Search

Background: GH-IGF-I axis is mainly involved in the complex process of somatic growth but emerging evidence suggests that it also influences hypothalamic-pituitary-gonadal (HPG) function., Subjects: We report some data regarding long-term auxological and pubertal outcome of five female patients with hereditary forms of GH-IGF-I deficiency (Laron and GH-gene deletion syndrome) and a mean age of 23.4±5.3 yr (range 19-32)., Methods: All the patients received recombinant human IGF-I (rhIGF-I, Pharmacia and Upjohn, Stockholm, Sweden, and rhIGF-I, Genentech, San Francisco, CA, USA) from a mean age of 8.6 yr (range 3.2-14.2) up to the final height., Results: Final height was very disappointing (≤ -5.0 SD scores) and lower than target height in all the patients. Pubertal onset was delayed in most of them but menarche occurred spontaneously in all the patients. Median age at menarche was 15.1 yr. Menstrual cycles were regular for several years. Median duration of gynecological follow- up was 8.3 yr with the longest span of 17.2 yr., Conclusion: We can assert that GH-IGF-I axis has an essential role in promoting linear growth in humans and its physiological action cannot be replaced by pharmacological treatment in most patients with hereditary forms of IGF-I insufficiency as demonstrated by their subnormal final height. Our clinical observations can also support an essential role of IGF-I in genitalia growth but not in the function of HPG axis as demonstrated by the maintenance of regular menstrual cycles in the presence of subnormal levels of IGF-I after treatment discontinuation.

Background: Raised liver enzyme value is frequently detected in patients with Turner syndrome (TS), but its clinical importance is still unclear., Objective: To investigate the entity of liver involvement in TS and to avoid the invasiveness of liver biopsy, we planned to measure liver stiffness by transient elastography (TE)., Design: Cross-sectional study., Patients and Methods: Twenty-five consecutive patients with TS and a chronological age ≥ 12·5 years (mean age = 21·7 years), full pubertal development and final height's achievement were enrolled and investigated by blood biochemical analyses [glucose, insulin, aspartate-aminotransferase (AST), alanine-aminotransferase (ALT), gamma-glutamil transferase (GGT), alkaline phosphatase, cholesterol, triglyceride, HDL-cholesterol], ultrasonography and TE of the liver., Results: Of 25, 7 subjects (28%) showed liver enzyme levels higher than the normal upper limit. Mean liver stiffness value in the entire study group was 4·5 ± 1·7 kPa, being significantly higher in patients with abnormal liver enzymes than in those with normal liver biochemistry (6·0 ± 2·9 vs. 4·0 ± 0·9, P < 0·05). Strong correlations were found between TE values and ALT (P < 0·005), GGT (P < 0·0001), Body mass index (P < 0·05), HOMA index (P < 0·05), HDL-cholesterol (P < 0·05) and triglycerides (P < 0·0001)., Conclusions: We can assert that (i) liver stiffness, measured by TE, strongly correlates with liver enzyme levels in patients with TS ; (ii) the increased liver stiffness in patients with TS with biochemical signs of liver dysfunction is significantly related to metabolic syndrome parameters; (iii) TE may be an useful tool to select among patients with TS with elevated liver enzymes or other metabolic risk factors, those who deserve more invasive diagnostic procedures, namely liver biopsy, for the best characterisation of liver damage., (© 2010 The Authors. European Journal of Clinical Investigation © 2010 Stichting European Society for Clinical Investigation Journal Foundation.)

Aims: To ascertain the prevalence of Graves' disease (GD) in 1,323 Caucasian children with type 1 diabetes mellitus (T1DM), and to compare the course of GD in T1DM patients with the one observed in 109 Caucasian peer patients with GD but without T1DM (group B)., Results: Only 7 patients (0.53%) of the T1DM series also presented with GD (group A)which was diagnosed many years after diabetes presentation. At GD diagnosis, the prevalence of preclinical hyperthyroidism was higher in group A (p = 0.0001), whereas serum TSH receptor antibodies (TRABs) were higher in group B (p = 0.04). The subsequent course with methimazole therapy and after its withdrawal was very similar in both groups., Conclusions: GD prevalence in T1DM patients was 0.53%, i.e. almost identical to the one reported in the general population. GD was diagnosed many years after T1DM presentation. At GD diagnosis, the clinical picture was milder and TRAB serum levels were lower in diabetic patients. Preclinical diagnosis and early treatment of GD were not associated with better responsiveness to therapy. Screening programs based on periodical TRAB assessments are not useful in T1DM., (Copyright © 2011 S. Karger AG, Basel.)

