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PubMed2004

Application of gonadotropin releasing hormone in hypogonadotropic hypogonadism--diagnostic and therapeutic aspects.

BACKGROUND: Puberty is the result of reactivation of the gonadotropin releasing hormone (GnRH) pulse generator resulting in an increasing release of GnRH by the hypothalamus, which stimulates the gonadotropic cells of the pituitary to synthesize and secrete LH and FSH. Hypogonadotropic hypogonadism (HH) is often the result of GnRH deficiency. The clinical picture is characterized by the absence of pubertal development and infertility. It is difficult to differentiate HH from delayed puberty since low gonadotropin and low testosterone levels are found in both conditions. We hypothesized that long-term GnRH administration may differentiate between the two conditions by a difference in the increase of gonadotropins, the idea being that in normal delayed puberty the pituitary of the patient has been primed with GnRH during the fetal and early postnatal period. PATIENTS: Seventeen adolescents suspected of having hypogonadotropic hypogonadism were treated with pulsatile GnRH for 7 days. At the present time, the diagnosis of these patients is known and the results of the long-term GnRH stimulation have been evaluated according to the present diagnosis. RESULTS: The results show that the increase in gonadotropins following GnRH treatment is similar in both conditions. Therefore, at a prepubertal age a normal delayed puberty cannot be distinguished from hypogonadotropic hypogonadism using long-term GnRH stimulation. Long-term pulsatile GnRH treatment is a physiological therapy for the induction of puberty. Unlike testosterone it has the advantage of stimulation of testicular growth and fertility, as well as virilization, in males. We have treated 68 male patients with HH with pulsatile GnRH. The results show testicular growth and virilization in all the patients and spermatogenesis in 58 patients. Wearing a portable pump is cumbersome. However, the patients were very motivated and adapted very easily to this inconvenience. When spermatogenesis had developed, GnRH treatment was changed to human chorionic gonadotropin (hCG) administration 1-2 times per week intramuscularly or subcutaneously. During hCG therapy spermatogenesis was maintained or even improved. At least ten patients fathered children. CONCLUSION: Pulsatile GnRH cannot distinguish between a normal delayed puberty and a hypothalamic defect in still prepubertal patients. Pulsatile GnRH offers an appropriate way to initiate testicular growth including virilization and fertility in males with hypogonadotropic hypogonadism.

Adolescent↗
PubMed1995

Adult outcome of normal children who are short or underweight at age 7 years.

OBJECTIVES: To evaluate the adult growth outcome (at age 23) of children who are short or underweight at age 7 years in whom no identifiable pathological cause exists for their poor growth. DESIGN: Longitudinal follow up of a birth cohort. SETTING: The national child development study (1958 birth cohort) of Great Britain. SUBJECTS: 523 children with a height or a weight below the fifth centile at age 7. Of these, 70 (13.4%) were excluded because they had a longstanding illness that could account for their poor growth. The remaining 453 subjects, who were followed to age 23, provided the base group from which those with additional data, such as parental height, were obtained. RESULTS: 55/174 (31.6%) boys who were short at age 7 became short men; 60/211 (28.4%) girls who were short at age 7 became short women. Among boys who were underweight at age 7, 46/160 (28.7%) were still underweight at age 23, while 61/200 (30.5%) girls underweight at age 7 became underweight women. Having short parents did not increase the probability of being small as an adult. Children with delayed puberty were as likely to remain small as those in whom puberty was not delayed. CONCLUSIONS: One in three normal children who was short or underweight at age 7 became a short or underweight adult. This informs the management of short children and may be valuable when prolonged growth hormone treatment for short stature is being considered.

Adolescent↗
PubMed1992

Effects of oral testosterone undecanoate on growth, body composition, strength and energy expenditure of adolescent boys.

