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Role of magnetic resonance imaging in the diagnosis and prognosis of growth hormone deficiency.

OBJECTIVE: In patients with congenital GH deficiency (GHD), magnetic resonance imaging (MRI) has revealed morphological abnormalities such as pituitary hypoplasia, absence of the stalk and ectopia of the posterior pituitary (PPE). Our study was aimed at investigating the possible relationship between neuroradiological images and the presence of isolated GH or multiple pituitary hormone deficiency. DESIGN: We studied 121 patients, aged 0.3-25 years, with isolated GHD (IGHD, 81 cases) or multiple pituitary hormone deficiency (MPHD, 40 cases). Of 81 IGHD patients, 50 were at prepubertal and 22 at pubertal age, while 9 had a delayed onset of puberty. Out of 40 MPHD patients, 25 were at prepubertal age and 15 at the age of puberty. RESULTS: Pituitary hypoplasia, defined as a gland with a height of less than -2 SD for age, was observed more frequently in prepubertal (66%) than pubertal (18%) IGHD patients. It was also found in the majority of MPHD patients of prepubertal (76%) and pubertal age (80%), and of IGHD patients with delayed onset of puberty (100%). Mean +/- SEM pituitary height was significantly lower (P < 0.001) in both prepubertal IGHD (-2.70 +/- 0.20 SD) and MPHD children (-3.10 +/- 0.39 SD) than in IGHD patients with normal onset of puberty (-1.55 +/- 0.2 SD). A significantly greater pituitary height was observed in IGHD patients with normal onset of puberty (-1.55 +/- 0.20 SD) than in MPHD patients at the age of puberty (-4.38 +/- 0.61 SD, P < 0.001) and in IGHD subjects with delayed onset of puberty (-4.06 +/- 0.41 SD, P < 0.001). An important increase (P < 0.02) in the height of the pituitary gland was found in 6 of the 9 patients with delayed puberty when they were re-evaluated after completing their spontaneous pubertal development. The frequency of other MRI abnormalities (PPE, stalk transection) was significantly higher in MPHD patients than in IGHD patients (P < 0.001). CONCLUSION: Our results confirm the usefulness of MRI in the evaluation of children affected by GH deficiency. The association of gland hypoplasia with other MR abnormalities could suggest the presence of multiple anterior pituitary deficiencies. Finally, puberty seems to play an important role in the increase of pituitary size in multiple pituitary hormone deficiency and isolated GH deficiency patients.

Adolescent↗

[Puberty].

Puberty commences in girls 1.5-2 years earlier than in boys. Whereas the production of sexual hormone in the female increases gradually, testosterone secretion in the male rises steeply within two years. In connection with this boys are suffering more often from emotional disturbances than girls during puberty. During the last 150 years the onset of puberty has considerably advanced. In the middle of the last century, menarche occurred at age 17; today, however, at age 12.5. This secular acceleration is caused by improved nutrition, mainly with proteins. Presupposition for the earlier onset of puberty is an earlier arriving at the developmental stage (height, weight, bone maturation) which formerly was characteristic for prepubertal children of 10/11 years. Also the physiologic variants, i.e., the so-called early normal puberty and constitutional delay of growth and adolescence, base on prepubertal differences in growth velocity and growth hormone secretion. In contrast to this, the pathologic variants of sexual development, i.e., true sexual precocity and pubertas tarda s.s., are caused by various pathologic processes located in one of the three areas: hypothalamus, pituitary, or gonads.

Adolescent↗

Medial preoptic area, estrogen, and the peripubertal desensitization to the negative estrogen feedback in female rats.

Bilateral lesions placed in the medial preoptic area (MPOA) markedly diminished the luteinizing hormone-(LH-) and follicle-stimulating hormone- (FSH-) inhibiting effects of s.c. injected or intrahypothalamically implanted estradiol benzoate (EB) in ovariectomized immature rats. Desensitization to the negative estrogen feedback was also recorded in immature rats implanted into the MPOA with a mixture of 1 part EB and 240 or 360 parts cholesterol. Estrogen implants located in the hypothalamic ventromedial-arcuate region were ineffective in this regard. Whereas precocious puberty resulted from the implantation of EB into the MPOA, a delay of puberty onset was induced by medial preoptic implants of the antiestrogen clomiphene citrate which also enhanced the LH-suppressing effect of s.c. administered EB in prepubertal females. It is proposed that an increase of the estrogen concentration in the MPOA inactivates medial preoptic neurons that exert a restraining influence on tonic LH (and FSH) secretion by sensitizing the mediobasal hypothalamus to the negative feedback action of estrogen. This mechanism may be involved in the control of the onset of puberty in female rats.

Animals↗

Growth in Crohn's disease.