A boy aged 7.6 years presented to our Unit of Paediatric Endocrinology for evaluation of obesity. Progressive weight gain (10 kg) started 6 months earlier after an accidental penetrating orbital injury on the right eye. During this period the child has been treated with oral betamethasone (0.5 mg/day) for 1 month and dexamethasone 2% ocular drops (2 hourly by day) for 6 months. Physical examination showed he was 113.5 cm in height (-1.5 SD), weight 36.0 kg, blood pressure 110/90 mmHg (90th centile), body mass index 28 (+5 SD), truncal obesity, buffalo hump, "moon-face", increased lanugo hair and supraclavicular fullness. Endocrinological work-up revealed undetectable levels of basal adrenocorticotropic hormone (ACTH), basal and ACTH-stimulated cortisol and 24 h urine excretion cortisol, confirming the diagnosis of iatrogenic Cushing syndrome. The abrupt withdrawal of ocular glucocorticoids by the parents evoked two adrenal crises; 4 months later the patient recovered. In conclusion, we would alert doctors that every formulation of glucocorticoids, no ocular drops excluded, can determine severe systemic side effects and iatrogenic Cushing syndrome.

Context: McCune-Albright syndrome (MAS) is a disorder caused by a post-zygotic gain-of-function mutation in the gene encoding the Gs-alpha protein. Sexual precocity, common in girls, has been reported in only 15% of boys, and little is known on the long-term evolution of MAS in males., Objective: In a boy with MAS, we studied spermatogenesis, testis histology, and immunohistochemistry with the aim to shed light on seminiferous tubule activity., Design: A boy who presented at the age of 2.9 years with sexual precocity, monolateral macroorchidism, increased testosterone levels, and suppressed gonadotropins was followed up until the age of 18., Results: Throughout follow-up testicular asymmetry persisted and gonadotropin and testosterone pattern did not change. At the age of 18, inhibin B was undetectable while alpha-immunoreactive inhibin was within normal range. Anti-Mullerian hormone level was slightly subnormal. Sperm cells were 3,900,000 per ejaculate. Histology of both testes showed spermatogonia, spermatocytes, and, in some tubes, matured spermatozoa. Sertoli cells were markedly stained with anti-inhibin alpha-subunit antibody in both the testes. There was no immunostaining of Sertoli, Leydig, or germ cells with anti-betaA or anti-betaB antibody. MAS R201H mutation was identified in both the testes., Conclusion: The 15-year follow-up in this boy with MAS demonstrated that autonomous testicular activation and gonadotropin suppression persisted over time. This provides an interesting model of active spermatogenesis despite long-term FSH suppression. It also suggests that FSH is needed for the full expression of the inhibin betaB-subunit gene, an expression previously reported in the germ and Leydig cells of normal adult subjects.

Objective: To investigate the association between juvenile autoimmune thyroiditis (JAT) and thyroid cancer in pediatric patients., Design: We conducted a retrospective study among children and adolescents affected by JAT., Settings: Data from 6 Italian pediatric endocrinology centers were collected., Participants: Three hundred sixty-five children and adolescents affected by JAT diagnosed at 3.6 to 17.0 years of age., Interventions: All patients underwent clinical examination and thyroid function test every 6 to 12 months and thyroid echography every 12 to 24 months. Fine-needle aspiration biopsy was performed in 39 patients with nodule diameter of 1 cm or larger, as well as in 4 patients with nodule diameter of less than 1 cm and echographic findings suspicious for neoplasm. Twenty-three patients underwent surgery., Main Outcome Measures: Thyroid function, echographic pattern, nodule diameter, the presence of lymphadenopathy, and cytologic and histologic diagnoses were considered., Results: Thyroid nodules were found in 115 patients; findings in 11 of these were consistent with papillary carcinoma, with 5 exhibiting lymph node metastasis. The prevalence of male sex among patients with cancer was greater than that among patients with JAT (odds ratio [OR], 2.95; 95% confidence interval [CI], 1.44-6.20). The growth of nodules during levothyroxine sodium therapy (OR, 15.60; 95% CI, 1.87-181.90) and the finding of lymphadenopathy (OR, 5.44; 95% CI, 1.05-30.50) were statistically significantly associated with the presence of cancer, while uninodularity and hypoechogenicity were not., Conclusions: The observed prevalences of thyroid nodules and thyroid cancer in our JAT case series were 31.5% and 3.0%, respectively. Papillary carcinoma was the only histotype detected. The finding of lymphadenopathy, a lack of response to levothyroxine therapy, and nodule hypoechogenicity suggested malignancy. Fine-needle aspiration biopsy was reliable in selecting patients for referral to surgery.

