A thyroxine dosage of 8 μg/kg per day is appropriate for the initial treatment of the majority of infants with congenital hypothyroidism

 The adequate l-thyroxine dosage for the initial treatment of infants with congenital hypothyroidism is a subject of controversy. Some recommend higher dosages (> 10 μg/kg/day) to ensure adequate levels, while others advocate lower dosages to permit normalisation of thyroid status. The aim of this study was to evaluate the␣results of a treatment strategy using an initial dosage of 7.5–8.0 μg/kg per day, TSH measurements being␣taken at 15 and 30 days of treatment. Fifty one newborns infants with primary congenital hypothyroidism␣detected by neonatal screening were treated with the same therapeutic strategy. A mean l-thyroxine dosage of 7.9 μg/kg per day at the onset of treatment and 6.6 μg/kg/d at 2 months, normalised the FT₄ and FT₃ levels at 15 days in 100% and TSH levels at 2 months in 90% of cases. Many patients showed elevated levels of FT₄ and a systematic higher initial dosage could expose many infants to a dangerous hyperthyroidism. Patients with abnormal TSH levels at 2 months already had higher TSH levels in the first 8 weeks of life and, despite higher l-thyroxine dosage, also exhibited lower FT₄ and FT₃ levels. These patients who needed an early increase in dosage had already shown a more profound ante and neonatal hypothyroidism. This subgroup of patients require a higher dosage of thyroxine and early assessment of FT₄, FT₃ and TSH levels are required for optimum dosage choice. Conclusion Even though a subgroup of patients may require a higher dosage of l-thyroxine, an initial␣dosage of 7.5–8.0 μg/kg per day, with an early assessment of␣FT₄, FT₃, and TSH levels, is adequate for the treatment of the majority of infants with congenital hypothyroidism. Received: 17 August 1995 / Accepted 10 June 1996     

Influence of long-term carbamazepine treatment on thyroid function

We have studied the effects of carbamazepine on thyroid function in sixteen recently diagnosed epileptic children and thirteen epileptic children receiving long-term carbamazepine therapy and compared these findings with the thyroid function of thirteen healthy control subjects. Thyrotropin (TSH), tri-iodothyronine (T₃), thyroxine (T₄), free tri-iodothyorinine (FT₃) and free thyroxine (FT₄) serum levels were determined in both recently diagnosed but as yet untreated epileptic children and normal controls. These hormone levels were determined again after 2 months of treatment and 12 months of treatment in epileptic children. No statistically significant difference was found in the endocrine parameters of untreated epileptic children and the normal control group. After both 2 months and 12 months of carbamazepine therapy, serum levels of T₄, FT₄ and FT₃ were found to be low, but the serum T₃ concentration was unaffected. Baseline TSH levels were not changed during carbamazepine therapy either. Serum TSH levels increased rapidly after thyrotropin-releasing hormone stimulation in both the before and 12 months after carbamazepine treatment groups, but the response was higher in the 12 months treatment group. The findings of the present study suggest that accelerated hormone metabolism is responsible for hormonal changes found in patients treated with carbamazepine. Carbamazepine also had effects on the function of the hypothalamo-pituitary axis.     

Circulating thyroid antibodies and thyroid function studies in children and adolescents with insulin-dependent diabetes mellitus

Significant high titres (1400–125,600) of circulating thoroid microsomal antibodies (MCHA) were found in the sera of 5 out of 59 non-ketoacidotic, insulin-dependent diabetic (IDDM) patients (mean age 14.5 years). Among these five patients (four females, one male), all of whom were over 11 years, two also had thyroglobulin antibodies. Increased thyrotropin (TSH) response to TRH was found in 3/5 MCHA positive patients and in 3/54 without circulating MCHA. Serum thyroxine (T₄) and free T₄ (FT₄) average values were significantly lower (P<0.01 and P<0.001) in diabetics (7.1±1.8g/dl and 10.2±3.1 pg/ml, x±SD) as compared to normal sex and age matched controls (8.9±1.9 g/dl and 12.2±2.2 pg/ml, respectively). T₄ and FT₄ values were inversely related to the duration of the disease. Subnormal T₄ values were found in six (five females and one male) patients, four of whom had subnormal FT₄ values. No patient had low triiodothyronine (T₃) and high reverse T₃ (rT₃) values, i.e. none displayed the biochemical pattern of the low T₃ syndrome described with ketoacidotic status. This indicates also a satisfactory compensation of IDDM in all the patients. At the time of study no patient (including also those with circulating MCHA and TGHA and with TSH hyper-response to TRH) showed either thyroid size enlargement or clinical features of thyroid dysfunction including impaired growth and bone age retardation.Abbreviations MCHA thyroid microsomal antibodies - IDDM insulin-dependent diabetes mellitus - TSH thyrotropin - T₄ serum thyroxine - FT₄ free T₄ - T₃ triiodo thyronine - FT₃ free T₃ - rT₃ reverse T₃ - TGHA thyroglobulin antibodies - TRH thyrotrophin releasing hormone     

