Hyperthyroid Children Research Articles

Evaluation of Hypothyroidism and Hyperthyroidism in Children Below Five Year of Age Residing in Lahore


 
 
 
 Hypothyroidism and hyperthyroidism occur due to insufficient production and over production of thyroid hormones. Identification of thyroid diseases at neonatal and developing years enable physicians to treat thyroid dysfunction at the appropriate time and correspondingly aid to find hyperthyroidism in children below 3.5 year of age which is rare in children below five years of age. Objectives: 1To determine hyperthyroidism and hypothyroidism in children below 5 years of age by a biochemical screening of FT3, FT4, and TSH in the blood sample. 2Determine the prevalence of thyroid dysfunction in children. Methods: 5ml blood samples were collected from hypothyroid and hyperthyroid children. Blood samples were centrifuged. Levels of FT4 and FT3 in the serum was determined by radioimmunoassay (RIA) and level of TSH was determined by immuno-radiometric Assay (IRMA). Samples were analyzed, by computerized gamma counter. Thyroid hormone level distribution was analyzed by using Chi-Square and T-Test. Results: Sixty five children were selected for the study, 34 male and 31 female children. Among 13 abnormal children, 4 (30.8%) were hyperthyroid because of their TSH level < 0.3 mIU/L and remaining 9 (69.2%) children were hypothyroid there TSH > 5.0 mIU/L. Goiter was found in three children which is a rare entity in children below 5 years of age. The goiter was found in children who had hypothyroidism. Conclusion: There was no significant age difference between hypothyroid and hyperthyroid children. The prevalence of hyperthyroidism and hypothyroidism was more in female as compared to male but the difference was not significant. There was no significant difference in the normal concentration of serum of thyroid hormone between male and female children.
 
 
 

Internal exposure of Chinese children from a typical coastal city to bisphenols and possible association with thyroid hormone levels

Bisphenols (BPs) are widely used in consumer products, and human exposure to BPs is nearly ubiquitous. However, human biomonitoring data are scarce, especially for children. In this study, we quantified eight BPs in the serum of 345 children from a typical coastal city in China. Bisphenol A (BPA), bisphenol F (BPF), and bisphenol S (BPS) were frequently detected (63% BPA, 68% BPF, 43% BPS), with geometric mean (GM) concentrations of 1.6, 0.08, and 0.04ng/mL, respectively. The other five BPs had low detection frequencies (<5%). The distribution of BPA, BPF, and BPS in children's serum samples was independent of sex whereas the concentrations of BPS and BPF both significantly increased with age (P<0.01). The GM values of estimated daily intake for BPA and BPS were 0.61 and 0.014μg/kg body weight (bw)/day, respectively, indicating a relatively higher exposure risk of BPA in comparison with BPS. Compared with the population with euthyroid or nonhyperthyroid thyroid dysfunction, children with hyperthyroidism suffered higher exposure to BPA. By multiple linear regression analysis, thyroid-stimulating hormone showed a significantly negative relationship with log10-BPA concentration for euthyroid children (R2=0.477, P<0.001), whereas a significantly positive correlation (R2=0.753, P=0.033) was found for hyperthyroid children.

Association between iron status and thyroid function in Nepalese children.

