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Biallelic loss-of-function mutations of AIRE cause the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) syndrome. However, single nucleotide mutations may cause a milder phenotype. In this paper, we describe an unusual and mild phenotype in a mother and her two children (son and daughter) who carry a rare heterozygous mutation of AIRE.The son presented with alopecia and subclinical hypothyroidism due to Hashimoto's Thyroiditis (HT); the daughter had alopecia, vaginal mycosis, stomach pains and subclinical hypothyroidism due to HT; and the mother had alopecia, vaginal mycosis and stomach pains. Organ- and non-organ-specific autoantibodies were evaluated as well as antibodies against interleukin-17A, -17F, -22 (IL-Abs) and interferon -α and -ω (IFN-Abs). The organ- and non-organ-specific autoantibodies screening was negative in the son, while the daughter was positive for liver-kidney microsomal antibodies (LKMAbs) and the mother was positive for glutamic acid decarboxylase antibodies (GADAbs). Daughter and mother were also positive for IFN-Abs. Analysis of the AIRE gene identified a rare heterozygous R203X mutation in all three family members.We describe for a first time a family with heterozygous R203X AIRE mutation causing an APECED-like condition, as confirmed by presence of IFN-Abs. The unusual mild phenotype should be reassuring for the patients and assist in their clinical management.

Pediatric thyroid diseases cover a large spectrum of congenital and acquired forms, ranging from congenital primary or central hypothyroidism, autoimmune thyroid disease, iodine deficiency, rare genetic defects of thyroid hormone action, metabolism and cell membrane transport to benign nodules and malignant tumors. The previous 15 papers of the textbook Paediatric Thyroidology gave a systematic overview of the current knowledge and guidelines on all these diseases. In this final paper, the authors collected a series of patient histories from their clinics illustrating frequently encountered clinical problems and providing key learning points and references to each case. Although not fully comprehensive, it aims at providing relevant clinical knowledge on thyroid diseases of the neonate, the child, and the adolescent.

In obese children, both spontaneous and stimulated growth hormone (GH) secretion are impaired but a normal or increased height velocity is usually observed. This study was undertaken to explain the discrepancy between impaired GH secretion and normal height velocity. We evaluated the GH bioactivity (GH-BIO), GH serum level by immunofluorimetric assay (GH-IFMA), insulin-like growth factor-I (IGF-I), IGF-II, and IGF binding protein-1 (IGFBP-1), IGFBP-2, and IGFBP-3 in 21 prepubertal obese children (13 boys and eight girls) aged 5.7 to 9.4 years affected by simple obesity and in 32 (22 boys and 10 girls) age- and sex-matched normal-weight controls. The results were as follows (obese versus [v] controls): GH-IFMA, 4.84 +/- 3.54 v 23.7 +/- 2.04 microg/L (P.001); GH-BIO, 0.60 +/- 0.45 v 1.84 +/- 0.15 U/mL (P.001); IGF-I, 173.8 +/- 57.2 v 188.6 +/- 132.6 ng/mL (nonsignificant); IGF-II, 596.1 +/- 139.7 v 439.3 +/- 127.4 ng/mL (P.001); IGFBP-1, 23.25 +/- 14.25 v 107 +/- 165.7 ng/mL (P.05); IGFBP-2, 44.37 +/- 62.18 v 385.93 +/- 227.81 ng/mL (P.001); IGFBP-3, 3.31 +/- 0.82 v 2.6 +/- 0.94 microg/mL (P.05); and IGFs/IGFBPs, 1.32 +/- 0.32 v 1.07 +/- 0.34 (P.05). In conclusion, in prepubertal obese children, not only immunoreactive but also bioactive GH concentrations were low. In these subjects, therefore, nutritional factors and insulin may contribute to sustain normal growth also by modulating several components of the IGF-IGFBP system.

Increased fat mass, decreased lean mass, muscular mass and bone mineral density are characteristic of the body composition in GH deficiency, GH treatment reverses these abnormalities. Body composition was determined in 20 young adults with GHD diagnosed in childhood, whose GH treatment was stopped 1 year earlier. Reevaluation of GH secretion in these patients showed that 12 remained GH deficient (confirmed GHD) while eight recovered normal GH secretion (transient GHD). One year after stopping the GH treatment, patients with confirmed GHD showed an increased fat mass as compared with value at the end of the treatment; in addition a decreased bone mineral content was observed in the patients with low physical activity. There was no increased fat mass in transient GHD; however, these patients presented with low bone mineral content, as previously reported in adults with history of delayed growth and adolescence.