Unlabelled: The aim of the present study was to retrospectively re-evaluate a population of selected infants with congenital hypothyroidism (CH), in order to investigate whether sexual dimorphism affects: a) CH etiology; b) its biochemical severity at the time of screening and recall; c) patients' biochemical response to replacement treatment during the 1st yr of life; d) their bone maturation (BM) at birth; e) their psychomotor status at 1 yr. This retrospective study covers 192 infants (116 females) with persistent CH who were selected from a larger population of CH patients identified during a 10-yr period (1990-1999) by the screening programs of 5 northern, central, and southern regions of Italy. Thirty boys (39.5%) and 66 girls (56.9%) were found to have ectopia, whereas the remaining 46 boys and 50 girls exhibited the other causes of CH. When compared with the prevalence of the remaining causes that of ectopia was significantly higher in girls than in boys (66/116 vs 30/76; chi2=5.57, p<0.025), and sex ratio in ectopia was significantly different also compared with the orthotopic gland group only (66/84 vs 30/51; chi2=6.02, p<0.025). No differences between males and females were detected in the groups with either athyreosis or orthotopic gland. In no groups were there differences between sexes for gestational age, birth auxological data, percentage of newborns with bone retardation or developmental quotient at 1 yr. Thyroid tests at birth, age at TSH normalization and average thyroid tests under L-T4 treatment during the 1st yr did not differ between sexes in any of the groups., Conclusions: a) in the Italian population sexual dimorphism affects pre-natal thyroid migration but neither biochemical severity of ectopia, nor pre-natal bone maturation and psychomotor development; b) girls with CH do not require higher doses of initial therapy in order to achieve TSH normalization; c) future developmental and molecular studies on ectopia etiology in CH need to take into account the effect of sexual dimorphism.

Short stature is a well-recognized feature of Duchenne muscular dystrophy, whilst it has been reported rarely in Becker muscular dystrophy (BMD). Here we report two brothers with BMD, who exhibited a very different growth pattern. Whereas in the short brother (-2.2 SDS) molecular investigation revealed a G367A mutation in the short stature homeobox containing (SHOX) gene located in the Xp22.3 region, no abnormality was found in the brother with normal height (-0.1 SDS). Our data suggest that abnormal growth observed in a boy with BMD may be related to an additional genetic alteration, already known as correlated with short stature., ((c) 2007 S. Karger AG, Basel)

Subclinical hypothyroidism (SH) is a common clinical problem, particularly in adulthood and the elderly. Its prevalence is conditioned by several etiological and risk factors. The highest age- and sex-specific rates are in women over 60. SH may be associated with manifestations of mild thyroid failure, which may reverse under levothyroxine (L-T4) therapy. The risk of progression to overt hypothyroidism is distinctly higher in cases with underlying thyroid disease. A population routine screening is not generally recommended, but screening is encouraged in high-risk groups. L-T4 therapy may be indicated in subjects with TSH levels which are repeatedly and consistently elevated (>10 microIU/ml) and may be considered in those with TSH ranging between 4.5-5.5 and 10 microIU/ml, particularly if anti-thyroid antibodies are positive and/or hypothyroid symptoms are present. Treatment should be based, at least initially, on L-T4 low doses.

Turner's syndrome (TS) is a chromosomal disorder that results from the loss of the entire or a part of the X-chromosome and occurs in 1/2,500 female births. According to the majority of specific reports, intelligence in TS is generally found to be normal and the prevalence of mental retardation does not seem to be increased in TS except for those patients with a small ring X-chromosome. We evaluated 33 girls with TS with chronological age from 6-18 years. Intellectual assessment included the WISC III and the WAIS-R scales. Our results showed: 1) mean full scale intelligence quotient (FSIQ) was significantly lower than expected based on normative data (p < 0.0005); 2) no correlation was present between height and general intellectual ability; 3) mean performance intelligence quotient (PIQ) was significantly lower than both mean verbal intelligence quotient (VIQ) and FSIQ (p < 0.0025 and p < 0.01, respectively), and most patients had a VIQ-PIQ discrepancy; 4) the frequency of mental retardation in our study group was significantly higher than that observed in the general population (15.1% vs 2.3%, p < 0.025); 5) a significant association was found between karyotype and VIQ, and the best score was achieved in the subgroup of patients with structural abnormalities of the X-chromosome. In the light of these findings we conclude that the clinical picture in TS may encompass a slightly reduced FSIQ, VIQ and especially an inadequate PIQ, but this neurocognitive profile is not significantly affected by statural impairment. Since these neurocognitive defects can be responsible for misdiagnosed school difficulties, we suggest that girls with TS should receive specialized educational support and multidisciplinary care.