BackgroundDeficiencies of iodine and iron may have adverse effect on thyroid function. This study was undertaken to investigate the association between iron status and thyroid function in Nepalese children living in hilly regions.MethodsA cross-sectional study was conducted among 227 school children aged 6–12 years living in hilly regions of eastern Nepal. Urine and blood samples were analyzed for urinary iodine concentration, free thyroxine, free triiodothyronine, thyroid stimulating hormone, hemoglobin, serum iron and total iron binding capacity, and percentage transferrin saturation was calculated.ResultsThe cohort comprised euthyroid (80.6 %, n = 183), overt hypothyroid (1.3 %, n = 3), subclinical hypothyroid (16.3 %, n = 37) and subclinical hyperthyroid (1.8 %, n = 4) children respectively. About 35.2 % (n = 80) children were anemic, 43.6 % (n = 99) were iron deficient and 19.8 % (n = 45) had urinary iodine excretion < 100 μg/L. Hypothyroidism (overt and subclinical) was common in anemic and iron deficient children. The relative risk of having hypothyroidism (overt and subclinical) in anemic and iron deficient children was 5.513 (95 % CI: 2.844−10.685, p < 0.001) and 1.939 (95 % CI: 1.091-3.449, p = 0.023) respectively as compared to non-anemic and iron sufficient children. Thyroid stimulating hormone had significant negative correlation with hemoglobin (r = −0.337, p < 0.001) and transferrin saturation (r = −0.204, p = 0.002).ConclusionsThyroid dysfunction, iron deficiency and anemia are common among Nepalese children. In this cohort, anemic and iron deficient children had poor thyroid function.

Diagnosis of Pediatric Hyperthyroidism: Technetium 99 Uptake Versus Thyroid Stimulating Immunoglobulins

Treatment with antithyroid drugs is effective in conditions of increased thyroid hormone production (mostly Graves' Disease; GD), but not in subacute thyroiditis (SAT) or autoimmune thyroiditis (AIT). Positive thyroid stimulating immunoglobulins (TSI) make GD likely. However, not all children with GD have increased TSI. Uptake studies with (123)I or (99)Tc ((99m)Tc) provide accurate and rapid diagnosis but are expensive and involve radiation exposure. Our objective was to compare TSI with (99m)Tc uptake for diagnosis of pediatric hyperthyroidism. We performed a retrospective chart review of hyperthyroid children who had both TSI estimation and (99m)Tc uptake assessment at presentation. Based on subsequent laboratory studies and follow-up, 37 had GD and 10 had non-GD thyroiditis. The TSI index was considered positive (TSI+) when it was above the upper limit of normal. (99m)Tc uptake was considered positive (Tc+) for any uptake >0.4% and negative (and low) (Tc-) for uptake ≤0.4%. Forty-seven youth (83% females), aged 12.3±4.6 years, presented with a suppressed thyrotropin (TSH) and elevated free thyroxine and total triiodothyronine. All 37 patients with GD were Tc+ (100% sensitivity and specificity). The sensitivity of TSI for diagnosing GD was 84%, and the specificity was 100%. Six patients with GD were discordant with Tc+ but TSI-. Elevated TSI correlated with Tc+ (p=0.01) with a degree of agreement (kappa) of 0.69. (99m)Tc has excellent specificity and sensitivity in diagnosing GD. Given additional costs of (99m)Tc (two and a half times as much as TSI), it is reasonable to reserve (99m)Tc uptake assessment for hyperthyroidism of unclear etiology and negative TSI.

Children with hyperthyroidism younger than age 7 require higher mg/kg doses of methimazole to normalize free T4 compared to older children.

Hyperthyroidism is much less common in children <7 years vs. older children and less well studied. It was our impression that the youngest patients needed a higher weight-based dose of methimazole (MMI) to achieve euthyroidism. To compare the mean MMI dose needed to normalize free T4 in younger (<7 years) vs. older children and the time taken to normalize free T4. Based on chart review (2004-2012), patients were divided into groups based on age at diagnosis: <7 years (n=13), 7-12 years (n=30) and >12 years (n=40). Follow-up visits were reviewed until free T4 normalized. The mean dose of MMI (mg/kg/day) needed to normalize free T4 was 0.71 (±0.29) in the <7 group, significantly higher vs. the two older groups: 0.50 (±0.22) and 0.44 (±0.24). Months taken to achieve a euthyroid state was significantly longer in children <7 (6.23±3.91) vs. the older groups (3.10±2.12 and 3.18±2.86 months). Hyperthyroid children diagnosed before age 7 required higher initial doses of MMI and took a longer time to become euthyroid than older patients. Clinicians should consider starting with higher weight-based MMI doses when treating younger patients to more rapidly normalize free T4.

