Thyroid & Down Syndrome Abstracts

J Clin Endocrinol Metab (2005 Mar 8)

The effect of thyroxine treatment started in the neonatal period on development and growth of two years old Down syndrome children: a randomized clinical trial.

van Trotsenburg AS, Vulsma T, Rutgers van Rozenburg-Marres SL, van Baar AL, Ridder JC, Heymans HS, Tijssen JG, de Vijlder JJ.
Academic Medical Center, University of Amsterdam, Departments of Paediatric Endocrinology (A. S. P. v. T., T. V., S. L. R. v. R.-M., J. C. D. R., J. J. M. d. V.), Paediatrics (H. S. A. H.), and Cardiology (J. G. P. T.), Amsterdam; and University of Tilburg, Department of Paediatric Psychology (A. L. v. B.), Tilburg–both in the Netherlands.

OBJECTIVE: Context: Young Down syndrome children appear to have a mild form of congenital hypothyroidism that is rarely detected by neonatal screening and usually left un-treated. Objective: To investigate the effects of thyroxine treatment on development and growth of young Down syndrome children. Design, setting, and participants: Single-center, randomized, double-blind, 24-months trial (enrollment June 1999-August 2001) with nationwide recruitment, comparing thyroxine administration with placebo in 196 Down syndrome neonates. Intervention: Neonates were randomly assigned to treatment for two years with either thyroxine (N = 99; initial dose 8 microgram per kg) or placebo (N = 97). Daily thyroxine doses were adjusted at regular intervals to maintain plasma TSH in its normal and FT4 concentrations in its high-normal range. Placebo dose adjustments mirrored those of thyroxine. Main outcome measures: The primary outcome was mental and motor development at age 24 months, assessed with the Bayley Scales of Infant Development II. Results: At age 24 months, the developmental testing results of 90 thyroxine-, and 91 placebo-treated children were available for analysis. The thyroxine treated children had a 0.7 month smaller delay in motor developmental age (95% CI -1.4 to 0), corresponding to a difference of 7 motor developmental index points. The mental developmental age delay was also 0.7 month smaller in the thyroxine group (95% CI -1.5 to -0.1), but lacked statistical significance. Thyroxine treated children had greater gains in length (1.1 cm, 95% CI 0.2 to 2.0) and weight (378 grams, 95% CI 55 to 701). Conclusions: The data of our study provide evidence to support the hypothesis that thyroxine treatment may improve development and growth of young Down syndrome children. Thyroxine treatment should be considered in Down syndrome neonates, to maximize their early development and growth.
Arch Pediatr 4 (2): 116-20 (1997 Feb)

Anomalies du fonctionnement thyroidien des enfants trisomiques 21 [Anomalies of thyroid function in children with Down syndrome]

Toledo C; Alembik Y; Dott B; Finck S; Stoll C
Institut de Puericulture, CHU, 23, Strasbourg, France

BACKGROUND: Abnormal thyroid function was shown in children with Down syndrome (DS). This study was undertaken in order to specify these anomalies. POPULATION AND METHODS: Thyroid function of 105 children with DS aged from 3 months to 20 years was studied by evaluation of serum concentration of thyrotropin, free T4 (FT4), free T3 (FT3) andreverse T3 (rT3). Each DS child was matched to a control of the same age. RESULTS: The mean concentration of thyrotropin of children with DS was increased while the mean concentration of rT3 of the DS children was significantly decreased compared with the controls, as was the ratio rT3/TSH. When DS children are split into two groups, those with and those without increased thyrotropinemia, a significant decrease in the ratio rT3/TSH appeared in DS children with increased thyrotropinemia whereas there is no difference between these two groups regarding to level of FT4, FT3, rT3 and zincemia. However, in all DS children serum zinc levels were lower than in controls. Thyrotropin levels rapidly normalized after thyroxin treatment. CONCLUSION: One half of the children with DS have increased thyrotropinemia and all have a decreased rT3.
Life Sci 64 (12): 1037-44 (1999)

Thyroid stimulating hormone-receptor overexpression in brain of patients with Down syndrome and Alzheimer's disease

