Type 3 deiodinase and consumptive hypothyroidism: a common mechanism for a rare disease
Open accessAbstract
The major product secreted by the thyroid is thyroxine (T4), whereas most of the biologically active triiodothyronine (T3) derives from the peripheral conversion of T4 into T3. The deiodinase enzymes are involved in activation and inactivation of thyroid hormones (THs). Type 1 and type 2 deiodinase (D1 and D2) convert T4 into T3 whereas D3 degrades T4 and T3 into inactive metabolites and is thus the major physiological TH inactivator. The hypothalamic-pituitary-thyroid axis maintains circulating TH levels constant, while the deiodinases tissue-specifically regulate intracellular thyroid status by controlling TH action in a precise spatio-temporal fashion. Here we review the data related to the recent identification of a paraneoplastic syndrome called "consumptive hypothyroidism," which exemplifies how deiodinases alter substantially the concentration of TH in blood. This syndrome results from the aberrant uncontrolled expression of D3 that can induce a severe form of hypothyroidism by inactivating T4 and T3 in defined tumor tissue. This rare TH insufficiency generally affects patients in the first years of life, and has distinct features in terms of diagnosis, treatment, and prognosis with respect to other forms of hypothyroidism.
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There is one rare clinical entity for which measurement of rT3 is essential to determine the correct diagnosis: consumptive hypothyroidism.
“It should be mentioned that there is one rare clinical entity for which the measurement of rT3 is essential to determine the correct diagnosis: in consumptive hypothyroidism.”
From Can Reverse T3 Assay Be Employed to Guide T4 vs. T4/T3 Therapy in Hypothyroidism? (2019) · cites this paper as [21]
The Consumptive Hypothyroidism section describes elevated rT3 as a typical diagnostic clue and identifies the condition as rare. It does not say rT3 measurement is essential; it says diagnosis is based on detecting D3 activity in tumor tissue. Page numbers are unavailable in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredConsumptive hypothyroidism is a rare form of hypothyroidism identified in newborns with infantile hepatic hemangiomatosis.
“This is a rare form of hypothyroidism identified in newborns with infantile hepatic hemangiomatosis (21).”
From Can Reverse T3 Assay Be Employed to Guide T4 vs. T4/T3 Therapy in Hypothyroidism? (2019) · cites this paper as [21]
Consumptive hypothyroidism results from excess D3 produced by vascular, fibroblastic, and gastrointestinal stromal tumors, causing thyroid hormone elimination to exceed the thyroid gland's synthetic capacity.
“Consumptive hypothyroidism arises due to an excess of D3 produced by vascular, fibroblastic, and gastrointestinal stromal tumors, leading to an increased elimination of thyroid hormones that exceeds the synthetic capability of the physiologically stimulated thyroid gland.1,[72][73][74]”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [73]
Consumptive hypothyroidism usually requires aggressive thyroid replacement with gradual LT4 dose increases until TSH normalizes, and TSH should be measured more frequently than usual.
“Consumptive hypothyroidism usually requires aggressive thyroid replacement treatment, involving gradual LT4 dose increases until TSH normalizes, which should be measured more frequently than usual.”
From Refractory hypothyroidism: unraveling the complexities of diagnosis and management (2023) · cites this paper as [73]
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- Authors
- Luongo, C., Trivisano, L., Alfano, F., & Salvatore, D.
- Affiliations
- Federico II University Hospital (IT)
- Corresponding author
- Salvatore, Domenico
- Venue
- Frontiers in Endocrinology
- Publisher
- Frontiers Media SA
- Published
- 2013
- Volume
- 4
- Pages
- 115-115
- ISSN
- 1664-2392 (ISSN-L)
- PMC
- PMC3761349
- OpenAlex
- W2109271456
- Cited by
- 67
- References
- 58
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 2 · 2023: 9 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 5 · 2018: 4 · 2017: 10 · 2016: 3 · 2015: 2 · 2014: 2
- FWCI
- 0.34
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Frontiers in Endocrinology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- type 3 deiodinase, thyroid hormone inactivation, thyroxine, triiodothyronine, paraneoplastic syndrome, childhood hypothyroidism, hypothalamic-pituitary-thyroid axis
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