Evaluation of etiology, clinical profile and management outcomes in juvenile hypo and hyperthyroidism: A single centre experience

Objective: The aim of this study was to evaluate the etiology, clinical profile and response to treatment in physical, sexual and psychological aspects in juvenile hypo and hyperthyroidism. Materials and Methods: 63 patients of newly diagnosed overt hypothyroidism (TSH > 15μIU/ml and T4 12μg/dl) in 8-16 years age group presenting with various symptoms are followed for 1-2 years after starting treatment with levothyroxine/carbimazole. Dose was adjusted to maintain TSH/T4 in normal range. The response to treatment is monitored by physical, sexual and intellectual parameters. Results: Among 68 patients, 63 (92.6%) are overt hypothyroid and 5 (7.4%) are hyperthyroid. The age group included was 8-16 years. Among hypothyroid patients, puberty was attained within a year of treatment in patients with delayed puberty. There was improvement in cognitive function with treatment though statistically not significant. Positive TPO antibodies was associated with low T4 and high TSH (P < 0.05). Among hyperthyroid group (5 patients), chief complaints are goitre in 100%, weigt loss in 100% and proptosis in 60% (3 patients). Sexual maturity was appropriate for age Bone age was appropriate for chronological age. There was no significant difference in cognitive function with treatment. Conclusion: In juvenile age group, most common cause for hypothyroidism is Hashimotos thyroiditis and hyperthyroidism is Graves disease. Goitre and growth retardation are commonest mode of presentation of both hypo and hyperthyroidism.TPO antibodies is associated with severe hypothyroidism (low T4 and high TSH). Even hyperthyroid children presents with poor height gain. Height velocity and sexual maturity improve with treatment. Cognitive function was not significantly affected in hypo or hyperthyroidism.

Clinical Relevance of Thyroid-Stimulating Autoantibodies in Pediatric Graves' Disease—A Multicenter Study

The incidence of TSH receptor (TSHR) stimulating autoantibodies (TSAbs) in pediatric Graves' disease (GD) is controversial. This large, multicenter study evaluated the clinical relevance of TSAbs in children with GD both with Graves' orbitopathy (GO) and without orbital disease. We conducted a cross-sectional retrospective study. Sera were collected in seven American and European academic referral centers and evaluated in a central laboratory. PATIENTS AND SAMPLES: A total of 422 serum samples from 157 children with GD, 101 control individuals with other thyroid and nonthyroid autoimmune diseases, and 50 healthy children were studied. TSAbs were measured using a novel, chimeric TSHR bioassay and a cAMP response element-dependent luciferase. TSH binding-inhibitory Ig (TBII) and parameters of thyroid function were also determined. In 82 untreated children with GD, sensitivity, specificity, and positive and negative predictive values for TSAb and TBII were: 100 and 92.68% (P = .031), 100 and 100%, 100 and 100%, and 100 and 96.15%, respectively. TSAb and TBII were present in 147 (94%) and 138 (87.9%) of the 157 children with GD (P < .039), respectively; and in 247 (94%) and 233 (89%) of the 263 samples from this group (P < .0075), respectively. In children with GD and GO, TSAb and TBII were noted in 100 and 96% (P < .001), respectively. Hyperthyroid children with GD and GO showed markedly higher TSAb levels compared to those with thyroidal GD only (P < .0001). No significant differences were noted for TBII between the two groups. After a 3-year (median) medical treatment, the decrease of TSAb levels was 69% in GD vs 20% in GD and GO (P < .001). All 31 samples of euthyroid children with GO were TSAb positive; in contrast, only 24 were TBII positive (P = .016). All children with Hashimoto's thyroiditis, nonautoimmune hyperthyroidism, type 1 diabetes, and juvenile arthritis and the healthy controls were TSAb and TBII negative. Serum TSAb level is a sensitive, specific, and reproducible biomarker for pediatric GD and correlates well with disease severity and extrathyroidal manifestations.