Thyroid function in fullterm and preterm newborns

The development of the hypothalamic-pituitary-thyroid system in the fetus occurs through three phases: thyroid pituitary embryogenesis, maturation of hypothalamus, maturation of thyroid system, neuroendocrine control and T₄ tissue deiodination. Defects in early phases I and II lead to permanent disorders whereas abnormalities in phase III result in transient functional immaturities especially in preterms. Cord serum TSH, T₄ and T₃ were estimated in 450 newborns (390 full term>36 wk gestation and 60 preterms<36 wk). The mean cord TSH of 5·069±7·4 μ U/ml in full term was lower than 7·88±3·77 μ U/ml in preterms (P<0·01). The mean cord T₄ and T₃ were significantly higher (P<0·01) 9·716±6·44 μg/dl and 0·425±0·17 ng/ml in full term as compared to preterms 6·46±3·4 and 0·355±0·16 respectively. There was significant negative correlation of serum TSH (r=−0·84 and P<0·05) and positive correlation of serum T₄ (r=0·97, P<0·001) and T₃ (r=0·89, P<0·05) with gestational age. The relationship of these hormones to weight irrespective of gestational age was more significant when compared in newborns >3 kg and <2 kg rather than in all intermediate groups. No significant differences in these hormones were evident amongst the AGA and SGA infants above and below 36 weeks gestation. Transient hypothyroxinemia, and hyper-thyrotropinemia, transient primary hypothyroidism and low T₃ syndromes are some of the transient abnormalities of thyroid function and are more commonly encountered in preterms.     

Changes in thyroid function tests induced by 2 month carbamazepine treatment in l-thyroxine-substituted hypothyroid children

In five l-thyroxine-substituted hypothyroid children with partial epilepsy serum total thyroxine (T₄) and free T₄ (FT₄) significantly (P<0.01) decreased following 2 months of carbamazepine (CBZ) administration (20 mg/kg per BW per day) from mean (±SD) values of 12.7±1.1 g/dl and 15.5±1.8 pg/ml to mean values of 7.5±2.3 and 10.1±1.7, respectively. In all but one patient important changes in both serum total and free triiodothyronine (T₃, FT₃) were not observed; consequently T₃T₄ and FT₃FT₄ ratios significantly (P<0.05) increased in the whole series. Three subjects had post-treatment serum TSH that rose to hypothyroid levels parallel to a T₄ decrease. The negligible thyroid hormone secretion and the unmodified T₃-uptake (T₃U) or T₄-binding globulin (TBG) exclude direct effects of CBZ on thyroid gland and on carrier serum proteins, respectively. The findings observed, instead, might be due to accelerated T₄ metabolic clearance together with augmented T₄ to T₃ conversion rate, as previously demonstrated for diphenylydantoin. The sharp reduction in T₄ and FT₃ concentrations is the peripheral display of this event, which is associated with a decompensation of the metabolic status, as indicated by serum TSH enhancement. In all cases a supplement of l-thyroxine by itself was able to restore euthyroid TSH serum concentrations, suggesting that hypothyroidism in patients with partial epilepsy to whom CBZ had been administered requires a higher l-T₄ substitutive regimen.Abbreviations CBZ carbamazepine - DPH phentoin - T₄ thyroxine - T₃ triiodothyronine - TSH thyrotropin - FT₄ free T₄ - FT₃ free T₃ - rT₃ reverse T₃ - TBG thyroxine binding globulin - T₃U T₃ uptake - RIA radioimmunoassay Presented in part at the 23rd Annual Meeting of the European Society for Pediatric Endocrinology (Heidelberg, September 2–5, 1984) [5]     

Cord blood thyroid‐stimulating hormone and free T4 levels in Turkish neonates: Is iodine deficiency still a continuing problem?

