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[Hypothalamic dysfunction. 2 cases: the contribution of nuclear magnetic resonance, therapeutic trial of naltrexone].

Two cases of idiopathic hypothalamic dysfunction (one boy and one girl) are reported. Symptoms of hypothalamic dysfunction were noted by the age of 2 years: initial polyphagia and obesity with subsequent anorexia and emaciation were observed in one patient. Thermoregulation and thirst disorders, recurrent accesses of hypernatremia, acrocyanosis and profuse sweating were present. Impaired growth and delayed puberty in one case, and in the other hypogonadism, absence of growth hormone and gonadotrophins release in response to provocative stimuli were observed as well as abnormal thyroid stimulating hormone response to thyrotropin releasing hormone with hyperprolactinemia. Magnetic resonance imaging showed structural lesion in the lateral part of the lentiform nucleus in one case. Treatment with naltrexone, an opiate antagonist, had little if any effect.

Body Height↗

[Iron chelation in children].

Iron-chelating treatment is indicated in all children on prolonged transfusion therapy (i.e., chiefly patients with thalassemia and Blackfan-Diamond anemia). The purpose of iron-chelating treatment is to prevent the development of manifestations of iron overload including cardiac hemosiderosis and insulin-dependent diabetes mellitus (which are two potentially fatal complications), hepatic cirrhosis, hypoparathyroidism, hypothyroidism, and delayed puberty. Deferoxamine is the only effective iron-chelating agent and should be given in a daily dose of 40 mg/kg at initiation of the transfusion program. Administration is by subcutaneous infusions from 8 to 10 hours per day. The goal of iron-chelating treatment is to maintain serum ferritin levels between 500 and 1,000 ng/ml. This long-term treatment is a significant burden for patients and it can be hoped that non-toxic iron-chelating agents, active by mouth, will become available.

Adolescent↗

[Treatment of post-transfusion iron overload by deferoxamine].

Iron chelation therapy must be associated with the regular blood transfusions required for thalassaemia and other chronic anemias. We report here a study concerning 4 groups of patients, aged 6 to 28, regularly transfused at Necker Enfants-Malades hospital: a) 20 with thalassaemia major; b) 6 with thalassaemia intermedia; c) 2 with sickle cell disease and d) 2 with Blackfan-Diamond syndrome. The transfusion regimen consisting of monthly or quarterly transfusions varied as a function of the groups. Desferal was used in all patients. The dosage and the route of administration (IV, IM, SC) were adapted to the amount of iron transfused and to the nature of the disease. The serum ferritin level was considered as the indicator of the iron overload. Comparisons were established between the quantities of iron transfused, ferritin levels, and parameters such as dosage, route of administration and compliance to Desferal. During the period of study 3 patients died from cardiac failure due to transfusional hemosiderosis. Endocrine complications (diabetes 2 cases, hypocalcemia 3 cases, hypothyroidism 1 case and delayed puberty 7 cases) were observed. This high incidence of complications induced by post-transfusional iron overload has recently prompted us to improve the quality of chelation therapy through the use of the services of a specialized center where patients as well as their families can be trained more adequately in home care and self-treatment.

Adolescent↗

[The appearance of ovarian cysts in young sows after treatment with gonadotropin preparations for estrus induction].

In 72 (46%) of 155 gilts discarded for genetic reasons after performance testing and housed under fattening conditions no heat could have been detected during the first 30 days. The gilts were assigned alternatingly to a control group and four different treatments of delayed puberty. The induction of puberty was carried out by injections of 1000 iu PMSG, 400 iu HCG and 2 mg oestradiol benzoate, 400 iu PMSG and 200 iu HCG and 800 iu PMSG and 400 iu HCG. If there was no estrus gilts were slaughtered 12 days later for examination of the ovaries. Those coming into estrus were slaughtered 8 days after disappearance of estrus. Estrus could be induced in 69 to 94% of the gilts, whereas 40% of the untreated showed estrus signs. After treatment with PMSG and HCG in 40 and 87% of the gilts cysts were found whereas none of the untreated and 26 and 29% of those treated with PMSG und HCG + oestradiol benzoate revealed ovarian cysts. In addition, those gilts that had come into estrus during the first 30 days were given injections of either 1000 iu PMSG or 800 iu PMSG and 400 iu HCG. The injections were made either on the 5th, 10th or 15th day of cycle. In both latter groups significantly more gilts showed standing heat than after treatment at cycle day 5. The results of inspection of the ovaries at slaughter and steroid hormones could not be assigned to a defined stage of the physiological ovarian cycle.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[Constant flow alimentation in Crohn's disease of children].

