The Natural History of Subclinical Hyperthyroidism in Graves’ Disease: The Rule of Thirds
Open accessAbstract
BACKGROUND: There is little information regarding the natural history of subclinical hyperthyroidism (SH) due to Graves' disease (GD). METHODS: A prospective analysis was conducted of patients with SH due to GD between 2007 and 2013 with at least 12 months of follow-up. SH was diagnosed if serum thyrotropin (TSH) was below the laboratory reference range (0.4-4.0 mIU/L) and when thyroid hormones were normal. GD was confirmed by either a raised TSH receptor antibody (TRAb) level or uniform uptake on Technetium scan. RESULTS: Forty-four patients (89% female, 16% current smokers, and 5% with active Graves' orbitopathy) were diagnosed with SH due to GD. Over the follow-up period (median 32 months), approximately one third (34%) of the cohort progressed to overt hyperthyroidism, one third (34%) normalized their thyroid function, slightly less than one third (30%) remained in the SH state, while one person became hypothyroid. Multivariate regression analysis showed that older age and positive antithyroid peroxidase (TPO) antibody status had a positive association with risk of progression to overt hyperthyroidism, with hazard ratios of 1.06 ([confidence interval (CI) 1.02-1.10], p < 0.01) per year and 10.15 ([CI 1.83-56.23], p < 0.01), respectively, independent of other risk factors including, smoking, TRAb levels at diagnosis, and sex. CONCLUSIONS: A third each of patients with SH due to GD progress, normalize, or remain in the SH state. Older people and those with positive anti-TPO antibodies have a higher risk of progression of the disease. These novel data need to be verified and confirmed in larger cohorts and over longer periods of follow-up.
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Approximately one-third of patients with subclinical hyperthyroidism due to spontaneous Graves' disease undergo spontaneous resolution.
“Approximately one-third of patients with subclinical hyperthyroidism due to spontaneous GD undergo spontaneous resolution [78];”
From 2019 European Thyroid Association Guidelines on the Management of Thyroid Dysfunction following Immune Reconstitution Therapy (2019) · cites this paper as [78]
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Clinical aspects of thyroid function during ageing
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“Approximately one-third of patients with subclinical hyperthy-roidism due to spontaneous GD undergo spontaneous resolution [78]; similarly, some studies have reported spontaneous resolution of post-IRT GD in 20% of cases [13], while others did not [12, 77].”
Background
- Authors
- Zhyzhneuskaya, S., Addison, C., Tsatlidis, V., Weaver, J. U., & Razvi, S.
- Affiliations
- Queen Elizabeth Hospital (GB)
- Corresponding author
- Razvi, Salman
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2016-06
- Volume
- 26
- Issue
- 6
- Pages
- 765-769
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2358383112
- Cited by
- 22
- References
- 17
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2022: 2 · 2021: 1 · 2020: 5 · 2019: 3 · 2018: 4 · 2016: 3
- FWCI
- 3.35
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Newcastle University ePrints (Newcastle Univesity)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Pathology and Forensic Medicine › Ophthalmology and Eye Disorders
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- subclinical hyperthyroidism, Graves' disease, natural history (disease), thyroid peroxidase antibodies, age as risk factor, thyroid function normalization, hypothyroidism, TSH receptor antibodies, smoking
- MeSH terms
- Adult, Aged, Autoantibodies, Female, Graves Disease, Humans, Hyperthyroidism, Male, Middle Aged, Prospective Studies, Receptors, Thyrotropin, Severity of Illness Index, Thyroid Function Tests, Disease Progression, Graves Ophthalmopathy
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