Longitudinal changes of bone density and bone resorption in hyperthyroid girls during treatment.

Low bone mineral density (BMD) and increased bone turnover are common features of untreated hyperthyroidism in adult patients. The effect of treatment on BMD is still controversial. BMD and bone metabolism in hyperthyroid children have not been thoroughly investigated. In the present study, we measured spinal and whole body BMD by dual-energy X-ray absorptiometry in a group of 13 girls (aged 5.0-14.9 years) at diagnosis of hyperthyroidism. The bone resorption rate was assessed by urine measurement of N-terminal telopeptide of type I collagen (NTX). Hyperthyroid patients have been studied longitudinally during treatment. BMD values and NTX urine concentrations have been also determined in 155 healthy Caucasian girls (aged 2.4-24.2 years). Spinal and whole body bone density measurements were significantly lower compared with healthy controls in untreated hyperthyroid girls, after correction for differences in age and anthropometric measurements (p

Hyperplastic pituitary gland, high serum glycoprotein hormone alpha-subunit, and variable circulating thyrotropin (TSH) levels as hallmark of central hypothyroidism due to mutations of the TSH beta gene.

Inheritable isolated central hypothyroidism (ICH) due to mutations of TSH beta gene has been reported in few patients. For this reason the diagnostic criteria are vague. The disorder is usually characterized by undetectable TSH levels, although low/normal serum TSH, depending on TSH measurement methods, has been documented in some patients. Here we report an Egyptian girl with ICH due to a novel nonsense mutation of the TSH beta gene (Q49X). She was referred at 75 days of age for severe clinical signs of hypothyroidism, whose central origin was documented by normal serum TSH, low free T(4) and free T(3) levels, impaired TSH response to TRH, absence of (99)Tc thyroidal uptake, and antithyroid autoantibodies. Ultrasound revealed a hypoplastic thyroid, whereas magnetic resonance imaging showed a hyperplastic pituitary. All other pituitary hormones, including PRL, were normally secreted. A diagnosis of idiopathic ICH was made, and substitutive L-T(4) treatment was started at 81 days of age. At the age of 7 yr the patient had normal thyroid hormone levels, but was severely mentally retarded. Interestingly, the sella computed tomography scan had completely normalized. At 8 yr of age the patient was reinvestigated after 6-week L-T(4) withdrawal. TSH values were highly variable depending on the measurement method used, whereas extremely high levels of circulating free glycoprotein alpha-subunit were recorded. Despite the fact that mutant TSH beta lacks 60% of the C-terminal amino acid sequence, it forms with the alpha-subunit a heterodimer with preserved immunoreactivity in some TSH measurement methods, but the mutant heterodimer is completely devoid of bioactivity. In conclusion, high circulating free glycoprotein alpha-subunit levels, variable TSH levels, and, possibly, hyperplastic pituitary gland are the hallmark of ICH due to mutations of the TSH beta gene.

Bone turnover in neonates: changes of urinary excretion rate of collagen type I cross-linked peptides during the first days of life and influence of gestational age.

New markers have been used to monitor the changes of bone turnover occurring during growth. Data on bone turnover rate during the perinatal period are, however, very scarce. In the present study we evaluated bone turnover rate, assessed by the measurement of urinary N-terminal telopeptide of type I collagen (NTx) concentrations, at different gestational ages, and we documented the trend of bone turnover rate occurring in the first days after birth. Urine samples were obtained from 83 healthy full term newborn infants, 16 preterm, and 17 infants of diabetic mothers (IDMs). The first miction after birth was collected. Urine samples were also collected 24 and 48 h after birth. NTx was measured by an enzyme-linked immunosorbent assay (Osteomark, Ostex International, Inc. Seattle, WA). The relationship between NTx at birth and all the other variables has been evaluated using multiple regression analysis. The changes of NTx excretion over time and the effect of the groups were studied by multivariate analysis of variance (MANOVA) for repeated measures. We found a remarkable association between gestational age and NTx concentrations at birth (R = 0.56; p < 0.00001). NTx concentrations showed a progressive decrement, reaching a nadir between the 38th and the 42nd week of gestation. The NTx concentrations changed significantly during the first 48 h of life in the three groups. Moreover, preterm infants had NTx excretion values at birth significantly higher than full term infants (p < 0.001), whereas NTx excretion rates of IDMs were not different from those of the other two groups of subjects. In conclusion, gestational age seems to be the major determinant of bone turnover in neonates; NTx excretion rate is higher before term, it slows in proximity of delivery, and it increases significantly during the first 48 h of life. Preterm infants have higher bone turnover rate than full term infants. NTx excretion rate of IDMs was comparable with those of the control subjects.