Increased Sex Hormone-Binding Globulin Levels in Children and Adolescents with Thyrotoxicosis

Background: Thyrotoxicosis is a rare condition in pediatric patients, and optimal treatment can be difficult to achieve in some children. To our knowledge, no studies have evaluated sex hormone-binding globulin (SHBG) levels in hyperthyroid children and adolescents in relation to age- and gender-related normative data. Methods: SHBG serum levels were determined before and after 4 months of antithyroid therapy (ATT) in 10 children and adolescents with Graves' disease. A total of 903 healthy children and adolescents served as controls. Results: Serum SHBG levels were elevated (>2 SD) at diagnosis in all hyperthyroid children but normalized rapidly following ATT. At diagnosis, median SHBG was +2.51 SD (interquartile range 2.20-3.27) compared to healthy children without thyroid illness, and it declined significantly during ATT (-0.16 SD, -0.66 to 1.64; p < 0.05). Conclusion: This is the first study to demonstrate that serum SHBG levels are markedly increased in children with Graves' disease, and we suggest that SHBG may be an additional marker of thyroid hormone action in children, as has been shown in adults.

C‐Type natriuretic peptide forms in adult hyperthyroidism: correlation with thyroid hormones and markers of bone turnover

Plasma C-type natriuretic peptide (CNP) forms correlate with linear growth velocity in juveniles. In hyperthyroid children, plasma CNP products fall in parallel with height velocity and thyroid hormones (TH) as euthyroidism is restored. The effect of TH on CNP forms after completion of endochondral growth is unknown. To determine the effect of restoring euthyroidism on plasma CNP forms and bone turnover markers (BTMs) in hyperthyroid adults. We performed a prospective observational study in 20 adults (19 women) with acquired hyperthyroidism before and during carbimazole treatment. INTERVENTION AND MAIN OUTCOMES: Blood levels of CNP, amino-terminal propeptide of CNP (NTproCNP), TH and BTMs - bone-specific alkaline phosphatase, osteocalcin, procollagen type 1 amino-terminal propeptide and type 1 collagen C-telopeptide (CTx) - were measured before and during the first 6 months of carbimazole treatment and correlations determined. Both CNP and NTproCNP were significantly correlated with TH at baseline. As in children, decreases in CNP forms were closely associated with fall in TH. Significant associations were found between CNP forms and CTx. CNP production from tissues other than endochondral cartilage is responsive to TH. Strong temporal links with markers of bone resorption suggest that CNP may also participate in bone remodelling in the adult skeleton.

Plasma C‐type natriuretic peptide forms and thyroid status in prepubertal children with acquired thyroid disease

C-type natriuretic peptide (CNP) and thyroid hormone (TH) are essential for normal skeletal growth. Plasma CNP peptides correlate with growth velocity, but the relationship between thyroid status and CNP production is unknown. This study examined the impact of restoring normal TH levels on CNP and height velocity (HV) in children with acquired hypo- and hyperthyroidism. We performed a prospective, observational study in prepubertal children with acquired hypothyroidism (n = 15) and hyperthyroidism (n = 12). Blood levels of CNP, amino-terminal proCNP (NTproCNP), bone-specific alkaline phosphatase (BSAP), IGF-I and TH levels were measured before and during the first 6 months of standard treatment for hypo- and hyperthyroidism, and correlations were determined. At baseline, HV, CNP, NTproCNP and BSAP were significantly higher in hyper- than in hypothyroid subjects. Changes in TH after treatment were closely coupled to change in CNP and NTproCNP in hyperthyroid, but not in hypothyroid, children. In addition, a positive association of HV with CNP peptides was found during treatment of hyperthyroidism. Normalizing TH did not correlate with changes in BSAP or IGF-I in either group. Plasma CNP peptides are higher in children with hyperthyroidism than in those with hypothyroidism at diagnosis and, in hyperthyroid children, change concordantly with TH and HV during treatment. Differential responses of CNP in the two groups suggest CNP production is dependent on growth plate activity and not a direct effect of TH on CNP gene expression. Our findings suggest novel mechanisms underlying changes in skeletal response during treatment in children with acquired thyroid disease.

