Background/Aims: A mild increase in thyrotropin (thyroid-stimulating hormone; TSH) is common among Down syndrome patients but is rarely detected by neonatal screening at birth. We hypothesized that Down syndrome was associated with fetal hypothyroidism and tried to determine whether Down syndrome fetuses had evidence of hypothyroidism. Methods: We performed a prospective observational study on 13 fetuses with Down syndrome diagnosed prenatally. TSH and free thyroxine (FT4) levels were measured in fetal blood. The results were analyzed and compared with the findings from fetal sonography and histopathology. Results: Of the 13 fetuses, 6 had TSH values greater than the 95th percentile, and FT4 values were low. None of the fetuses had sonographic evidence of goiter. The thyroids were normal by gross examination but exhibited small follicles and histological features suggesting delayed maturation. Conclusion: The absence of goiter even in fetuses with hyperthyrotropinemia suggests a mild decrease in TSH responsiveness.

Salehi A, Faizi M, Colas D, Valletta J, Laguna J, Takimoto-Kimura R, Kleschevnikov A, Wagner SL, Aisen P, Shamloo M, Mobley WC: Restoration of norepinephrine-modulated contextual memory in a mouse model of Down syndrome. Sci Transl Med 2009;1:7ra17.
Van Trotsenburg AS, Vulsma T, Van Santen HM, Cheung W, De Vijlder JJ: Lower neonatal screening thyroxine concentrations in Down syndrome newborns. J Clin Endocrinol Metab 2003;88:1512–1515.
McGowan S, Jones J, Brown A, Reynolds L, Leyland K, Charleton P, Rahim M, Mansor M, Ritha S, Donaldson M; Scottish Down Syndrome Thyroid Screening Group: Capillary TSH screening programme for Down’s syndrome in Scotland, 1997–2009. Arch Dis Child 2011;96:1113–1117.
Myrelid A, Jonsson B, Guthenberg C, von Döbeln U, Annerén G, Gustafsson J: Increased neonatal thyrotropin in Down syndrome. Acta Paediatr 2009;98:1010–1013.
Thorpe-Beeston JG, Nicolaides KH, Gosden CM, McGregor AM: Thyroid function in fetuses with chromosomal abnormalities. BMJ 1991;302:628.
Pop VJ, Kuijpens JL, van Baar AL, Verkerk G, van Son MM, de Vijlder JJ, Vulsma T, Wiersinga WM, Drexhage HA, Vader HL: Low maternal free thyroxine concentrations during early pregnancy are associated with impaired psychomotor development in infancy. Clin Endocrinol (Oxf) 1999;50:149–155.
Pop VJ, Brouwers EP, Vader HL, Vulsma T, van Baar AL, de Vijlder JJ: Maternal hypothyroxinemia during early pregnancy and subsequent development: a 3-year follow-up study. Clin Endocrinol (Oxf) 2003;59:282–288.
Huel S, Guibourdenche J, Vuillard E, Ouahba J, Piketty M, Oury JF, Luton D: Use of ultrasound to distinguish between fetal hyperthyroidism and hypothyroidism on discovery of a goiter. Ultrasound Obstet Gynecol 2009;33:412–420.
Guibourdenche J, Noël M, Chevenne D, Vuillard E, Voluménie JL, Polak M, Boissinot C, Porquet D, Luton D: Biochemical investigation of fetal and neonatal thyroid function using the ACS-180SE analyzer. Clinical application. Ann Clin Biochem 2001;38:520–526.
Gruñeiro de Papendieck L, Chiesa A, Bastida MG, Alonso G, Finkielstain G, Heinrich JJ: Thyroid dysfunction and high thyroid stimulating hormone levels in children with Down’s syndrome. J Pediatr Endocrinol Metab 2002;15:1543–1548.
Boué J, Vignal P, Aubry JP, Aubry MC, Mac Aleese J: Ultrasound movement patterns of fetuses with chromosome anomalies. Prenat Diagn 1982;2:61–65.
Wiseman FK: Cognitive enhancement therapy for a model of Down syndrome. Sci Transl Med 2009;1:7ps9.
Polak M, Czernichow P: Thyroïdologie foetale; in Wémeau JL, Leclère J, Orgiazzi J, Rousset B, Schlienger JL (eds): La Thyroïde. Paris, Elsevier, 2001, pp 512–526.
Tüysüz B, Beker DB: Thyroid dysfunction in children with Down’s syndrome. Acta Paediatr 2001;90:1389–1393.
van Trotsenburg AS, Vulsma T, Rozenburg-Marres SL, van Baar AL, Ridder JC, Heymans HS, Tijssen JG, de Vijlder JJ: The effect of thyroxine treatment started in the neonatal period on development and growth of two-year-old Down syndrome children: a randomized clinical trial. J Clin Endocrinol Metab 2005;90:3304–3311.
Guibourdenche J, Frendo JL, Pidoux G, Vidau M, Luton D, Giovagrandi Y, Porquet D, Muller F, Evain-Brion D: Trophoblast production of a weakly bioactive human chorionic gonadotropin in trisomy 21-affected pregnancy. J Clin Endocrinol Metab 2004;89:727–732.
Konings CH, van Trotsenburg AS, Ris-Stalpers C, Vulsma T, Wiedijk BM, de Vijlder JJ: Plasma thyrotropin bioactivity in Down’s syndrome children with subclinical hypothyroidism. Eur J Endocrinol 2001;144:1–4.
Labudova O, Cairns N, Koeck T, Kitzmueller E, Rink H, Lubec G: Thyroid stimulating hormone-receptor overexpression in brain of patients with Down syndrome and Alzheimer’s disease. Life Sci 1999;64:1037–1044.
Van Trotsenburg AS, Kempers MJ, Endert E, Tijssen JG, Vijlder JJ, Vulsma T: Trisomy 21 causes persistent congenital hypothyroidism presumably of thyroidal origin. Thyroid 2006;16:671–680.
Trueba SS, Auge J, Mattei G, Etchevers H, Martinovic J, Czernichow P, Vekemans M, Polak M, Attié-Bitach T: PAX-8, TITF1, and FOXE1 gene expression patterns during human development: new insights into human thyroid development and thyroid dysgenesis-associated malformations. J Clin Endocrinol Metab 2005;90:455–462.
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