Pat Mahachoklertwattana

Short-term cyproheptadine therapy in underweight children: effects on growth and serum insulin-like growth factor-I.

BACKGROUND Cyproheptadine, an appetite stimulant, has been used in poor-appetite underweight children. Its beneficial effects on enhancing growth rate have been demonstrated. In contrast, an adverse effect on blunting growth hormone (GH) secretion has also been reported. To date, however, its effect on insulinlike growth factor-I (IGF-I), a GH-mediated growth factor, has not been documented. AIM To examine the effect of cyproheptadine therapy on growth and serum IGF-I in underweight children. METHODS Twenty-one underweight, otherwise healthy children were recruited. They were randomly assigned into cyproheptadine administration (n = 10) and placebo (n = 11) groups. The former received cyproheptadine for 4 months. Serum IGF-I levels were measured in both groups. RESULTS Weight and height velocities and IGF-I z-scores during cyproheptadine therapy were significantly greater in the intervention group than those of the placebo group. CONCLUSION Cyproheptadine therapy in underweight children increased caloric intake and serum IGF-I concentration and consequently enhanced growth velocity.

Eponym : de Quervain thyroiditis.

de Quervain thyroiditis is a self-limited inflammatory disorder of the thyroid gland. It is an uncommon disease in adults and very rare in children. Fritz de Quervain, a Swiss surgeon, who was an authority on thyroid disease, described the unique pathology of this disease. Granulomatous changes with giant cells in thyroid tissue are the pathological findings. Viral infection in genetically predisposed individuals has been proposed as the pathogenesis of the disease. Clinical hallmarks for the diagnosis are painful thyroid enlargement, elevated erythrocyte sedimentation rate, and C-reactive protein as well as decreased uptake of the thyroid gland on thyroid scintigraphy. In addition, thyrotoxicosis is present in about 50% of cases in early phase of the disease. Serum thyroglobulin level is usually elevated. Only symptomatic treatment with analgesics is usually required for pain relief. Glucocorticoid therapy may be used in severely ill patients. de Quervain thyroiditis is generally completely resolved without complications in 6-12 months. However, permanent hypothyroidism and recurrent disease have been reported in some patients.

Glucose metabolism in obese and lean adolescents with polycystic ovary syndrome.

Abstract Data on glucose metabolism in Asian adolescents with polycystic ovary syndrome (PCOS) are limited. Glucose metabolism assessment using an oral glucose tolerance test (OGTT) in obese and lean Thai adolescents with PCOS, and a comparison between the two groups were done. Thirty-one patients (19 obese, 12 lean) were enrolled. Their median (range) age was 14.9 (11.0–21.0) years. Eighteen patients had abnormal glucose metabolism (13 hyperinsulinemia, 4 impaired glucose tolerance, and 1 diabetes). Compared between obese [median (range) BMI Z-score, 1.6 (1.2–2.6)] and lean [median (range) BMI Z-score, 0.1 (–1.4 to 0.6)] patients, the frequencies of each abnormal OGTT category, areas under the curves of glucose and insulin levels, and insulinogenic index were not different; however, insulin resistance was greater in the obese group. In conclusion, a high proportion of our adolescents with PCOS had abnormal glucose metabolism. Therefore, OGTT should be performed in adolescents with PCOS for the early detection of abnormal glucose metabolism.

Exogenous subclinical hyperthyroidism during adolescence: effect on peak bone mass.

BACKGROUND Chronic subclinical hyperthyroidism induced by suppressive doses of L-thyroxine (L-T4) therapy, so-called exogenous subclinical hyperthyroidism, may cause diminished bone mass in postmenopausal women. The effect of subclinical hyperthyroidism during childhood and adolescence on peak bone mass, however, has not been evaluated. OBJECTIVE To determine whether exogenous subclinical hyperthyroidism during adolescence, the period of critical bone mass acquisition, would reduce peak bone mass. PATIENTS AND METHODS Eighteen female adolescents and young adults with Hashimotos thyroiditis and euthyroid goiter (aged 22.4 +/- 4.4 years) who had been treated with suppressive doses of L-T4, 127.5 +/- 23.7 microg/day, during adolescence (age at onset of subclinical hyperthyroidism, 14.2 +/- 1.5 years) for 6.3 +/- 3.4 years were enrolled in the study. Twenty-nine healthy female volunteers matched for age, weight, height and body mass index served as the controls. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. RESULTS BMD of the lumbar spine, radius, Wards triangle and total body were comparable in the two groups. In contrast, BMD of the femoral neck, trochanter and shaft of patients was slightly higher than those of controls. There were no correlations between BMD values and clinical parameters. CONCLUSION Exogenous subclinical hyperthyroidism during adolescence has no demonstrable detrimental effect on peak bone mass attainment.

Gonadal function of beta-thalassemics following stem cell transplantation conditioned with myeloablative and reduced intensity regimens.

Abstract Gonadal dysfunction is a complication following stem cell transplantation (SCT). There have been no reports of gonadal function in stem-cell-transplanted thalassemic survivors who received a reduced intensity conditioning regimen (RIC). We evaluated gonadal function in 47 β-thalassemic patients following SCT with either myeloablative or reduced intensity regimen. Thirty-six patients received a myeloablative regimen, the remaining 11 patients had an RIC regimen. Their median (range) age was 13.2 (5.9–25.8) years. There were 29 patients (62%) with gonadal dysfunction (26 with primary gonadal dysfunction and three with gonadotropin deficiency). Comparisons between patients who received myeloablative and RIC regimens, revealed no differences in gonadal dysfunction (56% vs. 82%, p=0.113, respectively). In conclusion, our study demonstrated high frequency of gonadal dysfunction in these patients. Even after receiving RIC, gonadal dysfunction was very common. To our knowledge, this study is the first to report gonadal function in children and adolescents with β-thalassemia disease who were pre-transplanted with RIC.