La fonction somatotrope a la periode neonatale est caracterisee par une discordance entre des taux eleves d'hormone de croissance (GH) et des taux bas d'IGF I. Cette etude a ete realisee pour tenter d'expliquer cette discordance et examiner notamment si elle peut etre le resultat d'une activite biologique diminuee de la GH. Nous avons determine les taux de GH bioactive (GH-BIO), de GH dosee par methode radio-immunologique classique (GH-RI), de proteine de liaison de la GH (GHBP), d'IGF I et de proteine de liaison de l'IGF (IGFBP) chez 27 prematures et 20 nouveau-nes a terme complet (NT), a j4 et pendant le premier mois de vie. A j4, la GH-RI et la GH-BIO etaient augmentees chez tous les nouveau-nes (p < 0,05) par comparaison aux temoins prepuberes; les taux de GHBP et IGF I etaient bas et positivement correles a l'âge gestationnel (p < 0,001). Les taux de GHBP et d'IGF I etaient positivement correles (p < 0,001). Les taux d'IGFBP-1 et l'IGFBP-2 etaient eleves et negativement correles a l'âge gestationnel (p < 0,005). Les taux d'IGFBP-3 etaient dans les limites des valeurs des enfants prepuberes et positivement correles a l'âge gestationnel (p < 0,005). Pendant le premier mois de la vie, les taux de GH-RI et de GH-BIO ont significativement diminue chez tous les nouveau-nes (p < 0,005), alors que I'IGF I augmentait chez les nouveau-nes prematures (p

A total of 478 patients, mean age 15.5 (3.6-25.3) years, suffering from Turner's syndrome, were studied in order to determine the frequency of autoimmune thyroiditis, which is defined as the presence of antithyroid antibodies (AT-Ab) and typical ultrasound findings. We found 106 (22.2%) patients positive for AT-Ab and of those 49 (10%) also had positive ultrasound findings, and were therefore considered to be affected by thyroiditis. This frequency is significantly higher (p < 0.001) than that seen in the normal population. Goitre was detected on clinical examination in only 16 (33%) and by ultrasound in 19 (39%) patients. Hormonal evaluation showed that 17 patients were euthyroid, 27 had compensated hypothyroidism, 2 were hypothyroid and 3 were in a hyperthyroid phase. Clinical signs or symptoms of hypothyroidism were absent in all hypothyroid patients. In patients with thyroiditis, neither a higher frequency of malformations and autoimmune diseases nor a correlation with karyotype, oestrogens or growth hormone therapy was found.Antithyroid antibodies, thyroiditis, thyroid hormones, thyroid ultrasound, Turner's syndrome G Radetti, Department of Paediatrics, Regional Hospital of Bolzano, via L Boehler 5, 39100 Bolzano, Italy

A total of 1419 children with type 1 diabetes mellitus was investigated in order to assess the true frequency of Hashimoto's thyroiditis (HT), diagnosed by microsomal and/or thyroglobulin autoantibodies, by ultrasound and in many cases also by fine needle biopsy. According to these criteria, 55 cases (3.9%) of HT were identified, a number significantly higher (P0.0001) than the distribution reported in the normal paediatric population. No typical antibody pattern was seen prior to the onset of HT, nor was an antibody threshold level found which could have been diagnostic for this disease. Patients with subclinical hypothyroidism were treated with L-thyroxine and were investigated regarding the behaviour of anti-thyroid autoantibodies; however, no significant changes were seen. The data showed a high frequency of HT in diabetic children, and therefore we recommend that children with type 1 diabetes mellitus should be screened for thyroid autoantibodies and those positive should undergo periodic thyroid function testing.

