Clinical and hormonal response to general anaesthesia in patients affected by different degrees of mental retardation.

BACKGROUND: Poor or no clinical signs of psychological distress are usually observed in patients affected by severe or profound mental retardation (MR). The aim of this study was to use clinical and hormonal parameters in order to compare the amount of stress in patients affected by different degrees of MR undergoing general anaesthesia for dental care. METHODS: Nine patients affected by mild or moderate MR (group A: intellective quotient > 35) and 12 affected by severe or profound MR (group B: intellective quotient < 36), undergoing general anaesthesia for dental care, were studied. The reaction to venipuncture before anaesthesia induction and the recovery from anaesthesia were assessed by clinical scores. Cardiac rate and arterial pressure were recorded before and after venipuncture and after removing the endotracheal tube. Cortisol and prolactin, two hormones affected by stress, were determined in plasma the day prior to surgery (1), after anaesthesia induction (2), and after removing the endotracheal tube (3). RESULTS: During venipuncture, group B was significantly less reactive than group A (p < 0.05) and showed no arterial pressure increase while group A presented a significant increase of systolic pressure; conversely, the groups shared the same hormonal pattern at time 2 (cortisol did not change, prolactin increased significantly). Postoperatively A and B groups did not differ regarding cardiac rate and arterial pressure, while a wider range of postoperative scores was observed in group A in which a further prolactin increase was registered at time 3. CONCLUSIONS: Clinical evaluation can underestimate the stress to which patients affected by severe or profound MR are subjected during anaesthesia induction.

IGF-I levels in prepubertal and pubertal children with Down syndrome.

BACKGROUND: Growth retardation is a main feature of Down syndrome but it is still unclear whether an alteration of the GH/IGF-I axis is present in this condition. Concerning IGF-I levels, they have been found reduced by some authors but normal by others. METHODS: On these bases, IGF-I levels have been assessed from prepubertal to late pubertal stages of gonadal maturation in a large group of children and adolescents with Down syndrome (DS, 68 M, 45 F, 12.5 +/- 0.6 yr; prepubertal n = 39, pubertal n = 74) with those in a group of normal children and adolescents (NS, 75 M, 87 F; 11.1 +/- 0.4 yr; prepubertal n = 94, pubertal n = 68). RESULTS: Within each group, IGF-I levels were gender-independent while showed age-related variations with positive association with pubertal stage--peaking up in pubertal stage IV--(DS: r = 0.6, NS: r = 0.4, both p < 0.0001) and testosterone (DS: r = 0.6, NS: r = 0.5, p < 0.001) or estradiol (DS: r = 0.6, NS: r = 0.5, p < 0.001) levels. Considering whole groups, mean IGF-I levels in DS were slightly but significantly lower than those in NS (257.9 +/- 12.5 vs 310.8 +/- 12.6 micrograms/l, p < 0.02). Analyzing individual IGF-I levels in DS with respect to normal ranges per pubertal stage, more than 85% of IGF-I levels resulted within the normal limits. These results demonstrate that IGF-I levels in DS patients are generally within the normal range--though a slight reduction of mean IGF-I levels is present--and follow normal age-related variations with clear cut increase at puberty and positive association with gonadal steroid levels. CONCLUSIONS: This evidence points toward the need to clarify the GH/IGF-I axis function and activity in DS patients.

Growth hormone administration normalizes the ovarian responsiveness to follicle-stimulating-hormone in the early stages of the follicular maturation in women with Down syndrome.

To investigate the sensitivity of ovary to follicle-stimulating hormone (FSH) during the early follicular phase of the human menstrual cycle in patients with Down Syndrome (DS) six postmenarchal patients with Down Syndrome and twelve normoovulatory women were studied. Randomly, DS patients were submitted in two consecutive cycles to a treatment with GH (0.1 IU/Kg i.m.) or saline for 3 days. Pure FSH (75 IU) was given i.v. at day 3 and plasma levels of LH, FSH, E2, Testosterone, DHEAS, Androstenedione, GH and IGF-I were assayed in samples collected for a period of 26 h after the injection. Data were compared with those obtained from controls receiving pure FSH or saline. In control patients FSH injection increased E2 stimulated area under curve (AUC). This value was significantly greater than that found in DS patients, who exhibited an E2-stimulated AUC superimposable to saline treated controls. In DS GH plasma concentrations were significantly lower than in control group (p < 0.05). The treatment with GH is able to normalize the ovarian response to FSH in DS patients at levels similar to those found in FSH treated controls. Moreover in GH treated cycles, both GH and IGF-I plasma concentrations were higher at time of FSH injection with respect to those found in the cycles where saline was given. These results indicate that the ovarian sensitivity to FSH in patients with DS is blunted. Lower GH plasma levels found in this group may in part account for this biological feature, since GH treatment is able to restore the ovarian response, probably via an increase of IGF-I plasma concentrations.

Ovarian sensitivity to follicle stimulating hormone is blunted in normo-ovulatory women with Down's syndrome.