Hipertiroidismo en niños y adolescentes

Background: Hyperthyroidism (HT) prevalence is 0.1/100,000 children and 1/100,000 adolescents and Graves Disease is the most frequent etiology. Objective: To evaluate the clinical presentation, etiology and treatment in hyperthyroid children. Method: Retrospective review of clinical charts of children under 15 years-old, between June 2004 and August 2005. Hyperthyroidism diagnosis was performed with suppressed TSH and increased thyroid hormones leveis. Etiological study was done by TRAb, ATPO, ATG, thyroid echotomography and I 131 capture. Results: 26 patients were evaluated; 84.6% females and age at diagnosis was 9.8 ± 3,5 years-old (range: 3,8 - 14,5). Goiter was the most frequent clinical sign (96,2%), tachicardy and swelling. Etiology: Graves Disease (73%),Hashitoxicosis (15,3%) andunknown etiology (11,5%). Treatment: 88,4% began with anti-thyroid drugs (DAT): 78% PTU and 22% Tiamazol. 62.5% became euthyroid after 6 months and 79.1% after 12 months. 31.5% of GD presented hypothyroidism at 6.3 ± 4 months of DAT, requiring LT4 substitution. I 131 was applied to 4 children (16.6%); 3 due to hepatic compromise pre or post PTU use and 1 girl for missing treatment, developing a thyrotoxic torment. Thyroidectomy was done in 2 patients (8.3%), both with GD; 1 for giant goiter without DAT response at 19 months and 1 for persistant hyperthyroidism after 25 months of DAT. 92% received (3-blockers (Propanolol) for adrenergic symptoms for 5 ± 4 months. Conclusions: Goiter was the most frequent pediatric HT symptom and Graves disease the main etiology. DAT treatment control HT in 76.9% patients and no adverse reactions with I 131 were observed. These resUIts promote DAT treatment as first line in HT management, prefering Tiamazol for its better adherence and less adverse reactions. Radioiodide therapy and thyroidectomy are alternatives if treatment fails in pediatrics HT.

Low Cortical Bone Density Measured by Computed Tomography in Children and Adolescents with Untreated Hyperthyroidism

To determine whether increased thyroid hormones levels have an effect on various bone components (cortical vs cancellous bone). The anthropometric and 3-dimensional quantitative computed tomography (CT) bone measurements, including bone density (BD), cross-sectional area (CSA) of the lumbar spine and femur, and cortical bone area (CBA) of the femur, of 18 children and adolescents with untreated hyperthyroidism were reviewed and compared with those of age-, sex-, and ethnicity-matched historical controls. No significant differences in height, weight, body mass index (BMI), or pubertal staging between patients and controls were found. Cortical BD was significantly lower (P < .001) in children and adolescents with hyperthyroidism compared with historical controls. After adjusting for weight and height, no difference in femur CSA between hyperthyroid children and historical controls was evident. No significant correlations among thyroid hormone levels, antithyroid antibody levels, and cortical BD values were found. As determined by CT, cortical bone is the preferential site of bone loss in children and adolescents with untreated hyperthyroidism.