A novel germline mutation in the TSH receptor gene causes non-autoimmune autosomal dominant hyperthyroidism.

OBJECTIVE: Clinical and genetic investigations were undertaken in a case of familial hyperthyroidism, with onset of thyrotoxic symptoms varying between childhood/adolescence. METHODS: Automatic sequence analysis was carried out of the TSH receptor (TSHR) gene. Functional studies were undertaken of mutant TSHR in transient expression experiments in COS-7 cells including the evaluation of cAMP accumulation and of protein expression by flow cytometry, as well as the calculation of specific constitutive activity (SCA). RESULTS: In four affected cases, the age of onset of thyrotoxic manifestations of non-autoimmune origin varied between 5 and 18 years. The disease transmission was typically autosomal dominant. TSHR gene sequence revealed the presence of a germline heterozygous substitution at codon 597 leading to the novel mutation V597F. This residue is located in the 5th transmembrane domain of the receptor protein in a critical region for membrane targeting and signal transduction. Functional studies of the V597F mutant indicate an 11-fold increase in SCA, associated with a reduction in receptor protein expression on the cytoplasmic membrane. CONCLUSIONS: Description was made of a family with non-autoimmune autosomal dominant hyperthyroidism carrying a novel mutation of TSHR leading to the increment in specific constitutive activity. Factors that may influence the clinical expression of TSHR germline mutations are discussed.

Identification of a novel polymorphism in the fibronectin type II domain of the SEL1L gene and possible relation to the persistent hyperinsulinemic hypoglycemia of infancy.

SEL1L, a human gene located on chromosome 14q24.3-q31, is highly expressed in adult pancreas. It is proximal to D14S67 (IDDM11) a proposed type I diabetes susceptibility locus. Considering the organ specific expression of SEL1L, a fundamental role of SEL1L in pancreatic growth can be hypothesized. While screening for mutations in young diabetic patients, in children affected by persistent hyperinsulinemic hypoglycemia of infancy (PHHI), in patients with non-functional endocrine tumours and in over 100 control subjects, we identified a novel polymorphism (D162G) residing on the fourth exon of the gene. This exon encodes for the fibronectin type II domain and the nucleotide change involves a highly conserved amino acid. The D162G polymorphism induces a major change in the amino acid composition producing a possible disruptive role in collagen binding.

Spatial sustained attention: better focused than divided?

Visuospatial attention was studied using three different reaction time tasks in a sustained attention paradigm (N = 35). Contrasting with findings from a phasic attention paradigm, our results suggest an equal ability to divide or focus sustained attention in the left and right fields in simple RT, a Go/No go-task, and choice RT.

[Atrial natriuretic factor in normal newborn infants and its effects on kidney function in anoxic syndrome and respiratory distress]. / Studio sul comportamento del fattore atriale natriuretico nei neonati normali e suoi effetti sulla funzionalità renale in corso di sindrome anossica e di distress respiratorio.

The Authors have studied 26 newborns suffering from anossic syndrome and/or respiratory distress. In them are valued as well as the renal function, also the behaviour of atrial natriuretic factor (F.A.N.). As a group of control 25 healthy and to term newborns were studied. In all subjects studied, but more specifically in the anossic, it became evident a net increase of F.A.N., which however was within the normal ranges about the 15th year of life. The Authors conclude that in normal newborn this behaviour of F.A.N. reflects the important circulation modification which is certified after birth, whereas in pathological newborns, in whom 69% of cases a functional renal failure is present, the increase of F.A.N. is not without significance in the shortening of time of re-establishment of renal function.