Labudova O; Cairns N; Koeck T; Kitzmueller E; Rink H; Lubec G
University of Vienna, Department of Pediatrics, Austria

Thyroid hormone abnormalities are strongly associated with Down Syndrome (DS) with elevated thyroid stimulating hormone (TSH) levels as the most consistent finding. Using subtractive hybridization for gene hunting we found significant overexpression of mRNA levels for the TSH- receptor (TSH-R) in brain of a fetus with DS. Based upon this observation we determined TSH-R protein levels in five brain regions of patients with DS (n=8), Alzheimer disease (AD, n=8) and controls (C, n=8). Western blots revealed significantly elevated immunoreactive TSH- R protein(s) 40 kD and 61 kD in temporal and frontal cortex of patients with DS and, unexpectedly, in AD. Levels for the 40 kD protein in temporal cortex were 1.00 ± 0.036 (arbitrary units ± SD) in C, 1.35 ± 0.143 in DS, 1.52 ± 0.128 in AD; in frontal cortex: 1.00 ± 0.046 in C, 1.10 ± 0.03 in DS, 1.10 ± 0.038 in AD. Levels for the 61 kD protein in temporal cortex were 1.01 ± 0.015 in C, 1.47± 0.013 in DS, 1.623 ± 0.026 in AD; in frontal cortex: 1.02 ± 0.020 in C, 1.18 ± 0.123 in DS, 1.48 ± 0.020 in AD. These results show that elevated brain immunoreactive TSH-R is not specific for DS and maybe reflecting apoptosis, a hallmark of both neurodegenerative disorders, as it is well-documented that the thyroid hormone system is involved in the control of programmed cell death.
Research in Developmental Disabilities 12 (3): 287-96 (1991)

Thyroid function in Down syndrome

Pueschel SM; Jackson IM; Giesswein P; Dean MK; Pezzullo JC
Department of Pediatrics, Rhode Island Hospital

The thyroid function of 181 patients with Down syndrome was investigated. When compared with a control group of 163 children we found T4 and FT4 levels to be significantly lower and T3 and TSH levels to be significantly higher in the Down syndrome population. Of the 181 patients with Down syndrome, 29 (16%) showed evidence of either uncompensated or compensated hypothyroidism: 11 (6%) had both low T4 and high TSH levels, 14 (8%) had only high TSH values, and 4(2%) had only low T4 values. One of the patients with Down syndrome had a significantly elevated T4 level. Studying different age groups, we observed a decline of the mean T4, FT4, T3, FT3, and TBG values with advancing age. T4, T3, and TSH blood levels obtained in 1988 were slightly but not significantly lower when compared with values from 1985. Because thyroid dysfunctions in patients with Down syndrome are more common than in the general population, periodic thyroid hormone function tests should be performed in persons with Down syndrome in particular as they advance in age. Thus, individuals with significantly abnormal results can be identified early before clinical symptoms become manifest. If patients with Down syndrome are found to have a thyroid hormone disorder, appropriate treatment should be forthcoming, which in turn will enhance their quality of life.
Am J Med Genet 36 (2): 148-54 (1990 Jun)

Autoimmune thyroiditis associated with mild "subclinical" hypothyroidism in adults with Down syndrome: a comparison of patients with and without manifestations of Alzheimer disease

Percy ME; Dalton AJ; Markovic VDCrapper McLachlan DR; Gera E; Hummel JT; Rusk AC; Somerville MJ; Andrews DFWalfish PG
Department of Obstetrics and Gynaecology, University of Toronto, Canada

Serum tests of thyroid function were compared in Down syndrome (DS) patients with and without manifestations of Alzheimer disease (AD). Relative to control individuals, DS patients had, overall, lower meantotal T4 (P = 0.070) and T3f (P = 0.015), higher T3U (P = 0.013) and TSH (P = 0.020), no difference in free T4, and higher thyroid antithyroglobulin (ATA) (P = 0.033) and antimicrosomal autoantibody (AMA) titres (P = 0.0097). Similar trends were apparent in DS males and females, and in DS patients off all drugs. In an analysis of case/control pairs with corrections for age and sex, DS patients with AD manifestations (n = 9) had significantly lower T3 (P = 0.029) and higher AMA (P = 0.043) than paired control individuals, whereas DS patients without AD manifestations (n = 20) had significantly lower T3 (P = 0.013) but higher ATA (P = 0.0065). T3 was significantly lower in the DS patients with AD manifestations than in the unaffected (P = 0.0013). These data suggest that autoimmune thyroiditis associated with a mild "subclinical" form of hypothyroidism is common in adult DS patients and more pronounced inpatients with AD manifestations than in those without. This "subclinical" hypothyroidism may contribute to cognitive deficits in ageing DS patients.
J Ment Defic Res 34 (2): 187-93 (1990 Apr)