Background: The objectives of this study were to determine the cord blood thyroid‐stimulating hormone (TSH) and free T₄ (FT₄) levels in Turkish neonates and to determine whether these variables reveal iodine deficiency. Methods: We collected 818 cords from healthy mothers at parturition and measured levels of FT₄ and TSH. We also measured cord blood FT₄ and TSH levels in different stages of gestation and gender. We grouped the neonates according to cord serum TSH levels, either being less (Group A) or greater (Group B) than 10 mIU/L. Group A included 589 neonates (300 girls [51%] and 289 boys [49%]) and Group B included 229 neonates (105 girls [45%] and 124 boys [55%]). Results: The percentage of subjects with cord blood TSH < 10 mIU/L and >10 mIU/L was 72% and 28%, respectively. Although cord TSH levels in Group B were greater than those in Group A (P < 0.001), cord blood FT₄ levels in Group B were lower than those in Group A (P < 0.05). There was no difference between both sex in terms of birthweight and maternal age. TSH and FT₄ levels did not vary according to neonate sex during gestation, except for from week 37 to 41. TSH levels of male neonates at the 41st week of gestation were higher than those of female neonates (P < 0.05). There were no effects of birthweight on TSH and FT₄ levels if the neonate was lighter than 2500 g at birth. TSH levels of male neonates were higher than those of female neonates when their birthweights were <2500 g (P < 0.05). There was no significant difference in TSH levels according to birthweights in male neonates. Conclusion: Our data provide the normative data for cord blood TSH and FT₄ levels in Turkish neonates and show that iodine deficiency is a still a public health problem in Turkey. These measurements can be useful for detection and verification of hypothyroidism in a screening program for congenital hypothyroidism as well as evaluation of the success of the iodination program.     

Evaluation of the pituitary-thyroidal axis in newborns undergoing exchange transfusion

To evaluate whether the hypothyroxinaemia, previously noted in hyperbilirubinaemic newborns immediately after exchange transfusion for Rh or AB0 incompatibility, was due to impairment in the secretion of thyroid stimulating hormone (TSH) by the pituitary, we studied the thyroid hormone response to thyrotropin releasing hormone (TRH) and compared this response to that seen in a control population of healthy neonates. All infants studied responded with a brisk TSH increase; 30 min after TRH injection the mean TSH concentration of the hyperbilirubinaemic patients was 37 U/ml, ten times their basal level, which was not different from the value noted in the control population.No significant change in total thyroxine (T₄), 3,5,3 triiodothyronine (T₃), free thyroxine (FT₄) or 3,3,5 triiodothyronine (rT₃), (FT₄) or (rT₃) was noted after TRH administration in either group of neonates. In addition the effect of exchange transfusion on the thyroid axis of hyperbilirubinaemic newborns was evaluated. Before the exchange transfusion TSH, T₄, rT₃, T₃ and FT₄ levels were higher in the hyperbilirubinaemic newborns than in donor blood; immediately post-exchange transfusion TSH and T₄ concentrations of the hyperbilirubinaemic neonates decreased significantly and remained significantly below pre-exchange values 30h later.Newborns undergoing an exchange transfusion respond appropriately to TRH stimulation and seem to have an intact pituitary-thyroidal axis.Abbreviations T₄ total thyroxine - FT₄ free thyroxine - T₃ (Ru) T₃ resin uptake - T₃ 3,5,3 triiodothyronine - rT₃ 3,3,5triiodothyronine - TSH thyroid stimulating hormone - TRH thyrotropin releasing hormone - RIA radioimmunoassay     

Autoimmune thyroid disease in Libyan children and young adults with type 1 diabetes mellitus

