G. B. Pozzan

Natural course of subclinical hypothyroidism in Down’s syndrome: Prospective study results and therapeutic considerations

Pathogenesis, natural course and therapeutic management of subclinical hypothyroidism (SH) in Down’s syndrome (DS) remain object of debate in literature. In the present study thyroid function, antithyroid antibody (ATA) prevalence and serum lipid concentrations were investigated in a group of 344 Down patients (DP) and data were compared with those obtained from a control group of 257 age and sex matched healthy subjects. Thyroid function and ATA prevalence were also studied in 120 parents of DP. SH prevalence was clearly higher in DP (32.5% of cases) than in controls (1.1%) and parents (0%). Similarly, ATA prevalence was higher in DP (18% of cases) than in controls (5.8%) and parents (6.6%). In spite of this, no correlation was found in DP between SH and ATA prevalences, since ATA were detected in 18.7% of SH-DP and in 15.8% of euthyroid DP. Thus, circulating ATA were not detected in the majority of SH-DP. No significant differences regarding T4, FT4, T3 and serum lipid levels among SH and euthyroid DP and controls were found. Moreover, TSH levels were only slightly increased, generally less than 10 μU/ml, in most cases of SH-DP. Follow-up was longer than 24 months (range 2–7 years, mean 3.1) in a group of 201 DP: two different patterns of SH course were observed, mainly depending on the presence or the absence of circulating ATA. In particular, 35.7% of ATA-positive SH-DP developed a clinically evident thyroid disease (overt hypothyroidism or hyperthyroidism), while no similar case was recorded among ATA-negative SH-DP. On the contrary, a significant number of these patients (33.9% of cases) showed a spontaneous normalization of TSH levels. The present data suggest that: a) DS per se seems to be a clinical risk condition in developing thyroid autoimmune diseases, b) SH represents a very common conditions in DP and in most cases it appears to be independent of the presence of circulating ATA, c) SH alone, that is in the absence of detectable ATA, does not seem to be predisposing condition to develop a clinically evident thyroid disease, as a spontaneous normalization of TSH levels is often observed. From the therapeutic point of view, it seems unlikely that L-thyroxine substitutive therapy could lead to some improvement in SH-DP in the absence of detectable ATA. A wait and see policy with frequent thyroid function screening could be considered adequate, thus avoiding chronic hormonal therapy at least in DP in whom TSH levels tend to spontaneously normalize. On the contrary, L-thyroxine should not be delayed in ATA-positive SH-DP due to the frequent evolution towards an overt thyroid disease.

The Italian National Survey for Prader-Willi syndrome: an epidemiologic study.

Twenty‐five medical centers and the Prader–Willi Syndrome (PWS) Association collaborated on a study which attempted to identify all people with genetically confirmed diagnosis of PWS living in Italy. Investigators of the participating centers contacted PWS subjects and/or their family, filled in a specially developed form with the required data and forwarded this information by email. The study identified 425 subjects (209 males and 216 females, between the ages of 0.4–46.7). Two hundred thirty‐eight patients had del15, 104 had UPD15, 4 demonstrated a translocation affecting chromosome 15 and 79 showed a positive methylation test. There were fewer subjects found over the age of 35, probably due to the low rate of identification of older PWS patients as well as the high mortality rate. There were a greater number of male children and adolescents with PWS whilst, amongst adults, there were more females. As expected, the majority of subjects with PWS were obese, especially in adult life. Nevertheless, it is noteworthy that 26% of patients aged between 6 and 17 were normal weight. A total of 212 subjects had received GH treatment, of which 141 were still receiving therapy, while the remaining 71 had stopped. In children and adolescents (233 cases), 89 subjects had never undergone GH therapy. Eighteen PWS patients had died in the past 20 years. Obesity‐related cardiovascular and respiratory diseases were the cause of death, both during childhood and after 18 years of age. Three children died suddenly whilst undergoing GH therapy. Respiratory infection and cardiac illness were the causes of death in two cases. There was no definitive cause of death found in the third case. Overall, there was no increase in number of deaths during GH treatment, suggesting that GH administration in patients with PWS, as a group, does not increase the risk of death.

Hyperthyroid-induced chorea in an adolescent girl

Hyperthyroidism is invariably accompanied by nervous system dysfunctions. Irritability, emotional lability and hyperkinesia are the signs and symptoms most frequently observed. Chorea or choreoathetosis are only rarely associated with hyperthyroidism. It is the purpose of this work to describe the case of a young girl in whom chorea was the main manifestation of thyrotoxicosis. The chorea receded and disappeared as the patient became euthyroid. Hyperthyroidism, therefore, is to be considered an unusual cause of chorea and every patient with choreiform movements should be examined also for thyroid function.