Down's syndrome and thyroid disorder

Dinani S; Carpenter S
Department of Psychiatry, Brentry Hospital, Bristol, England

The thyroid status of 106 adults with Down's syndrome was assessed. Six were previously diagnosed as hypothyroid and were already receiving thyroxine. A further 37 patients showed abnormal thyroid function. Biochemical evidence of hypothyroidism (T4 less than 50 nmol/l and T.S.H. greater than 4 mu/less than) was found in one person. Six patients were found to have an unequivocally elevated T.S.H. but normal T4 (T4 greater than 50 nmol/l and T.S.H. greater than 20 mu/l) and 29 were found to have a modest elevation of T.S.H.but normal T4 concentration (T4 greater than 50 nmol/l and T.S.H. between 4 and 20 mu/l). There was one patient with mildthyrotoxicosis (T4 = 180 nmol/l and T.S.H. less than 0.1 mu/l). Clinical findings were of little use in making a diagnosis of hypothyroidism in this group of patients. A raised level of thyroid microsomal auto-antibodies was found in about a third of the patients, this occurred more commonly in females and slightly more often in those with a raised thyroid stimulating hormone. The importance of this is discussed. Recommendations for regular biochemical screening are made.
Am J Med Genet Suppl 7: 238-41 (1990)

Relationship of autoimmunity to thyroid dysfunction in children and adults with Down syndrome

Zori RT; Schatz DA; Ostrer H; Williams CA; Spillar R; Riley WJ
Department of Pediatrics, University of Florida, Gainesville 32610

The extent to which autoimmunity contributes to thyroid dysfunction in Down Syndrome (DS) individuals has not been clarified. We studied 61 persons (34 males and 27 females) with DS (age 5 months to 48 years)for the presence of thyroid autoantibodies (thyroid microsomalantibodies and thyroglobulin antibodies), pancreatic islet cell autoantibodies, gastric parietal cell autoantibodies, andadrenocortical autoantibodies. Thyroid function was determined by measurement of TSH. HLA-A, B and -DR typing was performed on 52 subjects. Forty of 61 subjects (66%) had thyroid dysfunction: elevated TSH values (greater than 5 mcIU/ml) were found in 35 of 61 individuals; 3 subjects had previously documented Hashimotothyroiditis and were on therapy for hyperthyroidism; and 2 persons had Graves disease. No age or sex variation was detected. Seventeen (28%) subjects had thyroid autoantibodies. Fifteen of the 17 had thyroid dysfunction. Twelve of 25 subjects (48%) over 10 years with thyroid dysfunction had thyroid autoantibodies compared to only 3 of 15 (20%) under the age of 10 years. However, children less than of 10 years tended to have higher TSH values. Only 1 individual who had thyroid antibodies had gastric parietal cell autoantibodies present. Islet cell and adrenocortical autoantibodies were not found in any individuals. Neither thyroid dysfunction nor thyroid autoantibodies correlated with any HLA allele. These findings suggest that thyroid dysfunction in individuals with DS of all ages is a common heterogeneous disorder which cannot be solely explained on the basis of autoimmunity. We recommend that thyroid function be followed closely whether or not thyroid autoantibodies are present.
J Genet Hum 37 (4-5): 389-93 (1989 Dec)

Anomalies de la fonction thyroidienne chez les enfants trisomiques 21 [Anomalies in thyroid function in children with trisomy 21]

Stoll C; Alembik Y; Dott B; Finck S
Institut de Puericulture, Centre Hospitalo-Universitaire, Strasbourg, France

