Piero Pirazzoli

Short stature and celiac disease: A relationship to consider even in patients with no gastrointestinal tract symptoms

To determine the incidence of celiac disease in a group of nonselected children with short stature, duodenal biopsy was performed in 60 unselected children with short stature (below third centile) and absence of gastrointestinal tract symptoms. Examination revealed probable celiac disease in five children (8.3%). Analysis of the results of other tests that might possibly be considered as alternatives to biopsy (e.g., xylose test, antireticulin antibodies, gastrointestinal tract symptoms in the first two years of life, bone age, serum iron, iron load, triglyceride load) led us to conclude that no test or clinical measurement could have allowed us 100% certainty in making the correct diagnosis. None of the children with celiac disease had growth hormone deficiency. We conclude that asymptomatic celiac disease represents a cause of short stature that cannot be ignored, and that only by intestinal biopsy can all such patients be identified.

CAN ANTIGLIADIN ANTIBODY DETECT SYMPTOMLESS COELIAC DISEASE IN CHILDREN WITH SHORT STATURE

Duodenal biopsy and tests for antigliadin antibodies were done in 108 children with short stature unassociated with gastrointestinal symptoms. Other investigations for causes of growth failure were also carried out. In 88 patients, the cause of short stature could not be determined (group I). In 9 patients (8.3%) biopsy showed total villous atrophy, indicating probable coeliac disease (group II), while 7 patients had mild partial villous atrophy (group III). 4 patients (3.7%) had complete growth hormone deficiency. Antigliadin antibodies detected by immunofluorescence (IFL-AGA) were positive in 8 of the 9 group II patients. Symptomless coeliac disease is therefore a commoner cause of short stature than is hypopituitarism; by use of the IFL-AGA test it is possible to select patients for biopsy, thereby identifying most of the coeliac patients. If duodenal biopsies had been limited to IFL-AGA positive patients, 18 biopsies would have been carried out and coeliac disease would have been diagnosed in 8 of the 9 patients.

How many cases of true precocious puberty in girls are idiopathic

Fifteen girls with true precocious puberty were examined by computerized tomography. In seven hypothalamic hamartomas were suspected. A pneumoencephalogram was performed in six cases (one patient refused), with the following results. In five, the radiological features were highly suggestive of tuber cinereum hamartoma. All of our patients with pubertal signs appearing before the age of 2 years and 80% of the girls with early menstruation were in the group with suspected hamartoma. The luteinizing hormone and follicle-stimulating hormone levels of these five girls were significantly higher than those observed in the other girls with idiopathic precocious puberty. We conclude that there is a high frequency of small hypothalamic masses (suspected hamartoma) in girls with true precocious puberty (33% of the patients in our group), that it is important to confirm the presence of the mass with pneumoencephalography, and that surgery for diagnostic and therapeutic purposes should be carefully considered, given the absence of any neurologic symptoms for a long time after the appearance of the first pubertal signs.

Intravenous high-dose immunoglobulin treatment in recent onset childhood narcolepsy with cataplexy

We report on the outcome of intravenous high-dose immunoglobulin (IVIg) treatment in four children with narcolepsy and cataplexy, in whom the early diagnosis and the extreme disease severity were indications for this potentially efficacious therapy. One of four patients showed an objective and persistent improvement in clinical features during and after IVIg treatment. Our data partially support the recent report of the efficacy of IVIg treatment in early diagnosed narcolepsy with cataplexy and support the need for a controlled multicenter clinical trial on IVIg in narcolepsy.

CYP21 analysis and phenotype/genotype relationship in the screened population of the Italian Emilia–Romagna region

We have genotyped the patients with congenital adrenal hyperplasia due to 21‐hydroxylase deficiency identified from March 1980 to December 1997 through a combined program of neonatal screening and case survey in the Emilia–Romagna Region (Italy). We have also analysed retrospectively the possible advantages of genotypical neonatal classification.

High Prevalence of Precocious Puberty and Obesity in Childhood Narcolepsy with Cataplexy

STUDY OBJECTIVES We analyzed the potential predictive factors for precocious puberty, observed in some cases of childhood narcolepsy with cataplexy (NC) and for obesity, a much more common feature of NC, through a systematic assessment of pubertal staging, body mass index (BMI), and metabolic/endocrine biochemical analyses. DESIGN Cross-sectional on consecutive recruitment. SETTING Hospital sleep center and pediatric unit. PATIENTS Forty-three children and adolescents with NC versus 52 age-matched obese children as controls. INTERVENTIONS N/A. MEASUREMENTS AND RESULTS Patients underwent clinical interview, polysomnographic recordings, cerebrospinal fluid hypocretin-1 measurement, and human leukocyte antigen typing. Height, weight, arterial blood pressure, and Tanner pubertal stage were evaluated. Plasma lipid and glucose profiles were analyzed. When an altered pubertal development was clinically suspected, plasma concentrations of hypothalamic-pituitary-gonadal axis hormones were determined. Children with NC showed a high prevalence of overweight/obesity (74%) and a higher occurrence of precocious puberty (17%) than obese controls (1.9%). Isolated signs of accelerated pubertal development (thelarche, pubic hair, advanced bone age) were also present (41%). Precocious puberty was significantly predicted by a younger age at first NC symptom onset but not by overweight/obesity or other factors. In addition, overweight/obesity was predicted by younger age at diagnosis; additional predictors were found for overweight/obesity (short disease duration, younger age at weight gain and lower high-density lipoprotein cholesterol), which did not include precocious puberty. NC symptoms, pubertal signs appearance, and body weight gain developed in close temporal sequence. CONCLUSIONS NC occurring during prepubertal age is frequently accompanied by precocious puberty and overweight/obesity, suggesting an extended hypothalamic dysfunction. The severity of these comorbidities and the potential related risks require a multidiagnostic approach and a tailored therapeutic management.