Abnormal linear growth is frequent in children and adolescents with Crohn's disease. The typical pattern is of growth retardation associated with delayed skeletal maturation. Puberty is also frequently delayed. Over 50% of patients may have a subnormal height velocity, and approximately 25% will have short stature. The endocrine status is characterized by normal growth hormone secretion and a slightly subnormal serum level of insulin-like growth factor I, which is related to nutritional status. Principal therapeutic options are intestinal resection for localized disease, and enteral nutrition--using a polymeric diet--for more widespread disease, particularly involving the small intestine. Growth responses to both modalities are often excellent and produce considerable psychological benefit. Optimum therapy is achieved by close collaboration between gastroenterologists and endocrinologists, and by the use of auxological methods to document pre- and post-therapeutic management.

Adolescent↗

Induction of puberty by pulsatile gonadotropin releasing hormone.

15 girls and 17 boys with delayed or arrested puberty were treated with gonadotropin releasing hormone (GnRH) for a mean of 1.04 years. GnRH was administered subcutaneously in a pulsatile fashion at 90 min intervals, and the dose was increased as required to maintain progression of puberty, initially only at night and subsequently over 24 h. Initial GnRH dose was 1-2 micrograms per pulse in the girls and 2-4 micrograms per pulse in the boys. The effect of treatment was monitored by serial overnight gonadotropin profiles in all patients and with pelvic ultrasound in the girls. The clinical features, growth acceleration, endocrinology, and ovarian ultrasound morphology of puberty were those seen in normal children. Measurement of spontaneous gonadotropin pulsatility after treatment had been discontinued allowed the distinction between 20 patients with hypogonadotropic hypogonadism and 12 who had constitutional delay of growth and puberty. 2 girls and 6 boys did not respond to the treatment regimen. These findings indicate that normal puberty is GnRH dependent.

Adolescent↗

Ethanol blocks the central action of IGF-1 to induce luteinizing hormone secretion in the prepubertal female rat.

Insulin-like growth factor-1 (IGF-1) is emerging as a signal of peripheral origin capable of acting centrally to induce luteinizing hormone (LH) secretion and accelerate the initiation of female puberty. Since we have shown previously that ethanol (ETOH) can suppress prepubertal LH release and delay female puberty, we hypothesized that these detrimental effects might be due, at least in part, to the drugs ability to alter the central actions of IGF-1. Thus, we have investigated the effects of ETOH on IGF-1 induced LH release in vivo, and on IGF-1 induced prostaglandin-E2 (PGE2) and LH-releasing hormone (LHRH) release in vitro from rats during the juvenile phase of development as well as from rats during the early stage of first proestrus. For the in vivo experiment three initial jugular blood samples were taken at 10-min. intervals from all rats, then the animals received either a 3g/Kg dose of ETOH or an equal volume of saline by gastric gavage. The rats were subsequently left undisturbed for 90 min. to allow time for ETOH absorption, then a single blood sample was drawn from each rat. Finally, IGF-1 (200 ng/3 microl) was microinjected into the third ventricle of all animals and five more blood samples were withdrawn at 10 min. intervals. We demonstrated that IGF-1 induced the release of LH (p<0.01) in the saline controls from rats in both phases of pubertal development. Conversely, this effect of IGF-1 was blocked by ETOH in both developmental groups. For the in vitro experiment, median eminences (MEs) were dissected, then incubated in the presence or absence of ETOH (50 mM). The amount of PGE2 and LHRH released was measured from the same samples following the addition of IGF-1 (100 ng/ml). As above, similar responses were observed from rats in both developmental phases. IGF-1 stimulated the release of PGE2 (p<0.001) and LHRH (p<0.01) from the incubated nerve terminals in the absence of ETOH; however, these effects were blocked by the presence of ETOH. Thus, these combined in vivo and in vitro results suggest that ETOH can acutely block IGF-1 induced LH release during the juvenile-peripubertal transition period, and that this is a centrally mediated action which is due to the diminished formation of PGE2 resulting in decreased LHRH release.

Animals↗

The role of pro-inflammatory cytokines in inflammatory bowel disease growth retardation.

Childhood inflammatory bowel disease (IBD) especially those with Crohn disease is commonly complicated by faltering growth and pubertal delay. Pro-inflammatory cytokines are often elevated in IBD and may affect linear growth and puberty either systemically or at the level of the growth plate. Further study of the underlying mechanisms of the deleterious effects of cytokines on the growth plate may improve management of faltering growth in childhood IBD. Well-controlled clinical studies of the respective effect of nutritional support, immunomodulatory therapy, biological agents and growth and puberty promoting agents on managing faltering growth also require further attention.

Adolescent↗

The role of nongonadal restraint of gonadotropin secretion in the delay of the onset of puberty in the rhesus monkey (Macaca mulatta).

