A 51-year-old Caucasian male developed Graves’ thyrotoxicosis following long-standing treatment for hypothyroidism. After a short period of treatment with carbimazole, he developed agranulocytosis and required total thyroidectomy. In this relevant case report, we review several pathogenetic mechanisms that explain the transformation of autoimmune hypothyroidism into Graves’ disease and the possible approaches to the management of agranulocytosis secondary to antithyroid medications. Further studies are required to determine the best way to manage severe thyrotoxicosis when agranulocytosis develops due to antithyroid medications.
Hypothyroidism ; Antithyroid Agents ; Carbimazole ; Agranulocytosis

We characterize the clinical and laboratory characteristics of 5 patients with Graves’ thyrotoxicosis whose serum free thyroxine (fT4) concentration decreased unexpectedly to low levels on conventional doses of carbimazole (CMZ) therapy. The initial fT4 mean was 40.0 pM, range 25-69 pM. Thyroid volume by ultrasound measured as mean 11 ml, range 9.0-15.6 ml. Initial TSI levels measured 1487% to >4444%. Serum fT4 fell to low-normal or hypothyroid levels within 3.6 to 9.3 weeks of initiating CMZ 5 to 15 mg daily, and subsequently modulated by fine dosage adjustments. In one patient, serum fT4 fluctuated in a “yo-yo” pattern. There also emerged a pattern of low normal/low serum fT4 levels associated with discordant low/mid normal serum TSH levels respectively, at normal serum fT3 levels. The long-term daily-averaged CMZ maintenance dose ranged from 0.7 mg to 3.2 mg. Patients with newly diagnosed Graves' hyperthyroidism who have small thyroid glands and markedly elevated TSI titres appear to be “ATD dose sensitive.” Their TFT on ATD therapy may display a “central hypothyroid” pattern. We suggest finer CMZ dose titration at closer follow-up intervals to achieve biochemical euthyroidism.
carbimazole ; Thyroid Stimulating Immunoglobulin ; Immunoglobulins, Thyroid-Stimulating ; Immunologic Tests ; Graves disease

A 24-year-old Chinese woman with Graves' disease presented with myositis two months after treatment with carbimazole. The patient's myositis resolved with hydration and cessation of carbimazole. No other causes of myositis were found, and a change in the medication to propylthiouracil was uneventful. Review of the literature suggests a possible genetic susceptibility, as the majority of reported cases are Asian in origin, similar to patients who present with thyroid periodic paralysis. Changing the antithyroid drugs (ATDs) administered, decreasing the dose of pre-existing ATDs in the treatment regimen or addition of levothyroxine has been shown to result in clinical improvement of this complication. These observations suggest various mechanisms of carbimazole-induced myositis in the treatment of Graves' disease, including the direct effect of ATDs on myocytes, immune-related responses secondary to ATDs and rapid decrements in thyroid hormone with ensuing myositis.
Antithyroid Agents ; adverse effects ; Carbimazole ; adverse effects ; Female ; Genetic Predisposition to Disease ; Graves Disease ; drug therapy ; Humans ; Myositis ; chemically induced ; genetics ; therapy ; Young Adult

Adult ; Carbimazole ; therapeutic use ; China ; Cholestyramine Resin ; therapeutic use ; Female ; Graves Disease ; drug therapy ; Humans ; Hyperthyroidism ; drug therapy ; Patient Admission ; Sepsis ; complications ; Thyroid Gland ; drug effects ; Treatment Outcome

Thyroid disorder is a common disease. Graves' disease is the most frequent cause of thyrotoxicosis and pharmacological treatment is current trends worldwide. Because of the severe adverse effects of propylthiouracil, methimazole or carbimazole should be selected as the drug of choice except for special situations such as women in the first trimester of pregnancy, thyroid storm, or in patients with severe side effects to methimazole. Treatment should continue for 12 to 18 months, but duration can be adjusted depending on the patient. For hypothyroidism, synthetic levothyroxine is the mainstay of treatment. In order to avoid overtreatment, the dosage of levothyroxine should be determined in consideration of the patient's age, sex, bodyweight, general condition, and comorbidities. In subclinical hypothyroidism, thyroid hormone replacement is suggested in patients with thyroid stimulating hormone concentrations >10 mIU/L. For non-elderly patients with high titers of thyroid autoantibodies, patients with dyslipidemia, pregnant patients, and women with infertility or ovulatory dysfunction, treatment with levothyroxine can be considered.
Antithyroid Agents ; Autoantibodies ; Carbimazole ; Comorbidity ; Dyslipidemias ; Female ; Graves Disease ; Humans ; Hyperthyroidism ; Hypothyroidism ; Infertility ; Methimazole ; Pregnancy ; Pregnancy Trimester, First ; Propylthiouracil ; Thyroid Crisis ; Thyroid Diseases ; Thyroid Gland ; Thyroiditis ; Thyrotoxicosis ; Thyrotropin ; Thyroxine