Background/purpose: Different studies have evaluated testicular hormonal dysfunction in adolescent varicocele but with variable results. Recently, inhibin B has been proposed as a marker for spermatogenesis and Sertoli cell function. The aim of the present study was to study in a homogeneous cohort of adolescents inhibin B and other hormones to detect whether untreated varicocele may be associated with any modifications of these factors., Methods: Sixteen adolescents (mean age, 14.5 +/- 1.0 years), at Tanner stages 4 to 5 with grade II or III left-sided varicocele, underwent hormonal evaluation of inhibin B, basal testosterone, and both baseline and GnRH stimulated FSH and LH levels. Thirteen unaffected adolescents of age-matched and pubertal development were used as controls., Results: Patients with varicocele showed a significant reduction in the testicular volume of the affected side (13.3 +/- 4.1 vs 15.8 +/- 4.8 mL; P = .002) and significant reduced levels of inhibin B compared with controls (271.9 +/- 70.2 vs 327.1 +/- 34.9 pg/mL; P = .042). Inhibin B levels were significantly correlated with testes volume (r = 0.62; P = .0097). Other hormonal parameters were similar in both varicocele and control groups., Conclusion: Inhibin B is reduced in adolescents with untreated varicocele, and it is positively correlated with testicular volume. This could be an early marker for Sertoli cell damage, with possible implications for spermatogenesis and could represent a new indication for varicocele repair.

The clinical implications of the association between testicular microlithiasis (TM) and germ cell tumor (GCT) of the testis are still debated since the natural history of incidentally discovered TM has not been defined. Therefore, it is questionable whether TM can be considered as a precursor of malignancy. We are reporting the case of a 9-yr-old boy with a mixed GCT who had presented 3 yr earlier with TM and hydrocele. This evolution suggests that testicular GCT may develop some years later in a boy with pre-existing and incidentally discovered TM. Our case history and other reports of the literature might suggest a strong association between both conditions, thus vindicating the view that individuals with TM should have clinical and ultrasound follow-up. Longitudinal evaluation may be particularly indicated in the patients with additional testicular dysgenetic features, apart from TM.

Background: Testis enlargement in McCune-Albright syndrome (MAS) is generally bilateral and associated with clinical and biochemical manifestations of sexual precocity., Case Report: We describe for the first time an unreported clinical expression of MAS in a 4.6-year-old boy presenting with monolateral testis enlargement and no signs of sexual precocity or other clinical manifestations of MAS at the time of presenting with macroorchidism. Both testosterone and LHRH-stimulated gonadotropin levels were in the prepubertal range. Serum inhibin B was increased to a pubertal level indicating Sertoli cell activation. The histological and immunocytochemical evaluation of the enlarged testis revealed Sertoli cell hyperplasia with no mature Leydig cells. Mutation R201C of GNAS1 gene, classically responsible for MAS, was identified in DNA samples from the right testis biopsy and leukocytes., Conclusions: (a) MAS should be taken into consideration in the clinicopathological approach to a boy with monolateral macroorchidism; (b) testicular enlargement may be only the presenting clinical manifestation of MAS and is not necessarily linked to manifestations of peripheral precocious puberty; (c) testicular autonomous hyperfunction in MAS may be restricted to Sertoli cells, as also demonstrated previously by others., (Copyright 2006 S. Karger AG, Basel.)

Objectives: a) To describe a very extended inbred pedigree with Wolfram syndrome (WS) (OMIM #222300); b) to report both the clinical picture and evolution in this large family and a peculiar mutation which has been reported hitherto only in Italian patients., Design: The five-generation pedigree from Sicily was reconstructed through a proband with all the main manifestation of WS, born to a couple of healthy consanguineous parents. DNA examination was performed in both patients and healthy family members., Results: In all seven patients we found a homozygous 16-bp deletion in exon 8 of the WFS1 gene that introduces a stop codon in position 454., Conclusions: This inbred pedigree is the largest with WS described in the literature. Its analysis definitively confirms the view of autosomal recessive inheritance in WS. The 16-bp deletion appears to be a relatively frequent mutation only in Italian patients. Before examining the entire coding region of the WSF1 gene a preliminary screening for the 16-bp deletion in exon 8 might be suggested when a new Italian case of WS is investigated.