Enteral nutrition in children with Crohn's disease is a preferred treatment of acute attacks. When maintained for three months, it effectively acts on digestive symptoms, makes possible the resumption of growth and onset of a delayed puberty. In contrast, it does not appear to modify the long-term course of the disease: 7 out of 10 patients had relapses 3 to 6 months after interruption of enteral nutrition.

Adolescent↗

The Langer-Giedion syndrome: report of a 22-year old woman.

A 22-year-old woman with the Langer-Giedion syndrome and delayed puberty is presented. Pertinent features include a bulbous nose, sparse hair, protruding ears, multiple cartilaginous exostoses, cone-shaped phalangeal epiphyses, short stature, microcephaly, and mental retardation. She is the oldest patient thus far described with this condition, and is compared to the ten previously published cases. The clinical course of patients with the Langer-Giedion syndrome and the possibility of malignant change in the exostoses have not been established.

Adult↗

Studies of pathophysiology in primary amenorrhea.

Patients with primary amenorrhea underwent stimulation with luteinizing hormone releasing hormone (LRH) before and after clomiphene administration to determine the maturational status of the hypothalamic-pituitary-gonadal axis, and to assess the development of feedback control mechanisms. Four patients with clinically recognizable conditions served as models. One patient had panhypopituitarism with undetectable baseline FSH and LH values, no response to LRH or clomiphene, and no detectable feedback control. One patient with a "specific" hypothalamic hypogonadotropism had low baseline gonadotropins with a normal response to LRH and no positive or negative feedback mechanisms reflected by no change in LRH response after clomiphene. A patient with delayed puberty due to low bodyweight had low FSH and LH baseline values and an "immature" response to clomiphene, characterized by lowered baseline gonadotropins and an increased peak LH following LRH stimulation. The fourth patient, with an adolescent polycystic ovarian syndrome, had a high baseline LH, normal FSH, hyperresponse to LRH, and a "mature feedback control" as evidenced by an increase in baseline FSH and LH, and a decrease in the LRH response while on clomiphene. The remaining patients showed inappropriate responses. They are regarded as having defects rather than dysfunctions, and the possible abnormalities are discussed in relation to the clinical findings.

Amenorrhea↗

The pineal gland in relation to growth and development in children.

The biorhythm of melatonin in human newborns is established later than that of either serotonin or N-acetylserotonin. Towards the end of the first year of life, the melatonin rhythm is a well established phenomenon and its nocturnal increment is equal to that seen in the pre-school children. Following this period the magnitude of nighttime melatonin increment starts declining and is closely associated with advancing skeletal age. This association between the magnitude of nocturnal increment and skeletal age is also noted in pathological subjects, lower skeletal age with greater magnitude of increment or advanced skeletal age with less increment. Although no inverse relationship between plasma melatonin and gonadotropins could be detected in children, there emerged a marked negative association between melatonin and growth hormone. GRF-induced GH stimulation suppressed melatonin in children as well as in adults. Melatonin pretreatment blocked GRF-induced increment of GH in rats. When animals were given either melatonin or growth hormone, one suppressed the other. It is possible that melatonin-induced growth hormone suppression is somatostatin mediated.

Adolescent↗

[Osteocalcin in children of short stature and its nocturnal variations].