OBJECTIVE: We determined the effect of 3 months of daily, 40 mg oral testosterone undecanoate on growth, body composition, hand grip and quadriceps muscle strength, and total free-living daily energy expenditure in boys with constitutionally delayed puberty. DESIGN: Double blind, placebo controlled study. PATIENTS: Eighteen boys with constitutionally delayed puberty, mean (SD) age 13.2 (1.6) years. MEASUREMENTS: Body composition measurements were made by skinfold thickness, bioelectrical impedance and stable isotope dilution (H2(18)O) methods. Energy expenditure was assessed by the doubly-labelled water (2H2(18)O) technique. RESULTS: Height velocity increased from 5.4 (0.8) to 8.1 (0.6) cm/year (P < 0.05) in the 3 months after active therapy. Fat-free mass increased more with therapy (2.7 (0.3) kg) over the 6-month study period than with placebo (1.7 (0.4) kg, P < 0.5). Height velocity increases correlated with daily increases in fat-free mass (r = 0.68, P = 0.005) in the study group as a whole. Energy expenditure and muscle strength increased similarly in both groups. Predicted adult height decreased in the group which was treated with testosterone undecanoate. CONCLUSIONS: Testosterone undecanoate (40 mg daily for 3 months) significantly increased height velocity and fat-free mass velocities after 6 months but not muscle strength, endurance or total daily energy expenditure.

Administration, Oral↗
PubMed1980

Age at first conscious ejaculation: a milestone in male puberty.

The age of occurrence of the first conscious ejaculation was registered in 263 boys belonging to two categories: (1) 128 boys (70 normal controls, 22 boys with unilateral cryptorchidism with normal puberty, and 36 boys with delayed puberty) who had been under regular follow-up throughout puberty. All underwent a complete physical examination at intervals of 3 to 6 months, and in most a wrist X-ray was made within three months of the first ejaculation. (2) A group of 135 boys examined and questioned at their school served as additional controls. Eighty of these reported ejaculations. Despite a wide range in the chronological age at occurrence of the first conscious ejaculation, the mean bone age in all groups, including that with delayed puberty, was 13 1/2 +/- 1/2 years (SD), with a range between 12 1/2-15 1/2 years. There was no correlation between the age at first ejaculation and testicular volume, pubic hair or penis length. It is proposed that the age at the first conscious ejaculation be used as an index of maturation in male puberty.

Adolescent↗
PubMed2004

The skeletal phenotype of men with previous constitutional delay of puberty.

It is presently unclear whether men with a history of constitutional delay (CD) of puberty are osteopenic. This study compares auxology, bone mass, size, and density of 32 men (age, 21-33 yr) with previous CD with 45 controls. Using dual-energy x-ray absorptiometry, areal bone mineral density (aBMD) and volumetric bone mineral density at the lumbar spine (LS) and femoral neck (FN), hip strength analysis, and total-body and body segment (arms, legs, trunk) measurements were determined. Auxological variables, body composition, the muscle-bone relation, and the effect of prior androgen treatment were studied. Men with previous CD were shorter (P < 0.001) and had shorter height-adjusted arms compared with controls. Height-adjusted total-body bone mineral content (BMC) (P = 0.004), aBMD (P = 0.016), and bone area (P = 0.006) but not lean tissue mass (P = 0.507) were lower in CD men compared with controls; consequently, their BMC to lean tissue mass ratio was reduced (P < 0.001). Segment length-adjusted BMC and bone area of arms (P < 0.001) and legs (P < 0.03), but not trunk were lower in CD men than in controls. They had lower LS aBMD (P = 0.044) but normal LS and FN volumetric bone mineral density. Size-adjusted LS width and the hip cross-sectional area were lower than in controls. There was no difference in anthropometric or dual-energy x-ray absorptiometry results between untreated (n = 15) and androgen-treated (n = 17) CD men.We conclude that men with previous CD have normal LS and FN volumetric density but reduced total-body bone mass, which was explained by reduced limb bone mass and size. Together with the reduced LS bone width and hip crosssectional area, these skeletal characteristics suggest impaired periosteal expansion during puberty. The skeletal phenotype of CD males may be altered by their late onset of puberty.