Hypertensive cardiomegaly caused by an aldosterone-secreting adenoma in a newborn

A case of primary hyperaldosteronism and cardiomegaly due to a unilateral adrenal adenoma in a newborn is presented. Some peculiarities, most likely in relation to the onset of the disease during fetal life were evident: plasma Cortisol was slightly increased before surgery, plasma renin activity was elevated 9 months after surgery and mineralcorticoid receptors remained suppressed 4 months after surgery. Unilateral adrenalectomy reversed both hypertension and cardiomegaly. We speculate that cardiomegaly was related to both hyperaldosteronism and hypertension and that individual factors are involved in the pathogenesis of cardiomegaly in hyperaldosteronism.

Growth hormone secretory pattern in non-obese children and adolescents with Prader-Willi syndrome

Abstract The aetiology of impaired growth hormone (GH) secretion in Prader-Willi syndrome (PWS) remains controversial due to the common occurrence of obesity. To further clarify whether suboptimal GH secretion in PWS is an artefact of excess weight, we evaluated both GH immunological activity and GH bioactivity after arginine administration in 23 non-obese PWS patients [seven females, aged 6.9±0.9 years, body mass index (BMI) SDS 0.63±0.26], in comparison with a control group of 32 healthy subjects, matched for age, gender and BMI (10 females, aged 7.9±0.3 years, BMI SDS 0.21±0.20). Serum GH concentration was measured with a time-resolved immunofluorometric assay (IFMA), while GH bioactivity was evaluated by the Nb2 cell bioassay. Serum IGF-I concentrations were measured by double-antibody RIA. GH mean peak after pharmacological stimulation was significantly lower in PWS individuals compared with controls when measured either by IFMA (6.05±1.23 μg/L vs. 23.7±1.06 μg/L, p<0.0001) or by Nb2 (6.87±0.55 μg/L vs. 12.88±0.19 μg/L, p<0.0001). Analysis of integrated GH secretion (AUC) confirmed that the PWS group differed significantly from the control subjects (387.9±76.1 μg/L/h vs. 1498.1±56.2 μg/L/h, p<0.0001); the same result was obtained when the GH rise after arginine administration was expressed as nAUC (278.2±53.3 μg/L/h vs. 1443.6±52.5 μg/L/h, p<0.0001). PWS patients had an IGF-I SDS significantly lower than those found in control subjects (p<0.0001). Subnormal IGF-I values were present in 19 PWS individuals (82.6%) and two healthy controls (6.2%). These findings are in agreement with the hypothesis that a complex derangement of hypothalamus-pituitary axis occurs in PWS.

Somatosensory pathway dysfunction in uremic children

Neurophysiological studies have shown defects in peripheral conduction in up to 75% of adults with end-stage renal disease (ESRD), though abnormalities of central conduction seem more variable. There are no comparable pediatric data. We therefore measured median nerve somatosensory evoked potentials (SEPs) in 10 children with ESRD, maintained by hemodialysis, who had no neurological signs or symptoms, and compared the results with those for age-matched controls. The latencies of N9, P14, N20 and P22, and interpeak latencies, N9-N20, N9-P14 and P14-N20, were not significantly different between the two groups (Students t test). However, the children with ESRD were significantly retarded in growth and when arm length was taken into account, a significant difference in peripheral conduction was revealed. There was no correlation with other indexes of disease severity (parathormone, aluminium, Hb, Na, K, Cl, BUN and creatinine). SEPs appear to reflect subclinical changes in peripheral conduction in sensory pathways in children with ESRD which are not correlated with other measures of disease severity.

A Multicenter Italian Study on Prader-Willi Syndrome

Prader-Willi Syndrome (PWS) is a relatively common disorder with an incidence estimated at about 1:10,000 (Holm, 1981) which represents the most common dysmorphic/genetic form of human obesity. The primary features of this condition include infantile hypotonia, failure to thrive, hypogonadism and developmental delay followed by development of obesity, Short stature, mental retardation and behavior problems. Mild dysmorphism is part of the Syndrome. About 59% of patients with PWS have an interstitial of the proximal long arm of chromosome 15 (Ledbetter et al, 1987).