Acute suppurative thyroiditis in young children.

We report two children with acute suppurative thyroiditis (AST). They presented with typical features of AST, which include fever, painful goiter and biochemical euthyroidism. An anatomical defect predisposed to thyroid infection, pyriform sinus fistula, was identified in one patient. Both patients responded well to surgical pus drainage and antibiotic treatment. Anatomical defects must be sought in all children with AST to perform specific surgical treatment and prevent recurrent infection.

Use of in vivo gene expression of isolated bone marrow mesenchymal stromal cells to study the pathophysiology of osteoporosis in patients with severe thalassemia.

We compared osteoblast differentiation gene expressions in the isolated CD105+ mesenchymal stromal cells from bone marrow in 10 patients with severe thalassemia and 12 normal donor controls. The fold expressions of osteoblast differentiation genes of CD105+ cells from patients with thalassemia were lower than those of normal donors but increased after being cultured in Dulbeccos modified Eagles medium with 10% fetal calf serum. Moreover, the fold expressions of these genes of CD105+ cells from normal donors when cultured with 10% pooled serum of patients with thalassemia were lower than when cultured with 10% pooled serum of normal donors. We have also presented the evidence of reversible suppressed expression of these genes in CD105+cells from patients with thalassemia when cultured in pooled serum of normal donors. Moreover, healthy donor CD105+ cells exhibited lower expression of these genes when cultured in pooled serum of patients with thalassemia compared with pooled serum of normal donors indicating the existence of circulating factors in thalassemic serum impairing the differentiation of mesenchymal stromal cells to osteoblasts.

Under-recognized Hypoparathyroidism in Thalassemia

Objective: Symptomatic hypoparathyroidism [symptomatic hypocalcemia without elevated serum parathyroid hormone (PTH)] in patients with thalassemia is relatively rare. Asymptomatic mild hypocalcemia without elevated PTH, which is considered hypoparathyroidism, may be more common but under-recognized. Methods: Sixty-six transfusion-dependent thalassemic patients and 28 healthy controls were enrolled. Serum calcium (Ca), phosphate (P), creatinine (Cr), albumin, intact PTH, 25-hydroxyvitamin D (25-OHD), plasma intact fibroblast growth factor-23 (FGF-23), urinary Ca, P and Cr were measured. Tubular reabsorption of P was calculated. Results: Thalassemic patients had significantly lower median serum Ca levels than the controls [8.7 (7.8-9.7) vs 9.6 (8.7-10.1) mg/dL, p<0.001]. Hypoparathyroidism was found in 25 of 66 (38%) patients. Symptomatic hypoparathyroidism was not encountered. Thalassemic patients also had significantly lower median plasma FGF-23 levels than the controls [35.7 (2.1-242.8) vs 53.2 (13.3-218.6) pg/mL, p=0.01]. In patients with hypoparathyroidism, median plasma FGF-23 level was significantly lower than that of normoparathyroid patients [34.8 (2.1-120.0) vs 43.1 (3.2-242.8) pg/mL, p=0.048]. However, serum P, Cr, intact PTH and 25-OHD levels were not significantly different in the two groups. Conclusion: Hypoparathyroidism was not uncommon in patients with transfusion-dependent thalassemia treated with suboptimal iron chelation. Plasma intact FGF-23 level in hypoparathyroid patients was lower than that of normoparathyroid patients.

Acute Effects of Blood Transfusion on Insulin Sensitivity and beta-Cell Function in Children with beta-Thalassemia / HbE Disease

Objective: To assess the acute effects of blood transfusion on insulin sensitivity and pancreatic β-cell function in thalassemia patients. Methods: Fifty children and adolescents with β-thalassemia/HbE disease were enrolled in a prospective cohort study. Hemoglobin, serum ferritin and oral glucose tolerance test (OGTT) were performed prior to, and one week after blood transfusion. Insulin sensitivity indices [homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR), whole body insulin sensitivity index (WBISI)] and β-cell function indices [HOMA of β-cell function (HOMA-β), insulinogenic index (IGI), and disposition index (DI)] were calculated from glucose and insulin levels obtained during the OGTT. Results: Following blood transfusion, hemoglobin and serum ferritin increased significantly; 8.5 to 10.1 g/dL (p<0.001) and 1764 to 2160 ng/mL (p<0.001), respectively. β-Cell function indices also increased significantly [median HOMA-β: 74.3 vs. 82.7 (p=0.033); median IGI: 59.6 vs. 79.3 (p=0.003); median DI: 658 vs. 794 (p=0.01)]. However, the insulin sensitivity index (WBISI) tended to decrease and the insulin resistance index (HOMA-IR) tended to increase although this did not reach significance. Multivariate analysis showed that pre-transfusion serum ferritin was the major factor negatively associated with WBISI and positively associated with HOMA-IR, but pre-transfusion hemoglobin had no significant association with insulin sensitivity indices post-transfusion. Conclusion: This study demonstrated that acute increases in serum ferritin and hemoglobin following blood transfusion in patients with thalassemia might contribute to an increase in insulin secretion and to a trend towards increased insulin resistance.

Serum glypican 4 level in obese children and its relation to degree of obesity

Previous adult studies have demonstrated associations of serum glypican 4 (Gpc4) and obesity parameters and insulin sensitivity. However, an association of serum Gpc4 and glucose metabolism remains contradictory. Study of serum Gpc4 in obese children has not been conducted. We aimed to determine serum Gpc4 levels in obese children with various degrees of obesity.