P. Tassoni

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.

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.

Differences in somatomedin-C between short-normal subjects and those of normal height*

We evaluated basal somatomedin-C (SmC) levels in 98 subjects 2 to 16.6 years of age, with height less than 3rd centile (Tanner), and in 274 healthy controls 2 to 15.8 years, with height greater than 10th centile. Growth-retarded subjects were defined as short-normal when they had normal GH release (greater than 8 ng/ml) in at least one of three tests: arginine, L-dopa, and sleep. In control subjects, there was a significant positive correlation between SmC levels and chronologic age, bone age, and pubertal stage (pubic hair, breast or testicular volume). The same correlations were present in short-normal subjects, but SmC levels were significantly lower than in normal children. The percentage of subjects with very low SmC values (less than or equal to 0.25 IU/ml in those older than 6 years, and less than 0.1 IU/ml in those younger than 6 years) was higher in the short-normal group of children older than 6 years. In growth-retarded subjects, SmC values were significantly higher (P less than 0.005) in subjects with normal GH response in at least one of the two pharmacologic tests, compared with those with normal GH response only during sleep. We conclude that short-normal subjects have, on average, low SmC values, which might indicate insufficient GH release. Therefore, current criteria to define GH deficiency and children needing treatment may be too restrictive.

GH, ACTH, LH AND FSH BEHAVIOUR IN THE FIRST SEVEN DAYS OF LIFE

Abstract. 43 neonates, born vaginally after spontaneous labor between the 38th and the 42nd week of pregnancy, were examined. GH and ACTH levels were assayed in 14 newborn infants. LH and FSH were determined in the remaining 29 patients (16 boys and 13 girls). Samples were collected from all infants for the assay of the above mentioned hormones at the 2nd, 6th, 12th and 24th hour of life, then every day for 7 consecutive days. During the whole first week of life plasma GH gave values that were significantly higher than those found in subjects over four years of age. The highest mean value of plasma ACTH was found at the 2nd hour of life (162.2±34.1 pg/ml). Then, there is a significant fall in the hormone level beginning with the 12th hour (p<0.01). Minimum level was reached on the 7th day. Plasma hCG‐LH presents its maximum mean value at the 2nd hour, both in boys and girls (48.5±16.2 and 33.0±24.9 mU/ml, respectively). After this, plasma hCG‐LH decreases progressively. No significant differences between the two sexes were found. Even though the mean values of plasma FSH do not change significantly, during the whole test period, they do demonstrate a sex difference (significantly higher values in the females) from the fifth day afterwards.

Response to growth hormone therapy in patients with growth hormone deficiency who at birth were small or appropriate in size for gestational age

OBJECTIVE To determine long-term growth response to growth hormone (GH) therapy in patients with isolated GH deficiency who had been small for gestational age and in those who had been appropriate in size for gestational age. DESIGN Longitudinal, case-control study. SETTING Pediatric clinic, endocrinology center, University of Bologna, Italy. PATIENTS Sixteen GH-deficient children, small for gestational age with unknown cause, and 16 GH-deficient children, appropriate in size for gestational age, who were matched for chronologic age, bone age, pubertal stage, and target height at the beginning of treatment and were treated for 36 months. INTERVENTION Recombinant human GH given subcutaneously at a dose of 20 IU/m2 per week in six doses per week for 36 months. MEASUREMENTS Growth hormone levels (fluoroimmunoenzymatic method), levels of insulin-like growth factor I (radioimmunoassay), and complete 36-months auxologic follow-up. RESULTS Patients who were small for gestational age had a modest improvement in height for chronologic age but no increase in predicted final height. Patients who were appropriate in size for gestational age had significantly better improvement in both measurements (multivariate analysis of variance: F = 6.3 (p < 0.001) and F = 3.8 (p < 0.05), respectively). Catch-up growth was similar during the first year of therapy for the two groups, after which the linear growth velocity decreased more rapidly in the small-for-gestational-age patients (multivariate analysis of variance: F = 4.9 (p < 0.05)). CONCLUSIONS The constitutional component of the statural deficiency of small-for-gestational-age children seemed to prevail over hormonal deficiency during treatment with GH. Further follow-up to final height is necessary to evaluate these different responses.

Thyroid Function and Prolactin Levels in Insulin-dependent Diabetic Children and Adolescents

We evaluated serum thyroid hormones, TSH, and prolactin before and after induction of TRH and thyroid microsomal autoantibodies in 91 diabetic children and adolescents (mean age 11.11 ±4.13 yr), with illness ranging from a few days to 14.25 yr, and in 127 “short-normal” subjects (mean age 10.32 ± 3.18 yr). All were clinically euthyroid. The control pubertal subjects showed T4, rT3, TBG, and rT3/T3 ratio values that were significantly lower than those of prepubertal subjects. The PRL area was significantly higher in pubertal than in prepubertal females. In diabetic patients, differences between pubertal and prepubertal subjects were similar to those of controls regarding T4 levels and PRL area only. T3, T4, and fT3 appeared to be significantly lower than in controls, while the rT3/T3 ratio was higher. A negative correlation (r = −0.277, P = 0.009) between T3 and HbA1 levels was demonstrated. Furthermore, thyroid function was not different in subjects with or without retinal changes or in subjects with or without residual B-cell function. Microsomal autoantibodies were observed in 6.25% of the subjects examined, though none showed any clinical or humoral sign of impaired thyroid function. In conclusion, the lower T4 and rT3 values detected in pubertal controls suggest an increased efficacy of peripheral thyroid activity in this particular life span. Considering the fact that, in diabetic children, such a decrease in rT3 at puberty is not present and that the T3 value in diabetic children is persistently lower than in controls, it would seem that even diabetic children show a “low T3 syndrome”, as in adult diabetic subjects.

EFFECT OF OBESITY ON THE HYPOTHALAMO‐PITUITARY‐GONADAL FUNCTION IN CHILDHOOD

Abstract. In 22 normal and 35 obese boys a gonadal function test (2 000 IU of hCG i. m. daily for three days and assays of plasma testosterone before and after the hCG administration) was carried out. All the “short normal” children and 31 obese subjects underwent the LH‐RH test (50 μg i.v.). While basal testosterone was similar in the two groups of children, after hCG testosterone was significantly (p<0.001) lower in the obese boys. In the normal children a significant positive correlation between bone age and basal and after hCG testosterone was demonstrated; this correlation was not found in the obese boys. The pituitary reserve of gonadotrophins did not show significant differences between the two groups of children. Finally a significant positive correlation (p<0.01) between the LH curve area during the LH‐RH test and bone age was found only in the normal boys.