Serum osteocalcin (Gla-P) was measured in 65 children with normal stature for age and in 116 children with growth retardation, excluding endocrine disorders, in matched groups according to age: 1-6 years (n = 33); 7-10 years (n = 49); 11-14 years (n = 72); 15-18 years (n = 27). Thirty of these patients were retested at 2 weeks interval. In addition, Gla-P and growth hormone (hGH) were assayed in blood samples obtained every 20 minutes during sleep in 12 children with growth retardation. In younger children, Gla-P levels were significantly lower in patients with growth retardation, when compared with normal children. In contrast, this difference was no longer significant in children above 11, with either normal or delayed puberty. However, important intra-individual variations of Gla-P levels were observed on blood samples obtained at 2 weeks interval. A nocturnal periodicity in Gla-P was found; Gla-P rose slightly during sleep in the patients studied, maximum concentration being reached between 4 and 6 AM. No correlation between integrated concentrations of hGH and Gla-P was found. Gla-P determination may be of interest in the evaluation of young children with short stature. Standardized conditions of blood sampling for Gla-P use in children remain to be determined.

Adolescent↗

Health aspects of cannabis.

Marijuana seems firmly established as another social drug in Western countries, regardless of its current legal status. Patterns of use vary widely. As with other social drugs, the pattern of use is critical in determining adverse effects on health. Perhaps the major area of concern about marijuana use is among the very young. Using any drug on a regular basis that alters reality may be detrimental to the psychosocial maturation of young persons. Chronic use of marijuana may stunt the emotional growth of youngsters. Evidence for an amotivational syndrome is largely based on clinical reports; whether marijuana use is a cause or effect is uncertain. A marijuana psychosis, long rumored, has been difficult to prove. No one doubts that marijuana use may aggravate existing psychoses or other severe emotional disorders. Brain damage has not been proved. Physical dependence is rarely encountered in the usual patterns of social use, despite some degree of tolerance that may develop. The endocrine effects of the drug might be expected to delay puberty in prepubertal boys, but actual instances have been rare. As with any material that is smoked, chronic smoking of marijuana will produce bronchitis; emphysema or lung cancer have not yet been documented. Cardiovascular effects of the drug are harmful to those with preexisting heart disease; fortunately the number of users with such conditions is minimal. Fears that the drug might accumulate in the body to the point of toxicity have been groundless. The potential deleterious effects of marijuana use on driving ability seem to be self-evident; proof of such impairment has been more difficult. The drug is probably harmful when taken during pregnancy, but the risk is uncertain. One would be prudent to avoid marijuana during pregnancy, just as one would do with most other drugs not essential to life or well-being. No clinical consequences have been noted from the effects of the drug on immune response, chromosomes, or cell metabolites. Contamination of marijuana by spraying with defoliants has created the clearest danger to health; such attempts to control production should be abandoned. Therapeutic uses for marijuana, THC, or cannabinoid homologs are being actively explored. Only the synthetic homolog, nabilone, has been approved for use to control nausea and vomiting associated with cancer chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Analgesics↗

Treatment failure in celiac disease due to coexistent exocrine pancreatic insufficiency.

A 17-year-old white adolescent had a history of chronic diarrhea, delayed puberty, and growth failure. Investigations excluded cystic fibrosis, Shwachman syndrome, and endocrine causes of growth failure. Severe steatorrhea was diagnosed from fecal fat studies, and a jejunal suction biopsy showed total villus atrophy, consistent with a diagnosis of celiac disease. Following introduction of a gluten-free diet, his appetite and growth improved, but he continued to have abdominal discomfort and loose offensive bowel motions. One year later, severe steatorrhea was present. A repeat jejunal biopsy showed partial recovery of villus architecture. Serum immuno-reactive trypsinogen level was low, which was highly suggestive of exocrine pancreatic failure. Results of quantitative pancreatic stimulation test confirmed the presence of primary pancreatic insufficiency. After introduction of oral pancreatic enzyme supplements with meals, his gastrointestinal symptoms resolved and growth velocity accelerated. Previously, primary pancreatic insufficiency has only been described in elderly patients with long-standing untreated celiac disease. This case, however, emphasizes that pancreatic failure can occur with celiac disease at any age. Determination of a serum immunoreactive trypsinogen level should be considered a useful screening tool for pancreatic insufficiency in patients with celiac disease who have not responded to a gluten-free diet.

Adolescent↗

Behavioral and endocrinological effects of single injections of monosodium glutamate in the mouse.

