Children with insulin-dependent diabetes mellitus (IDDM) were examined for scleroderma-like changes of digital sclerosis and joint contractures. Of the 104 patients, 19 (18%) demonstrated these features; five patients had both multiple joint involvement and skin changes; three were studied in detail. All three had restrictive pulmonary disease. Histopathology of skin in these three patients demonstrated increased accumulation of collagen in the lower dermis. In two of the patients, the extractability of collagen in 0.5 N acetic acid was decreased by about 50% as compared with normal controls, which suggests increased cross-linkage of collagen. In addition, the mean nonenzymatic glycosylation of collagen in these three patients was 13 times that of controls. The results indicate that distinct histopathologic and biochemical changes can be detected in the skin of these patients. The results further support the hypothesis that nonenzymatic glycosylation may alter the turnover of collagen, thus contributing to the development of a scleroderma-like syndrome with skin, joint, and pulmonary findingsin patients with IDDM.

104 children with IDDM were examined for induration and thickening of the skin and for joint contractures. Five patients had both multiple joint involvement and skin changes; 3 were studied in detail. Their diabetes ranged from 7-16 years in duration and was characterized by short stature, hepatomegaly, 4 to 6 hospitalizations each year, and glucosylated Hgb levels of 12-16%. All 3 had restrictive pulmonary lung disease. Histopathology of skin biopsies (bxs) demonstrated increased accumulation of collagen in the lower dermis. Three skin bxs were homogenized and compared to 6 bxs from age matched controls. The extractability of collagen in 0.5 N acetic acid was decreased to about ½ normal in 2 of the patients, suggesting increased cross-linkage of collagen. The amount of hexose bound to protein in a ketoamine linkage was assayed as the 5-hydroxymethylfurfural derivative. In patients, the mean non-enzymatic glucosylation was 4.0 (range 0.9-8.5) ng hexose/ug hydroxyproline which was 13 times that of controls (mean=0.3, range 0.2-0.4, ng hexose/ug hydroxyproline). The results suggest that non-enzymatic glucosylation may alter the packing, cross-linking and turnover of collagen, thus contributing to the development of a scleroderma-like cutaneous syndrome in IDDM.

A 2-year-old boy became ill with diabetic ketoacidosis complicated by severe rhabdomyolysis. He completely recovered from the rhabdomyolysis, but has persistent insulin-dependent diabetes mellitus (IDDM). Serological studies showed that the patient's serum contained high titers of coxsackievirus B4 antibody, suggesting that the development of rhabdomyolysis and IDDM may have been related to this infection. A review of the records of 133 patients admitted with onset of IDDM disclosed one additional patient with marked myoglobinuria, and 11 patients with orthotolidine-positive urine in the absence of hematuria. These findings suggest that myoglobinuria may not be uncommon at the onset of IDDM.

The results of medical and surgical therapy were determined in 107 hyperthyroid children. After surgery, 85% of patients were rendered free of hyperthyroidism; however, 62% became hypothyroid. After medical treatment, 30% of patients were euthyroid and 2% became hypothyroid. The relapse rate, however, was higher after medical (22%) than after surgical (9%) therapy. Serious drug-related complications (arthritis-, hepatitis-, and collagen disease-like syndromes) occurred in 14% of patients. Complications occurred in 9% of surgically treated patients, but recurrent laryngeal nerve injury or permanent hypoparathyroidism did not occur. In medically treated patients, both a goiter size less than three times normal prior to treatment and a reduction in goiter size to less than two times normal at the completion of therapy correlated with a successful outcome.

A pediatric patient (pt) with Graves disease and circulating anti-Tg antibody (ab) levels developed ICGN characterized by mesangial, subendothelial and subepithelial dense deposits by electron microscopy. Renal cortex tissue examined by direct immunofluorescence (IF) demonstrated granular glomerular immunoglobulin (Ig) and complement (C1) deposition. Indirect IF demonstrated granular glomerular and mesangial deposits of HuTg. Indirect IF also showed that eluates of the pt's kidney contained (ab) reactive with thyroid follicular cells and colloid. CICs were demonstrated in the pt's sera by both the Raji cell assay and CIq solid phase assay. The indirect IF Raji assay demonstrated HuTg in ICs bound to the Raji cells. That HuTg was the antigenic component of CICs was further documented by a marked decrease Raji cell binding of CICs in the pt's sera when the sera was preincubated with HuTg. ICs eluted from both renal cortex tissue and CICs bound to Raji cells were analyzed by immunoelectrophoresis techniques and found to contain HuTg. We concluded that HuTg-anti-HuTg CICs have nephritogenic capacity and are important in induction and perpetuation of ICGN.

Between November 1964 and August 1978, 66 patients underwent subtotal thyroidectomy for hyperthyroidism. Fifty-seven of these patients have been followed for more than 2 yr postoperatively and form the basis for this report. The mean age of these patients was 11 7/12 yr. There wre no deaths in this series and no recurrent laryngeal nerve injuries. Hyperthyroidism recurred in 4 patients from 10 to 60 mo following surgery (mean of 30 mo). Patients with relapse had a significantly larger gland at operation, but no difference in estimated thyroid remnant. Those patients with larger glands at exploration need a relatively larger percentage of the gland removed to prevent recurrent hyperthyroidism.

During the past ten years, subtotal thyroidectomy for hyperthyroidism was performed upon 43 children at Childrens Hospital of Los Angeles. There were no deaths, no recurrent laryngeal nerve injuries and no permanent hypoparathyroidism. During the one to ten year follow-up period, one patient had recurrent hyperthyroidism develop and was treated with 131I. Twenty-five patients are hypothyroid and require thyroid supplement; 14 are euthyroid and receiv no medication. Postoperative thyroid function did not correlate well with gland remnant size, degree of fibrosis or the extent of lymphoid follicle formation. Lymphocytic infiltration was more severe in patients who had hypothyroidism develop postoperatively. Transient hypocalcemia developed in 22 patients. The effectiveness and safety of the surgical treatment for hyperthyroidism in children is reaffirmed, and it is advocated for consideration over 131I or prolonged medical therapy.