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[Determination of growth hormone binding protein in a normal population and in subjects with short stature due to growth hormone resistance].

With the procedure which uses gel-filtration and high pressure liquid chromatography (HPLC) the authors measured the GH-binding proteins in 96 healthy subjects aged 6 months to 40 years. In the blood 45% of the GH is bound to the BP. The diagnosis was confirmed by our method in 13 patients with Laron type dwarfism and in four patients the GH receptor defect had been proved. The parents, the brothers and sisters showed significantly lower GH-BP II (principal GH-BP) levels. Possible regulation of GH-binding proteins in human plasma was examined. Eight children with isolated GH deficiency had a very low level of plasma GH binding activity (mean +/- SEM) (10.2 +/- 1.1% of radioactivity). Under GH treatment the hormone binding to high affinity BP (GH-BP II) increased in every patient to reach the mean value of 18.5 +/- 1.4%. This increase was related to a higher binding capacity without any significant change in the binding affinity. In nine boys with pubertal delay, the GH specific binding to peak II-BP (GH-BP II) was found to be normal (30.6 +/- 3.7%); it decreased significantly following testosterone treatment. In four boys with precocious puberty, the specific GH binding to peak II BP was low (16.6 +/- 1.1%). It increased significantly to 21.6 +/- 1.1% of radioactivity after treatment with LH-RH analogue. GH and testosterone have an opposite role in the regulation of the high affinity GH-BP.

Adolescent↗

[Bone mass formation in childhood and risk of osteoporosis].

The appearance of postmenopausal osteoporosis is correlated with the peak bone mass achieved during adolescence and the bone loss during adult life. The magnitude of the peak bone mass depends on genetic (race, sex, heredity), nutritional (calcium supplementation, obesity) and environmental factors as well as physical activity. Sex steroids and other hormonal factors involved in puberty, like growth hormone and insulin-like growth factors, are very important in the bone mass increase during this period. This is confirmed by studies in men with histories of constitutional delay of puberty, who have a decreased bone mineral density, and in children with precocious puberty treated with GnRH analogs, where the reduction in bone mineral density previously demonstrated seems at least completely reversible.

Bone Density↗

[Nocturnal growth hormone secretion in children with constitutional and acquired developmental delay].

We investigated the spontaneous secretion of GH during sleep (20.00 to 8.00) in 76 children with short statute. No difference could be found between a group of 12 children with familiar short stature or a group of 28 children with familial delay of growth and development: mean GH level 5.88:5.71 maxima 26.9:25.4 ng/ml, and integrated concentration of GH 2360:2617 ng x min/ml. 14 children with severe growth hormone deficiency proven by 2 stimulation tests, secreted significantly lower amounts of GH (mean 0.83 ng/ml, maximum 2.9 ng/ml, integrated concentration 371 ng x min/ml). 22 children with nonfamilial delay of growth and development presented values being lower than the first two groups, but higher than the group of GH deficiency patients (mean 3.07 ng/ml, maximum 13.8 ng/ml, integrated concentration 1429 ng x min/ml). Since in these children the anamnesis revealed events like breech delivery, shock or commotio cerebri as the history of patients with GH deficiency does, these events apparently cause the defective GH secretion in nonfamilial delay of growth and development.

Adolescent↗

Diabetic retinopathy in Mauriac's syndrome. Paradoxical deterioration with improved metabolic control.

We report four children with marked short stature, hepatomegaly, and delayed adolescence. Initial funduscopy demonstrated only occasional microaneurysms in two children and a single intraretinal hemorrhage in another. Improved control required large increases in insulin dosage. Growth rate improved significantly and hepatomegaly regressed. Puberty progressed rapidly in two older patients with poor final height. Paradoxically, with improved control, retinopathy progressed rapidly. One child with proliferative retinopathy in both eyes developed vitreous hemorrhage and blindness in one eye. Two required pan retinal photocoagulation with no further progression of their retinopathy. These rapidly progressive retinal changes remain unexplained. We advise caution when correcting metabolic derangements of diabetic patients who have been poorly controlled for a prolonged period.

Adolescent↗

Exercise and female adolescents: effects on the reproductive and skeletal systems.

It is generally accepted that exercise is beneficial for young women, since it increases cardiovascular fitness and reduces adiposity. Too much exercise can have negative effects on the reproductive and skeletal systems, however, including primary and secondary amenorrhea thought to be caused by several factors including low body weight and improper nutrition. Primary and secondary amenorrhea present similar patterns of luteinizing hormone and follicle stimulating hormone suppression, probably involving the hypothalamic-pituitary-gonadal axis and possibly also the hypothalamic-pituitary-adrenal axis. Recent research has also suggested that leptin (a hormone made by the fat cell) is a possible link between menstrual cycles and fat and energy levels. The female athletic triad consists of three interrelated problems: eating disorders, amenorrhea, and osteopenia. The most serious aspect of hypoestrogenism is its effect on bone growth of elite athletes; those with delayed menarche show a higher incidence of scoliosis, stress fractures, and osteopenia than do girls with normal menarche. The higher incidence of bone problems may be linked to a lower rate of bone accretion, which may lead to lower peak bone mass. Unfortunately, the loss may be irreversible. In addition to decreasing training and gaining weight, treatment for menarcheal delay may include oral contraceptive therapy.