Non-autoimmune hyperthyrotropinemia has been previously reported among children born prematurely. The aim of this study was to follow up their thyroid function, volume, and structure and to investigate the relationship with growth, IGF-I, lipid profile, and insulin sensitivity.Seventy-two children born prematurely (33.2±2.2 weeks), 26 appropriate (AGA) and 46 small for gestational age (SGA), were evaluated at the age of 7.6±2.3 yr (time 1) and at the age of 11.4±2.3 yr (time 2). We also measured TSH, free T(3) (fT(3)), free T(4) (fT(4)), thyroperoxidase antibodies (TPO-Ab), thyroglobulin antibodies (TG-Ab), thyroid ultrasound, auxological parameters, lipid profile, glucose, and insulin level.In the AGA group TSH was similar in both times (2.7±1.0 vs 3.0±0.9 mU/l) and above the upper normal limit in 4 (15.4%) subjects at time 1 and in 6 (23.7%) subjects at time 2 (ns). In the SGA group, TSH was similar in both times (2.8±1.2 vs 2.5±1.0 mU/l) and above the upper normal limit in 11 (23.9%) subjects at time 1 and 5 (10.8%) subjects at time 2 (ns). fT(4) and fT(3) were always normal and TPO- and TG-Ab absent. Thyroid volume increased progressively, but significantly only in the AGA group (p=0.0005). The thyroid structure was always normal and there was no influence on the growth and the biochemical profile.Some ex-premature babies show a mild and variable thyroid dysfunction, which does not seem to evolve toward an overt thyroid dysfunction.

Alterations in thyroid function and structure have been reported in obesity. Function reverses to normal after weight loss, but nothing is known about structure.To evaluate the effect of weight loss on thyroid function and structure in obese children.The study was conducted in 72 overweight and obese children. Measurement of free T(3) (fT(3)), free T4 (fT(4)), TSH, antithyroid- antibodies and a thyroid ultrasound was performed at the beginning (phase 1) and after a period of 1.8±1.0 yr of lifestyle intervention (phase 2).Height SD score (SDS), body mass index SDS, total fat mass did not change from phase 1 to phase 2. Percentage of fat free mass decreased significantly (p0.05). Waist/height ratio decreased (0.6±0.1 vs 0.5±0.1; p0.05) as well as waist/hip ratio (0.9±0.1 vs 0.8±0.1; p0.05). In phase 1, TSH was 2.8±1.7 mU/l; in phase 2, it was 2.2±0.9 mU/l (p0.05); 17.2% of children showed a TSH level above the normal range (3.6 mU/l) in phase 1, and 6.2% in phase 2 (p0.05). fT(4) was 10.8±2.2 pg/ml in phase 1 and 10.7±1.9 pg/ml in phase 2. fT(3) was 4.4±1.3 pg/ml (phase 1) and 3.9±1.1 pg/ml (phase 2) (p0.05). Thyroid volume was -0.5±0.8 SDS (phase 1) and -0.5±1 SDS (phase 2). A non-significant improvement in thyroid structure was observed.In conclusion, healthier lifestyle improves body composition, thyroid function, and structure.

Objective: The aim of the study was to determine the iodine status in Albania following 11 yr of iodine prophylaxis and to evaluate factors influencing the outcome. Design: Eight hundred and forty children, aged 6–13 yr, living in 4 different regions and 365 pregnant women living in the same areas, were enrolled for the study. The prevalence of goiter was assessed by palpation and ultrasound imaging and the urinary iodine and the iodine concentration in the salt of different commercial brands were evaluated. Presence of goiter in the family and their eating habits were also investigated as well as the use of iodized salt in the household. Main outcome: In children, the prevalence of goiter was 57.6% by palpation and 24.4% by ultrasound imaging. Median urinary iodine was 86.2 μg/l, with pronounced geographical variations (range 3.52–1079 μg/l). In particular, 29.1 % of the children had urinary iodine

Bone development is a key process in the growing child. It is, therefore, of paramount importance to survey this process, which is characterized by increasing length and size of the bone together with its progressive mineralization. The bone status can be evaluated by different techniques, each of them having its pros and cons. Furthermore, it should be underlined that the results of bone assessment depend not only from the employed technique but also from the auxological characteristics of the subjects. It is, therefore, the aim of this review to examine the characteristics of the various methods of bone evaluation, such as dual energy X-ray absorptiometry (DEXA), peripheral quantitative computed tomography (pQCT), ultrasound and metacarpal index and to explain how changes in bone structure and geometry may influence the results.