Adolescent↗
PubMed2001

Growth failure in the child with inflammatory bowel disease.

Once considered rare in pediatric practice, chronic inflammatory bowel disease (IBD) is now being recognized with increasing frequency in children of all ages. In IBD, growth failure may be the only clinical presentation; it is imperative to perform a detailed history and physical examination to search for other systemic and gastrointestinal manifestations of the disease. IBD can have a significant impact on linear growth, weight gain, and bone mineralization, and can cause delays in the onset of puberty. Delays in growth and sexual development can be early indicators of disease activity, and assessment of growth and development should be performed frequently. Nutritional therapy is important not only to correct undernutrition, but also as therapy for IBD. Delayed puberty can have a significant impact on the self-esteem of the adolescent patient and diminish final adult height. Loss of bone mineral density is especially significant during a period in which the majority of bone accretion is expected to occur. These issues present unique problems to the gastroenterologist caring for a child or adolescent with IBD and require specific types of monitoring and interventions.

Adolescent↗
PubMed2005

Reconsidering the sex differences in the incidence of pubertal disorders.

The age range of normal puberty is determined statistically; therefore, a similar percentage of boys and girls should present early or late puberty. However, far more girls present with precocious puberty and more boys with delayed puberty. We suggest that the gender differences in the incidence of pubertal disorders may be due to the following: The signs of puberty are more readily detected in girls, whereas male genitalia may not be examined during a physical examination. The description of the onset of puberty in boys is not uniform. The secular trend towards earlier pubertal maturation is more intense in girls than in boys. Therefore, there may be a fall in the age that correspond to the 3rd and 97th centiles for onset of puberty in girls while the ages at these centiles remain practically unchanged in boys. The high ratio of males to females with constitutional delay of puberty may also be attributed to the late appearance of the pubertal growth spurt in boys. The sex differences in the incidence of pubertal disorders may be due to gender dimorphism in the secular changes of pubertal maturation, to the difficulty of detecting the onset of puberty in boys and to the physiological sex differences in the timing of the pubertal growth spurt.

Adolescent↗
PubMed1994

Empty sella in children and adolescents with possible hypothalamic-pituitary disorders.

Several computed tomographic scan studies have described empty sellae in children with hypothalamic-pituitary disorders. Magnetic resonance imaging, however, is a more precise technique for visualizing the intrasellar content, such as the stalk and pituitary lobes. Using magnetic resonance imaging, we studied 339 children and adolescents (mean age +/- SD, 12.7 +/- 4.5 yr) with possible hypothalamic-pituitary disorders to ascertain the frequency of primary empty sella and examine its relationships with other intrasellar abnormalities, pituitary function, and adverse perinatal events. One hundred and ninety-three patients had isolated GH deficiency, 43 had multiple pituitary hormone deficiency, 10 had diabetes insipidus, 17 had hypogonadotropic hypogonadism, 5 had idiopathic delayed puberty, 47 had precocious puberty, and 24 had other hypothalamic pituitary disorders of hyperfunction. One tenth (10.9%) of the patients (37 cases) had empty sella, with a marked variation of incidences among the disorders listed above. A statistically higher frequency of subjects with empty sellae was found only in patients with multiple pituitary hormone deficiency. Patients with and without empty sellae were not different in regard to age or sex. The incidence of empty sella in the various groups of patients was as follows: isolated GH deficiency, 8.8% (17 cases); multiple pituitary hormone deficiency, 34.9% (15 cases); hypogonadotropic hypogonadism, 5.9% (1 case); idiopathic delayed puberty, 40% (2 cases); and precocious puberty, 4.2% (2 cases). No patients with isolated diabetes insipidus or other hypothalamic-pituitary disorders had empty sellae. In the patients with empty sellae, abnormalities of the stalk or posterior lobe were found in 1 patient with isolated GH deficiency (5.9%), 13 patients with multiple pituitary hormone deficiency (86.7%), and no patients with puberty disorders. Likewise, adverse perinatal events were found only in 1 patient with isolated GH deficiency and 9 patients with multiple pituitary hormone deficiency. These findings suggest that empty sella is not rare in children and adolescents evaluated for hypothalamic-pituitary disorders, particularly if there is multiple pituitary hormone deficiency. Empty sella can be found regardless of abnormalities of the stalk and posterior lobe, and adverse perinatal events do not seem to be the primary etiological factor. Empty sella is usually associated with pituitary hypofunction, but it can be found in patients with hyperfunction of the hypothalamic-pituitary-gonadal axis.