[Elevated atrial natriuretic peptide (ANP) levels and normotension in Bartter's syndrome in childhood]. / Elevati livelli di peptide atriale natriuretico (ANP) e normotensione nella sindrome di Bartter dell'infanzia.

The authors describe a case of Bartter's syndrome, a variety of disease in the newborn, and they point out the most specific of the disease symptoms, that is the normal PA in presence of elevated plasma renin activity. So it was necessary to determine the ANP, the values of which, controlled for a period of 18 months, appeared above the normal ones. The authors conclude that this date would better explain the apparently contradictory date of the normotension.

[Low levels of somatomedin C and short stature in the Silver-Russell syndrome]. / Bassi livelli di somatomedina C e ipostaturalità nella sindrome di Silver-Russell.

The authors describe one case of Silver-Russell syndrome, emphasized the etiopathogenetic aspects connected to it. As regards the short stature, they have proved that the syndrome is related to low levels of somatomedin C (SmC). Moreover, they emphasized that ambiguous genitalia gets more and more frequently a peculiar features of syndrome.

[Growth deficiency and renal tubular acidosis. The possible etiopathogenic mechanisms]. / Deficit di crescita ed acidosi tubulare renale. Possibili meccanismi etiopatogenetici.

The authors have studied two cases of renal tubular acidosis in 2 children underlining that a possible defective mechanism of growth is based on alteration of the receptors of somatomedine C to level of cartilage. The deficit of receptors could be the consequence of the alterations of the acidosis on cartilage.

[Prevention of acute hypertensive encephalopathy in the course of acute post-streptococcal glomerulonephritis in children: considerations in 31 cases]. / La prevenzione dell'encefalopatia acuta ipertensiva in corso di glomerulonefrite acuta post streptococcica (GNAPS) nel bambino: considerazioni su 31 casi.

The authors analysed 31 cases of an acute hypertensive glomerulonephritis. The antihypertensive efficacy of two medicines: a vasodilator (dihidralazine) and a diuretic (Furosemide) was underlibed an these patients. Their efficacy was evident not only in the stabilization of P.A. around normal values on three days, but also on the disappearance of signs of on hypertensive encephalopathy whereas these ones were present.

[Potential diagnostic role of renal sonography in acute post-streptococcal glomerulonephritis (APSGN) "with minimal urinary signs"]. / Possibile ruolo diagnostico dell'ecografia renale nella Glomerulonefrite acuta post-streptococcica (G.N.A.P.S.) "a segni urinari minimi".

The Authors studied 8 patients with an average age of eight and a half affected with G.N.A.P.S. with "minimum urinary signs". A renal ecography carried out in a diagnostic approach showed in 7 cases out of 8 the constant presence of an increased volume of the kidney, associated with hyperecogenicity and 3rd degree thickening of the cortical. They conclude that this information could be of great use for a rapid diagnostic orientation in forms of G.N.A.P.S. "with minimum urinary signs".

[Fetal polyuria and decrease of electrolytes in amniotic fluid as principal markers of neonatal Bartter's syndrome]. / La poliuria fetale e la diselettrolitemia del liquido amniotico quali principali markers della varietà neonatale della sindrome di Bartter.

The above mentioned after a careful investigation of the modern pathogenic aspects of Bartter's syndrome, evaluated the markers that are useful for the prenatal diagnosis of Bartter's syndrome, they pointed out, as in both cases the presence of polyhydramnios not associated with ecographically detectable fetal malformations, elevated chloride in the amniotic fluid, accompanied in one case by increased levels of aldosterone, in the other case by the increase of K, as being reliable markers for the prenatal diagnosis of these conditions.

[Parasitic arthritis: a case report]. / Le artriti parassitarie: descrizione di un caso clinico.

In Protozoan-type infections muscular and/or articular manifestations are not unusual. They are directly correlated to the presence of the parasite in the organism. In such cases a good diagnostic support can be given by the demonstration of the parasitic infection, the inefficacy of the classical therapy with FANS or steroids, and the good results obtained with a specific antiparasitic therapy. The most significant data that emerge from this description regard the possibility that when an arthritis or an arthralgia cannot be defined a parasitic infection has also to be excluded.

