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.

Bone histomorphometry in children and adolescents with beta-thalassemia disease: iron-associated focal osteomalacia.

Thalassemia/hemoglobinopathy is a hereditary disease that causes chronic anemia and increased erythropoiesis. Consequently, an expansion of bone marrow spaces may contribute to osteopenia/osteoporosis. However, the pathogenesis of bone changes is not yet known. We, therefore, carried out the study on bone histomorphometry and biochemical and hormonal profiles in children and adolescents with suboptimally treated beta-thalassemia disease with the hope of gaining some new insight into the cellular and structural alterations of thalassemic bone. Seventeen patients underwent iliac crest bone biopsy for histomorphometric analyses. Bone mineral density (BMD) measurements were performed by dual energy x-ray absorptiometry. Most patients had growth retardation and delayed bone age. BMD was low especially at the lumbar spine. Serum IGF-I levels were almost always low. Bone histomorphometry revealed increased osteoid thickness, osteoid maturation time, and mineralization lag time, which indicate impaired bone matrix maturation and defective mineralization. In addition, iron deposits appeared along mineralization fronts and osteoid surfaces. Moreover, focal thickened osteoid seams were found together with focal iron deposits. Dynamic bone formation study revealed reduced bone formation rate. These findings indicate that delayed bone maturation and focal osteomalacia are the pathogenesis of bone disease in suboptimally blood-transfused thalassemics with iron overload. Iron deposits in bone and low circulating IGF-I levels may partly contribute to the above findings.

Difference in goiter rates between two areas in Mae Hong Son Province despite an equally sufficient iodine supply.

The study was designed to investigate the problem of endemic goiter and iodine supplementation in Mae Hong Son, Thailand. Routine school data still showed high goiter rates in many areas. Six such schools and five schools with declining prevalence of goiter were selected. A single examiner examined all the children. Their weight, height, body mass index, ethnicity, history of iodine intake and migration were recorded. Urine samples were collected for measuring iodine and thiocyanate levels. From 653 children, 105 and 13 were found to have grade 1 and 2 goiter status, respectively. Median values of urine iodine level in children from all schools suggested sufficient iodine supplementation. Multivariate analysis showed that hilltribe minorities had a 2.09 times higher risk of endemic goiter than Thai children. Urine thiocyanate levels among children from high prevalence schools were significantly higher than those from low prevalence schools. No other significant correlation was found. Possible roles of other known and unknown goitrogens should also be investigated.

Electrophysiological and immunological study in myasthenia gravis: diagnostic sensitivity and correlation.

OBJECTIVE: To determine the diagnostic sensitivity of repetitive nerve stimulation (RNS), single fiber electromyography (SFEMG) and acetylcholine receptor antibody (AChRAb) in myasthenia gravis (MG), and to compare the degree of SFEMG abnormality between ocular and generalized MG and between seronegative and seropositive patients. METHODS: The sensitivities of RNS, SFEMG and AChRAb were estimated. SFEMG abnormality was compared between ocular and generalized MG and between seronegative and seropositive patients. RESULTS: Abnormal RNS, abnormal SFEMG and AChRAb were detected in 62%, 93% and 38% of 42 ocular, and 80%, 99% and 73% of 70 generalized cases, respectively. The degree of SFEMG abnormality was significantly greater in the generalized than ocular patients and was significantly greater in the seropositive than seronegative patients in both extensor digitorum communis and orbicularis oculi muscles. CONCLUSION: SFEMG is a very sensitive and useful test for MG. A correlation between SFEMG abnormality and clinical phenotype or severity and between SFEMG abnormality and AChRAb seropositivity was demonstrated. SIGNIFICANCE: The sensitivities of RNS, SFEMG and AChRAb in the diagnosis of MG were documented. The differences in severity between the ocular and generalized MG and between the seronegative and seropositive MG were confirmed and quantitatively determined by SFEMG.

High prevalence of "biochemical" adrenal insufficiency in thalassemics: is it a matter of different testings or decreased cortisol binding globulin?

CONTEXT: High prevalence of "biochemical" adrenal insufficiency (AI) in thalassemics has been reported. However, "clinical" AI is rare. AIM: The aim was to determine whether cortisol binding globulin (CBG) or tests used in assessing adrenal function contributed to the abnormally high prevalence of biochemical AI. SETTING: The study was conducted at Ramathibodi Hospital, Mahidol University, Bangkok, Thailand. PARTICIPANTS: Participants included 56 children and adolescents with thalassemia and 44 controls. MAIN OUTCOME MEASURES: Serum CBG and adrenal function test results assessed by 1 µg cosyntropin test and insulin tolerance test (ITT) were measured. Free cortisol index (FCI) calculated by total cortisol (TC)/CBG and calculated free cortisol (cFC) were determined. RESULTS: Mean (sd) CBG levels were comparable between patients and controls [45.2 (11.0) vs. 47.0 (8.6) mg/liter]. Peak TC, FCI, and cFC after cosyntropin test were lower in thalassemics [TC, 15.2 (4.0) vs. 18.9 (3.1) µg/dl; FCI, 3.4 (0.8) vs. 4.2 (1.2) µg/mg, P <0.001; and cFC, 1.03 (0.38) vs. 1.44 (0.61) µg/dl, P = 0.008]. Thirty of 56 thalassemics (53.6%) had AI, defined as having peak TC of less than 16 µg/dl. ITT was performed in 26 of those 30 patients. Five of 26 patients had peak TC after an ITT of at least 20 µg/dl. As a result, the estimated frequency of AI in the entire patient group was reduced by approximately 10%. CONCLUSION: The 1 µg cosyntropin test could be an adrenal function screening test in thalassemics. However, for definite diagnosis, ITT should be performed in those having peak total cortisol of less than 16 µg/dl after the 1 µg cosyntropin test.