Diabetes mellitus is a common autoimmune endocrine disorder associated with organ-specific autoantibodies which are frequently detected at the time of diagnosis. Some of these antibodies are specific to the pancreas (GAD, IA2, ICA) while others are related to different autoimmune diseases. Aim of the study: To define the prevalence of thyroid autoimmune disease in Libyan patients with type 1 diabetes mellitus (T1DM) since no similar studies have been performed in Libya. Materials and methods: Blood samples were collected from 218 patients with T1DM who are followed by the Pediatric Department, Tripoli Medical Center, Libya. All sera were analyzed in Italy (Laboratory of Immunopathology and Allergy, Udine). The patients were composed of 123 females (56.4%) and 95 males (43.6%), mean age 12.2 ± 4.6 years (range 2.1–24.5 years), mean duration of diabetes 4.7 ± 4.0 years (range 0.1–17.5 years). Sera were tested for anti-thyroperoxidase (TPO) and anti-thyroglobulin antibodies (TG). TSH and FT4 concentrations were measured in all subjects. GAD, IA-2 was also measured. Results: Of the diabetic children, 23.4% were positive for anti-microsomal peroxidase antibodies (TPO-Ab) and 7.8% for antithyroglobulin antibodies (TG-Ab); whereas 6.9% of the patients were positive for both TPO-Ab and TG-Ab. Of the T1DM patients who were positive for TPO-Ab, 66.6% were females. The majority (57%) of the patients who were positive for TPO had diabetes for longer than 5 years. Five patients (2.3%) had evidence of subclinical hypothyroidism whereas two patients (0.9%) had overt hypothyroidism. Two patients had subclinical hyperthyroidism and two (0.9%) had overt hyperthyroidism. Interestingly, 16.2% of patients were positive for both thyroid and pancreatic antibodies. Conclusions: The prevalence of autoimmune thyroid disease in type 1 diabetic patients is higher than in the general population. A routine screening strategy should be implemented with the determination of anti-thyroid antibodies and TSH in type 1 diabetic patients, particularly in girls, and in patients with diabetes of more than 5 years duration. Patients who have positive TPO antibodies may need the assessment of thyroid function at shorter intervals.     

A case of familial thyroxine binding globulin excess associated with growth hormone deficiency

A 7 years 3 months old Japanese boy with familial thyroxine binding globulin (TBG) excess associated with growth hormone (GH) deficiency is reported. The patients height was 106.4 cm (- 2.86 s.d.) and his bone age was 5 years and 3 months. He had no goiter and his developmental milestones were normal. The serum thyroid stimulating hormone (TSH) was 2.8 μU/mL, triiodothyronine (T₃) 3.1 ng/mL, thyroxine (T₄) 23.4 μg/dL and free T₄ 1.8 ng/dL. The serum TBG level was beyond 80.0 μg/mL, with normal TSH response to the thyrotropin-releasing hormone (TRH) test. Familial study revealed that his grandmother, mother, uncle, younger sister and younger brother had high TBG and T₃ levels, thus an X-linked co-dominant transmission was suggested. The peak GH responses to insulin and clonidine hydrochloride were 5.8 and 8.2 ng/mL, respectively. The mean nocturnal GH concentration was 2.5 ng/mL. His growth velocity increased from 4.8 to 8.4 cm/year and his serum TBG levels decreased gradually after human growth hormone (hGH) treatment.     

Thyroid function in fullterm and preterm newborns

The development of the hypothalamic-pituitary-thyroid system in the fetus occurs through three phases: thyroid pituitary embryogenesis, maturation of hypothalamus, maturation of thyroid system, neuroendocrine control and T₄ tissue deiodination. Defects in early phases I and II lead to permanent disorders whereas abnormalities in phase III result in transient functional immaturities especially in preterms. Cord serum TSH, T₄ and T₃ were estimated in 450 newborns (390 full term>36 wk gestation and 60 preterms<36 wk). The mean cord TSH of 5·069±7·4 μ U/ml in full term was lower than 7·88±3·77 μ U/ml in preterms (P<0·01). The mean cord T₄ and T₃ were significantly higher (P<0·01) 9·716±6·44 μg/dl and 0·425±0·17 ng/ml in full term as compared to preterms 6·46±3·4 and 0·355±0·16 respectively. There was significant negative correlation of serum TSH (r=?0·84 and P<0·05) and positive correlation of serum T₄ (r=0·97, P<0·001) and T₃ (r=0·89, P<0·05) with gestational age. The relationship of these hormones to weight irrespective of gestational age was more significant when compared in newborns >3 kg and <2 kg rather than in all intermediate groups. No significant differences in these hormones were evident amongst the AGA and SGA infants above and below 36 weeks gestation. Transient hypothyroxinemia, and hyper-thyrotropinemia, transient primary hypothyroidism and low T₃ syndromes are some of the transient abnormalities of thyroid function and are more commonly encountered in preterms.     

