Partial growth hormone deficiency and changed bone quality and mass in type I trichorhinophalangeal syndrome.

The trichorhinophalangeal syndromes (TRPSs) are syndromes due to haploinsufficiency of genes in the chromosome 8q24.12 region. Type I TRPS is characterized by typical facial features including sparse, brittle and fine hair, bulbous nose, and a long philtrum, as well as skeletal abnormalities. Growth retardation is a feature frequently found in these patients, who commonly are of short stature; however, only one case with growth hormone deficiency has been described in a TRPS patient and that patient had type II TRPS. Skeletal morphological abnormalities have been studied, but investigation of bone metabolism and quality in this kind of patients are not available. In this report we describe two cases of type I TRPS with partial growth hormone deficiency and significant bone mass and quality impairment, which was unresponsive to GH treatment.

Precocious puberty in a girl with floating-harbor syndrome.

Floating-Harbor syndrome (FHS) is a rare genetic disorder characterized by short stature, delayed bone age, mild to moderate mental retardation, speech problems, and peculiar craniofacial features. In these patients pubertal development has been reported to be normal. In this paper, we describe a girl with FHS who developed precocious puberty. FHS diagnosis was made at 2 years 5 months on the basis of peculiar clinical features. At 7 years 7 months, the girl began pubertal development; her height was 112.5 cm (-2.42 SDS) and pubertal staging was B2 PH2 AH1. LHRH test underlined LH and FSH peak values of 11.7 mIU/ml and 6.2 mIU/ml, respectively. Plasma levels of 17beta-estradiol were normal (8.5 pg/ml). Ophthalmological and neurological examinations, including nuclear magnetic resonance imaging of the brain, were normal. Treatment with gonadotrophin-releasing hormone analogue was begun. At 10 years 1 month, because of reduced height velocity, her growth hormone secretion was evaluated with diagnosis of neurosecretory dysfunction; hGH therapy was begun. The patient showed a good response to hGH treatment, reaching a normal adult height (156.1 cm; -1.20 SDS). This report suggests that, in patients with FHS, precocious puberty should be taken into consideration; in these patients, a careful endocrinological followup for the possible presence of growth and pubertal disorders is needed.

Thyroid hypoplasia of the left lobe in two girls affected by Williams syndrome.

Williams syndrome is a well-recognized disorder, having an incidence of 1 in 20,000 live births. However, thyroid function in these patients is rarely studied. This paper reports thyroid hypoplasia of the left lobe in two girls affected by Williams syndrome, suggesting that it may be a feature of this syndrome.

Undetectable serum IgA and low IgM concentration in children with congenital hypothyroidism.

Some studies suggest thyroid hormones may regulate the human immune system. In order to evaluate the effect of thyroid hormone deficiency on antibody production, we evaluated serum IgA and IgM concentrations in 83 children with congenital hypothyroidism (CH), diagnosed by neonatal screening. Patients were compared to two healthy, age-matched control groups. Patients with permanent CH had a significantly higher frequency of undetectable IgA concentrations (thyroid agenesis, P<10(-5); thyroid ectopy, P=0.013) and lower concentrations of IgA (thyroid agenesis, P<10(-6); thyroid ectopy, P<10(-5); dyshormonogenesis, P=0.0002) and IgM (thyroid agenesis, P=0.0002; thyroid ectopy, P<10(-6); dyshormonogenesis, P=0.0017) compared to control group. No difference was observed between patients with transient hypothyroidism and controls. A significant correlation was observed between serum IgA and IgM concentrations and fT4 levels. IgA and IgM deficiency is correlated with the severity of congenital hypothyroidism and may help to evaluate the duration and severity of thyroid hormone deficiency during prenatal life.

Thyroid function and morphology in patients affected by Williams syndrome.

OBJECTIVE: To evaluate the prevalence of abnormalities of thyroid function and morphology in a cohort of patients with Williams syndrome (WS). METHODS: Serum concentrations of free-T3, free-T4, TSH, thyroperoxidase antibodies (TPOA) and thyroglobulin antibodies (TgA), as well as ultrasonographic data, of 20 patients with WS (12 females and eight males), aged 1.7-34.9 years, were evaluated. RESULTS: Three cases (15%) of subclinical hypothyroidism were identified. Overt hypothyroidism was diagnosed in two cases (10%). Thyroid antibodies were negative in all patients. Fourteen patients (70%) showed thyroid hypoplasia involving the entire gland. In these patients, the left thyroid lobe appeared usually, but not significantly, reduced compared with the right thyroid lobe. One patient (5%) showed thyroid hemiagenesis. Only five patients (25%) showed a thyroid with normal volume, and of these five, one patient showed marked thyroid hypoplasia of the left lobe. In all WS patients with diagnosis of subclinical or overt hypothyroidism, thyroid hypoplasia was detected. No cases of subclinical or overt hypothyroidism were found in WS with normal thyroid volume. CONCLUSIONS: This study confirms the presence of alterations of thyroid function in WS and also suggests the frequent occurrence of abnormalities of thyroid morphology in these patients. Patients with WS should be monitored for thyroid function and a thyroid ultrasound screening should be considered, especially in those patients with changes in thyroid function.

Bone status evaluation with calcaneal ultrasound in children with chronic rheumatic diseases. A one year followup study.

