Endocrinol Metab.  2015 Dec;30(4):620-625. 10.3803/EnM.2015.30.4.620.

Refractory Graves' Disease Successfully Cured by Adjunctive Cholestyramine and Subsequent Total Thyroidectomy

• Yang Y
• Hwang S
• Kim M
• Lim Y
• Kim MH
• Lee S
• Lim DJ
• Kang MI
• Cha BY

• KMID: 2169675
• DOI: http://doi.org/10.3803/EnM.2015.30.4.620

Abstract

The three major forms of treatment for Graves thyrotoxicosis are antithyroid drugs, radioactive iodine therapy and thyroidectomy. Surgery is the definitive treatment for Graves thyrotoxicosis that is generally recommended when other treatments have failed or are contraindicated. Generally, thyrotoxic patients should be euthyroid before surgery to minimize potential complications which usually requires preoperative management with thionamides or inorganic iodine. But several cases of refractory Graves' disease have shown resistance to conventional treatment. Here we report a 40-year-old female patient with Graves' disease who complained of thyrotoxic symptoms for 7 months. Her thyroid function test and thyroid autoantibody profiles were consistent with Graves' disease. One kind of thionamides and beta-blocker were started to control her disease. However, she was resistant to nearly all conventional medical therapies, including beta-blockers, inorganic iodine, and two thionamides. She experienced hepatotoxicity from the thionamides. What was worse is her past history of serious allergic reaction to corticosteroids, which are often used to help control symptoms. A 2-week regimen of high-dose cholestyramine improved her uncontrolled thyrotoxicosis and subsequent thyroidectomy was successfully performed. In conclusion, cholestyramine could be administered as an effective and safe adjunctive agent for preoperative preparation in patients with severe hyperthyroid Graves's disease that is resistant to conventional therapies.

Keyword

Graves disease; Drug resistance; Cholestyramine resin

MeSH Terms

Adrenal Cortex Hormones
Adult
Antithyroid Agents
Cholestyramine Resin*
Drug Resistance
Female
Glycogen Storage Disease Type VI
Graves Disease*
Humans
Hypersensitivity
Iodine
Thyroid Function Tests
Thyroid Gland
Thyroidectomy*
Thyrotoxicosis
Adrenal Cortex Hormones
Antithyroid Agents
Cholestyramine Resin
Iodine

Figure

• 

  Fig. 1 Thyroid ultrasonography showed mild enlargement of both thyroid lobes with heterogenous echogenicity (A) and increased vascularity (B).

• 

  Fig. 2 Free thyroxine (FT4), total triiodothyronine (T3), and thyroid stimulating hormone (TSH) levels during treatment. The dark gray area in the figure indicates the duration of cholestyramine use until total thyroidectomy. CA, cholestyramine; PTU, propylthiouracil; MMI, methimazole; KI, potassium iodide; PPL, propranolol; HD, hospital day.

• 

  Fig. 3 The postoperative pathology specimens showed right dominant diffuse goiter and no definite nodule was identified; Right thyroid gland was 7.8×4.4×2.2 cm in size and 28.7 g, left thyroid was 6.0×2.4×1.5 cm and 20.6 g, respectively. The final histologic finding was diffuse hyperplasia, consistent with Graves' disease.

Reference

1. Moon JH, Yi KH. The diagnosis and management of hyperthyroidism in Korea: consensus report of the korean thyroid association. Endocrinol Metab (Seoul). 2013; 28:275–279.

2. Weetman AP. Graves' disease. N Engl J Med. 2000; 343:1236–1248.

3. Langley RW, Burch HB. Perioperative management of the thyrotoxic patient. Endocrinol Metab Clin North Am. 2003; 32:519–534.

4. Li H, Okuda J, Akamizu T, Mori T. A hyperthyroid patient with Graves' disease who was strongly resistant to methimazole: investigation on possible mechanisms of the resistance. Endocr J. 1995; 42:697–704.

5. Sebastian-Ochoa A, Quesada-Charneco M, Fernandez-Garcia D, Reyes-Garcia R, Rozas-Moreno P, Escobar-Jimenez F. Dramatic response to cholestyramine in a patient with Graves' disease resistant to conventional therapy. Thyroid. 2008; 18:1115–1117.

6. Saleem T, Sheikh A, Masood Q. Resistant thyrotoxicosis in a patient with Graves' disease: a case report. J Thyroid Res. 2011; 2011:649084.

7. Solomon BL, Wartofsky L, Burman KD. Adjunctive cholestyramine therapy for thyrotoxicosis. Clin Endocrinol (Oxf). 1993; 38:39–43.

8. Mercado M, Mendoza-Zubieta V, Bautista-Osorio R, Espinoza-de los. Treatment of hyperthyroidism with a combination of methimazole and cholestyramine. J Clin Endocrinol Metab. 1996; 81:3191–3193.

9. Tsai WC, Pei D, Wang TF, Wu DA, Li JC, Wei CL, et al. The effect of combination therapy with propylthiouracil and cholestyramine in the treatment of Graves' hyperthyroidism. Clin Endocrinol (Oxf). 2005; 62:521–524.

10. Kaykhaei MA, Shams M, Sadegholvad A, Dabbaghmanesh MH, Omrani GR. Low doses of cholestyramine in the treatment of hyperthyroidism. Endocrine. 2008; 34:52–55.

11. Hoogenberg K, Beentjes JA, Piers DA. Lithium as an adjunct to radioactive iodine in treatment-resistant Graves thyrotoxicosis. Ann Intern Med. 1998; 129:670.

12. Pandey CK, Raza M, Dhiraaj S, Agarwal A, Singh PK. Rapid preparation of severe uncontrolled thyrotoxicosis due to Graves' disease with iopanoic acid: a case report. Can J Anaesth. 2004; 51:38–40.

13. Ozbey N, Kalayoglu-Besisik S, Gul N, Bozbora A, Sencer E, Molvalilar S. Therapeutic plasmapheresis in patients with severe hyperthyroidism in whom antithyroid drugs are contraindicated. Int J Clin Pract. 2004; 58:554–558.

14. Dahlberg PA, Karlsson FA, Lindstrom B, Wide L. Studies of thyroid hormone and methimazole levels in patients with Graves' disease on a standardized anti-thyroid drug regimen. Clin Endocrinol (Oxf). 1981; 14:555–562.

15. Butani L. Corticosteroid-induced hypersensitivity reactions. Ann Allergy Asthma Immunol. 2002; 89:439–445.

16. Lin D, Suwantarat N, Bornemann M. Cholestyramine for thyrotoxicosis? J Fam Pract. 2013; 62:E1–E2.

17. Northcutt RC, Stiel JN, Hollifield JW, Stant EG Jr. The influence of cholestyramine on thyroxine absorption. JAMA. 1969; 208:1857–1861.