Thyroid Hormone and Attention in School-Age Children with Congenital Hypothyroidism

The relationship between attention and thyroid hormone was examined using a retrospective database of 85 7-year-old children with congenital hypothyroidism who received psychological evaluations and thyroid function tests on the same day. Four unique subgroups with different levels of thyroxine and thyrotropin were compared on psychological tasks and measures of attention. Children with high levels of both hormones were found to be significantly more distractible on an index of cognitive attention but were reportedly less hyperactive. Level of thyroxine accounted for over 10% of the variance in attention.     

Maternal TSH-Receptor Antibodies and TSH Antibodies in Screening for Congenital Hypothyroidism

ABSTRACT. Serum samples from 30 mothers who had given birth to at least one child with a positive neonatal thyrotropin (TSH) screening test were analysed for TSH-receptor antibodies. One mother with hypothyroidism after thyroiditis who had two sons who had had transient congenital hypothyroidism, showed significantly elevated concentrations of TSH receptor blocking IgG antibodies in her serum. The three daughters of another mother had neonatal hyper-thyrotropinaemia but normal thyroid hormone levels. This woman had elevated serum levels of TSH but was clinically and biochemically euthyroid. The apparent hyperthyrotropinaemia in this family was due to an artifact in the TSH radioimmunoassay caused by maternal anti-TSH IgG antibodies. It is obvious that placental transfer of maternal IgG antibodies to the thyroid TSH receptor is one cause of transient congenital hypothyroidism. Likewise, maternal IgG directed against TSH interferes with radioimmunoassays of TSH and the results may be falsely interpreted as hyperthyrotropinaemia. It is concluded that in neonatal hyperthyrotropinaemia analysis of the mother's serum is indicated, and that maternal TSH receptor blocking antibodies must be considered as a cause of congenital hypothyroidism, especially if the mother has a history of thyroid dysfunction.     

Circulating Autoantibodies to Thyroid Hormones: A Diagnostic Pitfall

ABSTRACT. Circulating autoantibodies to thyroid hormones are occasionally detected and may cause confusion, because symptoms and signs are inconsistent with the measured thyroid hormone values. We present a 5 1/2 year old girl with Hashimoto's thyroiditis and false high concentrations of free thyroxine and total triiodothyronine.     

The Value of Neonatal Serum Thyroglobulin Determinations in the Follow-up of Patients with Congenital Hypothyroidism

ABSTRACT. Serum thyroglobulin was determined in 68 newborn infants with positive screening tests for congenital hypothyroidism. In 38 infants the diagnosis was confirmed (patients), but the remaining 30 were euthyroid at follow-up (controls). The mean thyroglobulin concentration at the age of 2 weeks did not differ significantly between the patients and the controls (179 vs. 125 μg/l). Thyroid scintigraphy was performed in 15 patients. All seven with thyroid aplasia, based on ^99mTc pertechnetate scintigraphy, had measurable thyroglobulin (> 2 μg/l) and thyroid hormones in their serum. This indicates that total absence of thyroid tissue is very rare in Swedish patients with congenital hypothyroidism. Scintigraphy based on ^99mTc does not permit detection of small amounts of thyroid tissue. The neonatal concentrations of thyroglobulin did not correlate with the results of Griffiths test at 3 years and are therefore not useful for prognosis of psychomotor development. We conclude that neonatal measurement of thyroglobulin is of limited value in the follow-up of patients with congenital hypothyroidism.     

Multivariate Analysis of Psychomotor Development in Congenital Hypothyroidism

ABSTRACT. In the Finnish programme of screening for congenital hypothyroidism (CUT), thyroid replacement therapy is started very early (at a median age of 6 days). Our experience with the first 50 patients detected by this programme confirms that clinically relevant mental retardation is avoided by early therapy. But some intrauterine damage is inevitable and its degree correlates with the severity of the CHT. Age at the start of therapy, in our narrow range, did not appear to influence the outcome, as we found only a paradoxical positive correlation between the two. Our results suggest that thyroid hormone is transferred from the mother to her hypothyroid child during delivery.     