TSH-receptor Antibodies Determined by the First, Second and Third Generation Assays and Thyroid-stimulating Antibody in Pregnant Patients with Graves' Disease

The measurement of TSH receptor antibody (TRAb) has been recommended to predict the risk of neonatal hyperthyroidism (NH) in pregnant women with Graves' disease (GD). For the first generation TRAb (TRAb1) assay with commercial kit (Brahms, Berlin, Germany; or Cosmic co., Tokyo, Japan) an arbitrary limit of 40 U/l or 50% was suggested to indicate risk when measured late in pregnancy. In order to substitute TRAb1 with the second generation TRAb using porcine TSH receptor (pTRAb2) and human recombinant TSH receptor (hTRAb2) and the third generation TRAb (TRAb3) assay for this purpose, we measured TRAb in these four methods late in pregnancy in a total of 62 pregnant women with Graves' disease. The data showed that no cases with TRAb1 >50% has been missed if the TRAb1 assay was replaced by the pTRAb2, hTRAb2 or TRAb3 assay using their equivalent cut-off value of 70%, 10 IU/l, and 75%, respectively, but that an additional group of women would have been included in the risk group, especially in the TRAb3 assay. Next, the effect of maternal TRAb on thyroid function of offspring was studied in the 47 pregnant women with GD (43 with TRAb1 <50% and 4 with TRAb1 >50% during late pregnancy). In 2 women who gave birth to hyperthyroid children at days 6 and 14 of life, the maternal sera had strongly positive levels of TRAb1 (73.5% and 84.1%), pTRAb2 (84.9% and 91.5%), hTRAb2 (40.68 IU/L and 89.70 IU/L) and TRAb3 (92.1% and 93.5%) late in pregnancy, with one case displaying high positive (1114.3%) thyroid stimulating antibody (TSAb) level and the other case had moderate positive (433%) TSAb level. Of the remaining 45 women, 43 had TRAb1 <50% and the other 2 had TRAb >50% including 1 with low TSAb positive and 1 with positive thyroid stimulating blocking antibody (TSBAb) and negative TSAb; all of them gave birth to euthyroid children. Finally, a serial study regarding TRAb in 23 women with Graves' disease during pregnancy showed that TRAb1, pTRAb2, hTRAb2, TRAb3 value and TSAb level decreased significantly as pregnancy progressed. In conclusion, the present study supported TRAb as a useful marker to predict the risk of NH.

Attentional Processing in Hyperthyroid Children Before and After Treatment

The management of craniopharyngiomas is complex and controversial. The perception that they are benign tumours cured by radical surgical resection is not borne out by their often difficult excision, propensity to recur and invade, and high late morbidity and mortality from direct brain injury. Their central location makes visual or pituitary dysfunction and/or hydrocephalus common presenting features. The most important consequence of craniopharyngiomas is hypothalamic injury which may result in severe, crippling and life-threatening sequelae, such as adipsia, morbid obesity, sleep, and behavioural and cognitive disorders. Evidence suggests that unless the tumour is smaller than 2-4 cm in the mid-line and completely resectable without additional hypothalamic or visual compromise, the surgical approach should be conservative even if this leaves residual tumour. Adjuvant focal radiotherapy to residual or recurrent disease has proven efficacy in long-term tumour control. Thus concerns regarding the potential late toxicity of radiotherapy to the developing brain need to be balanced against the recognised morbidity and mortality of recurrent tumour and repeated neurosurgical interventions. Hypothalamic damage is in many cases surgically induced. Given the devastating consequences of such an injury this should be avoided at all costs. Thus the aims of primary treatment should be to relieve tumour-associated compression symptoms, preserve (or improve) vision and hypothalamo-pituitary function, and minimise tumour recurrence with its attendant high morbidity and mortality. National registration and management by multidisciplinary teams in specialised centres according to nationally agreed risk adapted treatment strategies are likely to improve outcomes, as has been demonstrated for example in adult pituitary tumours. Because of the rarity of craniopharyngiomas, international collaborative trials are necessary to properly inform future therapies.

Attentional processing in hyperthyroid children before and after treatment.