Adolescent↗
PubMed2006

A proposal for a pediatric version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index based on the analysis of 1,015 patients with juvenile-onset systemic lupus erythematosus.

OBJECTIVE: To devise a modified version of the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) for use in children and adolescents with systemic lupus erythematosus (SLE), based on the frequency and distribution of damage in patients with juvenile-onset SLE and the sources of damage that are most suitable for inclusion in a pediatric damage index. METHODS: In this cross-sectional study, damage was assessed through the SDI. Clinical assessments included evaluation of growth failure and delayed puberty, which were believed to be important sources of damage that are not incorporated in the SDI but should be included in a pediatric version of the instrument. RESULTS: A total of 1,015 patients with juvenile-onset SLE in 39 countries were enrolled in the study. Of these, 405 patients (39.9%) had an SDI score of > or =1 (mean +/- SD score 0.8 +/- 1.4). Renal damage (13%), neuropsychiatric damage (10.7%), and musculoskeletal damage (10.7%) were observed most frequently, followed by ocular damage (8.2%) and skin damage (7.6%). Growth failure and delayed puberty were recorded in 15.3% and 11.3% of patients, respectively. A pediatric version of the SDI was devised, with inclusion of growth failure and delayed puberty as new domains. CONCLUSION: We propose a modified version of the SDI for use in patients with juvenile-onset SLE. This new instrument warrants prospective validation in other populations of patients seen in different clinical or research settings.

Adolescent↗
PubMed1985

Mouse vomeronasal organ: effects on chemosignal production and maternal behavior.

Adult male mice excrete a urinary chemosignal that accelerates puberty in females, whereas group-housed female mice excrete a urinary chemosignal that delays puberty in young females. We found that: (1) the excretion of the puberty-acceleration chemosignal by males persisted in the absence of the vomeronasal organs and (2) the puberty-delay chemosignal was not present in the urine of group-housed females whose vomeronasal organs had been surgically removed (VNX), but was present in the urine of group-housed females subjected to sham surgery (SHAM). These results suggest that in males, vomeronasal chemoreception does not affect the excretion of the puberty-acceleration chemosignal, but that in females, the vomeronasal organ receives chemosignals that influence the excretion of the puberty-delay chemosignal. Additionally, we found no difference between SHAM and VNX females in rates of conception, litter size, pup growth, pup recognition, or maternal behavior, indicating that normal maternal processes are expressed in the absence of an intact accessory olfactory system.

Animal Communication↗
PubMed1983

Relationship of somatomedin-C concentrations to pubertal changes.

The plasma somatomedin-C concentration increases above adult values during the teenage years. We studied the relationship of pubertal variables and the adolescent growth spurt to the changes in plasma total Sm-C concentration in normal volunteers and in boys with delayed puberty. The rise in plasma Sm-C concentrations was gradual and correlated positively with pubertal variables rather than with age. By midpuberty, plasma Sm-C had usually risen twofold. The Sm-C level in midpubertal girls (3.1 +/- 1.1, SD, U/ml) was greater than that in midpubertal boys (1.9 +/- 0.50, P less than 0.05). The Sm-C concentration in sexually mature teenagers was two to three times greater than that of adults. Both estrogens and androgens correlated independently with the plasma Sm-C concentration. The data are compatible with the hypothesis that pubertal estrogen or testosterone levels cause an increase in Sm-C, an effect possibly mediated by stimulation of growth hormone secretion, whereas greater estrogen exposure inhibits Sm-C generation, possibly by a direct effect. Plasma Sm-C concentrations correlated significantly with linear growth velocity until the age of peak pubertal growth velocity. Maximum Sm-C values were observed after the peak pubertal growth velocity was achieved, as height velocity was decelerating, and remained above adult levels for at least two to six years, at which time linear growth had virtually ceased. In boys with delayed puberty, Sm-C values resembled those of boys of like pubertal stage more closely than those of boys of similar age. Depressed plasma Sm-C values were found in some boys with delayed puberty; however, these did not preclude subsequent normal linear growth during sexual maturation.