Altered frequency of the menstrual cycle accompanied by pain are manifestations of functional anomalies of the female reproductive system. These symptoms require prompt and accurate diagnosis and therapy to prevent a chronic condition that can seriously disturb the adolescent's psychic well being. The most common anomalies of the menstrual cycle and the causes of altered cycle frequency are outlined, as are useful criteria for diagnosing premenstrual syndrome dysmenorrhea and for distinguishing the causes and alterations in frequency and amount of menstrual discharge from other disturbances, including amenorrhea and abnormal uterine bleeding. The treatment of dysmenorrhea and quantitative alterations of the menstrual cycle is the focus of this article.

Hyperparathyroidism is a disease characterized by hypercalcemia with hypophosphoremia resulting from increased secretion of parathyroid hormone (PTH). The disease may be divided into 3 forms: a) primary, b) secondary, c) tertiary (secondary refractory form). Primary hyperparathyroidism is rare in children; hyperplasia is more frequent during the early years of life (neonates and infants) and is difficult to distinguish from adenoma in children. The disease may be asymptomatic; elevated calcemia levels (1213.5 mg/dl) are accompanied by anorexia, asthenia and persistent stipsis; severely elevated concentrations (13.5 mg/dl) are accompanied by nausea, vomiting, polyuria due to osmosis, with dehydration and progressive onset of lethargy, stupor and coma. Osteopenia or osteitis fibrosa cystica may be present due to augmented bone resorption. Height and weight increases are altered due to anorexia and dehydration. Differential diagnosis includes iatrogenic causes of hypercalcemia (excessive vitamin D intake, prolonged immobilization, etc.) and idiopathic familial hypercalcemia. Emergency treatment is required in cases of extremely elevated hypercalcemia (Ca13.5-14 mg/dl), due to risk of injury to the heart, the central nervous system, the gastrointestinal tract and the kidneys. The 4 cardinal points of treatment are: hydration, calciuresis, inhibition of bone calcium resorption, treatment of the cause underlying hyperparathyroidism. Secondary hyperparathyroidism is found in cases where chronic hypocalcemia is present, particularly in chronic renal failure, untreated deficiency rickets, chronic intestinal malabsorption, hepatobiliary disease, types I and II vitamin D-dependent rickets, tubular acidosis or Fanconi's syndrome. The tertiary form is distinguished by the autonomous nature of the parathyroid glands which have become hypertrophic/hyperplastic due to uncontrollable, chronic severe renal failure. It can also be of iatrogenic origin due to excessive intake of inorganic phosphates in familial hypophosphatemic rickets or chronic vitamin D deficiency.

The aim of the study was to investigate the influence of an acute administration of 22-kDa hGH (22-kDa GH) on 22-kDa GH and 20-kDa GH serum levels, biological activity of GH (Nb2-GH) and on 22-kDa/20-kDa GH ratio, in order to verify whether the assessment of the GH isoforms could be a potential tool for diagnosing GH abuse. Twenty-eight children (21 M, 7 F), age 10.4 +/- 0.8 y, affected by idiopathic isolated GH deficiency and 10 children (8 M, 2 F), age 9.2 +/- 2.3 y affected by constitutional growth delay, were evaluated. After an overnight fast, a basal blood sample was obtained between 8 a.m. and 9 a.m. and a dose of 22-kDa GH was then administered subcutaneously (0.1 U/Kg). Blood was drawn after 2, 4 and 6 h, for the evaluation of 22-kDa GH, Nb2-GH and 20-kDa GH serum levels. Similar results were obtained in patients and controls: a significant rise, although of variable amplitude, of 22-kDa GH and Nb2-GH was found (p < 0.001) and the maximum peak was detected after 4 h in the majority of subjects. No acute changes in 20-kDa GH serum levels were observed. The 22-kDa/20-kDa GH ratio increased progressively, due to the rising levels of 22-kDa GH. A positive correlation was seen between 22-kDa GH and Nb2-GH levels at baseline and at 2, 4 and 6 h (p < 0.014, r = 0.99). Since in normal subjects the ratio of endogenous 22-kDa GH and 20-kDa GH is constant, an altered ratio of 22-kDa/20-kDa GH is highly suggestive of GH abuse. The short period of time available for the evaluation however (within 3 h from GH injection), severely limits this investigational tool in athletes.

