Jorma Mäenpää

Natural course of juvenile autoimmune thyroiditis

Forty-six patients with juvenile autoimmune thyroiditis were followed for an average of 6.5 years. The diagnosis was based on a firm goiter and on cytologic findings of lymphocytic thyroiditis. The thyroid function and the size of the thyroid gland were regularly evaluated, and thyroid cytologic findings reevaluated once about 4.5 years after the diagnosis was made. Initially, 24 patients were euthyroid, 16 subclinically hypothyroid, and six hypothyroid. At the end of follow-up, 29 patients were euthyroid, six subclinically hypothyroid, and 11 hypothyroid, but there had been an extensive exchange of individual patients among these three groups. At cytologic reevaluation, the changes were virtually unaltered. Thyroid antibodies and circulating immune complexes were repeatedly tested: on one or more occasions, 85% of the patients had positive test results for thyroid antibodies, and about 50% for circulating immune complexes. Hypothyroidism at the end of follow-up correlated with the initial hypothyroid state and with thyroglobulin antibodies of IgG class detected by enzyme immunoassay. The best predictors of the final hypothyroid state were female sex, initial hypothyroidism, IgG thyroglobulin antibodies by EIA, and IgG circulating immune complexes assayed by conglutinin-binding test-EIA.

Gonadotropin-releasing hormone test and human chorionic gonadotropin test in the diagnosis of gonadotropin deficiency in prepubertal boys

The discriminatory power of a gonadotropin-releasing hormone test and a human chorionic gonadotropin test in diagnosing gonadotropin deficiency was studied in 23 prepubertal boys with hypogonadotropic hypogonadism (HH). The boys were originally referred because of genital hypoplasia, delayed sexual maturation, or suspicion of HH. The diagnosis of HH was established clinically, in most cases after follow-up of several years. The results were compared with those of a reference group consisting of 44 prepubertal boys with incomplete testicular descent. Post-hCG serum testosterone level was the most sensitive discriminating variable, and was subnormal in 11 of 12 boys with HH (in one of 16 in the reference group). Post-GnRH serum LH concentration was the second most sensitive, and was subnormal in 15 of 23 boys with HH (two of the reference group). Our data indicate that post-hCG testosterone levels are of greater value than post-GnRH gonadotropin levels in the diagnosis of HH in prepubertal boys.

JUVENILE GOITROUS AUTOIMMUNE THYROIDITIS

In recent years it has become evident that autoimmune thyroiditis (AIT) is by no means a rare disease in children and adolescents (23, 33, 34, 38). It is not clear whether the apparently increasing prevalence of AITl is due to better diagnostic tools and increasing interest in the disease or to a real increase in morbidity. The first alternative seems more probable. The purpose of this paper is to describe the clinical and immunological findings in 22 goitrous children with AIT. The radioiodide studies and investigation of intrathyroidal iodine and protein distribution have been presented elsewhere (26, 31, 32).

Finnish national screening for hypothyroidism

National cord blood screening for congenital hypothyroidism has operated in Finland with complete coverage since 1980. A low frequency of false positives, 0.08%, was achieved by supplementing the TSH screen with a T4 determination in borderline samples. Among 175188 infants the incidence of (unconfirmed) hypothyroidism was 1/2637. The median age at start of therapy was 6 days. The programme imposed a 2–3 week therapy on the false positive cases. This did not appear to cause any adverse effects. A mechanism for masking congenital hypothyroidism was observed: two athyroid infants were euthyroid at birth because of feto-fetal transfusion.

Beneficial effects of palatable guar and guar plus fructose diets in diabetic children.