Adolescent↗
PubMed1986

Endogenous opioid inhibitory tone on LH secretion in normal puberty and in several pubertal disturbances.

To further evaluate the role exerted by endogenous opioids on LH secretion a naloxone challenge (0.08 mg/Kg b.w. i.v.) was performed in 23 healthy children at different stages of puberty, in 5 adolescents in different period of menstrual cycle, in 3 case of idiopathic precocious puberty (PP), in 7 cases of delayed puberty (DP), in 4 females affected by hypogonadotropic hypogonadism (HH) and in 6 patients affected by polycystic ovary disease (PCOD). Naloxone does not induce any significant change on LH plasma levels in prepubertal healthy children and in all the cases of PP and DP. Similarly there was no LH response in healthy adolescents neither in HH nor in PCOD, the response to naloxone appears only in preovulatory and luteal phases. These data indicate that the central opioid system regulating LH secretion in humans is active only at more advanced stages of puberty and it does not seem to play a role in the beginning of sexual maturation. Moreover gonadal steroids seem to play a fundamental modulatory role on opioid-controlled LH secretion.

Adolescent↗
PubMedDate not supplied

[Empty sella syndrome: 2 cases to show its polymorphism].

Magnetic resonance imaging has proved to be the best technique to visualise the sella and juxtasellar area and it is used successfully to evaluate children with hypopituitarism or other endocraniological disorders in this area. The Authors present two cases of "empty sella syndrome", both characterized by growth hormone deficiency associated with precocious puberty in one case and with delayed puberty in the other one. The Authors stress the importance of magnetic resonance imaging in defining the morphological aspects of the hypothalamo-pituitary region and that empty sella can be associated either with pituitary hypofunction or hyperfunction.

Adolescent↗
PubMed1983

Effect of period of grouping of donors and duration of stimulus exposure on delay of puberty in female mice by a urinary chemosignal from grouped females.

Females housed at a density of 8 mice/cage had to be grouped for a minimum of about 10 days before their urine was capable of producing delays for first vaginal oestrus in test females comparable to the delays occasioned by treatment with urine from females grouped for 30 days or longer. Young test females had to receive a minimum daily exposure of 1-2 h to the chemosignal to produce the complete delay of puberty.

Animals↗
PubMedDate not supplied

[Cranial irradiation induces premature activation of the gonadotropin-releasing-hormone].

BACKGROUND: CNS-irradiation in prepubertal children with leukemia or brain tumors can lead to precocious or in high doses to delayed puberty. The underlying mechanisms of these disorders are unknown. METHODS: A new animal model of experimentally induced pubertal disorders by cranial irradiation has been developed. In infantile or juvenile (12 - 23 days old) female rats precocious or delayed puberty have been induced by selective cranial Co60-irradiation (4 - 18 Gy). At age of 32 - 38 days or 3 months relevant hormone parameters have been studied basal and after stimulated conditions. RESULTS: Low radiation doses (5 or 6 Gy) led to accelerated onset of puberty as well as elevated LH- and estradiol levels. High radiation doses (9 - 18 Gy) caused retardation of sexual development, lower gonadotropin levels and growth retardation associated with growth hormone deficiency. After cranial irradiation with 5 Gy the release rates of the inhibitory neurotransmitter gamma-aminobutyric-acid (GABA) from hypothalamic explants were significantly lower (p < 0,05). The gonadotropin-releasing-hormone (GnRH) expression in the hypothalamic preoptic area of irradiated animals (5 Gy) was significantly higher than in controls (p < 0,05). CONCLUSION: The GnRH-pulse generator is very radiosensitive as low dose irradiation causes precocious puberty, whereas high dose irradiation is associated with delayed sexual maturation. Radiation induced precocious puberty might be caused by damage to inhibitory GABAergic neurons leading to desinhibition and premature activation of GnRH neurons. Our animal model of cranial irradiation seems to be suitable to study neurotransmitter disorders, molecular mechanisms and potential preventive intervention of radiation induced pubertal changes.