Ovarian sensitivity to follicle stimulating hormone (FSH) during the early follicular phase of the human menstrual cycle was studied in six post-menarchal patients with Down's syndrome and 12 normo-ovulatory women. Pure FSH (75 IU) was given i.v. to six controls and six Down's syndrome patients, while saline was administered to the remaining six controls. Plasma concentrations of luteinizing hormone (LH), FSH, oestradiol, testosterone and growth hormone (GH) in samples collected for a period of 26 h after the injection were assayed. In control patients FSH injection increased oestradiol stimulated area under the curve (AUC). This value was significantly higher than that found in Down's syndrome patients (P < 0.02), who exhibited an oestradiol-stimulated AUC equivalent to saline-treated controls. In Down's syndrome, GH plasma concentrations were significantly lower than in the control group (P < 0.05). These results indicate that the ovarian sensitivity to FSH in patients with Down's syndrome is blunted. Lower GH plasma concentrations found in this group may in part account for this biological feature.

Structural variants of chromosome 9: a possible association with hypogonadotropic hypogonadism.

We report two cases of structural variations of chromosome 9 associated with hypogonadotropic hypogonadism and azoospermia in adolescent boys. One patient also had a partially imperforated urethral meatus. Histological examination revealed that both had hypotrophic and underdeveloped testes. There was no LH and FSH response to LH-RH stimulation nor was there any response to naloxone tests. Basal and HCG stimulated plasma testosterone values were below normal prepubertal levels. As the administration of gonadotrophins did not improve the clinical and hormonal findings, alternative androgen therapy was necessary to achieve secondary sexual characteristics. Although they reached a good level of androgenization, their testes were still very small and azoospermia remained, as confirmed by repeated semen analyses. A possible association between chromosome 9 polymorphisms and hypothalamo-pituitary axis abnormalities is suggested. It is hypothesized that structural variants of chromosome 9 are not unrelated occurrences. Furthermore, and in view of the fact that they can lead to a high risk of azoospermia and infertility, such variants call for clinical investigation.

Bilateral non-communicating paraurethral meatus in Prader-Willi syndrome.

Prader-Willi syndrome (PWS) is a complex multisystemic congenital disorder due to an interstitial deletion of chromosome 15q11-13 or to maternal uniparental disomy. Molecular genetic testing is complex, and often requires DNA from both parents, which is not always available. An accurate medical history and presenting clinical signs are frequently the only tools for the clinical diagnosis of this syndrome, therefore it is important to have complete and accurate criteria. The presence of a bilateral non-communicating paraurethral meatus in a 9-year-old female patient affected by PWS, previously unreported in the literature, should induce clinicians to look for this sign when examining such patients.

Clinical and roentgenographic findings in a patient with primordial microcephalic dwarfism type Caroline Crachami.

We describe a patient with primordial microcephalic dwarfism with severe intrauterine growth retardation and severe and progressive postnatal deficit in length, weight and head circumference. The patient was extroverted and sociable but mildly mentally retarded. He had marked delay of bone maturation and an enlargement of the sella turcica. This child and two previously reported patients [Boscherini et al., Eur J Pediatr 137:237-242, 1981] have many characteristics in common with Caroline Crachami, the famous "Sicilian dwarf". We think that these patients belong to a separate category of microcephalic primordial dwarfism.

[General anesthesia in Prader-Willi syndrome]. / Anestesia generale nella sindrome di Prader-Willi.

The case of a woman of 27 affected by the Prader-Willi syndrome who underwent general anaesthesia for dental surgery is reported. The patient presented severe mental retardation, small stature, moderate muscular hypotonia, hyperphagia, obesity, and diabetes mellitus. Premedication consisted of diazepam and atropine; anaesthesia was induced with propofol and maintained with propofol, fentanyl and N2O; muscle paralysis was obtained with atracurium. A small glottis was observed at laryngoscopy so that a 6 mm cuffed tube was inserted. Surgery lasted 75 minutes; the patient recovered promptly a few minutes following the end of propofol infusion; no postoperative complication was recorded. As hypoglycemia can occur during and after surgery in the Prader-Willi syndrome, plasma samples for glucose, NEFA, insulin, cortisol, and growth hormone (GH) were collected prior to the induction of anaesthesia (A), 20 minutes after starting surgery (B), at the end of surgery (C), and 3 hours later (D). In spite of the infusion of glucose, hyperglycemia was observed just in C and D samples (A:77; B:88; C:245; D:279 mg/dl). Stable NEFA values, within the normal range, were observed (A:77; B:88; C:245; D:279 mg/dl) suggesting poor or absent lipolysis. Insulin decreased progressively during surgery (A:10.5; B:8.8; C:5.4; D:7.0 mU/L). Cortisol peaked in B (A:9.5; B:20.9; C:13.4; D:4.8 micrograms/dl), suggesting normal hypothalamic reactivity to the surgical stimulus. Finally very low GH levels were observed (A:0.04; B:0.07; C:0.06; D:0.09 ng/ml) suggesting GH deficiency, which had possibly affected the size of patient's glottis. Our data support the hypothesis that hypoglycemia in the Prader-Willi syndrome originates from inadequate lipolysis during starvation.