Sensorineural Deafness in Congenital Hypopituitarism with Severe Hypothyroidism

ABSTRACT. Marked sensorineural hearing loss was documented in an 18-year-old boy with untreated congenital anterior panhypopituitarism. The clinical manifestations of the hypothalamic thyroid failure were unusually severe in this patient. Seemingly this is the first case report of perceptive-cochlear deafness in a subject with non primary congenital hypothyroidism.     

Monomeric Calcitonin Secretion in Infants with Congenital Hypothyroidism

ABSTRACT. We have determined CT levels in whole serum (iCT) and by an extraction method (exCT) in 25 infants affected by congenital hypothyroidism (CH)–11 athyreotic and 14 dysgenetic–at age 25 days, before the institution of therapy, and at age 2 years. In hypothyroid patients at age 25 days the iCT and exCT levels were similar to those found in controls of the same age. At age 2 years the iCT and exCT levels decreased in both groups of patients. However, whereas the levels of iCTin hypothyroids were similar to those found in controls of the same age, the levels of exCT were significantly lower in hypothyroids than in controls; moreover they were significantly lower in athyreotic than in dysgenetic patients. At this age, after calcium infusion, exCT levels significantly increased in dysgenetic but not in athyreotic patients. We hypothesize that CT deficiency in CH is due to increased degradation of human CT by the substitutive therapy, which, stimulating proteolytic enzymes, destroys the biologic activity of CT. An extraction procedure improves the sensitivity and specificity of the CT assay and it must be used when CT deficiency is suspected. In addition we suggest that the measurement of exCT levels after Ca infusion might be useful to distinguish dysgenetic from athyreotic patients.     

Congenital Hypothyroidism and Cystic Fibrosis

ABSTRACT. We report a case of dysgenetic congenital hypothyroidism associated with cystic fibrosis. Impaired exocrine pancreatic secretion and/or transit abnormalities secondary to the treatment of meconium ileus resulted in decreased absorption of l -thyroxine and difficulties in management of hypothyroidism.     

A Case with Hyperthyroidism Who Had Been Treated with Thyroid Hormone Because of Congenital Hypothyroidism

We encountered a case with hyperthyroidism at the age of 14 who had been diagnosed with congenital hypothyroidism (CH) and had received thyroid hormone replacement therapy. At the age of 16 d, the patient was referred to our hospital because of positive results at neonatal screening for CH. Serum level of TSH was 91.0 μU/ml and serum level of T4 was 6.9 μg/dl. The patient was diagnosed as having hypothyroidism, and hormone replacement therapy was started. Thereafter the dosage of thyroid hormone was adjusted and increased gradually as he grew to a maximum dose of 110 μg/day at the age of 11. Until the age of 13, the patient’s serum levels of TSH were within the normal range; then, at the age of 13 yr and 4 mo, his serum level of TSH dropped to a level below the detectable range. The dosage of administered thyroid hormone was tapered off and eventually eliminated at the age of 14. A thyroid scan and a radioactive iodine uptake test demonstrated a diffuse goiter with homogeneous uptake of radioactive iodine; the uptake rate was 60% at 24 h, and the serum level of TSH receptor antibody (TRAb) was 62.5% at that time. Administration of an antithyroid drug was started after confirmation that our patient had developed hyperthyroidism. There have been no case reports similar to our case.     