Low thyroxinaemia occurs in the majority of very preterm newborns

Transient hypothyroxinaemia with normal thyroid stimulating hormone (TSH) levels is a well-known condition in preterm neonates and is generally assumed to be a harmless epiphenomenon of prematurity. This assumption is, however, based on studies that included very few neonates with a gestational age (GA) below 30 weeks. We therefore measured serum free thyroxine (FT₄) and serum TSH on days 1 and 14 in 263 neonates with a GA between 26 and 41 weeks. In 13 infants (5%), transient hypothyroidism (low FT₄ and TSH>20 mU/l on day 14) was found. In the remaining 250 patients FT₄ on days 1 and 14 but not TSH correlated positively with GA. In neonates with a GA of 35–41 weeks, FT₄ increased postnatally to levels within or above the normal adult range. In contrast, in the very preterm group (26–31 weeks) the already low FT₄ levels declined to values significantly below the range observed in term neonates. A significant proportion of these neonates had FT₄ levels within the hypothyroid range. There was no difference in thyroid function between neonates treated with povidone-iodine or chlorhexidine.Conclusion Very preterm neonates have FT₄ levels on day 14 that are much lower than is generally assumed while TSH remains in the normal range. We therefore propose to measure FT₄ in all preterms with a GA below 33 weeks, during the 2nd week of life.     

Identification of the etiologies of chronic urticaria in children: A prospective study of 94 patients

Jirapongsananuruk O, Pongpreuksa S, Sangacharoenkit P, Visitsunthorn N, Vichyanond P. Identification of the etiologies of chronic urticaria in children: A prospective study of 94 patients.
Pediatr Allergy Immunol 2010: 21: 508–514.
© 2009 John Wiley & Sons A/S The etiologies of chronic urticaria (CU) in childhood remains incompletely understood because of limited data in children. The objective of this study was to examine some of the possible etiologies of CU in children by focusing on the functional autoantibody to FcεRIα and IgE, thyroid autoimmunity, urticarial vasculitis, parasitic infestation and food allergy. Children 4–15 yr of age with CU were investigated for complete blood count, erythrocyte sedimentation rate (ESR), antinuclear antibody (ANA), CH₅₀, free‐T4 (FT₄), thyroid stimulating hormone (TSH), anti‐thyroglobulin and anti‐microsomal antibody, autologous serum skin test (ASST), skin prick tests (SPT) for foods, food challenges, and stool examination for parasites. Ninety‐four children who met the criteria for CU were recruited. Patients with physical urticaria were excluded. Eosinophilia and elevated ESR were found in 23% and 13%, respectively. High ANA titers were found in 2%. None of these patients had clinical features of urticarial vasculitis, abnormal CH₅₀ level, abnormal TSH and FT₄. Anti‐thyroglobulin and anti‐microsomal antibodies were not detected. Positive ASST was found in 38%. There were no differences in medication requirement and CU remission between patients with positive and negative ASST. Parasites were found in 5% without clinical correlation. SPT to foods was positive in 35%. Positive food challenges were found in six/nine patients with positive history of food allergy and two/seven patients with negative history. Food avoidance was beneficial to the subgroup of patients with positive history of food allergy only.     

Distal splenorenal shunt with splenopancreatic disconnection for portal hypertension in biliary atresia

This study evaluated the long-term effects of distal splenorenal shunt with splenopancreatic disconnection (DSRS-SPD) on portal hypertension (PH) in biliary atresia (BA) patients. Five patients with BA underwent DSRS-SPD at the age of 3.3 to 8.5 years. They had been free from jaundice after hepatic portoenterostomy (HPE); however, they gradually developed gastroesophageal varices and hypersplenism. Portal venous pressure after anastomosis was 37.2 ± 6.1 cmH₂O, as high as that before anastomosis (37.8 ± 3.3 cmH₂O). Postoperatively, liver function tests became worse within 2 weeks; however, they returned to preoperative levels within 1 month without any further treatment. No patient developed a significant encephalopathy throughout the observed period. During follow-up of 4 to 12 years, the shunt was patent in all patients. Spleen size decreased after operation. Abdominal-wall venous dilatation completely disappeared in two of four patients. The platelet counts gradually increased and were significantly higher 3 years (126.6 ± 59.3 × 10³/mm³) after DSRS-SPD than preoperative values (66.0 ± 24.2 × 10³/mm³). White blood cell counts showed no significant changes. No patient developed a gastrointestinal hemorrhage postoperatively, although three had had repeated hemorrhages before the operation. Two patients showed disappearance of varices endoscopically at 2 years and 7 months after DSRS-SPD, respectively, but had recurrent varices at 7 and 11 years, respectively. The endoscopic findings regarding varices 3 to 7 years after DSRS-SPD were as follows: decreased number (80%); decreased length (40%); improvement of form (20%); improvement of fundamental color (60%); disappearance of red-color sign (100%); disappearance of gastric varices (75%); and disappearance of acute gastric mucosal lesions (100%). Although one patient later underwent liver transplantation because of progression of liver cirrhosis, all five are doing well. From these results, DSRS-SPD may prove to be a safe and feasible procedure for intrahepatic PH after HPE for BA and may improve gastroesophageal varices and hypersplenism on long-term follow-up. Accepted: 13 July 1998     