The neuroendocrine basis underlying timing of the onset of puberty in rhesus monkeys is examined in this review. The immediate stimulus responsible for the initiation of the pubertal process originates within the central nervous system and is relayed to the pituitary-gonadal axis by an intermittent pattern of gonadotropin releasing hormone (GnRH) secretion, which is viewed as being generated by a neural oscillator resident within the hypothalamus. While results of recent studies in male rhesus monkeys suggest that this hypothalamic oscillator is fully functional by the neonatal stage of ontogeny, sexual maturity in this species is not attained until after 3 to 4 yr of prepubertal development. This protracted delay in the onset of puberty cannot be accounted for by the "gonadostat" hypothesis, which states that increased sensitivity of the hypothalamic GnRH oscillator to gonadal steroid feedback is an essential feature of the prepubertal inhibition of gonadotropin secretion, because orchidectomy during neonatal development does not interrupt the prepubertal suppression of LH and FSH secretion. Instead, it is suggested that the prolonged phase of prepubertal development in higher primates is occasioned by nongonadal restraint of the hypothalamic GnRH oscillator which, in monkeys, appears to be brought into play during the second to third month of extrauterine life and sustained until approximately 3 yr of age. While the identity of the nongonadal inhibition responsible for the prepubertal quiescence of the neural oscillator governing pulsatile GnRH secretion remains to be determined, it does not appear to involve either the pineal or the adrenal.

Adrenal Glands↗

Urinary chemosignals and puberty in female house mice: effects of photoperiod and food deprivation.

Urinary chemosignals from male and female house mice alter the age of puberty in females and thus influence the onset of reproductive behavior. These chemosignal phenomena have been examined with respect to a variety of factors pertaining to the social and reproductive biology of the mice. The pair of experiments reported here tested whether two non-social, environmental factors might affect the presence of the chemosignals. Alteration in the photoperiod from the normal 12 hr light/day to 6 hr light/day and restricting food intake every other day significantly altered some of the chemosignal effects on puberty for urine from singly-caged adult male and female mice, but did not change the delay of puberty produced by treatment with urine from grouped females. The results conform with a general hypothesis that the urinary chemosignals in house mice that influence puberty in young females are effective in communicating the adequacy of conditions for reproduction to conspecifics.

Animals↗

[Plasma dehydroepiandrosterone sulfate (DHAS) in paediatric endocrinology (author's transl)].

The normal values of plasma DHAS were determined by measuring the levels in 637 normal subjects whose ages ranged from birth to adulthood. The changes induced by adrenal stimulation and suppression, and by testicular stimulation tests were studied. Knowledge of the normal values and the changes with age is essential for the interpretation of the results in children with endocrine disorders. Normal DHAS levels were found in cases of precocious puberty. High levels were found in pseudo-precocious puberty and in premature pubarche. Low levels were detected in primary or secondary adrenal insufficiency and in delayed adrenal puberty.

Adolescent↗

Depot testosterone in boys with anorchia or gonadotrophin deficiency: effect on growth rate and adult height.

Eleven teenage boys with bilateral anorchia and 12 with gonadotrophin deficiency were treated by injections of testosterone ester (enanthate) at an initial dose of 100 mg every six to eight weeks, rising to 250 mg every four weeks after three to four years. In the anorchic boys average adult height was 177.1 cm, compared with a mean mid-parental height of 174.4 cm, and mean predicted adult heights of 177.0 cm (Tanner-Whitehouse method) and 178.0 cm (Bayley-Pinneau method). In the patients with gonadotrophin deficiency, mean adult height was 176.9 cm, compared with a mean mid-parental height of 176.1 cm, and mean predicted adults heights of 174.0 cm (Tanner-Whitehouse method) and 177.3 cm (Bayley-Pinneau method). We conclude that this testosterone regimen allows achievement of full growth potential in such patients.

Adolescent↗

The effect of androgens on the pulsatile release and the twenty-four-hour mean concentration of growth hormone in peripubertal males.