单光子发射计算机断层显像对新生儿甲状腺功能减低的诊断价值

目的采用甲状腺单光子发射计算机断层显像(SPECT)探讨其对新生儿先天性甲状腺功能减低(甲低)的诊断价值。方法对经新生儿疾病筛查发现的19例甲低患儿,静脉注射99mTcO418.5～37.0MBq,15min后行甲状腺显像。结果甲状腺SPECT基本正常5例,单纯性肿大1例,肿大且放射性分布增加2例,异位、缺如各4例,显影不清3例。结论甲状腺SPECT对甲低原因如甲状腺发育不全、缺如和异位等可做出满意的判断,结合甲状腺显像和血清T3、T4、TSH检查,对新生儿甲低诊断具有重要意义。     

Thyroid function abnormalities among first‐degree relatives of Iranian congenital hypothyroidism neonates

Background: Congenital hypothyroidism (CH) is a relatively common metabolic disease in neonates. Until recent years the disorder was usually regarded as occurring in a sporadic manner. Over the past few years, however, a considerable proportion of familial cases have been identified, and possible roles of autoimmune factors suggested. The aim of the present study was to evaluate abnormality of thyroid function tests in first‐degree relatives of CH neonates and compared this to the normal population. Methods: From 2002 until 2007 thyroid function tests (T4 and thyroid‐stimulating hormone [TSH]) were done in randomly selected CH and normal neonates (n= 194 and n= 350, respectively) and their first‐degree relatives. Most mothers of the CH neonates and control groups were also evaluated for thyroid peroxidase antibody (TPOAb). Results: Thyroid function test in first‐degree relative of neonates with CH (361 parents, 136 siblings) were compared with those in control groups (665 parents, 478 siblings). Abnormal thyroid function tests were found in 85 patients in the CH group versus 96 patients in the control group; hypothyroidism was found in 75 (15.1%) and 57 subjects (5%) person in the CH and control groups, respectively (P < 0.05). Positive TPO antibody was found in 22 mothers (17.3%) of CH neonates in comparison with 65 mothers (32.5%) of control groups (P < 0.05). Frequency of hyperthyroidism in parents of control group had trend to be higher than parents of CH neonates (P= 0.05) Conclusion: Familial and genetic components play a role in inheritance of CH, but maternal thyroid autoimmunity may not play an important role in the development of CH in Iran.     

Transient primary hypothyroidism in the newborn: Experience of the Victorian Neonatal Thyroid Screening Programme

Abstract Between May 1977 and December 1986, the Victorian Thyroid Screening Programme tested approximately 570 000 newborns for congenital hypothyroidism. One hundred and sixty-six cases of primary hypothyroidism, confirmed by formal thyroid function tests, were identified, of which 24 were later found to be transient. In addition, there were two patients with permanent dyshormonogenesis who passed through a stage of being biochemically euthyroid and so could have been diagnosed mistakenly as transient hypothyroidism. Fourteen of the transient cases were due to excessive intake of iodine. In two, this was due to maternal ingestion of iodide during pregnancy and in 12 the babies received large amounts of topical iodine antiseptic. Two cases were caused by maternal anti-thyroid antibodies and in eight instances the cause was unknown. The large number of cases due to the topical application of iodine antiseptic emphasizes the need for caution when using this substance in neonates.     

Dissociating Attention Deficits in Children with ADHD and Congenital Hypothyroidism using Multiple CPTs

Recent studies suggest that children with different etiologies of attention disorder also differ as to the types of errors they make on attention tasks. Because these errors are reflective of the core deficits underlying their attention problems, we sought to compare error patterns in children with different attention disorders. Studied were 144 children aged 7–12 years, 43 with attention deficit hyperactivity disorder (ADHD), 35 with congenital hypothyroidism (CH), and 68 controls. Two variations of the continuous performance task (CPT) that differed in demands on inhibitory control and memory were used. One variation, the CPT: A-not-X task, required subjects to observe a continuous stream of letters shown at different rates on the computer screen and respond to all stimuli except "X". The other variation, the CPT: AX task, required them to respond whenever a specified combination of letter such as "A" followed by "X" appeared on the screen. On the CPT:A-not-X task, children with ADHD differed from controls in commission errors, signifying difficulty with inhibitory control, whereas children with CH differed in perceptual sensitivity or signal detection. Although the CH and ADHD groups both performed more poorly than controls on the CPT:AX task, children with CH made more errors to the first stimulus item, suggesting a problem holding information in memory, whereas children with ADHD made more errors to the second item, suggesting impulsivity. These results therefore signify the utility of these tasks in identifying the different mechanisms underlying the specific attention deficits of different groups of children.     

