Hypothyroidism as a Late Sequela in Patients with Graves' Disease Treated with Antithyroid Agents
Open accessAbstract
In 1971, thyroid function was evaluated in 15 unselected patients whose only therapy for diffuse toxic goiter was a course of thionamide drug treatment completed 20-27 yr earlier. One patient was frankly hypothyroid by clinical and laboratory criteria. The remaining 14 patients appeared clinically euthyroid and had a normal serum thyroxine (T(4)) concentration and thyroid radioiodine uptake (RAIU). Nevertheless, only 6 of 14 appeared to be entirely normal according to more refined criteria. The serum thyrotropin (TSH) concentration was markedly elevated in one patient and above the normal range (1.6+/-2.0; mean+/-2 SD) in five others. Thyroid stimulation with exogenous TSH revealed subnormal responses of the serum T(4)I, RAIU, or both, in 7 of 11 patients tested. An abnormal iodideperchlorate discharge test was found in 5 of 10 patients and appeared most abnormal in patients with abnormal RAIU responses to TSH. Fluorescent antimicrosomal antibody was found in the serum of 12 of the 15 patients, in contrast to an expected frequency of 7% in normal individuals of the same age. By the time a second major follow-up study was completed in 1978, two additional patients had become frankly hypothyroid. A third subject met accepted criteria for subclinical hypothyroidism. One of these subjects had had a clearly elevated serum TSH concentration in 1972, and the remaining two had exhibited the highest responses of serum TSH (36, 26 muU/ml) to thyrotropin-releasing hormone among 10 patients tested in 1972. One patient developed recurrent thyrotoxicosis in 1978, 25 yr after the onset of his first and only other apparent episode of hyperthyroidism. This patient was the only one who demonstrated a subnormal response to thyrotropin-releasing hormone in 1972. The remaining nine subjects that could be studied in 1978 exhibited varying combinations of abnormalities of thyroid function. It is concluded that progressive failure of thyroid function is a common occurence in long-standing Graves' disease, and it is suggested that this results from concomitant chronic thyroiditis. We postulate that this inherent tendency toward thyroid failure is exaggerated by surgery or radioactive iodine, explaining the progressive increase in, and inordinate frequency of, hypothyroidism after ablative modes of therapy in diffuse toxic goiter.
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In patients who remain euthyroid for more than 1 year (in remission), relapses can occur years later, and some patients eventually become hypothyroid.
“If the patient remains euthyroid for more than 1 year (i.e., they are in remission), thyroid function should be monitored at least annually because relapses can occur years later (171), and some patients eventually become hypothyroid (179).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [179]
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- Authors
- Wood, L. C., & Ingbar, S. H.
- Affiliations
- Harvard University (US)
- Venue
- Journal of Clinical Investigation
- Published
- 1979-11-01
- Volume
- 64
- Issue
- 5
- Pages
- 1429-1436
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC371292
- OpenAlex
- W2024399892
- Cited by
- 173
- References
- 35
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 6 · 2021: 2 · 2020: 4 · 2019: 10 · 2018: 4 · 2017: 2 · 2016: 5 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01am018416-11)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Health Sciences › Medicine › Pathology and Forensic Medicine › Ophthalmology and Eye Disorders
- Keywords
- Graves' disease, antithyroid drugs, thionamides, long-term sequelae, subclinical hypothyroidism, thyroid function, thyroid-stimulating hormone, thyrotropin-releasing hormone, thyroid-stimulating antibodies, chronic thyroiditis, thyroid failure, radioiodine therapy
- MeSH terms
- Adult, Aged, Female, Follow-Up Studies, Graves Disease, Humans, Hypothyroidism, Male, Middle Aged, Antithyroid Agents, Thyroid Function Tests, Thyroiditis, Thyrotropin, Thyrotropin-Releasing Hormone, Thyroxine, Time Factors, Triiodothyronine
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