Low Doses of Cholestyramine in the Treatment of Hyperthyroidism
Condition: Graves Disease
MeSH terms: Graves Disease; Hyperthyroidism
Study type: Interventional

Summary: 
      The enterohepatic circulation of thyroid hormones is increased in thyrotoxicosis.Bile-salt
      sequestrants (ionic exchange resins) bind thyroid hormones in the intestine and thereby
      increase their fecal excretion. Based on these observations, the use of cholestyramine has
      been tried. The present study evaluates the effect of low doses of cholestyramine as an
      adjunctive therapy in the management of hyperthyroidism
    

Detailed description: 
      The gastrointestinal tract has a role in thyroid physiology. Thyroid hormone is metabolized
      mainly in the liver, where it is conjugated to glucurunides and sulfates. These conjugation
      products are then excreted in the bile. Free hormones are released in the intestine and
      finally reabsorbed, completing the enterohepatic circulation of thyroid hormone. A very small
      portion of the daily production of thyroxin (T4) and triiodothyronine (T3), less than 10
      percent, is excreted in the stool (1-3). In people with normal thyroid function, this pathway
      of T4 and T3 recirculation contributes so little to hormone availability that patients who
      have gastrointestinal disease or are receiving drugs that decrease T4 absorption do not have
      abnormal thyroid function (4). However, the thyrotoxic states are characterized by an
      increased enterohepatic circulation of thyroid hormones, as well as an increased urinary and
      fecal excretion of both conjugated and free T4 (5,6).

      Cholestyramine, an ionic exchange resin sequesters T4 in the intestine and increases its
      fecal excretion. These phenomena were proven in hamsters in mid 1960s (7). Experimentally, it
      has been shown that 50 mg of cholestyramine can bind approximately 3000 μg of T4 (8) and
      therefore can enhance the clearance of thyroid hormones. Because of the increased
      enterohepatic circulation of thyroid hormones during hyperthyroidism, attempts have been made
      to sequester these hormones in the intestine using ionic exchange resins (9-13).
      Cholestyramine therapy has been studied in the treatment of thyrotoxicosis as an adjunctive
      therapy to thionamides, and has been found to decrease thyroid hormone levels rapidly. In
      several trials, cholestyramine in combination with methimazole (MMI) or propylthiouracil,
      caused a more rapid decline in thyroid hormone levels than standard therapy with thionamides
      alone (9-11,13). In all of these trials, cholestyramine was dosed at 4 grams orally two to
      four times a day.

      This study was conducted to examine the efficacy of combination therapy of lower doses of
      cholestyramine with MMI and propranolol for treating patients with Graves' hyperthyroidism.
    

Intervention name(s): Cholestyramine; Cholestyramine; Placebo powder
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 2 grams BID; 1 gram BID; 1 gram BID
Intervention MeSH terms: Cholestyramine Resin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: Hyperthyroidism; Cholestyramine