This randomized cross‐over study evaluates the effects of extended, guar and guar + fructose diets on the metabolic balance of children with insulin‐dependent diabetes mellitus (IDDM). We studied 22 children; mean age 12.2 years, mean duration of diabetes 4.4 years. The diet was supplemented for three weeks with guar in palatable form (5% of daily carbohydrate intake) and with guar + fructose (1 g of fructose/kg body weight, max 30 g/d) for another three weeks. A control group (8 children, mean age 12.3, duration of diabetes 4.3 years) followed the same experimental protocol without guar supplementation. The metabolic balance was assessed by glucosuria index (per cent of tests with less than 1% glucosuria from all urine tests) and measurements of red cell glycohaemoglobin A1c (HbA1c). Serum total and HDL‐choiesterol, C‐peptide, pancreatic and enteroglucagon were also measured. HbA1c decreased during guar (p<0.001) and guar + fructose diet (p<0.001). The glucosuria index improved (p<0.02) and the serum total cholesterol concentration decreased (p<0.02) during the experimental guar diets. Guar in acceptable form and quantity in the diet appears to improve metabolic control of diabetic children.

Antiphospholipid antibodies in children

Sera from children (n= 173) were tested for antiphospholipid antibodies (aPL) using an enzyme immunoassay detecting IgG anti‐cardiolipin antibodies (GPL). Sera from adults (n= 100) were also tested. GPL were detected more frequently and at higher levels in children than in adults. Eighty‐two percent of the children and 27% of the adults tested positive (≥ 10 GPL Uml‐1) for aPL (p <0.001). Values of 45 GPLUml‐1 or higher were detected in about 5% of the children, and 25 GPLUml‐1 or higher in about 5% of the adults. Normal values should be adjusted accordingly.

Childhood hyperthyroidism. Results of treatment.

Abstract. Mäenpää, J. and Kunsi, A. (Childrens Hospital, University of Helsinki and Aurora Hospital Helsinki, Finland.) Childhood hyperthyroidism. Results of treatment. Acts Paediatr Scand, 69: 137, 1980.—40 hyperthyroid children were followed for 0.2–12 (mean 4.5) years. The treatment was antithyroid drugs in 20, subtotal thyroidectomy after a drug trial in 18 and primary thyroidectomy in 2 patients. 4 patients who relapsed (3 after surgery and 1 after a drug trial) were given radioiodide. 11 of the surgically treated glands were nodular. At the follow‐up study 24 patients were euthyroid, 7 were on thyroxine therapy and in 5 others hypothyroidism was discovered. 2 subjects were still on antithyroid drugs and 2 relapsed. In 5 euthyroid patients the TRH test revealed a low thyroid reserve. In 28 of 34 subjects examined circulating antibodies to thyroid microsomes were present in high titres. Evidently, regular follow‐up is needed because of the high risk of hypothyroidism.

Acceleration of delayed growth with fluoxymesterone.

ABSTRACT. 61 boys with constitutional delay of growth and maturation, aged 9‐19 years and with a bone age (BA) lag of 1.3‐5.5 years, were administered fluoxymesterone (0.05‐0.24 mg/kg daily orally, relative dose increasing with age) to accelerate growth. The therapy was continuous and lasted 0.4‐3.6 years. The findings are compared with 37 observation periods in a similar group of untreated boys. Growth velocity increased in every treated boy during the therapy, the mean first‐year increment being 4.3±1.6 cm/year. For most boys this brought about a decrease in the height difference from peers, and so afforded the psychosocial relief that was the objective of the therapy. After therapy the velocity decreased slightly hi most boys, from a mean of 9.1±1.4 to 7.1±3.3 cm/year. The effect of the intervention on final height was assessed by three relatively independent methods of prediction. These were found to be equally valid in the 15 control boys for whom final heights are known. The effect appeared to vary individually, but on the average there appeared to be no loss of height potential. No individual boy with initial BA>10.5 years showed a substantial reduction in predicted final height.