连云港地区新生儿先天性甲状腺功能减低症及苯丙酮尿症筛查分析

目的 探讨连云港地区新生儿先天性甲状腺功能减退症（CH）及苯丙酮尿症（PKU）发病及分布特征。方法 采集生后72h新生儿155091例足跟血于干血滤纸片上。PKU采用盖氏细菌抑制法测血苯丙氨酸（Phe）水平、CH采用酶联免疫吸附试验（ELISA）或时间分辨荧光免疫法（TRFIA）测促甲状腺素（TSH）作为筛查指标。结果 确诊CH患儿64例，发病率4．126／万（1：2423）：经甲状腺核素显像41例，其中甲状腺异常23例（56％）；64例分布在全市的4县3个城区的45个乡镇（街道），男女性别和城乡发病率均无差异（P均〉0．05），发现1对双胞胎CH患儿；确诊苯丙酮尿症患儿15例，发病率为0．967／万（1：10339）：以上患儿父母未见近亲结婚和显性遗传家族史，母孕期正常，经干预治疗，患儿身体和智力发育与同龄儿比较无显著差异。结论 CH、PKU在连云港地区呈散发性分布，进行新生儿筛查是发现CH、PKU的唯一有效手段。     

Psychological Development at 7 Years of Age in Children with Congenital Hypothyroidism: Timing and Dosage of Initial Treatment

ABSTRACT. Sixty of 68 consecutive patients detected during the first two years of the Swedish screening programme for congenital hypothyroidism were Griffiths tested at the age 6.5–7.5 years. The test quotients of the patients could not be distinguished from those of reference population. Replacement therapy with 8.7 ± 2.8 μg of l -thyroxine (mean±SD)/kg/d had been started at 15.0 ± 7.1 days of life. Furthermore, normal results on Griffiths tests were also found in 13 patients with delayed normalization of serum TSH, i.e. ≥ 19 mU/l at the age of six weeks, as well as in patients with retarded skeletal maturity and/or very low neonatal serum levels of thyroxine, i.e. < 18 nmol/l and tri-iodothyronine, i.e. <0.92 nmol/l. Our findings indicate that replacement dose of 6–11 μg l -thyroxine/kg/d is adequate and allows normal psychological development if treatment is started early.     

Guidelines for Mass Screening of Congenital Hypothyroidism (2014 revision)

Purpose of developing the guidelines: Mass screening for congenital hypothyroidism started in 1979 in Japan, and the prognosis for intelligence has been improved by early diagnosis and treatment. The incidence was about 1/4000 of the birth population, but it has increased due to diagnosis of subclinical congenital hypothyroidism. The disease requires continuous treatment, and specialized medical facilities should make a differential diagnosis and treat subjects who are positive in mass screening to avoid unnecessary treatment. The Guidelines for Mass Screening of Congenital Hypothyroidism (1998 version) were developed by the Mass Screening Committee of the Japanese Society for Pediatric Endocrinology in 1998. Subsequently, new findings on prognosis and problems in the adult phase have emerged. Based on these new findings, the 1998 guidelines were revised in the current document (hereinafter referred to as the Guidelines). Target disease/conditions: Primary congenital hypothyroidism. Users of the Guidelines: Physician specialists in pediatric endocrinology, pediatric specialists, physicians referring patients to pediatric practitioners, general physicians, laboratory technicians in charge of mass screening, and patients.     

