Mifepristone increases thyroid hormone requirements in patients with central hypothyroidism: a multicenter study
Open accessAbstract
PURPOSE: Mifepristone is a glucocorticoid and progesterone receptor blocker that can be used for patients with hyperglycemia and Cushing syndrome in whom surgery failed to achieve remission or who were ineligible for surgery. We report a case series of patients with Cushing disease (CD) and central hypothyroidism that presented with increased levothyroxine requirements during mifepristone therapy. METHODS: Retrospective longitudinal case series of patients with CD and central hypothyroidism treated with mifepristone in a retrospective database at four pituitary centers in the United States. RESULTS: Five patients with CD were found, all women, median age 50 (interquartile range 47 to 64.5). They received mifepristone because no adequate response or intolerance to other drugs was observed. Mifepristone initiation was associated with a decrease in free thyroxine levels, mandating a dose increase of a median 1.83 (1.71 to 3.5) times the initial dose of levothyroxine to achieve normal levels. Weight loss was seen in four of five patients, ranging from 3.2 to 42.6 kg in up to 54 months of follow-up. CONCLUSIONS: Although the mechanism behind the decrease in thyroid hormone level is unknown, intestinal malabsorption, decreased residual thyroid function and increased inactivation of T4 via deiodinases are all potential causes. Whereas therapies for hypercortisolism aim to decrease features of hypercortisolemia such as weight gain and depression, hypothyroidism can hamper these goals. This case series raises awareness on the importance of assessment of thyroid status in patients receiving mifepristone to optimize clinical outcomes.
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Biological hypothyroidism is easily corrected a few days after withdrawal of drugs reducing intestinal absorption, while a longer time (weeks to months) is needed for drugs affecting in vivo metabolism.
“Biological hypothyroidism is easily corrected a few days after withdrawal of drugs reducing intestinal absorption, while a longer time (weeks to months) is needed for drugs affecting in vivo metabolism (87, 94).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [87]
Increased inactivation of LT4 via the monodeiodinase induced by mifepristone, rifampicin, and carbamazepine can reduce the T1/2 of LT4.
“Moreover, increased inactivation of LT4 via the monodeiodinase induced by mifepristone, rifampicin, and carbamazepine can reduce the T1/2 of LT4 (86–88).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [87]
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Consensus on diagnosis and management of Cushing's disease: a guideline update
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Self-citationLevothyroxine: conventional and novel drug delivery formulations.
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Medications and Food Interfering with the Bioavailability of Levothyroxine: A Systematic Review
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- Authors
- Guarda, F. J., Findling, J., Yuen, K. C. J., Fleseriu, M., & Nachtigall, L. B.
- Affiliations
- Harvard University (US)
- Medical College of Wisconsin (US)
- Barrow Neurological Institute (US)
- Oregon Health & Science University (US)
- Corresponding author
- Nachtigall, Lisa B
- Venue
- Journal of the Endocrine Society
- Publisher
- The Endocrine Society
- Published
- 2019-07-05
- Volume
- 3
- Issue
- 9
- Pages
- 1707-1714
- ISSN
- 2472-1972 (ISSN-L)
- PMC
- PMC6735735
- OpenAlex
- W2955001530
- Cited by
- 12
- References
- 18
- Citations by year
- 2024: 2 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 1
- FWCI
- 1.42
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of the Endocrine Society (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- UA Campus Repository (The University of Arizona) (acceptedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- mifepristone, Cushing's disease, central hypothyroidism, levothyroxine dose adjustment, hypercortisolism, glucocorticoid therapy, free thyroxine, weight loss, thyroid function monitoring
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