Summary background Osteoprotegerin (OPG) is a secreted member of the TNF receptor superfamily. OPG is made by osteoblastic cells and is expressed in a wide variety of cell and tissue types. It acts as a decoy receptor by binding the receptor activator of nuclear factors kB (RANKL) and preventing RANKL-induced osteoclast formation and differentiation. Numerous cytokines and hormones (TGF-β, PTH, vitamin D, glucocorticoids and oestrogens) exert their effects on osteoclastogenesis by regulating the production of OPG. patients and methods In the present study we compared serum OPG and RANKL concentrations in a group of normal children (1–14 years old) with those of pair-aged children affected by different diseases [Turner's syndrome (TS), early/precocious puberty (PP) and rheumatoid arthritis (RA)]. OPG and RANKL concentrations were measured by an enzyme immunoassay method using a commercial kit. results Mean (± SD) OPG level in normal children was 4·05 ± 1·63 pmol/l with no difference between males and females. OPG values in children 1–4 years old (5·87 ± 2·22 pmol/l) were significantly higher than in children 4–14 years old (3·55 ± 0·97 pmol/l). OPG levels in children with RA were significantly higher than in controls (6·33 ± 2·57 pmol/l vs. 4·05 ± 1·63 pmol/l, P 4 years are similar to those present in young adult men, with higher levels in the first 4 years of life. Although the meaning of the alterations of OPG levels observed in pathological conditions is still obscure, they appear potentially interesting in view of a key role played by this protein in bone homeostasis.

In 129 children, aged 12.6 +/- 3.8 years, affected by type 1 diabetes mellitus, the levels of dehydroepiandrosterone sulfate (DHEAS), cortisol, T3, fT3, T4, fT4, rT3, TSH, cholesterol, and triglycerides were evaluated and compared with those of a control group of 458 healthy age-matched children. The results were also correlated with hemoglobin HbA1C. The DHEAS-standard deviation score (DHEAS-SDS; -0.36 +/- 0.77) was significantly different from zero in diabetic children, while the cortisol serum level was higher than in control subjects (485 +/- 94 vs 359 +/- 132 nmol/l). Moreover, the DHEAS-SDS and DHEAS-SDS/cortisol ratio correlated negatively with HbA1c. Diabetic patients also showed lower T3 values (2.22 +/- 0.4 vs 2.32 +/- 0.3 nmol/l) and a higher rT3/T3 ratio (0.17 +/- 0.09 vs 0.15 +/- 0.05) than controls. There was a negative correlation between T3 and HbA1C. Cholesterol (4.77 +/- 1.08 vs 4.51 +/- 0.76 mmol/l) and triglycerides (0.82 +/- 0.53 vs 0.63 +/- 0.37 g/L) levels were higher in diabetic children and positively correlated with HbA1c, but not with DHEAS-SDS. We can therefore conclude that diabetes, particularly if poorly controlled, tends to induce a dissociation of cortisol and DHEAS secretion and a low T3 syndrome, similar to that seen in other illnesses.