SRD5A2 gene analysis in an Italian population of under-masculinized 46,XY subjects

Objective  The differential diagnosis of male under‐masculinization, including a wide spectrum of phenotypes and a heterogeneous genetic basis, is crucial for the correct management of the patients. To characterize an Italian population of under‐masculinized males, we performed the molecular analysis of the SRD5A2 gene (2p23), encoding the 5α‐reductase‐2 enzyme that converts testosterone (T) to dihydrotestosterone (DHT), and is required for full masculinization of the male foetus.

Prevalence and Characteristics of Coeliac Disease in Type 1 Diabetes Mellitus

Coeliac disease in patients with insulin-dependent diabetes mellitus has been reported (1-3) and the appearance of diabetes mellitus in subjects with coeliac disease in also well-known. In our recent study regarding a group of children with short stature (7), we reported that antigliadin antibody evaluation is the test most suited for this purpose. Thus, we used this method to study the exact prevalence of coeliac disease in a group of children and adolescents with type 1 diabetes mellitus. We examined 146 children and adolescents with insulin-dependent diabetes mellitus (IDDM) (76 males and 70 females) aged 2 3/12-22 7/12 years (mean k SD = 11.42?5.16), in whom duration of the disease varied from 0 to 17 2/12 years (mean f SD = 4.25k4.25). None of the children had gastrointestinal symptoms suggesting coeliac disease. A serum sample for antigliadin antibodies (AGA) as determined by immunofluorescence (IFL-AGA) (8) or by ELISA (ELISA-AGA) (6), islet cell antibodies (ICA), complement fixing islet cell antibodies (CfICA), thyorid microsomal (TMA), gastric parietal autoantibodies (PCA), liver-kidney microsome antibodies (LKM), non organ specific autoantibodies was obtained from each patient. Sixtynine patients were typed for HLA A, B, C and DR antigens. All patients who had antigliadin antibodies underwent jejunal biopsy. Informed consent was obtained from the parents and the children. Students t-test and 2 was used to analyze the results.

Functional studies of two novel and two rare mutations in the 21-hydroxylase gene

Congenital adrenal hyperplasia (CAH) is most commonly due to 21-hydroxylase deficiency and presents with a wide spectrum of clinical manifestations, from prenatal virilization and salt-wasting in the neonatal period to precocious pubarche and late-onset hyperandrogenic symptoms during adulthood. A limited number of mutations account for the majority of all mutated alleles, but a growing number of rare mutations are responsible for the disease in some patients. By sequence analysis of the CYP21A2 gene, we identified two novel (I171N and L446P) and two rare (R341P and R426H) mutations in seven Italian patients with CAH. One of the patients was diagnosed with mild non-classical CAH and was found to be a compound heterozygote (I171N/V281L), while all other patients showed severe phenotypes with latent or manifest salt-wasting. The residual activities measured after expression of the four mutant enzymes in COS-1 cells were all below 1% towards both natural substrates (17-OH-progesterone and progesterone) compared with the wild-type protein. All four mutations are, thus, associated with severe enzyme deficiency and are predicted to cause classic CAH if found in trans with other mutations causing severe enzyme deficiency.

Low serum inhibin B levels as a marker of testicular damage after treatment for a childhood malignancy.

Abstract The aim of this study was to evaluate the role of inhibin B and the determination of its concentration to diagnose testicular damage after treatment for a childhood malignancy. Thirty-seven males treated for Hodgkin disease (n=11) or non-Hodgkin lymphoma (n=26) were examined at a mean age of 16.9 ± 2.9 years. Mean age at the stop of therapy was 11.3 ± 3.0 years and in most cases the chemotherapy regimen included gonadal damaging alkylating agents. Thirty-three normal males (mean age 17.9 ± 4.1 years) were examined as controls. Serum samples were collected for determination of inhibin B, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone. Median inhibin values were significantly lower in patients than in controls (96.0 vs 225.0 pg/ml, P < 0.0001) and a strong negative correlation was found between inhibin B and FSH (r=−0.86, P < 0.0001), a weak correlation with LH (r = −0.32, P < 0.05) and no correlation with testosterone. In post-pubertal patients (i.e., over 16 years) a positive correlation was found between testicular size and inhibin level (r=0.53, P < 0.05), but not between testicular size and testosterone level. Pathological low levels (values that differed by more than 2 SD from the mean value of control subjects) were found in 20 patients for inhibin B and 8 for testosterone (P < 0.01) and pathological high values in 19 patients for FSH and 3 for LH. Conclusion This study confirms the role that inhibin B plays in the regulation of FSH secretion and provides further evidence of the utility of its evaluation as a direct indicator of male gonadal dysfunction.