Testosterone Levels ◽  
Testicular Steroidogenesis ◽  
Definition Of ◽  
Single Testis

A comprehensive study has been made of the hemicastrated rat from 2 to 12 months of age in order to define what might represent an ideal model in which to study testicular regulation. Although there was no compensatory hypertrophy in the remaining testis of the mature hemicastrated rat, levels of plasma testosterone fell significantly within 4 h after surgery in all age groups older than 3 months, and were restored to normal levels almost immediately, usually within 8 h. There were no significant changes in LH and prolactin, and the significant rise in FSH was sufficiently delayed (2 days or more) to suggest that none of these three hormones was implicated in any obvious way in the compensatory restoration of plasma testosterone levels. Although a single testis was capable of maintaining normal plasma testosterone concentrations, its response to human chorionic gonadotrophin at 24 h after hemicastration was significantly less than that of intact animals, suggesting that the single testis was functioning at near-maximal capacity. The hormonal responses to repetitive blood sampling and to sham-surgery simulated the response to hemicastration remarkably. However, these responses were never statistically significant in within-group analysis, and therefore did not obscure the significant fall of plasma testosterone levels in response to hemicastration. The basic mechanism by which plasma testosterone is restored in the hemicastrated rat is still unknown, but the options have been narrowed.

Sign in / Sign up

Export Citation Format

Share Document