Adolescent↗

Thyroid function and puberty.

Thyroid hormones are essential for normal growth, sexual development and reproductive function. During puberty, changes in thyroid functions and an increase in thyroid volume occur as an adaptation to body and sexual development. Hypothyroidism diagnosed late in prepubertal years, usually due to Hashimoto's thyroiditis, can cause a delay of puberty or incomplete isosexual precocity (development of breast and internal genitalia in girls and increased testis volume in boys without adrenarche). In contrast, normal pubertal development and adequate menarche have been documented in congenital hypothyroidism detected by neonatal screening and treated early. The effect of hyperthyroidism on pubertal development is not well known, but a short period of hyperthyroidism seems not to have major negative effects. In adolescence or young adulthood, menstrual dysfunction, infertility, and stillbirth or premature birth are associated with thyroid dysfunction.

Female↗

Delayed sexual development: a study of 252 patients.

A series of 252 patients with abnormalities of pubertal development are reported. Ovarian failure, followed by Rokitansky syndrome and then physiologic delay, are the most frequently encountered etiologies. Other etiologies are diverse and numerically less frequent. The average age of presentation, patient's height, somatic anomalies, diagnostic errors, and subsequent reproductive potential of each diagnostic group are reported. Only 35 (14%) of all patients presenting with abnormalities of pubertal development had subsequent normal reproductive potential. All of these patients were in the physiologic delay category.

Adolescent↗

Short day lengths delay development of the SNB neuromuscular system in the Siberian hamster, Phodopus sungorus.

The Siberian hamster, Phodopus sungorus, breeds seasonally. In the laboratory, the seasonal breeding can be controlled by photoperiod, which affects the durations of nightly melatonin secretions. Winterlike short day lengths induce gonadal regression in adult animals, and pups born and maintained in short days undergo gonadal development much later than animals born into long days. The spinal nucleus of the bulbocavernosus (SNB) and its target muscles, the bulbocavernosus (BC) and levator ani (LA), comprise a sexually dimorphic, androgensensitive neuromuscular system involved in male reproduction. The SNB neuromuscular system was studied in male Siberian hamsters maintained from conception in short-day (8:16 h light/dark cycle) versus long-day (16:8 h light/dark cycle) conditions. At 40-47 days of age, development of three components of the SNB neuromuscular system were all significantly delayed in hamsters raised in the short photoperiod: BC/LA muscle weight, the size of SNB motoneuronal somata, and the area of the neuromuscular junctions at the BC/LA muscles of short-day hamsters were each significantly reduced relative to those of longday counterparts. Thus, development of the SNB reproductive system is delayed under short day lengths in this species.

Animals↗

Arrested puberty associated with a Sertoli-Leydig cell tumor.

Androgen-producing ovarian tumors are rarely recognized as a cause of delayed or arrested puberty, despite their frequent association with secondary amenorrhea in the older patient. A case is discussed of a Sertoli-Leydig cell tumor in an 18-year-old girl resulting in arrest of breast development and primary amenorrhea.

Adolescent↗

[Treatment of precocious puberty with an LH-RH agonist (D-TRP6-LH-RH)].

Chronic administration of luteinizing hormone-releasing hormone (LH-RH) is currently considered as the most appropriate therapy of precocious puberty. A delayed release preparation of D-Trp-6-LH-RH (Décapeptyl in microcapsules) designed to release the agonist for 28 days after intramuscular injection of 60 micrograms/kg body wt was given to 12 boys and 26 girls with precocious puberty. Plasma levels of gonadotropins and sex steroids were suppressed to prepubertal levels within 3 weeks, whilst pituitary responses to LH-RH test were almost abolished within 7 weeks. A significant improvement of secondary sex characteristics, as well as gonadal size, was observed within 6 months. Growth velocity (cm/yr, mean +/- SD) was reduced in boys and girls from 9.9 +/- 3.4 and 9.6 +/- 3.3 respectively before treatment to 5.2 +/- 1.0 and 5.3 +/- 1.3 respectively during the third year of treatment. The mean ratio height age/bone age was just before treatment 0.91 in boys and 0.88 in girls and increased to 1 after 3 yr of treatment. This study shows that Décapeptyl in microcapsules induced a prolonged suppression of gonadal function and a relative blockade of bone maturation. A significant improvement of adult height relative to the effect of conventional treatments should be expected.

Female↗

Assessment of urinary continence in epispadias: review of 94 patients.