Antibodies against some bacterial antigens in children

The prevalence of bacterial antibodies was determined in 173 children aged 0–15 years. The prevalence of IgG Borrelia burgdorferi antibodies in titres > 500 in children less than 8 years of age was 6% while none of the older children had these antibodies in titres > 400. IgG Helicobacter pylori antibodies were detected only in children older than 6 years of age, with a prevalence of 6.5%, as were IgA H. pylori antibodies, with a prevalence of 3.7%. The prevalence of high‐titre IgG Campylobacter jejuni antibodies was 1.2%, that of IgA 1.8% and IgM 1.2%. The prevalence of high‐titre (> 500 IU/ml) antistreptolysin O was 3%, that of antistaphylolysin‐alpha (≥ 4 IU/ml) 2% and that of antiteichoic acid antibodies (titre 2) 2%. Low‐titre Yersinia antibodies were detected in 2%. High‐titre Bordetella pertussis antibodies were detected in 6% of recently vaccinated children and in 8% of children in their first years of school. In the latter, high‐titre antibodies were mainly of the IgM and IgA classes. Altogether 35 children tested positive for bacterial antibodies other than Bordetella pertussis antibodies. Clinical evaluation revealed a possible infection, suggested by the antibody, in 5 (3%) of the children. Two (vaccinated) children had evidence of whooping cough. Eight of the 35 children with high‐titre bacterial antibodies (23%) also had elevated levels of autoantibodies (but not autoimmune diseases).

GASTRIC FINDINGS IN ADOLESCENTS TREATED FOR GRAVES‘ DISEASE

It is well known that Graves’ disease is often associated with other autoimmune diseases. In the adult population this association most frequently involves atrophic gastritis (2, 7). Furthermore, Irvine et al. (3) observed that approximately 3 % of patients with autoimmune achlorhydric gastritis per follow-up year progress to latent pernicious anaemia. Abnormal gastric mucosa has also been revealed in autoimmune thyroiditis and hypothyroidism in both children and adults (2, 5). Little information on gastric mucosa is available concerning children and adolescents with Graves’ disease. We therefore considered gastric investigations important for juvenile patients with Graves’ disease, especially with a view to their long-term prospects. During the period 1965-1976 we treated 40 patients for hyperthyroidism. Criteria for the diagnosis and the clinical data have been presented elsewhere (6). After a follow-up period of 0.5 to 10.2 (mean 4.4) years, 33 patients (29 females, 4 males) underwent gastric investigations. The patients’ ages ranged from 11.1 to 24.8 (mean 19.1) at the time of the study. Methods for taking gastric biopsies, classifying the gastric histology, determining the serum vitamin B,, level and antibodies against gastric parietal cells, nuclei, intrinsic factor (3, thyroglobulin and thyroidal microsomes (6) have been reported earlier. The gastric acid secretion was studied with the pentagastrin test and the reference values described by Dodge were used (1). The gastric mucosa was abnormal in seven (26%) of 27 patients studied (Table 1). The mucosal damage was slight or moderate, whereas the most severe form, gastric atrophy was not found at all. Achlorhydria was merely found in three and a subnormal response to pentagastrin stimulation (hypochlorhydria) in four out of 29 patients studied. One of the two patients with atrophic gastritis had achlorhydria and the other had hypochlorhydria. Slight mucosal changes associated with hypochlorhydria in two and a normal mucosa was found in two achlorhydric and in one hypochlorhydric patient. Twelve (36 %) had gastric parietal cell antibodies, but only one of them had achlorhydria and two had hypochlorhydria. The serum B,, level in each patient was normal. None had antibodies against intrinsic factor or nuclei. Thyroglobulin antibodies were found in titres of 21 : 25 in 12 and microsomal antibodies in titres 3 1 : lo5 in 23 of 27 subjects who underwent gastric biopsy. According to Siurala et a]. (8) the frequency of gastritis is 29% in the age group 16-30 years in a Finnish rural community. In,their study the degree of gastritis was mainly mild: only four of the 48 subjects (8%) had atrophic gastritis. Gastric parietal cell and intrinsic factor antibodies were discovered in the age group 1 6 5 0 years in 31% and 195, respectively (4). The prevalence or the degree of gastritis in our patients did not differ from those in a normal population (8). Our patients with autoimmune thyroiditis or hypothyroidism (5) had more (39%) and severer forms of gastritis compared with the present series, but the difference is not statistically significant. Gastric parietal cell antibodies were, however, significantly more often found (in 36 %) than in normal population (4) (x’ 27.7, p<O.OOl), but