Treatment of neonatal mice with large, repeated doses of monosodium L-glutamate (MSG) produces a syndrome of obesity and endocrinological dysfunction generally attributed to a hypothalamic lesion. We have used single injections of MSG, administered on postnatal day four, to explore the lower end of the dose-response curve for this toxin. Major features of the MSG syndrome including hypophagia, obesity, hypoactivity, reduced pituitary protein content, decreased ovarian weight, delayed puberty and elevated plasma corticosterone levels were obtained at the highest dose. Of the variables measured, feeding disturbances and reduced pituitary and ovarian weights were the most sensitive indicators of damage. The extent of damage produced in the arcuate nucleus of the hypothalamus increased with increasing dose. A prominent lesion was also detected in the medial preoptic area of animals receiving the highest dose. Damage was not evident in other diencephalic structures associated with body weight regulation. Since little is known about the mechanisms underlying MSG obesity, a second study examined the contribution of ovarian hormones to obesity in MSG treated mice. Ovariectomy increased the body weights of animals injected with low but not high doses of MSG, suggesting that a reduction in ovarian function may contribute to the MSG obesity syndrome in the female. Measurement of hypothalamic monoamines and metabolites in these mice indicated that as with repeated doses of MSG, single injections of the toxin reduced hypothalamic dopamine levels. DOPAC levels were unchanged.

Adipose Tissue↗

LH-RH stimulated LH secretion in human endocrine disease.

The application of LH-RH provides means to describe the functional state of the hypothalamo-pituitary-gonadal axis and has helped to understand the regulation of gonadotropin secretion both under normal and pathological circumstances. At present, diagnostic LH-RH application appears to be most useful in patients with delayed puberty, where a biphasic response during an infusion of LH-RH excludes hypogonadotropic hypogonadism at an early clinical stage. An enhanced LH-RH induced response following exogenous intermittent LH-RH administration identifies the subgroup of hypogonadotropic patients who are suitable for subsequent LH-RH substitution therapy. In addition, subtle derangements of gonadotropin secretion have been described in a score of clinical conditions including the endocrine disorders discussed in this review. However, interesting as these observations may be theoretically, their practical value is often limited since a multitude of interfering factors, both exogenous and endogenous, results in a great variability in the obtained results, thus limiting the diagnostic value of the test in a specific patient. As of recently the clinical use of LH-RH includes its therapeutic application to replace low endogenous levels of LH-RH, whereas long-acting analogues of the natural decapeptide are employed to suppress gonadotropin secretion in an increasing field of endocrine disorders.

Adrenal Gland Diseases↗

Clinical diagnosis of disorders of puberty.

The authors emphasize the orderly sequence of events (consonance) characteristic of normal puberty. Loss of consonance of normal puberty indicates an underlying endocrine disorder.

Adenoma↗

Partial trisomy for the distal long arm of chromosome 5 (region q34 leads to qter). A new clinically recognizable syndrome.

This report describes a family in which eight individuals in three generations had mental retardation in association with a characteristic pattern of clinical problems and physical abnormalities including short stature, eczema, hernias, delayed puberty, dysmorphic facies and digital anomalies. The family history was consistent with a chromosomal rearrangement with transmission through balanced carriers. Routine ASG banding studies showed extra chromosomal material on a chromosome 16 but failed to demonstrate any differences between the affected individuals and the presumed carriers. However, subsequent studies utilizing trypsin banding and microspectrophotometry of individual chromosomes demonstrated that the affected individuals were partially trisomic for the distal band of the long arm of chromosome 5 and that 0.273 units of a chromosome 5 were translocated to chromosome 16. This definitive cytogenetic diagnosis permitted accurate prenatal diagnosis to be carried out on the fetus of a balanced carrier female. The application of these techniques to previously obscure familial dysmorphic syndromes is recommended.

Abnormalities, Multiple↗

Circadian rhythm in gonadotropin secretion in children with constitutional stature delay.

Plasma levels of luteinizing and follicle-stimulating hormones were measured for 24 hours in six subjects affected by constitutional stature delay associated with sexual maturation delay. The children in pubertal stage exhibited fluctuating plasma concentrations of these hormones which significantly increased during sleep, as in healthy pubertal subjects. Thus in this type of delayed puberty, the synchronization of augmented gonadotropin secretion with sleep develops later in chronologic age but it is strongly related to bone age.

Adolescent↗