The clinical course of Hashimoto's thryoiditis in children and adolescents: 6 years longitudinal follow-up

Forty-six children and adolescents with Hashimoto's thyroiditis were followed up for 5.9 +/- 0.3 years. The mean age at diagnosis was 12.4 +/- 1.7 years (range 9-15.4 yr). The patients were divided into three groups according to thyroid function: group 1 (n = 28) included patients who had normal concentrations of free thyroxine (FT4) and thyrotropin (TSH); group 2 (n = 8) included patients who had normal FT4 and elevated TSH, consistent with compensated hypothyroidism; group 3 (n = 10) included patients who had low FT4 and elevated TSH consistent with overt hypothyroidism. After 5.9 years of follow-up, four out of eight patients with compensated hypothyroidism had normal thyroid function and the other four patients developed overt hypothyroidism. Thyroxine therapy was administered in patients with overt hypothyroidism including the four patients with compensated hypothyroidism who later presented with overt hypothyroidism. All patients in both euthyroid and hypothyroid groups had normal growth and puberty. Final adult height was 0.43 +/- 0.80 SDS which was 1.58 +/- 3.03 cm above mid-parental height. The mean age at menarche (n = 43) was 12.4 +/- 1.1 years, which was not different from normal children. The goiter remained the same size in most of the patients with euthyroidism without thyroxine therapy, but decreased in patients with overt hypothyroidism after thyroxine therapy.     

Thyroid dysfunction in antiretroviral treated children

BACKGROUND: A high rate of thyroid disorders has been described in HIV-infected adults treated with highly active antiretroviral therapy (HAART), but data on children are lacking. We aimed to assess thyroid function in pediatric patients. METHODS: Fifty-two HIV-infected children receiving HAART were assessed for signs of thyroid dysfunction and serum concentrations of thyrotropin (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroglobulin (TG), reverse triiodothyronine (rT3), anti-TG and antimicrosomal (anti-TSM) antibodies. RESULTS: Eighteen (35%) children showed thyroid abnormalities: isolated low FT4 value in 16; subclinical hypothyroidism in 1; and symptomatic hypothyroidism in 1.Children with low FT4 values as compared with the 34 children without thyroid dysfunction were similar for stage of disease, number of patients with undetectable HIV-RNA, FT3, TSH, TG, rT3, anti-TSM and anti-TG values, whereas they had shorter duration of HAART exposure (P = 0.019) and lower CD4 cell percentage (P = 0.035). The thyrotropin-releasing hormone (TRH) test was normal in all children with low FT4 values. Among children with low FT4, FT4 concentrations correlated positively with CD4 cell percentage (P < 0.05) and duration of HAART exposure (P < 0.05).The case with subclinical hypothyroidism had high basal TSH (7.3 microunits/ml), normal TSH response to TRH test and normal FT4, FT3, TG, rT3, anti-TG and anti-TSM antibodies.The case with symptomatic hypothyroidism had low FT4 (6.6 pg/ml) and high TSH (44 microunits/ml), TG (55 ng/ml), anti-TG (666 IU/ml) and anti-TSM (123 IU/ml). CONCLUSION: Thyroid abnormalities occur frequently in HAART-treated children even in the absence of clinical symptoms. These data suggest a need of regular thyroid function monitoring.     

Changes in thyroid function after bone marrow transplant in young patients

BACKGROUND: Changes in thyroid function among young patients who received bone marrow transplantation (BMT) were evaluated. METHODS: The study included 91 patients (50 males) who underwent BMT from 1985 to 1995 at the age of 0.6-21 years. Sixty patients had neoplastic disease such as leukemia or lymphoma, and the remainder had non-neoplastic diseases. Preconditioning regimen for BMT included 12 Gy of fractionated-total body irradiation (TBI) for patients with neoplastic disease and 3-8 Gy of irradiation for the remaining patients, in addition to chemotherapy. Evaluation of thyroid function was performed by serial assessment of basal serum FT4, FT3, TSH concentrations as well as by TRH test. RESULTS: No patient had overt hypothyroidism or elevated basal TSH concentrations (>10 mU/L). However, 6 (7%) of patients experienced exaggerated peak TSH response to TRH stimulation several years after BMT. In 33 patients whose thyroid status was evaluated before, within 3 months, and 1 year after BMT, serum FT3 concentrations as well as peak TSH response to TRH stimulation significantly decreased immediately after BMT (<3 months) and normalized within 1 year. However, serum FT4 concentrations did not change significantly. One patient developed primary hypothyroidism and another developed follicular adenoma of the thyroid 5 and 12 years after BMT, respectively. CONCLUSION: Short-term changes in thyroid function after BMT can indicate euthyroid sick syndrome rather than tertiary hypothyroidism. It must be noted that overt hypothyroidism may occur several years after BMT, hence long-term follow-up of thyroid function is warranted.     