To determine whether specific components of attentional processing may be differentially disrupted during thyrotoxicosis, nine children with hyperthyroidism were assessed for intelligence and attention before and after one year of therapy. The attention test allowed for measurement of sustain, disengage, and shift subcomponents of attentional processing. Comparison with pediatric controls revealed lower nonverbal intelligence during thyrotoxicosis, which improved to normal following euthyroidism. On the attention task, an effect was observed during thyrotoxicosis only on the shift and disengage functions of attentional processing but not sustain. Attention results were unrelated to self-reported anxiety at time of testing. Results are discussed in terms of thyroid hormone activation of the prefrontal cortex, which is thought to be the cerebral substrate underlying the shift and disengage functions of attentional processing.

Remission in children with hyperthyroidism treated with propylthiouracil. Long-term results.

We treated 69 hyperthyroid children with propylthiouracil, of whom 53 remained under surveillance. Of these children, 34 (64%) had an initial remission, but relapses were frequent (47%). At this writing, 24 patients (45%) were in remission, with a mean duration of remission of 55 months (range, ten to 132 months). We found that the triiodothyronine level took significantly longer than the thyroxine (T4) level to return to normal. Thus, based on the T4 level alone, treatment may have been stopped prematurely in some patients, causing the relapse rate to be falsely high. The response to therapy did not depend on the size of the goiter nor on the initial levels of T4 or triiodothyronine. Six patients had adverse reactions, which were serious in two patients.

Insulin, glucagon and growth hormone responses during glucose, arginine and insulin tolerance tests in children with hyperthyroidism

There are many reports of glucose intolerance in adult patients with hyperthyroidism but few reports of glucose intolerance in hyperthyroid children. In this study, we measured plasma levels of glucose, insulin, glucagon and growth hormone in hyperthyroid children and control subjects by the use of three kinds of tolerance tests: an oral glucose tolerance test, an arginine tolerance test and an insulin tolerance test. In the oral glucose tolerance test, mean fasting glucose levels (79.6 +/- 1.4 mg/dl) rose to maximum levels (157.3 +/- 4.3 mg/dl) at 30 min in hyperthyroid children which were significantly higher than the levels in control subjects (p less than 0.01). The maximum levels of glucose fell slowly and returned to fasting levels at 180 min. In this test, plasma insulin levels increased from basal levels (12.7 +/- 1.9 microU/ml) to maximum levels (120.8 +/- 22.1 microU/ml) at 30 min in the prepubertal age group of hyperthyroidism. On the other hand, in the pubertal age group of hyperthyroidism, maximum levels of insulin were observed at 60 min, but not at 30 min. These maximum levels of insulin of both hyperthyroid age groups were significantly higher than those in the control subjects (p less than 0.05, p less than 0.01 respectively). There was no difference in insulin-glucose ratio at 30 min (delta IRI/delta BG) and insulinogenic index (I.I.) at 0 to 60 min between these two groups of hyperthyroid children and control subjects. However, I.I. at 0 to 120 min and 0 to 180 min decreased significantly in the pubertal age group of hyperthyroidism as compared with those in the control group (p less than 0.05, p less than 0.02 respectively). In the oral glucose tolerance test, plasma glucagon levels decreased from basal levels (74.1 +/- 4.3 pg/ml) to minimum levels (36.4 +/- 4.7 pg/ml) at 90 min in hyperthyroidism, which were significantly lower than those in the controls (p less than 0.05). However, there was no difference in -epsilon delta IRG/epsilon delta BG (cumulative glucagon response/cumulative glucose response) between the subjects with hyperthyroidism and the controls. On the other hand, lower responses of blood glucose, insulin, glucagon and growth hormone to arginine were observed in subjects with hyperthyroidism than in the controls. Moreover in the insulin tolerance test, there was no difference in glucagon and growth hormone response between the subjects with hyperthyroidism and the controls. Thus our conclusions are as follows: A marked increase in blood glucose after oral glucose load was observed in spite of normal insulin-glucose ratio in hyperthyroid children, suggesting the existence of peripheral insulin resistance.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac abnormalities in children with hyperthyroidism.