Elevated liver enzymes can be seen relatively frequently in patients with Turner syndrome (TS), while the pathogenesis of this remains unclear. Our epidemiological and prospective study aimed to investigate: a) the natural 2-yr course of liver disease in a selected cohort of young patients with TS, who had been preliminarily recruited on the basis of persistently elevated liver enzymes; b) the role of prolonged hormonal therapies in the etiology of liver dysfunction. From an overall population of 214 TS patients younger than 20 yr, only 19 (8.9%) were recruited, according to the following inclusion criteria: increased serum concentrations of one or more liver enzymes, exceeding the uppermost limit of the respective normal ranges, and persistence of these liver alterations for 6 months after the preliminary assessment. On the basis of the results of this prospective study, we can conclude that: a) the prevalence of liver abnormalities in girls and adolescents with TS is much lower and more strictly related to hormonal therapies than in TS adults; b) both autoimmunity and obesity are not frequently involved in the etiology of TS liver dysfunction; c) liver damage is either mild or moderate and its severity is not conditioned by karyotype; d) its course may be self-limiting; e) its natural history may be characterized in some cases by a slight deterioration of intrahepatic cholestasis, with no negative repercussions on liver synthetic function.

Children born small for gestational age (SGA) are known to be at risk for both short stature and type 2 diabetes mellitus in later life. To evaluate the influence of recombinant growth hormone (rhGH) therapy on insulin sensitivity, 24 children born SGA were treated with GH at traditional doses, from 0.23 mg/kg/week (group A) to 0.46 mg/kg/week (group B). We evaluated glycosylated haemoglobin, basal glucose and insulin levels before and 1 and 2 years after GH therapy. The homeostasis model assessment (HOMA) index was used to evaluate insulin sensitivity. After 2 years of GH therapy, glycosylated haemoglobin and basal glucose did not change significantly. Insulin sensitivity fell, but still remained within the normal range. In conclusion, 2-year GH therapy had beneficial effects in SGA children without changes in glucose homeostasis. Moreover, the insulin sensitivity reduction did not correlate to the GH dose used.

One of the toughest aspects which health-care workers have to face in the management of diabetes is informing the family. Thanks to specialized teams of pediatric diabetologists, specialized diabetes nursing staff, dieticians and psychologists, many of these problems have by now been solved. Over the past ten years, scientific research has made it possible to identify some "critical points" which arise as the child passes through the various developmental phases. Based on this research there has been an increasing tendency to highlight contact points between diabetic patient and family management of the illness, aimed at preventing incorrect behaviour during the different growth phases. The diabetological team should not only intervene when necessary, but also work with an eye to prevention so as to improve the quality of life of the child and its family, making it possible that a diabetic child quality of life is the same of a non-diabetic child. Team work is necessary so as to get to know and, where possible, improve, compliance in every family. This is obtained also through the acquisition and subsequent carrying out of questionnaires, which help in making the family understand that there is no difference between diabetic children and non-diabetic children. Data in literature, fortunately, seems to confirm this. Clear progress has also been made in the methods of administration thanks to the introduction of devices such as pens and microinfusors (CSII). Pen devices have greatly improved compliance of young diabetic patients, making them better able to manage administration on their own. Microinfusors, on the other hand, have not only improved metabolic control, bringing it closer to the physiological model, but have also had a positive effect on the quality of life of young people, and, as a consequence, of their families.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy and hemolytic anemia can be triggered by many drugs, by the ingestion of fava beans, and by metabolic imbalances. Nonetheless, only sporadic reports of hemolytic anemia due to G6PD deficiency in patients with type 1 diabetes mellitus (DM1) have been reported to date. We describe an 8 year-old Sicilian boy who suffered from hemolytic anemia some days after admission for DM1. On admission, acid-base equilibrium was normal but 4 days later he presented hemolytic anemia with G6PD deficiency, confirmed by personal and family history and laboratory evaluation. We suggest that the hemolytic crisis in this patient was triggered by the relative hypoglycemia that followed insulin administration. The interference of acidosis, infections, drugs, food or other triggering agents was excluded. This report demonstrates that hemolysis may represent a possible complication of DM treatment in patients with G6PD deficiency and we recommend careful clinical surveillance in these patients.

To assess whether short-term growth hormone (GH) treatment can improve the linear growth in children who were born small for gestational age (SGA), we started a randomized multicenter trial in 26 age- and sex-matched prepubertal children born SGA. During the 1st year of GH therapy, all children received GH 0.23 mg/kg/week, then during the 2nd year, 13 children received the same dose (group A), and in the other 13 children, the dose of GH was doubled, i.e., 0.46 mg/kg/week (group B). During the 1st year of therapy, the growth velocity significantly (p<0.0001) increased in all patients. During the 2nd year, group A showed a significant decrease of the growth velocity (p<0.015), whereas group B maintained the growth rate. The height in group A children significantly increased during the 1st and the 2nd year of GH therapy (p<0.000002 and p<0.000001, respectively), reaching the normal range in 8 out of 13 children at the end of 2 years of GH therapy. The height in group B children significantly increased during the 1st and the 2nd year of GH therapy (p<0.000001 and p<0.000001, respectively), reaching the normal range in all 11 children who completed the GH therapy. The height gain was similar in groups A and B treated with the same GH dosage during the 1st year of therapy. A greater increase in height gain was found in children of group B treated with the higher GH dosage during the 2nd year of therapy as compared with group A (p<0.02). Significant increases in insulin-like growth factor I (p<0.0001), acid-labile subunit (p<0.0002), and bone/chronological age ratio (p<0.0001) were found after the 1st year of GH therapy, but no significant changes were observed during the 2nd year, independently of the GH dose. In conclusion, the height velocity of children born SGA significantly increases during the 1st year of GH therapy, diminishes, but can decrease during the 2nd year, if the GH dosage is not raised., (Copyright 2004 S. Karger AG, Basel)