Borderline congenital hypothyroidism in the neonatal period

One of the most important etiological factors causing prolonged jaundice in the neonatal period is congenital hypothyroidism. Some infants may have abnormal thyroid function test results rather than overt congenital hypothyroidism. Although serum TSH levels are accepted as diagnostic when >20 microIU/l, TSH values higher than 7 microIU/ml cause a hypometabolic condition. In this study, we evaluated infants who had prolonged jaundice for hypothyroidism. A hundred and ten infants suffering from prolonged jaundice were admitted to our clinic during the study period. Among them, 61 infants had normal thyroid function results. Six patients had overt primary hypothyroidism. TRH stimulation test was administered to the 43 patients with mildly elevated TSH levels of between 5 and 20 microIU/ml. Peak TSH values were above 35 microIU/ml in seven patients, and these were considered as having an exaggerated response (borderline hypothyroidism). During the neonatal period, prolonged jaundice is a valuable diagnostic clue for hypothyroidism. In addition, the TRH stimulation test can be a diagnostic tool in evaluating infants with mildly abnormal thyroid function test results.     

Euthyroid sick syndrome in children with Hodgkin disease

Euthyroid sick syndrome is related to profound changes in thyroid metabolism induced by nonthyroidal diseases. To determine whether children with newly diagnosed Hodgkin disease might present thyroid abnormalities and to establish their predictive value, the authors performed regular thyroid function testing. Seven children (5 M, 2 F) with a mean age of 10.4 years (range: 4.6-15 years) at diagnosis were studied for a period of 6.9 years (4.2-10.5 years). Five patients presented at diagnosis with euthyroid sick syndrome characterized by borderline low thyroxine circulating levels (T3 0.8-1.3 ng/mL, FT3 1.5-1.7 pg/mL) and mildly raised TSH (4.6-5 microU/mL). Thyroid function turned normal within 6 months of therapy. Subsequently, 3 children developed overt hypothyroidism (T4 35-40 ng/mL, FT4 2-7 pg/mL, TSH 5.5-11 microU/mL) requiring substitution therapy. Euthyroid sick syndrome was not associated with a poorer outcome in terms of survival or long-term thyroid consequences. Thyroid function testing should be performed routinely at diagnosis and thereafter in children with Hodgkin disease to detect subtle abnormalities.     

Thyroid function in children with Down's syndrome]

The aim of the present study was to evaluate thyroid function in 45 Down's syndrome patients in order to verify the hypothesis of an increased risk of thyroid disorders associated with trisomy 21. A patient with subclinical hypothyroidism (TSH 16.6 microU/ml; T4 6.4 micrograms/dl) was diagnosed in a group of 28 subjects with Down's syndrome studied at a mean age of 6 years and 5 months using T3, T4, FT3, FT4, TSH assays and clinical examination. T4 and TSH values were also measured in 10 of these children at the neonatal screening. One infant presented transient neonatal hyperthyrotropinemia but later became euthyroid. The analysis of thyroid hormone values at the neonatal screening of other 17 subjects with Down's syndrome did not reveal other cases with thyroid function disorders. The results of this study highlight that altered thyroid functions are evident in children with trisomy 21 associated with heart anomalies. A careful clinico-endocrinological follow-up of patients with Down's syndrome is recommended in order to ensure an early diagnosis of thyroid function disorders and/or autoimmune diseases which might complicate the evolution of trisomy and negatively affect outcome.     

Three-year follow-up of borderline congenital hypothyroidism

The purpose of this study was to determine whether children with borderline hypothyroidism in the neonatal period had persistent hypothyroidism after 3 years of levothyroxine replacement therapy. Fourteen term infants with slightly abnormal newborn screening results (thyroxine <10th percentile, thyroid stimulating hormone ?TSH <40 microU/mL) were identified. The subsequent serum confirmatory TSH results of 12 subjects were modestly elevated (5.3 to 18.8 microU/mL, normal 0.6 to 4.6), whereas 2 subjects who had borderline confirmatory TSH (4.6 and 4.7 microU/mL) had abnormal TSH responses to thyrotropin releasing hormone testing. After 3 years of therapy, levothyroxine was discontinued in 13 patients, and repeat thyroid function tests were obtained 1 month later. Levothyroxine was not discontinued in one patient because he had an elevated random TSH (10 microU/mL) while receiving therapy. At 3 years of age, 13 patients had persistently abnormal thyroid function tests (TSH >4.6 microU/mL or a thyroid releasing hormone test result consistent with primary hypothyroidism), and levothyroxine was reinitiated. Only one patient had normal thyroid function studies. Although prospective studies are still lacking, we recommend levothyroxine replacement in newborns with borderline hypothyroidism.     