Serum D-lactate levels as a predictor of intestinal ischemia-reperfusion injury

Currently, no serum marker has proved helpful in diagnosing intestinal ischemia and reperfusion (I/R) injury. An experimental study was conducted to determine the value of serum D-lactate in detecting intestinal I/R injury. Thirty New Zealand White rabbits were divided into three groups of 10 animals each: sham-operation controls (S); I/R; and I/R plus mannitol treatment (M). Serum samples were obtained before operation (T₀), at the end of the ischemic period (T₁), after the first 30 min of reperfusion (T₂), and at the end of the reperfusion period (T₃). In Group S, mean D-lactate levels for T₀, T₁, and T₂ were 0 μg/dl, while T₃ was 5.8 ± 4.7 μg/dl. Before the operation (T₀), serum mean D-lactate levels were 0 μg/dl in all groups (S, I/R, M). Levels increased after 1 h of ischemia (T₁) in groups I/R (83.5 ± 25.6 μg/dl) and M (89.8 ± 19.9 μg/dl), but not in group S (0 μg/dl). The mean T₂ level in group I/R (231.6 ± 78.6 μg/dl) was statistically higher than in group M (140.1 ± 53.5 μg/dl) (P = 0.007). At the end of the reperfusion period, the mean T₃ level in group I/R (698.4 ± 360.4 μg/dl) was significantly higher than in group M (158.7 ± 61.4 μg/dl) (P = 0.000). In group I/R, mean D-lactate levels changed significantly at each time point (T₁ vs T₂, P = 0.001; T₂ vs T₃, P = 0.004). However, in group M the increase from T₁ to T₂ was significant (P = 0.012), but that from T₂ to T₃ was not (P = 0.293). As a result, the mean T₃ level was significantly higher than the T₂ level in group I/R (P = 0.004), but not in group M. This study confirmed a significance rise in D-lactate levels in animals with I/R injury compared to sham-operated and I/R injury plus M treatment. We suggest that serum D-lactate levels could be a useful marker of intestinal I/R injury before laparatomy. Accepted: 26 May 1998     

Hashimoto's encephalopathy: Identification and long-term outcome in children

ObjectiveTo identify the clinical findings of Hashimoto's encephalopathy (HE) in children and assess their neurological outcome.MethodsIn this retrospective observational study of 42 children with encephalitis dominated by acute neuro-behavioral features, eight met the diagnostic criteria of HE. Their biological, EEG and brain MRI characteristics were compared to those of the other 34 children. Their clinical outcome was also compared to that of 14 children with Hashimoto's thyroiditis (HT).ResultsAll eight HE children were girls and had high levels of anti-thyroid peroxidase (TPO) antibodies at onset (4043.3 ± 2969.8 IU/mL, inclusion criteria: TPO > 60 IU/mL) despite normal T4 and TSH levels in six of them. All HE children had abnormal EEG and brain MRI was abnormal in four of them. Relapses were observed in five children with a second relapse, despite steroid therapy, occurring sooner after the previous episode (median 18 days (range 17–188) vs 213 days (range 14–518)). Immunosuppressive therapy was started in all five children and two developed sequelae by the last follow-up visit (after 4 ± 1.3 years). Mean anti-TPO antibody titers were significantly higher in HE children than in those with Hashimoto's thyroiditis (HT) (4043.3 ± 2969.8 IU/mL vs 1980.9 ± 3449.9 IU/mL, p = 0.03). Four HE children subsequently developed hypothyroidism whereas only one HT patient presented encephalitis.ConclusionHE is characterized by suggestive clinical symptoms with high levels of anti-TPO antibodies and, in most cases, normal T4 and TSH titers. Despite steroid treatment, relapses and sequelae are frequent. HE may evolve toward HT, but the reverse appears to be rare.     