Abnormalities, Radiation-Induced↗
PubMed1991

Psychological development as related to puberty, body height and severity of illness in adolescents with cystic fibrosis.

The interrelations between delayed puberty, small stature, severity of illness and psychological development were studied in 64 adolescents with cystic fibrosis (CF). The study included 36 adolescents with asthma bronchiale, 47 adolescents with small stature (height less than 25th percentile) and 71 healthy controls with a height greater than or equal to 25th percentile. All adolescents and the parents of 40 youngsters with CF had extensive personal interviews. Eight aspects of independence and related aspects of self-perception were measured. In CF, delayed puberty and small stature were clearly correlated with less participation in some social activities, a lesser degree of ideal-formation and a less positive body attitude. Small stature appeared to have the same effects in healthy adolescents. Severity of illness in CF and asthma played a role of secondary importance. In general, the perceptions of parents were similar to or slightly more pessimistic than the self-perceptions of their CF children. The need for psychosexual counselling and training in social skills for adolescents with CF is stressed.

Adolescent↗
PubMed2005

Hypothalamic-pituitary-gonadal function in adolescent females with beta-thalassemia major.

OBJECTIVE: To evaluate the function of the hypothalamic-pituitary-gonadal axis in adolescent female patients with beta-thalassemia major. MATERIALS AND METHODS: A prospective study of the function of the hypothalamic-pituitary-gonadal axis function of 31 beta-thalassemia major females aged between 13 and 22 years and in 12 control females aged between 12 and 22 years. All were treated at Princess Rahma Teaching Hospital, Irbid, Northern Jordan between April 2001 and April 2003. RESULTS: Of the 31 beta-thalassemia major females, 13 (41.9%) had delayed puberty. Hypothalamic-pituitary-ovarian axis dysfunction was found in 15 patients (48.4%). Twelve patients (38.7%) had hypogonadotropic hypogonadism and 5 (16.1%) had ovarian failure. High levels of serum ferritin were significantly higher in patients with delayed puberty. CONCLUSION: Pituitary and ovarian dysfunction are common problems in beta-thalassemia major patients. The main possible cause is iron overload. This stresses the need for intensive and regular use of chelation therapy to prevent damage to the hypothalamic-pituitary-ovarian axis.

Adolescent↗
PubMed2003

Disorders of pubertal development.

Puberty is the period of life during which reproductive capability is acquired. It is characterized clinically by the acquisition of secondary sexual characteristics associated with a growth spurt, and on average takes 3-4 years. Early maturation is defined as the development of sexual characteristics before the age of 8 years in girls and 9 years in boys. Delayed puberty is defined when there are no signs of puberty at the age of 13.4 years in girls and 14 years in boys (2 SD above the mean of chronological age for the onset of puberty). There are many forms of premature sexual maturation: gonadotrophin-dependent (central, or 'idiopathic' or 'true' precocious puberty) and gonadotrophin-independent precocious puberty (McCune-Albright syndrome in girls, testotoxicosis in boys); isolated premature thelarche (in the forms of classical, atypical and variant); premature adrenarche (characterized by the production of significant quantities of androgens between 5 and 8 years of age); premature menarche. The differential diagnosis of delayed puberty is between constitutional delay of growth and puberty, pubertal delay secondary to chronic disease and hypogonadotrophic hypogonadism.

Adolescent↗