Short-term hyperthyroidism followed by transient pituitary hypothyroidism in a very low birth weight infant born to a mother with uncontrolled Graves' disease

Transient hypothyroxinemia in infants born to mothers with poorly controlled Graves' disease was first reported in 1988. We report that short-term hyperthyroidism followed by hypothyroidism with low basal thyroid-stimulating hormone (TSH) levels developed in a very low birth weight infant born at 27 weeks of gestation to a noncompliant mother with thyrotoxicosis attributable to Graves' disease. We performed serial thyrotropin-releasing hormone (TRH) tests in this infant and demonstrated that TSH unresponsiveness to TRH disappeared at 6.5 months of age. The maternal thyroid function was free triiodothyronine (FT(3)), 21.1 pg/mL; free thyroxine (FT(4)), 8.1 ng/dL; TSH, <0.03 microU/mL; thyroid-stimulating hormone receptor antibody, 52% (normal: <15%); thyroid-stimulating antibody, 294% (normal: <180%); and thyroid-stimulation blocking antibody, 9% (normal: <25%) on the day of delivery. A nonstress test revealed fetal tachycardia >200 beats per minute, and a male infant weighing 1152 g was born by emergency cesarean section. Thyroid-stimulating hormone receptor antibody was 16% and thyroid-stimulating antibody was 370% in the cord blood. We administered 10 mg/kg per day of oral propylthiouracil from day 1. Tachycardia along with elevated FT(4) and FT(3) levels in the infant decreased from 200/minute to 170/minute, 4.7 ng/dL to 2.9 ng/dL, 7.0 pg/mL to 4.8 pg/mL, respectively, in the first 33 hours. At 5 days, FT(4) and FT(3) were 1.1 ng/dL and 2.9 pg/mL, respectively, and we stopped propylthiouracil administration. Although FT(4) decreased to 0.4 ng/dL, TSH was quite low and did not respond to intravenous TRH by 14 days of age. We began daily levothyroxine 5-micro/kg supplementation. The responsiveness of TSH to TRH did not become significant until 4 months old and normalized at 6.5 months old. At this time, levothyroxine was stopped. We conclude that placental transfer of thyroid hormones may cause hyperthyroidism in the fetal and early neonatal periods and lead to transient pituitary hypothyroidism in an infant born to a mother with uncontrolled Graves' disease.     

Disorders of thyroid gland function--hypothyroidism in childhood. An ambulatory follow-up study

42 children with different kinds of hypothyroidism, who had been treated with thyroid hormones during several years, were thoroughly follow-up examined in 1988. Apart from few exceptions, patients in therapy attained standard data in length. Concerning skeleton maturation, clear differences between boys and girls were found. While male patients, with one exception, showed a retardation of bone-age, in females both, retardation and acceleration of bone-development were found. Serum concentration of FT4 and FT3 were chosen as hormonal parameter, and TSH was taken basal and after stimulation with TRH. Normal FT4 levels were found in 29 patients. In 5 children FT4 was significantly lower, in 8 cases an elevation of this serum-parameter was observed. Measurement of serum FT3 in 27 patients showed normal levels in 18 children. In 4 cases low and in 5 elevated FT4 levels were found. 29 patients had basal TSH concentrations within normal range, in 13 the estimated levels were elevated. TRH-stimulation carried out on 40 children showed normal serum TSH response for 13 of them. In 14 children an exaggerated TSH response to TRH occur, in 13 TSH still remain low after stimulation with TRH. Serum-GOT, -GPT, -Gamma GT and -CK were determined as encymic parameters. In 5 patients a typical hypothyroidism-associated GOT- and CK-elevation was found. 3 children showed an isolated rise of GOT-, 8 an isolated CK-elevation.     