Clinical symptoms and biochemical findings related to liver dysfunction are not generally reported among the presentation features of Type 1 diabetes mellitus (T1DM) in infancy and childhood. To our knowledge this is the first paper reporting two children with a clinical and biochemical picture of hepatic glycogenosis at the presentation of T1DM. In both cases at beginning of insulin therapy liver function and dimensions were absolutely normal, even though glycometabolic status had been severely altered for many days at T1DM onset. Both hepatomegaly and aminotransferase abnormalities were first found only some days after the institution of treatment with supraphysiological insulin doses. In both patients the improvement of glycometabolic control under insulin therapy was followed within some weeks by a complete physical and biochemical recovery, as typically reported in hepatic glycogenosis. These case reports demonstrate that hepatic glycogenosis can occur at any stage of T1DM and may even be one of its earliest manifestations, together with those classically reported at the onset of T1DM. Since long-standing hyperglycaemia and overinsulinisation are metabolic pre-requisites for hepatic glycogen storage, liver glycogenosis should be expected to be not uncommon during the first phases of T1DM, especially in the cases who are initially treated with supraphysiological insulin doses.

Self-control led therapy is vital in the treatment of insulin dependent diabetes mellitus (IDDM), allowing as it does, correct insulin therapy, a reduction in hospitalisation and modification of therapy for individual needs in relation to various factors. Undoubtedly it is the responsibility of the diabetes team (doctors, nurses, dietician, psychologist and social assistant) to instruct the patient and help him/her in this new situation. The patient must learn to live and develop normally, participating to the full in school, at work and in all social situations, by fully understanding how to manage the illness autonomously and how to prevent short and long-term complications. Thus, the team must set objectives: making the patient aware of his condition, giving him the knowledge of what to do and how to do it. In this way, quality of life can be improved for patients affected by this chronic illness and they can understand how to face the future with realistic optimism. Modern technology has brought many novelties into the diabetes field, such as the ever smaller and more accurate glucose meters, or finger-prick devices requiring minimal quantities of blood. They represent another step towards a less invasive or disruptive approach in the management of diabetes. Non-specialist press articles may raise false hopes, above all about new research in the field of diabetes, but at least they also raise awareness on a problem of national interest, i.e. insulin dependent diabetes mellitus.

In this study, which aims to investigate for the first time auditoty sensitivity in congenital central hypothyroidism (CH), we concluded that: (1) permanent sensorineural hearing loss may be observed not only in congenital primary disorders of thyroid function, as reported hitherto; (2) it may also be found in patients with congenital CH, at least when substitutive treatment is started many years after thyroid failure presentation; (3) the concept of a 'critical therapeutic window' in preventing hearing impairment also holds true for children with congenital CH; (4) the therapeutic window in CH is wider than in primary hypothyroidism; (5) this is probably due to the less severe thyroid impairment in the cases with a central origin of hypothyroidism. These conclusions were suggested by the following data obtained in a cohort of 10 patients with congenital CH who were euthyroid at the time of audiological evaluation thanks to long-standing substitutive therapy: (a) four out of 10 patients exhibited a bilateral sensorineural hearing loss; (b) hearing impaired patients were the oldest of the entire series at diagnosis of hypothyroidism and none of them was aged less than 7 years at the time of the start of replacement therapy; (c) a strong positive relationship was found between age at therapy start and hearing loss.