Retrospective Analysis of Infants Designated as Positive on Mass-Screening for Congenital Hypothyroidism at Kagoshima University

Mass-screening for congenital hypothyroidism has identified cases of mild hypothyroidism, transient hypothyroidism, and transient hyperthyrotropinemia as well as typical hypothyroidism. In this paper, we examine the clinical data of the cases found positive in the screening test at our hospital. From 1989 to 1999 there were 72 patients with positive screening tests who started levothyroxine sodium (l-T4; Thyradin-S) as supplement therapy. At the age of 3 to 4 yr the patients were re-evaluated to determine whether treatment should be continued. Thyroid scintigraphies were done at the same time. We divided these cases into 4 groups. Those in group 1A started l-T4 in early infancy without a TRH test because of obvious clinical evidence of hypothyroidism, and treatment was continued after re-evaluation (n=37). Those in group 1B also started treatment in early infancy without a TRH test, but treatment was discontinued after re-evaluation (n=20). Patients in group 2A started l-T4 after evaluation by a TRH test and treatment was continued after re-evaluation (n=14), while those in group 2B started treatment after a TRH test, but after re-evaluation, treatment was discontinued (n=1). In group 2A, only a low dose of l-T4 was needed, and a slightly elevated TSH and slightly decreased free T4 (FT4) were observed after the drug washout period. However, these patients had an exaggerated response to the TRH test at re-evaluation. These findings indicate that this group, forming not a small part of whole screening-positive subjects, had mild hypothyroidism. Such patients require careful follow-up and repeated evaluation to determine whether treatment should be continued.     

Psychomotor Development of Children with Congenital Hypothyroidism Diagnosed by Neonatal Screening

ABSTRACT. The psychomotor development in 68 children with congenital hypothyroidism diagnosed during the first two years of a nationwide neonatal screening programme in Sweden was assessed during their first three years of life. Replacement therapy with thyroxine was initiated at the age of 15±7 days (mean ± SD). Griffiths tests were performed in 15 patients at the age of 18 months and in 51 patients at 30–47 months. Their developmental quotients did not differ from those of control children, indicating that the psychomotor development in the children with congenital hypothyroidism was normal. In earlier studies of Swedish children with congenital hypothyroidism, diagnosed clinically before the age of three and a half years, the psychomotor development was found to be impaired. In contrast, the patients diagnosed by neonatal screening and given early therapy displayed normal results in Griffiths tests. This indicates that the age at the start of treatment is an important determinant for the prognosis.     

先天性甲状腺功能减低症患儿治疗前后血清ghrelin的动态变化

目的 观察甲状腺素替代治疗对先天性甲状腺功能减低症(CH)患儿血清ghrelin水平的影响.方法 研究对象为2007年10月-2008年3月在徐州医学院附属医院确诊并行治疗随访的CH患儿40例及健康体检儿童30例.分组:未治疗组包括甲状腺功能减低的CH患儿20例;治疗组包括新诊断或随访中经甲状腺素片治疗后甲状腺功能正常至少1个月的CH患儿20例;健康对照组年龄、性别相当的健康儿童30例.采用夹心法酶联免疫吸附试验测定3组儿童血清ghrelin水平,采用化学发光法测定三碘甲状腺原氨酸(T3)、四碘甲状腺原氨酸(T4)、促甲状腺激素刺激激素(TSH)水平,同时计算每个样本的体质量指数(BMI)用于相关分析.结果 1.未治疗组ghrelin水平[(2.35±0.23) μg·L-1]虽高于治疗组[(2.16±0.25) μg·L-1]和健康对照组[(1.96±0.27) μg·L-1],但差异无统计学意义(P=0.102).2.Ghrelin与年龄呈负相关(r=-0.325,P<0.05),但与性别、BMI、T3、T4、TSH无相关关系(Pa>0.05).结论 甲状腺激素对中枢或外周ghrelin的产生和分泌可能无调控作用.在不同生长发育时期,不同水平的ghrelin可能有不同的生理作用.