Between 1946 and 1980, 82 male and 12 female patients with epispadias were evaluated at our institution. Factors critical to the achievement of complete continence include deferral of an operation until the patient is at least 3 years old, a well developed bladder with adequate capacity and musculature, and maturation of the prostate at puberty in boys. Complete continence was obtained in 10 of the 12 female patients (83 per cent). Of 53 incontinent male patients undergoing an operation 18 (34 per cent) obtained complete urinary continence in the initial postoperative period but control was delayed until puberty in 19 additional male patients, for an over-all success rate in 37 of 53 patients (70 per cent). The significant increase in continence with the onset of puberty demonstrates the importance of expectant management of progress in a boy in relation to the potential contribution of prostatic maturation in the development of urinary control.

Adolescent↗

Progressive retinopathy with improved control in diabetic dwarfism (Mauriac's syndrome).

We report four children aged 11-18 1/2 yr first seen 7-14 yr after the diagnosis of insulin-dependent diabetes. At presentation, all had marked short stature, two had hepatomegaly, and the older three had delayed adolescence. They had been severely underinsulinized. Initial funduscopy demonstrated only occasion microaneurysms in two children and a single intraretinal hemorrhage in another. The youngest was normal. Improved control required large increases in insulin dosage. Growth rate improved significantly and hepatomegaly regressed. Puberty progressed rapidly in two older patients with poor final height. Paradoxically, with improved control, retinopathy progressed rapidly with appearance of multiple microaneurysms, nerve fiber layer infarctions, intraretinal microangiopathic changes, hemorrhages, exudates, and macular edema in all the patients and severe proliferation changes in three. One child with proliferative retinopathy in both eyes developed vitreous hemorrhage and blindness in one eye. Two required panretinal photocoagulation with no further progression of their retinopathy. These rapidly progressive retinal changes remain unexplained. We advise caution when correcting metabolic derangements of diabetic patients who have been poorly controlled for a prolonged period.

Adolescent↗

Cystic fibrosis in adolescents and adults.

Forty-five patients (25 male and 20 female) over 12 years of age with cystic fibrosis have been studied clinically, radiologically and physiologically. Their mean age at the first visit was 17 years; they were followed for a mean period of 4 years and attended at least every six months. The first symptom which developed before the age of five in 42 of the 45 patients was respiratory. Thirty-two of the 45 patients had severe lung disease (Group III) at the start of the study of the seven patients died during the study. Cough and sputum were almost universal, 23 had haemoptyses and eight pneumothoraces. Staphylococcus pyogenes, Haemophilus influenzae and Pseudomonas aeruginosa were the common pathogens isolated from sputum and the increasing prevalence of the latter was again confirmed. Acquisition of the mucoid strain of pseudomonas signified poor prognosis. Established infection was never eradicated. Forty-three patients had evidence of pancreatic insufficiency; in all but one patient the symptoms were mild and five patients abandoned dietary restriction and pancreatin without ill effect. Seven patients had symptoms of partial bowel obstruction (meconium ileus equivalent) but only one required surgical relief. The liver was enlarged in seven patients and the spleen was felt in three. Three patients had diabetes mellitus. The influence of cystic fibrosis on growth and development is reported--the growth spurt is late in the majority but growth failure is not confined to those with severe lung infection or malabsorption and in these circumstances remains unexplained. Mean weight was low in relation to height and puberty was delayed in both sexes.

Adolescent↗

New facets of androgen replacement therapy during childhood and adolescence.

The goals of androgen therapy for adolescents are to promote linear growth and secondary sexual characteristics, at the same time as permitting the normal accrual of muscle mass and bone mineral content. Secondary goals are mainly in the psychosocial sphere, in which pubertally delayed boys feel that they look too young, are not considered a 'peer' in their age group and have difficulty competing in athletic endeavours. These goals are irrespective of the causes of delayed pubertal development: constitutional delay of growth and puberty (CDGP), a transient but very common form of pubertal delay and, much less commonly, primary or secondary permanent hypogonadism. Not all boys with CDGP require testosterone therapy, but those that come to a referral practice are likely candidates, as the watchful waiting period has finished. Although a range of androgen preparations is available for adults (injectable, oral, implantable and cutaneous patches and gels), most are drug delivery devices that are appropriate for full adult androgen replacement. These doses are too large for the induction of puberty. Therefore, at present, the injectable form is the only one that is easily adaptable for the increasing amounts of androgen necessary for the various stages of pubertal development. All preparations deliver testosterone that is readily converted to dihydrotestosterone by 5-alpha reductase. The author's practice is to begin with injecting 50-75 mg of one of the long-acting esters (enanthate or cypionate) per month, and gradually escalate to 100-150 mg/month, before changing to twice monthly dosage. As most adolescents have delayed puberty, the therapy is needed for 6-18 months before the hypothalamic-pituitary-gonadal axis functions at the late adolescent/adult level in those with CDGP. Those with permanent hypogonadism will require lifelong therapy. Once adequate virilisation is induced, and virtually full adult height is reached, any of the therapies noted above can be used in those permanently hypogonadal, whether primarily or secondarily.

Adolescent↗