Pseudohypoparathyroidism with hypothyroidism (author's transl)

This is a report about three children suffering from pseudo-hypoparathyroidism type I and moderate primary hypothyroidism. The thyroid dysfunction was characterised by slightly low plasma thyroxine and high basal TSH showing an increased response to TRH. T3 and rT3 were within normal limits, the size of the thyroid glands and also bone age were normal. The plasma concentrations of T4 and TSH and the response of TSH to TRH were no different during hypocalcemia from those obtained in normocalcemia during vitamin D treatment. Thyroxine treatment could normalize T4 and TSH. Moderate hypothyroidism is frequently present in pseudohypoparathyroidism. It has to be assumed that the same genetical defect of the second messenger, already proved to exist in the kidneys of patients with pseudohypoparathyroidism may also exist in the thyroid gland.     

Thyroid dysfunction in children with Down's syndrome

Thyroid function tests were carried out on 320 children with Down's syndrome aged between 5 d and 10 y. Thyroid function was normal in 230 patients (71.9%) and abnormal in 90 (28.1%). Six patients (1.8%) had primary congenital hypothyroidism, one patient had acquired hypothyroidism and two had transient hyperthyrotropinaemia of the newborn. Sixteen of the remaining 81 patients (25.3%) had compensated hypothyroidism with increased thyroid-stimulating hormone (TSH) levels (11-20 mU l -1 ). Their T 4 levels were found to be either normal or close to the lower limit of normal. These cases were started on thyroxine therapy. Sixty-five of the 81 patients had a mild compensated hypothyroidism with mild TSH elevation (6-10 mU l -1 ). None of the patients had hyperthyroidism. The antithyroid antibodies were positive in the acquired hypothyroidism case.

Conclusion: The prevalence of congenital hypothyroidism was 1.8% in children with Down's syndrome while 25.3% of them had compensated hypothyroidism. It is suggested that Down's syndrome patients with normal thyroid functions and those with compensated hypothyroidism should be followed annually and every 3 mo, respectively. Besides congenital hypothyroidism cases, those with TSH levels between 11 and 20 mU l -1 may benefit from treatment with low-dose thyroxine.     

Changes in hypothalamic-pituitary function following bone marrow transplantation in children

Patients who undergo bone marrow transplantation (BMT) frequently experience impaired pituitary function, but precise assessment using repeated provocative tests has not been described. We studied 32 children (16 boys) who had BMT after receiving preparative irradiation. Assessment of pituitary function was performed by infusing insulin, luteinizing hormone-releasing hormone (LHRH), and thyrotropin-releasing hormone (TRH) on several occasions at various intervals during the follow-up period. Serum free thyroxine (FT4) and thyrotropin (TSH) levels tended to be low during the early period following BMT. Serum FT4 concentrations reverted to the low-normal range 1 year after transplant, and eight of 29 patients had subnormal and delayed TSH response to TRH consecutively. No children showed overt hypothyroidism. Basal and peak serum gonadotropin levels in response to LHRH were elevated in the patients who had received transplant around the time of puberty. Leydig cell function assessed by human chorionic gonadotropin test was normal. Three girls experienced menarche, and one male patient fathered a normal boy 7 years after BMT. Pituitary-adrenal function and prolactin secretion were not affected. A high incidence of transient hypothyroidism which did not require replacement therapy and gonadal failure among pubertal children were observed. Shielding of gonads should be attempted, if possible, at the time of preparative irradiation to prevent resultant hypogonadism.     

Long-term outcome of hormonal status in Taiwanese children with Hashimoto’s thyroiditis

The objective of this prospective study was to evaluate both thyroid function in children with Hashimoto’s thyroiditis and the necessity of lifetime thyroxine replacement therapy. A total of 47 patients with goiter and positive thyroid auto-antibodies participated in the study. Serum thyroxine and thyrotropin levels and titers of thyroid auto-antibodies were checked regularly throughout the follow-up period. At the beginning of the study, 25 patients were diagnosed as euthyroid, but at the end of the study, 22 patients initially diagnosed with euthyroidism remained euthyroid, while eight patients with subclinical hypothyroidism and three patients with overt hypothyroidism had become euthyroid. Thus, of the 22 patients with thyroid dysfunction at diagnosis, subclinical or overt, 11 became euthyroid during the follow-up period. The effect of thyroxine treatment on thyroid auto-antibody titers was not significant. Conclusion: Our data shows that Hashimoto’s thyroiditis in children has a benign course and that thyroid function in one half of the patients with thyroid dysfunction at diagnosis reverts to normal. Careful follow-up of thyroid function is important in order to determine the necessity and timing of thyroxine replacement therapy.     