The cardiac status of 18 hyperthyroid (HT) children (9 black and 9 white) was evaluated by echocardiography. Mitral regurgitation (MR) was diagnosed clinically in 33% (6 of the 9 blacks). None of the 9 white children had MR. Left ventricular end-diastolic diameter (LVEDD) and volume (LVEDV) did not differ from the predicted normal (PN) based on body surface area and heart rate, except in those with MR where increased LVEDD and LVEDV were noted (p less than 0.02). LV mass was +1.75 standard deviations (sigma) of the PN (p less than 0.01), due to increased wall thickness of LVEDV. Left ventricular output (LVO) was +0.35 sigma PN (p = ns); however, when compared to that of normal children, LVO of HT was higher (p less than 0.001) due to the increased heart rate. Enhanced left ventricular contractility was suggested by increased rate of dimensional change during ejection (peak dD/dt-syst), with a mean value of -11.39 cm/sec as compared to the normal of -9.54 cm/sec (p less than 0.01). A linear multivariate regression equation differentiated the cardiac status of HT from that of normal children. Following treatment to euthyroid state, MR disappeared in 2 and became less in 4 patients. LVO, LV mass, and peak dD/dt-syst also became less. Significant cardiac changes occur in children with hyperthyroidism, which may be reversible in part after euthyroidism is restored.

Effect of Thyroid Hormones on Human Mononuclear Leukocyte Lysosomal Acid Lipase Activity*

Lysosomal acid lipase (LAL), the enzyme which hydrolyzes lipoprotein cholesteryl esters, is under thyroid hormone regulation in experimental animals. To evaluate whether human LAL is also under thyroid regulation, we measured mononuclear leukocyte LAL activity in 31 hypothyroid, hyperthyroid, and euthyroid children under treatment. LAL activity was positively correlated with serum T3 and serum T4 levels, and was significantly higher in hyperthyroid children than in those who were hypothyroid. In another study, 5 adult euthyroid males were given 50 micrograms L-T3 every 8 h for 4 days. Their LAL activities increased significantly after treatment. The data suggest that LAL activity in man, as in experimental animals, is influenced by thyroid hormone status. Hormonal control of LAL activity may be important in the regulation of human cholesterol metabolism.

1119 THYROID HORMONE REGULATION OF HUMAN MONONUCLEAR LEUKOCYTE ACID LIPASE ACTIVITY

Low density lipoprotein (LDL) metabolism is sensitive to thyroid (T) hormone status. Receptor-mediated LDL degradation is increased in human skin fibroblasts by triiodothyronine (T3). Acid lipase (AL), the lysosomal enzyme which hydrolyzes cholesteryl esters (CE) in a number of tissues, is similarly regulated by T hormones: liver AL activity is reduced in hypothyroid rats and increased by T3 or thyroxine (T4). The relationship between AL activity and T status in man is not known but reduced AL activity is associated with hypercholesterolemia and T status is known to influence cholesterol levels in man. Eight hypothyroid and 14 hyperthyroid children at various stages of treatment had mononuclear leukocyte AL activity measured. T status was determined by measuring serum T3, T4, thyroid-stimulating hormone and thyroid-binding globulin. AL activity was positively correlated with serum T3 (AL = 2.48 log T3 + 2.45, r = 0.54, p <0.01). In a second study, five adult euthyroid male volunteers were treated for 4 days with 50μg T3 t.i.d. All showed decreased serum cholesterol (mean reduction 14%, p <0.05) and increased AL activity (mean increase 22%, p <0.05). These data suggest that AL activity in man is modulated by T3 levels. In addition to genetic control of AL activity, hormonal control of AL expression may be important in regulation of human cholesterol metabolism. (Supported in part by HL-18723).