Type 3 Deiodinase and Consumptive Hypothyroidism: A Common Mechanism for a Rare Disease

Abstract

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.

Use of liothyronine without levothyroxine in the treatment of mild consumptive hypothyroidism caused by hepatic hemangiomas

“…Most studies on this type of consumptive hypothyroidism report the use of levothyroxine or levothyroxine plus liothyronine for treatment [1][2][3][4][5][6][7][8][9][10][11][12]14]; while 1 study reported the use of liothyronine plus prednisolone [13]. However, there is no report of using liothyronine plus propranolol for the treatment of consumptive hypothyroidism.…”

Liver haemangiomas and consumptive hypothyroidism in association with three cutaneous haemangiomas

“…Consumptive hypothyroidism is a rare paraneoplastic syndrome that can occur in infants with hepatic haemangiomas. It results from the abnormal over‐expression of type 3 iodothyronine deiodinase (D3), a selenoenzyme responsible for inactivation of thyroid hormone molecules by converting T4 to reverse T3 (rT3), and T3 to 3,3′‐diiodothyronine (T2) . Under normal conditions, D3 regulates circulating levels of thyroid hormone and is restricted to the central nervous system, skin and some endocrine glands .…”

“…It results from the abnormal over‐expression of type 3 iodothyronine deiodinase (D3), a selenoenzyme responsible for inactivation of thyroid hormone molecules by converting T4 to reverse T3 (rT3), and T3 to 3,3′‐diiodothyronine (T2) . Under normal conditions, D3 regulates circulating levels of thyroid hormone and is restricted to the central nervous system, skin and some endocrine glands . However, biopsies have demonstrated over‐expression of D3 by hepatic haemangioma tissue …”

“…Under normal conditions, D3 regulates circulating levels of thyroid hormone and is restricted to the central nervous system, skin and some endocrine glands . However, biopsies have demonstrated over‐expression of D3 by hepatic haemangioma tissue …”

Role of thyroid hormones in the neoplastic process: an overview

“…Tumoral D3 activity is markedly elevated in vascular tumors, including infantile hemangioma and hemangioendothelioma in adults (Huang et al 2000, Luongo et al 2013, even to the extent of inducing clinical hypothyroidism (consumptive hypothyroidism). Opposing regulation of DIO3 or DIO1/ DIO2 expression has been reported in various human neoplasias, such as PTC, TSH tumors, BCC and colon cancer (de Souza Meyer et al 2005, Dentice et al 2007, 2012, Luongo et al 2013, Romitti et al 2016. Studies performed using 105 pituitary tumors demonstrated that D2 and D3 mRNA levels were significantly augmented in pituitary tumors compared with normal pituitary tissue.…”