Genetic Analysis in Children with Transient Thyroid Dysfunction or Subclinical Hypothyroidism Detected on Neonatal Screening

About 30% of children with elevated TSH levels during neonatal screening have a transient form of disorder. On the other hand, it has been reported that subclinical hypothyroidism persists in late childhood in about 30% of children found to be false-positive during neonatal screening. The aim of this study was to determine whether transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening are influenced by genetic background. The TSH receptor (TSHR), thyroid peroxidase (TPO) and dual oxidase 2 (DUOX2) genes, for which it has been reported that heterozygous defects cause neonatal transient thyroid dysfunction, were analyzed. Nine children with transient thyroid dysfunction or subclinical hypothyroidism detected during neonatal screening were studied. One child was heterozygous for a TSHR gene mutation (R450H), and another child was heterozygous for a TPO gene mutation (P883S). No children with mutation of the DUOX2 gene were identified. Genetic background may contribute to development of transient thyroid dysfunction and subclinical hypothyroidism detected during neonatal screening.     

Treatment for acute lymphoblastic leukemia in children is associated with papillary carcinoma of thyroid, but not with thyroid disfunction

AIM: The treatment of acute lymphoblastic leukemia (ALL) in children may cause sequelae, some appearing only at long-term follow-up. We investigated the thyroid gland morphology and the function of the pituitary-thyroid axis in a group of patients treated for ALL in childhood. METHODS: A cohort study was conducted at a tertiary medical center. Thirty-three children (22 males and 11 females; age: 11.9+/-3 years; range: 6 to 18 years) were studied. The mean age at the time of chemotherapy and prophylactic cranial irradiation (12-24 Gy) was 5.5+/-2.6 years (range: 1 to 14 years). The average length of the follow-up was 6.1+/-3 years (range: 2 to 12 years). Thyroid morphology (n=33) was evaluated by palpation and ultrasonography. Thyroid function (n=30) was evaluated measuring total T3 and T4, and by the thyrotrophin-releasing hormone (TRH) test. Prolactin secretion was assessed before and after injection of TRH to evaluate the diagnostic test accuracy. RESULTS: One out of the 33 children (3%) was found to have a papillary carcinoma of thyroid four years after ALL treatment. Thyroid function was normal in all the patients, however one case (3%) showed high TSH (9.2 microU/mL) and prolactin (37.5 ng/mL) basal levels, but normal responses to TRH (TSH = 17.8 microU/mL; prolactin = 82.3 ng/mL). These hormonal alteration were not confirmed at follow-up: TSH = 1.6 microU/mL and prolactin = 13.7 ng/mL. CONCLUSIONS: In this cohort of patients, the treatment of ALL was associated with one case of thyroid carcinoma, but it did not produce adverse effect on the thyroid function, at least after a follow-up lasted on average 6 years.     

Subclinical hypothyroidism in in vitro fertilization babies

Aim: Assisted reproduction technology is used widely all over the world. There is a great concern about the morbidity of in vitro fertilization (IVF) babies, but investigations are mostly related to mechanical conditions that are attributed to multiparity. This paper aimed to investigate the effect of IVF on thyroid functions in newborns. Methods: A total of 98 healthy, term IVF newborns were evaluated between postnatal 2–4 weeks of age by screening of thyroid functions between July 2006 and April 2008. Ten subjects were assessed as a study group whose thyroid‐stimulating hormone (TSH) levels were higher than 6.5 mU/L. Control group consisted of randomly selected 10 naturally conceived infants with hyperthyrotropinemia (whose TSH levels were higher than 6.5 mU/L but under 15 mU/L) with the same age. All children were thoroughly examined, and serum fT4, TSH, anti‐thyroid peroxidase and anti‐thyroglobulin antibodies were measured, and a thyrotropin‐releasing hormone (TRH) test was performed in all subjects in both groups. Results: Euthyroid hyperthyrotropinemia was diagnosed in approximately 10% of IVF babies. Exaggerated TSH levels to TRH were obtained in all IVF babies (subclinical hypothyroidism) but in none of the controls. A significant difference was noted in the concentration of TSH at the 20th min between the two groups (p < 0.001). Besides, sustained and delayed TSH responses were observed in IVF babies. Neonatal screening tests were negative in both of the groups. Conclusion: In IVF babies, despite normal neonatal screening tests, subclinical hypothyroidism might be observed that suggests the need for screening in this respect.     

