Hyperthyrotropinemia among children with Down syndrome: a benign entity or a marker of disease?

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SAT 622-631-Pediatric Endocrinology: Thyroid
Saturday, June 15, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SAT-624
Shanlee Marie Davis*1, Jennifer Marie Barker2 and Ellen Roy Elias1
1University of Colorado, Aurora, CO, 2Children's Hospital Colorado, Aurora, CO
Background:  Thyroid disease is common in Down syndrome (DS) with both congenital hypothyroidism and autoimmune thyroid disease occurring more frequently than in the general population.  Patients with DS are also more likely to have elevated Thyroid Stimulating Hormone (TSH) that may not represent a disease state.  Little is known about the prevalence or management of this subclinical hyperthyrotropinemia among children with DS.    

Methods:  Charts were reviewed for all children (0-18) with Down syndrome seen at Children’s Hospital Colorado primary care clinics in a 5 year period. Data on laboratory values, symptoms, and management were collected.   Subclinical hyperthyrotropinemia was defined as mildly elevated TSH (5-15) with normal or high T4, no symptoms attributable to hypothyroidism and without evidence of autoimmunity.

Results: 446 subjects met inclusion criteria. 169 (38%) had abnormal TSH on record: 6 (3%) had low TSH and were diagnosed with autoimmune hyperthyroidism, 20 (12%) were congenital hypothyroidism, and 143 (85%) was acquired elevation of TSH. Of those with acquired TSH elevation, 94 (66%) met the definition for hyperthyrotropinemia (TSH mean 9.9, range 4.95-14.9).  Average age of abnormal TSH was 2.7 years, 50% male. Among subjects with hyperthyrotropinemia, 29% were never treated with thyroid replacement hormone, 17% were initially treated but later taken off the medication, 37% remained on the same dose, and 17% had a dose increase.

Discussion:  In this retrospecitive chart review, more than 20% of children with DS had a presentation consistent with hyperthyrotropinemia. There was not a female predominance which suggests this is not simply a "pre-Hashimoto's" state.  Previous studies suggest hyperthyrotropinemia may be due to inadequate dopaminergic regulation of pituitary TSH secretion unique to DS and may not require treatment, however our study suggests the management of this clinical scenario varies greatly. Future research should focus on neurodevelopmental outcomes among children with DS and hyperthyrotropinemia to allow for development of management guidelines in this population given the high prevalence and frequent screening recommendations in DS.

(1) Faria et al., TSH Neurosecretory dysfuntion in Down syndrome: low risk of progression to Hashimoto’s thyroiditis, Arq Bras Endocrinol Metab 2011; 55:8. (2) Meyerovitch et al., Hyperthyrotropinaemia in untreated subjects with Down syndrome aged 6 months to 64 years: a comparative analysis. Arch Dis Child 2012: 97: 595-598. (3) Prasher VP. Down syndrome and thyroid disorders: a review. Downs Syndr Res Pract. 1999 Aug;6(1):25-42.

Nothing to Disclose: SMD, JMB, ERE

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm