Cardiac autonomic dysfunction in diabetic children.

OBJECTIVE: Adults with type 1 diabetes may have abnormal alterations in heart rate variability (HRV) due to cardiac autonomic neuropathy. This prospective study was performed to determine whether HRV can be used to detect subclinical autonomic neuropathy in diabetic children. RESEARCH DESIGN AND METHODS: We examined five time domain and three frequency domain HRV indices determined from 24-h Holter recordings in 73 diabetic children and adolescents aged 3-18 years (mean 12.1 years) with a mean duration of diabetes of 55 months. The measures were compared with normal ranges. Z scores were established for each parameter and were compared with classic risk factors of other diabetic complications. RESULTS: Most HRV indices were significantly depressed in children aged > or = 11 years, and the levels of HRV abnormalities were significantly correlated with long-term metabolic control (mean GHb for 4 years) in that age-group. In younger patients, HRV indices were within the normal range and were not correlated with the level of metabolic control. Illness duration and microalbuminuria but not short-term metabolic control (most recent GHb) were also independently predictive of HRV abnormalities. CONCLUSIONS: These results suggest that early puberty is a critical period for the development of diabetic cardiac autonomic dysfunction. Therefore, all type 1 diabetic patients should be screened for this complication by HRV analysis beginning at the first stage of puberty regardless of illness duration, microalbuminuria, and level of metabolic control.

Pubertal growth and final height in hypopituitary boys: a minor role of bone age at onset of puberty.

Twenty-two hypopituitary boys treated with human GH were studied longitudinally before and during puberty. Eight patients entered spontaneous puberty at a mean bone age of 12.4 +/- 1.0 (+/- SD) yr. Height velocity reached a mean peak of 6.8 cm/yr during the second year of spontaneous puberty. In these patients, the mean total height gain throughout puberty was 22.8 +/- 5.2 cm, and the mean final height was 158.6 +/- 7.2 cm. Fourteen patients received testosterone enanthate (100 mg/month, im) starting at a mean bone age of 13.6 +/- 1.1 yr. Height velocity was maximal (7.5 cm/yr) during the first year of therapy. The mean final height was 162.9 +/- 5.0 cm, with a mean pubertal gain of 15.9 +/- 3.8 cm. Genital development, peak height velocity, and increase in plasma testosterone levels occurred earlier during testosterone therapy than during spontaneous puberty. In both groups of patients, there was a positive correlation between the bone age at onset of puberty and the height at onset of puberty (r = 0.65). There was also a negative correlation between bone age and total pubertal height gain (r = -0.73). This reduction in pubertal height increase was less than expected for bone age at onset of puberty, which can be explained by a decrease in bone age velocity in relation to bone age at onset of puberty (r = -0.81). Therefore, advancement in bone age at the onset of testosterone therapy did not impair final height, whereas it may increase height at onset of puberty, which is the major factor in final height. We conclude that in GH- and gonadotropin-deficient boys 1) a reduced dosage of testosterone enanthate (25 mg twice a month, im) should be used to induce pubertal development, and 2) the major criterion to decide when to give testosterone is height reached at that time regardless of bone age.

Hypopituitarism and idiopathic delayed puberty: a longitudinal study in an attempt to diagnose gonadotropin deficiency before puberty.

Fifty-five hypopituitary patients (43 boys and 12 girls) treated with human GH were studied longitudinally before and during puberty, occurring either spontaneously or induced with testosterone enanthate (100 mg/month, im) in boys and ethinylestradiol (10 micrograms/day, orally) in girls. In addition, 53 boys with idiopathic delayed puberty (IDP) were studied. Gonadotropin integrated responses (IRs) during 90 min after the iv injection of 25 micrograms/m2 LRH, bone ages (BA), and plasma levels of dehydroepiandrosterone sulfate and testosterone were determined at least yearly. Prepubertal hypopituitary patients with gonadotropin deficiency were characterized by: 1) a lowered FSH IR to LRH in most boys and in all girls; 2) a low LH IR for BA; 3) adrenarche either absent or delayed BA; 4) height age close to BA; and 5) the presence of several pituitary deficiencies. In contrast, most prepubertal hypopituitary patients without gonadotropin deficiency showed: 1) a normal FSH IR to LRH; 2) a normal or intermediate (greater than or equal to 75 mIU/ml . 90 min) LH IR for BA; 3) a normal adrenarche for BA; 4) a height age below BA; and 5) isolated GH or GH plus TSH deficiencies. A significant linear correlation was found between LH IR and the logarithm of plasma testosterone. The slopes and levels were similar in controls and hypopituitary boy without gonadotropin deficiency. In IDP, the level was significantly higher. All data obtained in these patients show that the increase in plasma testosterone and the clinical onset of puberty are delayed for the observed pubertal pattern of LH responsiveness. It is concluded that the study of several clinical and biological features, especially the gonadotropin IR to LRH, are of predictive value for the diagnosis of normal or deficient gonadotropic function in prepubertal patients with IDP and hypopituitarism.