Oxandrolone (Ox) and testosterone (T) are used as growth-promoting agents in the therapy of boys with constitutional delay of growth and adolescence. Although the mechanism of action of these androgens is not known, it is recognized that T enhances GH release during GH stimulation tests. We studied the effects of T and Ox on the mean concentration of GH, the pattern of GH secretion, and somatomedin-C (SmC) concentrations in boys with short stature and/or delayed sexual development to determine whether their growth-promoting effects might be mediated through endogenous GH release. Ten boys received Ox (0.1 mg/kg . day, orally) for 65 +/- 5 days (mean +/- SD), and five boys received T propionate (7.5 mg, im, for 7 days), followed by T enanthate (100 mg, im, monthly for 3 months). Serum GH was measured in samples obtained at 20-min intervals for 24 h before and 65 +/- 5 days (mean +/- SD) after the initiation of therapy. SmC levels were measured twice during the same 24-h period before and 65 +/- 5 days (mean +/- SD) after initiation of therapy. In the boys treated with T, there were significant increases in the mean concentration of GH (mean increase, 4.3-fold; range, 2-12), in the number of GH pulses 10 ng/ml or greater [1.6 +/- 2.0 vs. 4.8 +/- 1.5/24 h (mean +/- SD)], and in the SmC levels [0.82 +/- 0.46 vs. 2.3 +/- 0.4 mu/ml (mean +/- SD)]. There were, however, no significant changes in the boys treated with Ox. Both Ox and T significantly improved the growth rates; however, T increased the growth rate by 0.95 +/- 0.24 (mean +/- SD) cm/months, and Ox increased the growth rate by 0.24 +/- 0.26 (mean +/- SD) cm/month. These results indicate that T, but not Ox, at the doses tested increases GH secretion in boys with short stature and/or delayed sexual development. This increase in GH secretion may contribute to the increased growth rate in males at puberty.

Adolescent↗

Effects of early handling upon puberty: correlations with adrenal stress responsiveness.

Handling of rat pups for 5 min once a week prior to weaning to permit weighing of the litter significantly delays vaginal opening and ovulation and is associated with a reduction in the response to an ether stress administered at 60 days of age. Handling combined with replacement of the bedding material results in a further delay in puberty and a further reduction in the stress response. It is therefore necessary to follow uniform handling procedures in any study of a developmental process.

Adaptation, Physiological↗

Treatment of young rams with an agonist of GnRH delays reproductive development.

The objective of this study was to determine if the continuous treatment of young rams with an agonist of gonadotropin-releasing hormone (GnRH) in the period immediately prior to puberty would delay the onset of adult sexual behavior and retard testicular development. In the first experiment the GnRH agonist was shown to be effective in suppressing the plasma concentrations of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in adult wethers (neonatally castrated rams) when administered by either a biocompatible slow release implant (implant) or a mini osmotic pump (minipump) that released the agonist for 4 weeks. The minipumps were more effective than the implants in suppressing the secretion of LH and FSH. In a second experiment, administration of the GnRH agonist by implant or minipump to prepubertal rams for 16 weeks immediately prior to puberty inhibited the development of sexual behavior, reduced the plasma concentrations of testosterone, retarded testicular and epididymal development, and inhibited growth rates. The effects on sexual behavior were clearly reversible but testicular and epididymal weights were still reduced in treated rams 8 weeks after the end of treatment. These results indicate that the reproductive function of rams is sensitive to gonadotropins and testicular hormones immediately prior to puberty. The agonist of GnRH was successfully delivered to the rams in a biocompatible implant which may offer a practical means of manipulating reproductive function in young rams.

Animals↗

Are ambient short-day cues necessary for puberty in a short-day breeder?

Some exposure to long days (LD) is necessary for female sheep to achieve puberty during short days (SD). In this regard, a 5-wk block of long days in lambs otherwise raised in short days will result in puberty at the normal age. In the present study, Suffolk lambs were raised in various artificial photoperiods to assess the role of short days. An increase in circulating progesterone to luteal phase levels was used as the criterion for puberty. Controls exposed to short days except for 5 wk of long days between 17 and 22 wk (SD-LD-SD) began repetitive reproductive cycles at the expected age (34 +/- 0.7 wk, mean +/- SE). When the final block of short days was eliminated and exposure to long days was continued after 22 wk of age (SD-LD-LD), puberty was delayed (41 +/- 0.8 wk of age). Removal of the first block of short days (LD-LD-SD) did not prevent normal puberty, and the initiation of cycles (29 +/- 0.9 wk) occurred earlier than in controls. Lambs in which the pineal gland was denervated at 22 wk so that it was unable to transduce short-day cues after exposure to long days (SD-LD-X) exhibited puberty at an age (33 +/- 1.2 wk) similar to that of controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

Growth and development of children with chronic renal failure. Study Group on Pubertal Development in Chronic Renal Failure.

Preliminary results from an ongoing multicentre study on pubertal growth and sexual maturation in chronic renal failure are presented. Puberty was delayed by approximately 2.5 years in both sexes in children with chronic renal failure. There was also an irreversible decline in height SDS during puberty. The pulsatile secretion of growth hormone (GH) and luteinizing hormone (LH) were disrupted in patients on conservative treatment or dialysis compared with those in patients with renal transplants; the mean nocturnal GH level and the mean GH peak amplitude were increased, while the number of pulses and peak amplitude of LH were decreased. The biopotency of LH, expressed as the ratio of bioactive to immunoreactive LH, was suppressed in patients with renal transplants.

Child↗