Serum free cortisol index, free cortisol, and total cortisol in critically ill children.

BACKGROUND: In critical illness, serum total cortisol (TC) may not adequately reflect adrenal function because of reduced cortisol-binding globulin (CBG). AIM: To evaluate adrenal function of critically ill children, using free cortisol index (FCI), calculated free cortisol (cFC), and TC levels. METHODS: Thirty-two critically ill and 36 healthy children were included. All children underwent the 1 microg cosyntropin test. TC and CBG levels were measured. Basal and peak TC, FCI, and cFC were determined. RESULTS: Basal and peak TC, FCI, and cFC of critically ill children were significantly higher than those of the controls. Compared with TC, both basal and peak FCI and cFC of the patients were higher than those of controls to a greater degree. Use of FCI or cFC to diagnose adrenal insufficiency (AI) reduced the frequency of diagnosis of AI by 50%. CONCLUSION: FCI and cFC better reflect the dynamic changes of adrenal function of critically ill children.

Association between bone mineral density and erythropoiesis in Thai children and adolescents with thalassemia syndromes.

Increased marrow erythropoiesis in patients with thalassemia syndromes results in the expansion of bone marrow cavities and consequently decreases bone tissues, leading to osteoporosis. Whether the soluble transferrin receptor (sTfR), a marker of erythropoietic activity, correlates with the bone mineral density (BMD) in thalassemic patients has not previously been addressed. Forty-six children and adolescents with thalassemia syndromes, who were either not transfused or suboptimally transfused, were studied. BMD was determined by dual-energy X-ray absorptiometry. Blood samples were obtained in order to determine sTfR and hemoglobin. The patients were categorized into four groups: 1, beta-thalassemia/hemoglobin E (beta-thal/E) with transfusion-dependency (TD) (n = 18); 2, beta-thal/E with transfusion-independency (TI) (n = 15); 3, beta-thalassemia major (beta-major) (n = 6); 4, hemoglobin H (HbH) (n = 7). All patients had normal serum free thyroxine (FT4) and thyroid-stimulating hormone (TSH), and intact parathyroid hormone (PTH), serum calcium (Ca), phosphate (P), and 25-OH-vitamin D levels. The BMD of patients in the beta-major and beta-thal/E with TD groups were not significantly different. In comparison with the beta-major and beta-thal/E with TD groups, the beta-thal/E with TI and HbH groups had significantly higher BMD of the total body (TB), femoral neck (FN), and lumbar spine (LS), as well as higher levels of hemoglobin. In contrast, the sTfR levels of the beta-major, beta-thal/E with TI, and HbH groups were significantly lower than those of the beta-thal/E with TD group. The BMD of TB, FN, and LS was negatively correlated with the sTfR level, but positively correlated with the hemoglobin level. In conclusion, increased marrow erythropoiesis is one of the major determinants of reduced bone mass in thalassemic patients with either no transfusion or suboptimal transfusion.

Bone mineral density, biochemical and hormonal profiles in suboptimally treated children and adolescents with beta-thalassaemia disease.

OBJECTIVE: Thalassaemia/haemoglobinopathy is a hereditary disease causing increased erythropoiesis and expansion of the bone marrow cavity. As a consequence, there is a reduction in trabecular bone tissue resulting in osteopenia/osteoporosis. The present study was performed to assess bone mineral density (BMD) in children and adolescents with beta-thalassaemia disease and to determine biochemical and hormonal changes that may affect BMD. METHODS: Forty-eight children and adolescents with beta-thalassaemia were divided into two groups, transfusion-dependent (TD) (n = 16) and transfusion-independent (TI) (n = 32). All patients were treated suboptimally. BMD was determined by dual-energy X-ray absorptiometry. Bone maturation was assessed by radiographic bone age (BA). Blood and urine samples were obtained for the determination of biochemical and hormonal profiles, which included PTH, 25-hydroxyvitamin D (25-OHD), osteocalcin, bone-specific alkaline phosphatase, IGF-1, fT4, TSH and urine deoxypyridinoline. RESULTS: Most of the patients were short and underweight, and they had delayed BA with mean Z-scores of -2.77 in the TD and -2.04 in TI groups. The mean Z-scores of BMD in the TD vs. TI groups of total body, radius, femoral neck and lumbar spine were -2.09 vs.-1.49, -0.73 vs. -0.54, -1.93 vs.-1.17 and -3.45 vs.-2.43, respectively. Although the means BMD values in the TD group were lower than those in the TI group, they were not significantly different. Mean serum IGF-1 levels were lower in the TD than the TI groups, 11.6 and 24.9 nmol/l, respectively (P < 0.05). Other biochemical and hormonal profiles did not differ between these two groups. CONCLUSIONS: Patients with undertransfused severe beta-thalassaemia had more bone marrow expansion, lower serum IGF-1 levels and more delayed bone age than did patients with untransfused moderately severe beta-thalassaemia. Therefore, the severity of the disease appeared to be a primary factor for low bone mineral density in undertransfused patients in association with bone age delay and low serum IGF-1.