Quality of life and retrospective perception of the effect of growth hormone treatment in adult patients with childhood growth hormone deficiency.

Divergent findings on the quality of life (QoL) and the psychosocial functioning of adults treated during childhood with growth hormone (GH) because of GH deficiency (GHD) have been reported. In the present study we evaluated the QoL and the perception of the effect of former GH treatment in Belgian young adults with childhood GHD. Thirty-six patients (22 males) were included in the study. They all were treated during childhood with GH for GHD. QoL was evaluated with a standardised questionnaire: the Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). Psychosocial functioning, sexual experience and schooling were evaluated by semi-structured interviews and questionnaires. The influence of gender, type of hormone deficiency (isolated GHD vs multiple pituitary hormone deficiencies [MPHD]), age at the start of GH therapy (before 12 yr vs after 12 yr) and the height deficit at the start of GH therapy (< -3 SDS vs > -3 SDS) were studied. In addition, the patients' and parents' perception of height and of the effect of GH treatment was retrospectively evaluated by semi-structured interviews. Age (mean +/- SD) at the time of evaluation was 20.0 +/- 1.3 yr and final height was -0.5 +/- 0.9 SDS, comparable to mid-parental height (-0.6 +/- 0.8 SDS). The QoL-AGHDA score was 9 +/- 6. About half of the patients, especially those in whom GH treatment was started after the age of 12 years, complained of retrospective difficulties with self-confidence and social contact, and about one-quarter of the patients had current difficulties with self-confidence, social contact, contact with the opposite sex and with emotional life. Only 44% of the patients had had sexual intercourse--none of those with MPHD. According to the parents, the patients had and still have more difficulties with self-confidence and social contact than their siblings and/or peers, and they needed and still need more emotional support. In one out of four patients the parents expected difficulties in finding a job, in one out of three patients parents expected difficulties in leaving home or in having a stable relationship. The educational level of patients with a height deficit < -3 SDS at start of GH therapy was lower than in patients with a height deficit > -3 SDS. According to the parents, about half of the patients, especially those with MPHD, had more study problems compared to siblings. In all patients, satisfaction with final height and GH therapy was obvious. In conclusion, the psychosocial outcome of young adults with childhood GHD was more satisfying than in previous studies. This could be due to a more adequate GH treatment with better final height results. Nevertheless, more difficulties with respect to psychosocial functioning were observed in patients with MPHD, in patients in whom GH treatment was started after 12 years of age and in patients with a height deficit < -3 SDS at the start of GH therapy, underlining the need for early diagnosis and treatment of childhood GHD, and of continuing medical follow-up and psychosocial counselling, particularly in these subgroups of patients with GHD.

Diabetes mellitus, mental retardation, lipodystrophy and dysmorphic traits.

We report on a mentally retarded girl with dysmorphic facies (hypertelorism, upslanting palpebral fissures, blepharophimosis, prominent teeth), who suffered from juvenile-onset insulinopenic diabetes mellitus and lipodystrophy. She could represent an undescribed MCA/MR syndrome.

[Action of luteinizing hormone-releasing hormone (LH-RH) on gonadotropin secretion in normal subjects]. / Action de l'hormone hypothalamique libérant l'hormone lutéinisante (LH-RH) sur les gonadotrophines chez le sujet normal

PIP: Gonadotropin release after synthetic LH-RH injection was studied under a variety of experimental conditions. In male subjects, LH-RH (25 mcg) induces release of LH and FSH before and during puberty, but only of LH in adults. Larger doses of LH-RH do induce FSH release, with LH release proportional to LH-RH dose; FSH release is smaller than LH release and follows it. In prepuberal females, LH-RH induces a large release of FSH and a weak release of LH. In puberty, LH response becomes greater than FSH. In eugonadal women, FSH and LH responses are more marked during luteal phase than during preovulatory phase. Nonsequential hormonal contraceptives inhibit FSH and LH response to 50 mcg of LH-RH, but not to 100 mcg. In postmenopausal women, LH increases after 25 mcg of LH-RH; 200 mcg ethinyl estradiol for 5 days permits an increase of both gonadotropins. These results suggest that gonadotropin response to LH-RH depends on endocrine equilibrium and gonadal steroids which may modify the synthesis and/or release of pituitary gonadotropins. On the basis of selective LH response to small doses of LH-RH, ti is speculated that an FSH releasing factor may exist.^ieng