Progression From Subclinical to Symptomatic Overt Hypothyrodism
Objective: To report a case of Hashimoto's thyroiditis with rapid progression from subclinical to overt symptomatic hypothyroidism and to discuss the potential precipitating factors and the implications on clinical decisions about monitoring and treatment of early thyroid failure.
Methods: We describe a patient with long-standing subclinical hypothyroidism who had progression to severe overt hypothyroidism during a 2-month period, without an identifiable precipitating factor. All medical care was provided at a single institution, and all relevant medical records were reviewed.
Results: For at least 2 years, an 84-year-old man had a pattern of subclinical hypothyroidism, including normal levels of serum free thyroxine, serum thyrotropin concentrations ranging from 4.4 to 9.6 µIU/mL, and elevated levels of anti-thyroid peroxidase antibodies. During a 2-month period, symptoms of cold intolerance, a 4.5-kg weight gain, and fatigue developed, and the patient was found to have low free thyroxine and free triiodothyronine concentrations and a serum thyrotropin concentration of 80.9 µIU/mL. The patient did not use any medication previously identified as a trigger to the development of hypothyroidism, had no exposure to iodine or contrast administration, and reported no intercurrent infection that might explain the rapid progression of hypothyroidism.
Conclusion: Most patients with subclinical hypothyroidism have progression to overt hypothyroidism at a slow rate. Elderly patients with high antithyroid antibody titers may have a higher than previously recognized risk of rapid development of overt hypothyroidism, and earlier intervention with levothyroxine treatment may be indicated.
Hypothyroidism due to Hashimoto's thyroiditis is currently recognized as a chronic condition that typically develops during a period of several years. The earliest stage, characterized by a modest elevation in serum thyrotropin (TSH) concentration, normal free thyroxine concentration, and positive anti-thyroid peroxidase (TPO) antibodies, is referred to as early thyroid failure or subclinical hypothyroidism. The incidence of this early stage of thyroid failure is about 4% among the general population and as high as 20% among elderly women. Several studies have shown that a modest fraction of patients with subclinical hypothyroidism (approximately 3 to 5% per year, depending on age and magnitude of TSH elevation) have progression to overt hypothyroidism with a decline in serum free thyroxine concentration. The progression to overt thyroid failure is thought to be a gradual process. Two recent evidence-based medicine reports recommended against routine treatment of subclinical hypothyroidism to prevent progression to overt hypothyroidism.
Clinical and animal studies have indicated that various factors can result in the progression from lymphocytic infiltration of the thyroid to functional insufficiency ( Table 1 ). Clinical factors that can precipitate thyroid failure include exposure to iodine, infection, and several medications (for example, amiodarone, lithium, and interferon-alfa). Animal models have shown that mice with induced thyroid autoimmunity do not uniformly develop hypothyroidism without a second stimulus, such as an infection or cytokine administration. We describe a patient with long-standing subclinical hypothyroidism who had rapid progression to symptomatic overt hypothyroidism during a 2-month period, without any identifiable precipitating factor. The findings are discussed with respect to potential factors that contribute to the progression of overt hypothyroidism and the effect on the decision to initiate levothyroxine treatment in patients with subclinical hypothyroidism.
Objective: To report a case of Hashimoto's thyroiditis with rapid progression from subclinical to overt symptomatic hypothyroidism and to discuss the potential precipitating factors and the implications on clinical decisions about monitoring and treatment of early thyroid failure.
Methods: We describe a patient with long-standing subclinical hypothyroidism who had progression to severe overt hypothyroidism during a 2-month period, without an identifiable precipitating factor. All medical care was provided at a single institution, and all relevant medical records were reviewed.
Results: For at least 2 years, an 84-year-old man had a pattern of subclinical hypothyroidism, including normal levels of serum free thyroxine, serum thyrotropin concentrations ranging from 4.4 to 9.6 µIU/mL, and elevated levels of anti-thyroid peroxidase antibodies. During a 2-month period, symptoms of cold intolerance, a 4.5-kg weight gain, and fatigue developed, and the patient was found to have low free thyroxine and free triiodothyronine concentrations and a serum thyrotropin concentration of 80.9 µIU/mL. The patient did not use any medication previously identified as a trigger to the development of hypothyroidism, had no exposure to iodine or contrast administration, and reported no intercurrent infection that might explain the rapid progression of hypothyroidism.
Conclusion: Most patients with subclinical hypothyroidism have progression to overt hypothyroidism at a slow rate. Elderly patients with high antithyroid antibody titers may have a higher than previously recognized risk of rapid development of overt hypothyroidism, and earlier intervention with levothyroxine treatment may be indicated.
Hypothyroidism due to Hashimoto's thyroiditis is currently recognized as a chronic condition that typically develops during a period of several years. The earliest stage, characterized by a modest elevation in serum thyrotropin (TSH) concentration, normal free thyroxine concentration, and positive anti-thyroid peroxidase (TPO) antibodies, is referred to as early thyroid failure or subclinical hypothyroidism. The incidence of this early stage of thyroid failure is about 4% among the general population and as high as 20% among elderly women. Several studies have shown that a modest fraction of patients with subclinical hypothyroidism (approximately 3 to 5% per year, depending on age and magnitude of TSH elevation) have progression to overt hypothyroidism with a decline in serum free thyroxine concentration. The progression to overt thyroid failure is thought to be a gradual process. Two recent evidence-based medicine reports recommended against routine treatment of subclinical hypothyroidism to prevent progression to overt hypothyroidism.
Clinical and animal studies have indicated that various factors can result in the progression from lymphocytic infiltration of the thyroid to functional insufficiency ( Table 1 ). Clinical factors that can precipitate thyroid failure include exposure to iodine, infection, and several medications (for example, amiodarone, lithium, and interferon-alfa). Animal models have shown that mice with induced thyroid autoimmunity do not uniformly develop hypothyroidism without a second stimulus, such as an infection or cytokine administration. We describe a patient with long-standing subclinical hypothyroidism who had rapid progression to symptomatic overt hypothyroidism during a 2-month period, without any identifiable precipitating factor. The findings are discussed with respect to potential factors that contribute to the progression of overt hypothyroidism and the effect on the decision to initiate levothyroxine treatment in patients with subclinical hypothyroidism.
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