Thyroid hormones have been shown to be absolutely necessary for early brain development. During pregnancy, both maternal and foetal thyroid hormones contribute to foetal brain development and maternal supply explains why most of the athyreotic newborns usually do not show any signs of hypothyroidism at birth. Foetal and/or neonatal hypothyroidism is a rare disorder. Its incidence, as indicated by neonatal screening, is about 1:4000. Abnormal thyroid development (i.e. agenesia, ectopic gland, hypoplasia) or inborn errors in thyroid hormone biosynthesis are the most common causes of permanent congenital hypothyroidism. Recent studies reported that mutations involving Thyroid Transcriptor Factors (TTF) such as TTF-1, TTF-2, PAX-8 play an important role in altered foetal thyroid development. Deficiency of transcriptor factor (Pit-1, Prop-1, LHX-3) both in mother and in the foetus represents another rare cause of foetal hypothyroidism. At birth clinical picture may be not always so obvious and typical signs appear only after several weeks but a delayed diagnosis could have severe consequences consisting of delayed physical and mental development. Even if substitutive therapy is promptly started some learning difficulties might still arise suggesting that intrauterine adequate levels of thyroid hormones are absolutely necessary for a normal neurological development. Placental transfer of maternal antithyroid antibodies inhibiting fetal thyroid function can cause transient hypothyroidism at birth. If the mother with thyroid autoimmune disease is also hypothyroid during pregnancy and she doesn't receive substitutive therapy, a worse neurological outcome may be expected for her foetus. Foetal and/or neonatal hyperthyroidism is a rare condition and its incidence has been estimated around 1:4000-40000, according to various authors. The most common causes are maternal thyroid autoimmune disorders, such as Graves' disease and Hashimoto's thyroiditis. Rarer non autoimmune causes recently identified are represented by TSH receptor mutations leading to constitutively activated TSH receptor. Infants born to mothers with Graves' history may develop neonatal thyrotoxicosis. Foetal/neonatal disease is due to transplacental thyrotrophin receptor stimulating antibodies (TRAb) passage. It's extremely important recognizing and treating Graves' disease in mothers as soon as possible, because a thyrotoxic state may have adverse effects on the outcome of pregnancy and both on the foetus and newborn. Thyrotoxic foetuses may develop goitre, tachycardia, hydrops associated with heart failure, growth retardation, craniosynostosis, increased foetal motility and accelerated bone maturation. Neonatal Graves' disease tends to resolve spontaneously within 3-12 weeks as maternal thyroid stimulating immunoglobulins are cleared from the circulation but subsequent development may be impaired by perceptual motor difficulties. Hashimoto's thyroiditis is a very common autoimmune thyroid disease. In presence of maternal Hashimoto's thyroiditis, there are usually no consequences on foetal thyroid, even if antiTPO and antiTg antibodies can be found in the newborn due to transplacental passage. However there are some literature reports describing foetal and neonatal hyperthyroidism in the affected mothers' offspring.

To investigate the frequency and the effects of various degrees of maternal thyroid dysfunction in the first trimester of pregnancy, before the onset of fetal thyroid function, on psychomotor and audiological outcome of the offspring.In a cohort of 691 pregnant women, undergoing thyroid screening between the 8th and 10th gestational week, eight were found to have a subclinical form of hypothyroidism and one was frankly hypothyroid. Treatment with L-thyroxine was started soon after diagnosis was made. Their nine offspring had a psychomotor and audiological assessment at the age of nine months. Psychomotor development was evaluated with the Brunet-Lèzine test, while audiological function was assessed with auditory brainstem responses (ABR's).Psychomotor developmental quotients were not different in patients and controls (99 +/- 6 vs 101 +/- 4). Regarding ABR pattern, there were no significant differences between patients and controls. Moreover, no correlation was found between maternal fT4 and psychomotor as well as audiological outcome in the offspring.These findings are reassuring, since various degrees of maternal thyroid dysfunction in early pregnancy seem to have no adverse effects on the psychomotor and audiological outcome of the offspring up to nine months of age. A longer follow-up however is needed before definitive statements can be made.

We report the intra-uterine and postnatal thyroid status of a newborn, whose mother, affected with Hashimoto's thyroiditis superimposed on a previous Graves' disease, again became hyperthyroid during the third trimester of pregnancy. The mother had very high levels of anti-thyroid auto-antibodies, including TSH receptor auto-antibodies (TRAb) measured as TSH-binding inhibiting auto-antibodies (TBIAb). In order to exclude fetal thyroid dysfunction due to passive transplacental transfer of TRAb, fetal blood samples were obtained by cordocentesis at 21, 27 and 32 weeks of gestation. A transplacental transfer of TRAb was already seen at 21 weeks, but no alteration of fetal thyroid function was present at that time. In the following weeks, a rise in TRAb and circulating thyroid hormones was observed both in the fetus and mother, accompanied by overt hyperthyroidism in the mother and by growth retardation in the fetus. At birth, TRAb were shown to have stimulating activity both in the newborn and mother. This report documents the early transplacental passage of thyroid auto-antibodies and underlines the importance of close follow-up of pregnant women with auto-immune thyroid disorders.

The case of a 17-year-old male with isolated hypersecretion of dehydroepiandrosterone sulphate (DHEAS) is described. Cushing syndrome, congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency, an androgen producing adrenal tumour, and elevated plasma DHEAS due to an increased renal threshold were excluded. Selective renal vein catheterization confirmed bilateral, isolated adrenal DHEAS hypersecretion. The dexamethasone suppression suggests a functional nature of this alteration. This condition has to be considered in the differential diagnosis of excessive adrenal androgen production in males, or of hirsutism in females.

