In a Girl with Down Syndrome

GR Sridhar, Endocrine and Diabetes Centre, Visakhapatnam - 530002.
G.Nagamani, Endocrine and Diabetes Centre, Visakhapatnam - 530002.

 To Bottom  Article Index  Previous Article  Next Article

Synopsis: We report an adolescent girl with Down syndrome, who presented with hyperthyroidism. Autoimmune thyroid disorders may occur in children with Down syndrome, with hypothyroidism developing more frequently. Hyperthyroidism may also be associated with Down syndrome, and must not be missed.

Children with Down syndrome, or trisomy-21 may have coexistent autoimmune disorders (1,2). A variety of T cell abnormalities have been described in Down syndrome: increased Ia positive T cells and a premature increase in the 3G5 age related T cell subset (3). Among thyroid disorders, hypothyroidism has been reported more often than hyperthyroidism (4,5,6,7,8).

We describe a case of a girl with Down syndrome who presented with hyperthyroidism.

Case report: A 15 year old girl of Down syndrome diagnosed in the neonatal period, presented with symptoms of thyrotoxicosis: increased appetite, hair loss, difficulty in initiating sleep and lack of weight gain. A student of standard nine, her school performance had been adequate, except in mathematics. She attained menarche spontaneously, but had been amenorrheic for six months.

On examination, she had tachycardia (140 beats/min), a grade 1 goitre (35 gm), hand tremor and hyperkinesis. She had physical features of Down syndrome. Systemic examination was normal. Thyroid hormones were elevated: T3 3.1 ng/ml [N: 0.6-2.2 ng/ml], T4 18.4 ug/dl [N: 5-13 ug/dl] and TSH was 0.2 miu/ml [N: 0.3 -6.8 miu/ml]. 131 I radioiodine uptake was increased: 64% at two hours, 51% at 24 hours and 47% at 48 hours. Thyroid microsomal antibody was positive at 1:400 dilutions, and anti thyroglobulin antibody at 1:160. She was started on 25 mg of carbimazole a day with which there was clinical improvement. Her menstruation resumed, and she is euthyroid 12 months after initiation of antithyroid therapy.

Discussion: This girl with Down syndrome had the clinical, functional, biochemical and immunological features of hyperthyroidism. Most large series studying thyroid function in Down syndrome report that hypothyroidism is more common (4,5,6,7,8): only 1.4%(9) to 5% (6) of individuals with thyroid dysfunction have hyperthyroidism, whereas the prevalence of subclinical hypothyroidism is nearly 30% (7,10).

An Italian study showed that patients with Down syndrome who were positive for antithyroid antibody were more likely to develop clinically evident thyroid disease (5). This appears logical in view of the T cell abnormalities in Down syndrome (3). In contrast, a five-year annual follow up study in Australia suggested that thyroid dysfunction in Down syndrome may be related to inappropriate TSH secretion, or thyroid insensitivity to TSH (3). Similarly, an American study concluded that thyroid dysfunction in Down syndrome is a common heterogeneous disorder, which cannot be solely explained by autoimmunity (6). The few HLA studies in hyperthyroid individuals with Down syndrome reported the presence of HLA BW46 (11), and HLA A3, A9, B8, B15, DR3, DR5 when other autoimmune disorders coexisted (2).

In the past, attempts were made to correlate maternal thyroid disease causing Down syndrome in the offspring (12). Most recent studies have shown no such association (7).

In summary, children with Down syndrome must be screened for thyroid dysfunction, starting early in life; though hypothyroidism is more common, hyperthyroidism can also occur, and must not be missed.


  1. Patterson D. The causes of Down syndrome. Sci Am 1987;257(2):52-60
  2. Ruch W, Schurmann K, Gordan P, Burgin Wolff A, Girard J. Coexistent coeliac disease, Graves disease and diabetes mellitus type 1 in a patient with Down syndrome. Eur J Pediatr 1985;144:89-90
  3. Eisenbarth GS, Jackson RA. The immunoendocropathy syndromes. In (eds) Wilson JD, Foster DW. Williams Textbook of Endocrinology. WB Saunders, Philadelphia; 1992; pp1555-66
  4. Selikowitz M. A five-year longitudinal study of thyroid function in children with Down syndrome. Dev Med Child Neurol 1993; 35:396-401
  5. Rubello D, Pozzan GB, Casara D, Girelli ME, Boccato S, Rigon F, et al. Natural course of subclinical hypothyroidism in Down's syndrome: prospective study results and therapeutic considerations. J Endocrinol Invest 1995; 18:35-40
  6. Zori RT, Schatz OA, Ostrer H,Williams CA, Spillar R, Riley WJ. Relationship of autoimmunity to thyroid dysfunction in children and adults with Down syndrome. Am J Med Genet suppl 1990;7:238-41
  7. Pozzan GB,Rigon F, Girelli ME, Rubelli D, Busnardo B, Baccichetti C. Thyroid function in patients with Down syndrome: preliminary results from non -institutionalized patients in the Veneto region. Am J Med Genet suppl 1990;7:57 -8
  8. Sare Z, Ruvalcaba RH, Kelley VC. Prevalence of thyroid disorder in Down syndrome. Clin Genet 1978;14:154-8
  9. Friedman T, Kastner T, Pond WS, O'Brien Dr.Thyroid dysfunction in individuals with Down syndrome. Arch Intern Med 1989; 149:1990-3
  10. Cutler AT, Benezra Obeiter R, Brink SJ. Thyroid function in young children with Down syndrome. Am J Dis Child 1986; 140:479-83
  11. Tambyah PA, Cheah JS. Hyperthyroidism and Down syndrome. Ann Acad Med Singapore 1993; 22:603-5
  12. Fialkow PJ, Thuline HC, Hecht F, Bryant J. Familial predisposition to thyroid disease in Down's syndrome: controlled immunoclinical studies. Am J Hum Genet 1971;23:67-85

 Back to Top  Article Index  Previous Article  Next Article