The aim of this study was to investigate the influence of pre-treatment variables on subsequent insulin requirement (IR) and partial remission (PR) in children with insulin-dependent diabetes mellitus (T1DM). Sixty-seven children with newly diagnosed T1DM, admitted to our Clinic during a 3-year recruitment period, were longitudinally evaluated for 2 yr. Patients were characterized by sex, age, parental education, duration of symptomatic history at diagnosis, admission duration, ketoacidosis or absence of ketoacidosis and residual beta-cell activity. More than 80% of the children experienced a PR, which lasted more than 12 months in 41.7% and at least 24 months in 16.4% of cases. The prevalence of PR at different ages after T1DM onset was significantly lower in children diagnosed while younger than 5 years than in those diagnosed after 5 years. The mean duration of the remission period was 11.7 +/- 8.9 months, irrespectively of sex, duration of the symptomatic period preceding T1DM diagnosis, parental education, blood pH and base excess, HbA1c concentration and admission duration. Beta-cell residual function evaluated after glucagons stimulation test (basal and 6 min C-peptide) was statistically different in PR patients and in those who experienced no remission. Age at diagnosis was the only pre-treatment factor which, on stepwise regression analysis, affected both PR duration and IR at the end of follow-up. To conclude, honeymoon frequency and duration are strictly conditioned by both residual beta-cell function and IR at T1DM onset. Since IR is higher in younger subjects, early onset of T1DM can be considered the factor with the most detrimental influence on honeymoon incidence. Other pre-treatment variables have no significant impact on PR.

The aim of this prospective study was to evaluate the evolution of glucose tolerance (GT), insulin secretion and peripheral insulin sensitivity during a 3-yr follow-up in a homogenous population consisting of fourteen non-diabetic adults with thalassemia major (TM). All the patients underwent 2 OGTTs with a 3-yr interval and random measurements of fasting glycemia during the entire follow-up. At the time of both OGTTs, peripheral insulin sensitivity was assessed by both homeostatic model assessment (HOMA) index and a novel index derived from the OGTT. At the second OGTT patients exhibited both significantly higher fasting glucose concentrations and enhanced glycemic responses, with greater average glucose areas. GT deterioration over time was accompanied by a reduction of insulin sensitivity, with no concomitant change of insulin secretion. No patient developed diabetes mellitus (DM) during follow-up. To conclude, the natural history of glycometabolic status in TM adults seems to be characterized by a GT deterioration over time, which may probably reflect an increase of insulin resistance. GT deterioration is more evident in patients with the highest responses to the 1st OGTT and particularly in those with pre-existing impaired GT.

In childhood the traditional diagnostic approach to thyroid nodules consists of clinical, laboratory, and imaging evaluations. A safe and accurate procedure is needed to promptly identify patients who require surgery. In regard to the usefulness of fine needle aspiration biopsy, the data in the literature concerning children and adolescents are scanty. The aim of this study was to evaluate and compare the diagnostic accuracies of clinical, laboratory, and imaging data collected retrospectively in a group of pediatric patients with thyroid nodules submitted to fine needle aspiration biopsy. Forty-two patients who underwent surgery for thyroid nodules, recruited in 9 Italian pediatric endocrine units, were retrospectively studied. According to histological diagnosis, they were divided into 2 groups, 22 patients with benign lesions and 20 patients with malignant lesions. From clinical records we obtained data about 1) symptoms of neck compression; 2) cervical adenopathy; 3) thyroid function, calcitonin level, and antithyroid antibody titers; 4) ultrasonography; 5) (99m)Tc scintiscanning; and 6) cytology obtained with fine needle aspiration biopsy. Patients and nodule characteristics were analyzed statistically for associations with the presence of thyroid cancer. Among clinical findings, only adenopathy was significantly higher in the group with cancer (8 of 22 benign lesions vs. 16 of 20 malignant lesions; P = 0.006). Thyroid function and antibody titers were similar in the 2 groups, whereas the serum calcitonin level was elevated only in 1 patient with malignant lesions. Among ultrasonography findings, no significant statistical difference was found between the 2 groups with regard to number, dimensions, growth progression, or hypoechogenic pattern of the nodules. Regarding scintigraphic findings, no significant difference was found between the 2 groups. However, a positive correlation (r = 0.90; P < 0.0001) was found between fine needle aspiration biopsy cytological findings and histological diagnoses. The sensitivity, specificity, and accuracy of fine needle aspiration biopsy were 95%, 86.3%, and 90.4%, respectively. A multiple regression analysis showed that only fine needle aspiration biopsy (beta coefficient = 0.963; P < 0.0001) significantly contributed to detecting malignancy (multiple r = 0.973; P < 0.0001). This study provides strong evidence that fine needle aspiration biopsy is a safe technique even in childhood and adolescence, offering the best sensitivity, specificity, and accuracy in detecting malignancy compared with conventional approaches.