A total of 478 patients, mean age 15.5 (3.6-25.3) years, suffering from Turner's syndrome, were studied in order to determine the frequency of autoimmune thyroiditis, which is defined as the presence of antithyroid antibodies (AT-Ab) and typical ultrasound findings. We found 106 (22.2%) patients positive for AT-Ab and of those 49 (10%) also had positive ultrasound findings, and were therefore considered to be affected by thyroiditis. This frequency is significantly higher (p0.001) than that seen in the normal population. Goitre was detected on clinical examination in only 16 (33%) and by ultrasound in 19 (39%) patients. Hormonal evaluation showed that 17 patients were euthyroid, 27 had compensated hypothyroidism, 2 were hypothyroid and 3 were in a hyperthyroid phase. Clinical signs or symptoms of hypothyroidism were absent in all hypothyroid patients. In patients with thyroiditis, neither a higher frequency of malformations and autoimmune diseases nor a correlation with karyotype, oestrogens or growth hormone therapy was found.

Bone mineral density of the non-dominant forearm was measured by single-photon absorptiometry at a proximal site (PBMD) and at a more distal site (DBMC) in 9 competitive male swimmers, aged 18 to 23 years, who had been training for 12 +/- 2 years, 10.3 +/- 5.6 hours a week. The results were compared with 25 age-matched controls. PBMD was m +/- SD 0.57 +/- 0.02 g/cm2 in the swimmers and 0.57 +/- 0.05 g/cm2 in the controls. DBMD was 0.45 +/- 0.02 g/cm2 in the swimmers and 0.45 +/- 0.03 g/cm2 in the controls. No difference was found between the two groups. We can therefore conclude that swimming, in absence of gravity, didn't provide our athletes with an effective mechanical load capable to increase bone density of the forearm.

We studied in 10 children (3 boys and 7 girls), affected by precocious puberty and treated for a period of more than 6 months with the GnRH-analog Buserelin, the efficacy of the GnRH test versus the study of spontaneous nocturnal secretion of LH, testosterone and 17 beta-estradiol as a means of testing the gonadotropin suppression. All the subjects have shown a total suppression of LH during the GnRH test as well as a nocturnal profile of LH, testosterone and 17 beta-estradiol of a prepubertal pattern. Clinically all the patients were treated successfully. Considering the effectiveness of both investigations, we conclude that the GnRH test combined with clinical observation is a single and valid means of testing the pharmacological treatment for precocious puberty.

14 diabetic boys (five with a family history of diabetes and nine without) and 29 "short normal" boys were studied. A gonadal function test (2.000 IU of hCG i.m. for 3 days and plasma testosterone assay before and after the hCG administration) as well as an LH-RH test (50 microgram i.v.) were carried out. While basal testosterone level turned out to be similar in the two groups of children, it was significantly lower (p less than 0.01) after hCG than the mean value of the control group. This difference was mainly observed in those patients with a family history of diabetes. In the diabetic children, basal LH level was normal and the pituitary LH reserve was lower than in the control group. Both basal FSH level and FSH pituitary reserve were lower than in normal children. These data show that an alteration in the hypothalamus-pituitary-gonadal function is already evident in the diabetic child.

We describe a child with Down's syndrome who developed an insulin-dependent diabetes mellitus at the age of 8 years and hypothyroidism at the age of 17 years. Because of the well known tendency to autoimmune diseases of patients with Down's syndrome, an autoantibody screening was undertaken. Only a low titre for gastric parietal cell antibodies was repeatedly found, but a gastric biopsy did not reveal chronic atrophic gastritis. Thyroid function should be checked periodically in patients with Down's syndrome since they might suffer from hypothyroidism which may not be recognized for a long time because of its latent onset.

A child with the Bardet-Biedl syndrome associated with Hirschsprung's disease and multiple anterior pituitary hormone deficiencies is described. The importance of endocrine assessment of such patients who show disturbance of growth or puberty is emphasized.