Thyroid function of 60 children with Down (DS) aged 3 months to 16 years was studied by evaluation of serum concentration of ultra-sensitive thyroid stimulating hormone (TSH), free T4 and T3 (FT4, FT3), total T4 and T3 (T4 and T3) and reverse T3 (rT3). Each DS child was matched to a control of the same age. The concentration of TSH was increased in DS children while the concentration of rT3 of the DS children was significantly decreased compared to the controls as was the ratio rT3/TSH. These results showed that thyroid function of DS children is abnormal.
Arch Intern Med 149 (9): 1990-3 (1989 Sep)

Thyroid Dysfunction in Individuals with Down Syndrome

Friedman DL; Kastner T; Pond WS; O'Brien DR
Developmental Disabilities Center, Morristown Memorial Hospital, NJ 07960

A group of 138 community-based patients with Down syndrome were examined for evidence of autoimmune thyroid dysfunction at the time of their referral for routine health care services provided as part of a model program. Twenty-eight patients (20.3%) were found to have previously unrecognized hypothyroidism, and 2 patients (1.4%) had previously unrecognized hyperthyroidism. In addition, 66 patients were tested for thyroid autoantibodies, and 26 were found to have positive antimicrosomal and/or antithyroglobulin antibody test results. There was no statistically significant association between age or sex and the mean thyrotropin value or the presence of thyroid autoantibodies. The relationship between the mean thyroxine level and sex was mildly significant. Of the patients with hypothyroidism, 78.5% were female, and most were between the ages of 30 and 50 years. However, a higher-than-expected number of patients with autoimmune hypothyroidism were under age 30 years. These findings highlight the lack of adequate health care services available to persons with Down syndrome who live in the community. All persons with Down syndrome must undergo regular clinical and laboratory screening for the presence of thyroid disease.
Am J Dis Child 142 (2): 1302-6 (1988)

Growth Studies in Infants and Children with Down's Syndrome and Elevated Levels of Thyrotropin

Sharav T, Collins RM, Baab PJ.
Hadassah-WIZO-Canada Research Institute, Jerusalem, Israel

A retrospective survey of 147 patients with Down's syndrome (age range, 4 months to 27 years) showed that 60% had a thyrotropin (TSH) level higher than 5.7 mU/L in the presence of high or normal thyroxine levels. The remaining 40% of the group had low to normal TSH values. High TSH levels were predominant in patients under 4 years of age (94 children), ie, during the phase of active growth, and showed a declining trend with increasing age. All 94 infants had delayed growth of all parameters including head circumference, height, and weight, as compared with normal infants, and growth was particularly retarded in patients with TSH levels greater than 5.7 mU/L. Thyroid dysfunction, expressed as a high TSH concentration, is associated with growth retardation in children with Down's syndrome who are younger than 4 years.
Am J Dis Child 139 (6): 636-9 (1985 Jun)

Thyroid dysfunction in Down syndrome

Pueschel SM; Pezzullo JC

We investigated the thyroid function of 151 patients with Down syndrome. Compared with a control group of 89 siblings nearest in age to their brother or sister with Down syndrome, the mean thyroid-stimulating hormone (TSH) value was significantly higher in patients with Down syndrome than in subjects without Down syndrome. However, the mean thyroxine (T4) levels in both groups were nearly the same. In the Down syndrome group there was a trend for TSH values to increase and for T4 values to decrease with advancing age. Of the 151 patients with Down syndrome, ten had both significantly elevated TSH levels (greater than or equal to 9.5 microU/mL) and significantly decreased T4 levels (less than or equal to 5.5 micrograms/dL), 21 had only abnormally high TSH values, seven had only markedly increased T4 levels (greater than or equal to 12.0 micrograms/dL), and three had only significantly decreased T4 levels. The intellectual function of patients with both abnormal TSH and T4 levels was significantly lower (mean IQ, 41.7) than that of Down syndrome patients with only increased TSH values (mean IQ, 53.8) and that of Down syndrome patients with normal thyroid function (mean IQ, 55.3). This study provides further evidence that there is an increased prevalence of thyroid dysfunction in patients with Down syndrome.