[Variations in renal hemodynamics during acute renal insufficiency in anoxic neonates]. / Studio delle modificazioni dell'emodinamica renale in corso di insufficienza renale acuta nel neonato anossico.

The purpose of this study is to verify if the increase of renal resistance, along with the consequent reduction of glomerular filtrate, and the activation of renina-angiotensin system, could be attributed to not only neonatal acute hypoxia but to other factors as well. These factors could provoke an increase in renal vascular resistance (R.V.R.), a reduction of renal blood flow (R.B.F.) and renal glomerular filtrate (R.G.F.) condition. These components are present in angiotensin as well as in endothelin (ET1), a potent peptide from vascular endothel with vasoconstricting action and whose secretion increases during hypoxia. The Authors have studied and compared two groups of newborns. The first group of newborns was affected by perinatal asphyxia or hypoxia of variable seriousness. It included 24 newborns with gestational age between 37 and 41 weeks and with a birth weight between 3.200 gms and 3.500 gms. The second, control group, was made of an identical number of newborns of the same gestational age with a weight adequate to the birth age. The dosage of the ET1 was evaluated on the plasma, using the RIA method. The diagnostic criteria for this evaluation included clinical and biohumoral evidence (tab. 1). Between the two groups, group 1 with anoxic syndrome showed the more intense increase of ET1. This increased is due to either an increase value of plasmatic creatinine that is present in normal situations or in physiopathologic role played by the ET1 in course of acute renal failure after asphyxia.

[Does the therapy with indomethacin interfere with growth in Bartter's syndrome in childhood?]. / La terapia con indometacina interferisce con l'accrescimento nella sindrome di Bartter dell'infanzia?

The authors describe a new-born form of Bartter's syndrome treated for about 6 years with Indomethacin in a quantity of 2 mg/Kg/die except short periods, during which it was given triamterene in a quantity of 2 mg/Kg/die. While with the first medicine the growth of height has had an average increase of about 9 cm a year, with the second one there hasn't been any result neither on growth nor on the rest of symptomatology. The A.A. on the base of recent experimental data think that the deficiency of height could be due to a scanty affinity of peripherical receptors and SmC, that could be removed from the provision of Indomethacin.

[Determination of the urinary secretion of beta 2-microglobulin combined with sequential renal scintigraphy using H123 for the early diagnosis of pyelonephritis in children]. / La determinazione dell'escrezione urinaria della beta 2 microglobulina associata alla scintigrafia renale sequenziale con H123 per la diagnosi precoce di pielonefrite nell'infanzia.

The acute pyelonephritis diagnosis in the infancy is often known very late or it is even underestimate that's why the general adopted criteria normally give no a certainty of the exact centre and the real damage entity. For this reason the authors have adopted a diagnostic protocol, which is based on the association of the urinary excretion dosage of beta 2 microglobulin, with sequential renal scan with Hippuran 123. In cases when the urinary beta 2 microglobulin was increasing, we could check a correspondent alteration of scintigraphic secretory phase. All that has permitted, in whale cases, of establishing with precision and at the right time the centre and the renal damage entity.

[Evaluation of kidney damage in neonatal anoxia syndrome: a 1-year follow-up]. / Valutazione del danno renale in corso di sindrome anossica neonatale: follow-up di un anno.

In thirty-three newborns with anoxic syndrome was valued the renal injury making use of usual parameters of renal function (Blood urea nitrogen, creatinine, FeNa, Clcr) and furthermore the rate of urinary excretion of beta 2-microglobulin, a marker of tubular damage. All the parameters at the beginning of follow-up were altered. Further monitoring of these showed that BUN, creatinine, FeNa, Clcr were normalized in a short time. Differently beta 2-microglobulin was altered up to the end of follow-up in thirty-one newborns; the values were much lower than original. These results show an high incidence of tubular suffering in the ischemic-anoxic syndrome and a tendency to protract in the time.