We have evaluated the thyroid function in 30 children and adolescents (average age 13 2/12 +/- 3 10/12 years) suffering from type 1 insulin-dependent diabetes (average duration of illness 5 +/- 3 3/12 years). We divided them into group A (good control) and group B (poor control), according to whether they had presented an HbA1C value lower or higher than 10%. The results obtained have been compared with a group of 30 normal patients of the same age. Both groups of diabetics presented T4 values which were notably lower than the control group (P less than 0.05). T3 was appreciably diminished both in group A (P less than 0.05) and in group B (P less than 0.01) and presented a negative correlation with HbA1C, only in group A however. The rT3/T3 ratio, on the other hand, was significantly increased in group B with respect to the controls. No significant differences were found with regard to FT3 and FT4, nor any correlations among thyroid hormones, C peptide, duration of illness, and daily insulin requirement. Our results indicated that the tendency to the low T3 syndrome, already described in adult diabetics, is also identifiable in young diabetics, particularly if poorly controlled.

We describe two children with Leri-Weill syndrome (Dyschondrosteosis), one of which showed the clinical features at very early age. Stature was moderately reduced in both, due to shortening of the bones of the legs. Furthermore were evident in them the clinical and radiological features of the propositus and of their affected parents are described. The problems concerning the early recognizing of the disease and the genetic inheritance are discussed.

The clinical usefulness of the measurement of basal TSH by an ultrasensitive assay (IRMA) versus the TRH test has been challenged in 49 children treated with L-thyroxine. They were given suppressive or replacement therapy depending on the underlying disease. An absent response of TSH to TRH could be predicted from a basal TSH value less than 0.1 mU/l in 88.8% of the cases, while only in 77.7% from a basal TSH value = 0.1 mU/l. A basal TSH value found in the range of the normal children always predicted a normal TRH test. We conclude that a sensitive TSH assay has some clinical application in monitoring L-thyroxine therapy, but can not absolutely replace the TRH test.

We investigated the serum thyroid hormones an the degree of diabetic control in 30 children and adolescents suffering from type 1 insulin-dependent diabetes, first while they were being treated with porcine insulin (group A) and then while 23 of them, random selected, were being treated with human insulin (group C). The purpose of our study was to evaluate if the change to human insulin would result in better metabolic control and disappearance of the tendency to the low T3 syndrome that was evidenced in group A. If we compare group A with group C, it can be seen that the degree of diabetic control is higher in group C (decrease in HbA1C), but that the tendency to the low T3 syndrome has not disappeared. Then we selected inside the groups A and C the patients in good metabolic control, and called them respectively group B and group D. If we compare group B with group D it can be seen that there is not any significant difference at all between them and that both groups show a tendency to the low T3 syndrome if compared with the control group (group K). In conclusion, we may state that substituting porcine with human insulin has not brought about any significant metabolic improvement in our patients, as can be seen from the persistent tendency to the low T3 syndrome.

SHOX (Short HOmeoboX containing gene) (OMIM 312865) is the single gene found in the “short stature critical region”, a 170 kb DNA segment of the pseudoautosomal (PAR1) region identified through genotype/phenotype correlations in X/Y abnormalities.1 The finding of a mutation generating a premature stop codon in exon 5 of SHOX , cosegregating with idiopathic short stature (ISS), provided evidence for the involvement of this gene in growth retardation, including the short stature of Turner syndrome.1 At the heterozygous level, large deletions or point mutations of the SHOX gene have been found in families affected by Leri-Weill dyschondrosteosis (LWD, OMIM 127300), a dominantly inherited skeletal dysplasia with disproportionate short stature owing to mesomelic shortening of the forearm and lower leg and Madelung deformity of the arm.2,3 In addition, the biallelic inactivation of the SHOX gene was shown in fetuses with Langer-type mesomelic dysplasia (OMIM 249700),2,3 a recessive form of dwarfism which was confirmed as the homozygous counterpart of LWD, as previously proposed on a clinical genetic basis.4 Some authors reported mutations in all the LWD cases studied,3,5 whereas others found SHOX mutations in about 60% of the cases.6,7 The same proportion of SHOX gene mutations are reported in the present study based on the analysis of a large group of Italian LWD families. Patients and families were recruited, after informed consent, in the context of a collaborative study in several Italian paediatric endocrinology centres. Height and sitting height were measured to nearest 0.1 cm using a Harpenden anthropometer and measurements were converted into centiles, according to the Tanner tables. All subjects were submitted to x ray examination including the forearms and lower legs. Inclusion criteria for the study were: (1) normal karyotype, with lack of demonstrable sex chromosome abnormality using …