Evidence of mitochondrial dysfunction in obese adolescents

Aim: Although obesity and weight gain generally are anticipated to be caused by an imbalance between energy intake and energy expenditure, the significance of thyroid hormones (TH) remains unclear. Examination of mitochondrial function may reflect intracellular thyroid hormone effect and elucidate whether a lower metabolic rate is present. Methods: In a group of 34 obese adolescents (age <16 years and body mass index above the age‐related 95th percentile), and an age‐ and gender‐matched group of 32 lean adolescent, thyroid stimulating hormone (TSH) and basal oxygen consumption were measured and mitochondrial function in peripheral blood monocytes was determined by flow cytometry. Results: Significant increase in TSH (3.06 ± 1.56 mU/L vs. 2.33 ± 0.91 mU/L, p < 0.05) and a decrease in VO₂ (129 ± 16 mL O₂/m²*min vs. 146 ± 15 mL O₂/m²*min, p < 0.05) were observed in obese adolescents compared with lean adolescents. Flow cytometry analysis demonstrated a lower mitochondrial mass (6385 ± 1962 a.u. vs. 7608 ± 2328 a.u., p < 0.05) and mitochondrial membrane potential (11426 ± 3861 a.u. vs. 14017 ± 5536 a.u., p < 0.05) in obese adolescents compared with lean adolescents. These results are even more pronounced in adolescents with obese mothers. Conclusion: In obese adolescents, the increased TSH and lowered VO₂ propose a lowered basal metabolic rate and the impaired mitochondrial function suggests a decreased thyroid hormone stimulation of mitochondrial energy production. The maternal in‐heritage is suggestive of a basal metabolic defect or mitochondrial resistance for TH.     

GADA positivity at onset of type 1 diabetes is a risk factor for the development of autoimmune thyroiditis

Kordonouri O, Charpentier N, Hartmann R. GADA positivity at onset of type 1 diabetes is a risk factor for the development of autoimmune thyroiditis. Aim: To evaluate whether the presence of diabetes‐specific autoantibodies may predict the development of autoimmune thyroiditis (AIT) in children with type 1 diabetes (T1D). Methods: Glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase IA2 antibodies (IA2A), and insulin autoantibodies (IAA) were determined at T1D onset in 341 children and adolescents. Thyroid antibodies (anti‐TG, anti‐TPO), thyroid stimulating hormone (TSH), T₃ and T₄ were measured in 335 patients at T1D onset and thereafter annually with a follow‐up time of 1–15 yr. In case of thyroid antibody positivity and/or TSH elevation, thyroid gland sonography was performed. Treatment with l ‐thyroxine was started if persistent elevation of TSH and/or thyroid volume was present. Results: The majority of patients (92.1%) had at least one T1D antibody (71.6% GADA, 73.0% IA2A, and 44.9% IAA). GADA positive patients were older than those without GADA (p < 0.001). Thyroid autoimmunity was found in 15 of 335 patients (4.5%) at T1D onset with female preponderance (p = 0.013). At the end of follow‐up, 70 patients (20.9%) had developed thyroid autoantibodies [cumulative incidence (CI) 0.36 ± 0.06 at 10 yr of T1D]. In 30 patients (9.0%), AIT was diagnosed up to 9.4 yr after T1D onset (CI 0.24 ± 0.06 at 10 yr). AIT incidence was not influenced by IAA or IA2A positivity. In multivariate analysis, GADA positive patients were estimated to have a 3.5‐fold increased risk of AIT (CI 0.31 ± 0.11 at 10 yr) compared to those without GADA (p = 0.024). Conclusion: Based on the present results, a special focus should be given to GADA positive patients concerning screening for AIT as they are at increased risk to develop autoimmune thyroiditis.     