We retrospectively investigated growth response to therapy of 12 patients with idiopathic growth hormone deficiency (GHD), who received GH (0.6-0.7 IU/kg/week) in daily subcutaneous injections from before 2 years of age and for a period of 60 months, in order to ascertain whether very early treatment can enable GHD children to catch-up quickly and completely their initial height deficiency. The onset of therapy was followed in all patients during the 1st year by a significant growth spurt, which persisted, even though attenuated, during the following 4 years. Height deficiency for chronological age (CA) significantly and progressively decreased during the entire study period (from -3.7 +/- 1.9 to -1.0 +/- 1.0 SDS, p < 0.0025), with a cumulative height gain of 2.7 +/- 1.6 SDS. In spite of this catch-up growth no patient attained the target percentile by the 5th year of therapy and their average height (CA) was still lower with respect to the average target height (TH) at the last check-up. Because of the significant bone age (BA) delay still persisting in most patients, a further and complete catch-up growth is likely to occur during the next years of treatment, as suggested by the finding that average height (BA) at the last examination was higher than average TH. It is concluded that: a) in spite of modern therapeutical schedules with daily GH injections and frequent adjustments of doses, GHD children, even though treated from before two years of age, fail to catch-up completely their initial height deficiency, at least by the 5th year of therapy; b) a more prolonged treatment is probably needed to allow them to attain their target percentile. This emphasizes the importance of both early diagnosis and long-lasting treatment.

Short stature and short trunk have been reported in thalassaemic patients. We report a study on stature and body proportions in 476 patients (2-36 years old) with beta-thalassaemia major, followed in 12 Italian centres. Auxological data (standing height, sitting height, subischial leg length, target height), haematological data (age at first transfusion, age at start of desferrioxamine [DFX] chelation, mean dose of DFX, ferritin values) and information regarding the presence of endocrine disorders and of bone lesions, were collected and analysed according to the age of the patients, in order to investigate the natural history of the disproportion and the role of siderosis, DFX toxicity and endocrine disorders. Our data indicate that about 18% of thalassaemic patients exhibit short stature; disproportion between the upper and lower body segments is present in 14%; however, a short trunk despite normal stature is present in another 40% of patients. This is due to a spinal growth impairment which starts in infancy and progressively aggravates. We think that a short trunk is peculiar to the disease itself; however, other factors such as hypogonadism, siderosis, or DFX-induced bone dysplasia are probably involved in aggravating the body disproportion in these patients.

Literature data on statural growth effect of growth hormone (GH) treatment of children with GH deficiency (GHD) appears disappointing when treatment had late onset. It seems therefore that GH treatment should be started as early as possible, thus requiring early diagnosis. This study was undertaken: 1) to define the main characteristics of early onset GHD which may help the clinician for early diagnosis; 2) to evaluate the effect of a GH treatment on the statural growth of early onset GHD, when treatment is started before 1 year of age. Sixteen children with GHD diagnosed before 1 year of age were included in the study; all of them received a GH treatment before 1 year of age and for a minimal duration of 5 years; four had isolated GHD secondary to a GH gene deletion (type 1A GHD). Based on this series, the main anamnestic and clinical characteristics of early onset GHD are: frequent perinatal pathology, short birth height in more than half of the cases, relatively elevated birth weight in all cases, poor statural growth with neonatal onset, associated signs (hypoglycemia, special facies, micropenis, cryptorchidism, liver dysfunction). The effect of GH treatment (> or = 5 years) on statural growth was limited and transient in children with type 1A GHD, and resulted in an incomplete catch-up growth in children with sporadic GHD, their mean height remaining significantly below their target height.

Thirteen growth hormone deficient infants underwent substitutive treatment for a least 9 years, since less than 5 years of age until adulthood. They presented with average growth failure reaching 4.1 SDS and attained an adult mean height close to target height. In eight subjects final height exceeded the respective target height and only three patients failed to achieve an end height within the target range. The analysis of the factors conditioning ultimate stature pointed out that height outcome correlated negatively with chronological age at therapy initiation and positively with height at puberty onset. It is concluded that full catch-up growth to target percentile is possible in growth hormone-deficient children, provided that substitutive treatment is begun within the 5 years of life. This conclusion is substantiated for the first time by data on end stature.

The present retrospective study is based on a historical follow-up of 49 boys with constitutional delay of growth and puberty (CDGP) who went into puberty spontaneously (27 cases) or induced by depotestosterone treatment, 50 mg/ month for 6 months (22 cases). At the time of puberty the two groups of boys were similar in bone age, height deficiency, target height (TH) and had similar predicted final heights (FH). Their FH was measured and compared with TH calculated from measured parents' heights. FH did not significantly differ between the untreated boys and those treated. In the two groups of patients FH was similar and corresponded to both TH and height predicted at puberty onset. This study confirms that most boys with CDGP spontaneously attain a FH within the target range (24/27 cases). A short-term and low dose course of depotestosterone can be used without adverse effects on FH. The Bayley-Pinneau method can be generally considered accurate for predicting FH in CDGP, although significant discrepancies between FH and predicted height have been recorded in a fair number of both untreated and treated boys.