OBJECTIVE: To evaluate at baseline and after one year the bone status in children with chronic rheumatic diseases (CRD) using quantitative ultrasound techniques. METHODS: We evaluated bone status in 67 children, 52 female, 15 male, age range 2.80 to 18.10 years; 46 juvenile idiopathic arthritis, 11 juvenile dermatomyositis, and 10 systemic lupus erythematosus. Twenty-seven of 67 patients were taking only nonsteroidal antiinflammatory drugs (NSAID), 11 were given NSAID and methotrexate (MTX), 15 were also receiving steroids (prednisone), and 14 patients were given steroids and alendronate. Broadband ultrasound attenuation (BUA) by bone was determined at the left calcaneus using two 12.5 mm diameter, 1 MHz transducers mounted in hand-held calipers linked to a pediatric contact ultrasound bone analyzer. RESULTS: At baseline in the whole patient group mean BUA values and Z scores were significantly lower than in controls: 41.84 +/- 21.64 vs 61.69 +/- 17.42 dB/MHz (p < 0.001); Z score -0.91 +/- 1.07 vs 0.09 +/- 0.62 in controls (p < 0.001). At one year followup in the patient group BUA values were significantly increased compared to baseline (BUA 46.43 +/- 21.51 dB/MHz; p = 0.002); no significant difference was found in Z score. The 15 children receiving steroids in addition to NSAID and MTX showed a decrease in BUA value at one year (NS), while Z scores were significantly reduced compared to baseline (-1.45 +/- 1.40 vs -1.08 +/- 1.11; p < 0.05). The 14 patients in the group receiving NSAID and MTX who also received alendronate showed significant increases in BUA (56.93 +/- 19.32 vs 44.21 +/- 15.67; p < 0.001) and Z score (-0.87 +/- 1.19 vs -1.56 +/- 0.82; p < 0.002). CONCLUSION: Contact ultrasound bone analysis at the calcaneus is a useful tool in the assessment and monitoring of bone status in children with CRD.

Changed bone status in human immunodeficiency virus type 1 (HIV-1) perinatally infected children is related to low serum free IGF-I.

INTRODUCTION: Adults and children affected by human immunodeficiency virus type-1 (HIV-1) infection show bone demineralization. Little is known about skeletal status using a quantitative high-frequency ultrasound (QUS) technique in these patients. OBJECTIVE: To evaluate the bone quality and assess the role of the IGF system in the bone metabolism and skeletal status of HIV-1 perinatally infected children. PATIENTS AND METHODS: Serum free and total IGF-I, IGFBP-3, serum osteocalcin level, urinary deoxypyridinoline concentration, spontaneous interleukin-6 (IL-6) release and broadband ultrasound attenuation (BUA) were evaluated in 44 prepubertal children who had perinatal HIV-1 infection. The patients were divided into two groups depending on the severity of their clinical condition: group 1 (23 children with no or mild clinical symptoms, mean age 8.0 +/- 2.9 years) and group 2 (21 children with severe clinical symptoms, mean age 8.58 +/- 2.47 years). Fifty-five healthy age- and sex-matched controls were analysed for comparison. RESULTS: Compared with group 1 and the controls, group 2 patients showed a significantly reduced BUA Z-score (P < 0.001), and significantly reduced concentrations of serum osteocalcin (P < 0.001) and urinary deoxypyridinoline (P < 0.001 and P < 0.05, respectively). Group 2 patients also showed significantly reduced serum free IGF-I (P < 0.001) and total IGF-I (P < 0.05) levels compared with the controls, but not with group 1. No statistically significant differences were found between the three groups with regard to IGFBP-3. Group 2 patients showed significantly higher spontaneous IL-6 release than group 1 patients and controls (P < 0.001). BUA Z-scores displayed a significant correlation with free IGF-I in group 2 (r = 0.96; P < 0.001), group 1 (r = 0.56; P = 0.005) and controls (r = 0.50; P < 0.001). CONCLUSION: Our study shows that only patients affected by perinatal HIV-1 infection with severe clinical manifestations present significant changes in bone quality and bone metabolism. Our data also show that impairment of skeletal status is related to reduction in serum total and free IGF-I. Children with perinatal HIV-1 infection, because of a considerable improvement in life expectancy, seem at great risk of not obtaining an optimal bone mass. A possible therapeutic approach should be considered in these children.

Association of low bone mass with vitamin d receptor gene and calcitonin receptor gene polymorphisms in juvenile idiopathic arthritis.

OBJECTIVE: To compare bone density with polymorphisms in the calcitonin receptor (CTR) and vitamin D receptor (VDR) genes in 50 patients with juvenile idiopathic arthritis and 80 matched controls. METHODS: Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry at the lumbar spine. Genomic DNA was isolated from EDTA blood samples by standard procedures. Polymerase chain reaction was performed using genomic DNA and 100 pmol of each oligonucleotide primer for VDR and CTR genes. Products from genomic PCR were digested by Alu I enzyme for CTR polymorphism and Fok I enzyme for VDR polymorphism. RESULTS: In the total population, higher prevalence of CC genotype (41.5%) for the CTR gene and FF genotype (59.8%) for the VDR gene was found, in agreement with data for Caucasian populations. No significant differences in distribution of CTR and VDR genotypes were observed between patients and controls. However, patients with TT genotype had lumbar BMD (L-BMD) that was lower in comparison to those with CC genotype (p = 0.04). For VDR gene polymorphism, we observed that patients with ff genotype had lower L-BMD in comparison with FF genotype (p = 0.02). Patients with heterozygosity for the 2 genotypes showed intermediate L-BMD. The differences in L-BMD among these groups did not seem to be related to corticosteroid therapy. CONCLUSION: Our data suggest that patients with particular VDR and CTR genotypes may be at higher risk to lose bone mass.