[Response of testosterone to chorionic gonadotropin stimulus in prepubertal cryptorchidism and retractile testes. Age-related changes in gonadal steroidogenesis. Authors'experience]. / La risposta del testosterone allo stimolo con gonadotropina corionica nei prepuberi criptorchidi e con testicoli retrattili. Modificazioni della steroidogenesi gonadica in rapporto all'età. Nostra esperienza.

The aim of this analysis is to evaluate the gonadal function in children with true undescended testes and in those with retractile testes, in order to verify a possible impairment of the testicular steroidogenesis due to the permanent or transitory anomalous position of the gonad outside the scrotum. The authors carried out a prospective study on 29 prepubertal children affected by true undescended testes (monolateral in 20 cases and bilateral in 9), as well as on 25 prepubertal children with retractile testes (monolateral in 10 cases and bilateral in 15), assaying the testosterone (T) levels, basal and 72 hours after stimulus with human chorionic gonadotrophin (HCG) administered in a single dose of 100 U/kg i.m. Further-more, to verify the hypothesis of a possible progressive reduction of the Leydig cells function, particularly in the gonads bilaterally affected, the authors also evaluated the testosterone response to gonadotrophic stimulus compared to age (> 0 < 4 years). This study in agreement with data already published, confirms the normality of gonadal function both in children with mono or bilateral true undescended testes and in those with retractile testes. The lower the age of the subject the higher is the peak of testosterone after stimulus, confirming the active steroidogenesis of the gonads in infants and small children and sustaining the "non quiescence" of this organ during infancy, even in cases of true undescended testes.

Basal body temperature curves and endocrine pattern of menstrual cycles in Down syndrome.

We examined the basal body temperature curves and the endocrine pattern of 20 cycles from women with Down syndrome with regular menstrual cycles. Data were compared with those obtained from an age-matched population of healthy women with regular menses. Growth hormone deficiency was excluded for women with Down syndrome by pharmacological tests. Women with Down syndrome showed a significantly higher incidence of anovulation and luteal defects than controls (p < 0.001). Overall, and in ovulatory cycles, estradiol and progesterone plasma levels were greater in controls than in women with Down syndrome. No difference was observed for gonadotropin and androgen circulating levels between the two groups. It is concluded that in women with Down syndrome with regular menses, ovulatory events were less frequent and often characterized by luteal defects. This could be ascribed to an impairment of both follicular and luteal functions. However, reproduction is possible in such patients.

Short stature in a patient with Klinefelter syndrome and growth hormone deficiency.

We report on a child with Klinefelter syndrome and short stature due to idiopathic growth hormone deficiency (IGHD). His height was below the mid-parental height, with a significant delay in bone age. Height velocity increased from 4.5 to 8.2 cm/year during 1 year of GH therapy and typical catch-up growth was observed. No adverse reactions to the treatment were observed. We wish to emphasize the rare association between Klinefelter syndrome and IGHD and the apparent effectiveness and safety of recombinant somatotropin treatment in aneuploid patients.

C4 serum levels in newborns of diabetic mothers: relationship with metabolic assessment during pregnancy.

Serum levels of C4 complement factor are lower in diabetic patients: it is supposed that this finding is related to genetic inheritance factors of diabetes. The purpose is to compare C4 levels in newborns of diabetic mothers with maternal metabolic control during pregnancy. The results suggest that metabolic control could influence the expression of genetic factors of diabetes; in fact C4 serum levels in newborns are significantly higher (p < 0.01) than controls, but not different from those observed in large newborns of non diabetic mothers.

[Evaluation of the testicular function using the HCG test in normal and cryptorchid children]. / Valutazione della funzione testicolare mediante hCG-test in bambini normali e criptorchidi.

The testicular function has been evaluated by a single dose hCG-test in normal and cryptorchid prepubertal boys using three different protocols. No remarkable difference has been observed using different posologic protocols. Testicular function in boys affected by cryptorchidism was similar to the testicular function in normal controls. However cryptorchid boys older than 6 years of age showed a significant reduction in testicular response to hCG-test in comparison to cryptorchid boys younger than 6 years of age.

Treatment of undescended testes with hMG and hMG plus hCG: clinical, hormonal and sonographic evaluation.

20 children (mean age 4, 6 yrs), of whom 13 had unilateral and 7 had bilateral cryptorchidism were treated with hMG: 40 I.U. three i.m. injections per week for six or eight weeks. Where there was no descent of testis, treatment was continued with hMG at the same dosage plus hCG 500 I.U. one i.m. injection per week for an additional four weeks. The children were tested for FSH, LH and Testosterone serum levels at the beginning of treatment and after 6, 8 and 14 weeks. We obtained testicular descent in 10 out of 20 cases treated. Ultrasonography enabled us to locate the undescended testes in all cases and to follow the response to treatment.