Autoimmune thyroid disease and allergic contact dermatitis: two immune-related pathologies in the same patient

A 12-year-old girl presented signs and symptoms of hyperthyroidism. She had a firm goiter (II°) and she stated that she felt constant warmth, nervousness and experienced palpitations. Autoimmune hyperthyroidism was diagnosed (TSH 0.022 mIU/L↓; fT4 21.0 pmol/L; fT3 7.5 pmol/L↑; antithyroperoxidase antibodies 1148.0 U/mL↑; antithyroglobulin antibodies 41.4 U/mL; thyroid-stimulating hormone receptor antibodies 2.3 U/L↑). Thyroid ultrasound showed multiple hypoechogenic areas with increased vascular flow. During treatment with methimazole, a small hyperpigmented and moderately irritated region was found on the right side of the umbilicus. It was not an allergic skin reaction to methimazole but the classic contact allergic dermatitis, probably a result of nickel in her belt. Two years after stopping the treatment she returned to clinics. She was euthyroid but manifested a firm goiter and ultrasonographic features of autoimmune thyroid disease. The diagnostic work-up concerning antithyroid antibodies is mandatory to confirm the ongoing autoimmune process with a long-term significance.     

Thyroid antibodies in children of mothers with auto-immune thyroid disease

In a cross-sectional study, 29 children aged between 1 month and 15.3 years (average age 6.8 years) born to mothers with Graves disease or Hashimoto thyroiditis were examined clinically, biochemically, and by sonography of the thyroid gland. At the time of examination all children were clinically euthyroid. Tests of thyroid peroxidase antibody, thyroglobulin antibody, TSH receptor antibody and free thyroxine (fT₄) gave normal results. In 3 children subclinical hypothyroidism with elevated TSH and normal fT₄ concentrations were found; one of these children had a minor decrease of total thyroxine. Three children with otherwise normal test results had marginally elevated tri-iodothyronine concentrations. Increased antibody titres were present in 8 out of 29 children. TSH function-blocking antibodies were elevated in 8 cases. In addition, cytotoxic antibodies were found in one of the children. The distribution pattern of antibodies was different in each child and unrelated to the type of maternal thyroid disease. Conclusion Children of mothers with auto-immune thyroid disease often have thyroid antibodies without signs of thyroid disease. Whether antibody-positive children have an increased risk of developing thyroid disorders later in life must be examined in a longitudinal study. Received: 15 December 1997 / Accepted in revised form: 16 February 1998     

Autoimmunthyreopathien bei Kindern und Jugendlichen mit Typ-1-Diabetes Häufigkeit und sinnvolles Screening

Background. Children and adolescents with type 1 diabetes are at increased risk for the development of autoimmune thyroid disease (Hashimoto thyroiditis and Grave's disease). Recommendations for screening have been very inconsistent. Method. Between 1996 and 1999, yearly determinations of serum TSH, fT4, fT3, thyroid peroxidase (TPO-) and thyroglobulin (Tg-) antibodies were done in 155 children and adolescents with diabetes. In those who were positive for thyroid antibodies and/or had a goiter thyroid sonography was performed. Specific therapy was instituted when overt hypo- or hyperthyroidism or subclinical hypothyroidism with goiter was present. No treatment was given to euthyroid patients who had positive thyroid antibodies but no goiter. Results. Between 1996 and 1999, autoimmune thyroiditis was diagnosed in 7 out of 155 children (all females). Hashimoto thyroiditis was present in 4, Grave's disease in 2 and thyroid antibody negative transient hyperthyroidism in one. Median age at diagnosis was 10.9 years, median duration of diabetes 3.1 years. The long-term course of thyroid autoantibody titers varied widely, there was no correlation with activity of hypo- or hyperthyroidism, predominant were TPO- antibodies. Four euthyroid children had elevated thyroid antibodies only, none developed a goiter or thyroid dysfunction so far. One child had subclinical hypothyroidism without thyroid antibodies and was treated with iodine. Of note were markedly increased HbA1c levels coincident with overt hyperthyroidism which decreased once euthyroidism was achieved. Conclusion. Routine screening for autoimmune thyroid disease in children and adolescents with diabetes is necessary. At onset of diabetes, thyroid function and antibodies should be determined to identify patients at risk. During follow-up, search for symptoms and signs of hypo- or hyperthyroidism or goiter as well as a determination of TSH once yearly is sufficient. If abnormal findings are present an extended work-up is necessary (see Fig. 1). Unexplained high HbA1c levels may be caused by unrecognised hyperthyroidism.