Thyroid dysfunction in multi-transfused iron loaded thalassemia patients.

Seventy-two transfusion-dependent iron loaded thalassemia patients were investigated for thyroid dysfunction by estimating circulating thyroid hormones (T4 and T3) and basal thyroid stimulating hormone (TSH). They were also evaluated for their liver function (biochemically) and iron overload by estimating serum ferritin. Thyroid failure (hypothyroidism) was documented in 14 patients (19.4%). In all, 3 groups were seen, i.e. Group 1: Normal T4, T3, TSH (58 patients: 80.6%); Group 2: Compensated hypothyroidism characterized by normal T4, T3 and raised TSH (9 patients: 12.5%); Group 3: Decompensated hypothyroidism characterized by decreased T4 and increased TSH (5 patients: 6.9%). Interestingly, impaired thyroid function could not be correlated with age, amount of blood transfused, liver dysfunction or degree of iron overload. It is postulated that an inter-play between chronic hypoxia, liver dysfunction and iron overload may be responsible for the thyroid damage.     

亚临床甲状腺功能减退症对患儿骨龄和身高的影响

目的 观察亚临床甲状腺功能减退症(甲减)对儿童骨龄(BA)、身高及甲状腺激素水平的影响.方法 选取30例亚临床甲减患儿为亚临床甲减组,30例体检健康儿童为健康对照组.对每位研究对象采用同一磅秤标准,测量其身高、体质量.采用Greulich-Pyle图谱法对各组儿童左手腕指关节正位片进行BA水平的评定;采用罗氏化学发光免疫分析仪E170检测各组儿童促甲状腺激素(TSH)、游离三碘甲腺原氨酸(FT3)、游离甲状腺素(FT4)水平.采用SPSS 17.0软件比较2组儿童BA、身高、TSH、FT3及FT4的差异;BA与身高、TSH、FT3及FT4间进行Pearson相关分析.结果 亚临床甲减组儿童的BA[(8.17±2.29)岁]、身高[(131.47±13.41) cm]水平均落后于健康对照组[(10.08±2.75)岁、(141.05±15.12) cm](t=2.92、2.60,Pa<0.05);TSH水平[(5.93±1.77) mIU·L-1]显著高于健康对照组[(2.66±1.28) mIU·L-1](t=8.17,P<0.001).亚临床甲减组儿童的BA与身高呈显著正相关(r=0.940,P<0.01);BA与TSH呈显著负相关(r=-0.450,P<0.05).亚临床甲减组FT3[(5.43±1.37) pmol·L-1]、FT4[(17.29±2.03) pmol·L-1]与健康对照组[(5.83±1.11) pmol·L-1、(17.22±1.96) pmol·L-1 ]比较差异均无统计学意义(t=1.24、0.14,Pa>0.05).结论 儿童亚临床甲减可引起BA、身高的落后,需要用药物进行干预治疗.     

Thyroid-stimulating hormone, prolactin, and growth hormone response to thyrotropin-releasing hormone in treated children with congenital hypothyroidism

The purpose of the present study was to assess thyroid-stimulating hormone (TSH), prolactin, and growth hormone responses to TRH stimulation in 12 congenitally hypothyroid children adequately treated with L-thyroxine from the first weeks of life. Although clinically euthyroid, six of these children were found to have abnormally high basal serum TSH concentrations despite clinical euthyroidism. Serum triiodothyroxine and L-thyroxine concentrations were normal and did not differ whether the children had elevated or normal basal serum TSH. All six of the children with high basal TSH had an exaggerated TSH response to TRH and 4 of them also had an augmented prolactin response to TRH. The children with normal basal TSH concentrations had normal TSH and prolactin responses to TRH. An abnormal ("paradoxical") elevation of growth hormone concentration in response to TRH was found in four of seven children in a separate group of patients who had prolonged, untreated primary hypothyroidism, but such responses were not found in any of the adequately treated children. These findings suggest the following conclusions: 1) the phenomenon of high serum concentrations of TSH in conjunction with normal L-thyroxine and triiodothyronine levels (and clinical euthyroidism), is prevalent in congenital hypothyroid patients. 2) These patients have an exaggerated response of their pituitary thyrotroph and lactotroph cells to TRH, presumably caused by selective and relative resistance of these cells to the inhibitory effects of thyroid hormones. 3) Congenital hypothyroidism is not associated with abnormal somatotroph cell responses to TRH.     

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.