Consumptive hypothyroidism

German: Konsumptive Hypothyreose

1 Definition

Consumptive hypothyroidism is a rare form of hypothyroidism. Unlike classical primary and secondary forms of hypothyroidism it doesn't result from reduced production or release of thyroid hormones from the thyroid gland but from increased degradation of thyroxine, which cannot be compensated by upregulated hormone synthesis in the thyroid.

2 Pathogenesis

Consumptive hypothyroidism occurs if the degradation rate of T4 is higher than thyroid's secretory capacity.

3 Etiology

Situations, where degradation rate of thyroid hormones is massively increased include:

• Paraneoplastic overexpression of type 3 deiodinase, e.g. in fibrosarcoma, hemangioma and gastrointestinal stroma tumours.^[1][2][3]
• Increased activity of type 3 deiodinase due to therapy with tyrosine kinase inhibitors^[4].

A rare form of consumptive hypothyroidism is an immunogenic type, where signaling is impaired due to antibodies to thyroid hormones^[5].

4 Diagnosis

Consumptive hypothyroidism should be suspected if a patient presents with explaining primary disease (e.g. neoplasia or formation of antibodies to thyroid tissue) and hypothyroidism with the requirement of a very high levothyroxine dosage, low T3 serum concentration and elevated rT3 concentration. Definitive diagnosis requires the detection of increased type 3 deiodinase activity in the tumour tissue. The diagnosis of consumptive hypothyroidism is also supported by postoperative improvement or even remission of hypothyroidism. In the differential diagnosis (especially if congenital hypothyroidism is to be excluded) increased concentration of thyroglobulin and the detection of normal thyroid tissue in an ultrasound investigation suggest consumptive hypothyroidism ^[2].

5 Therapy

A causal therapy of consumptive hypothyroidism requires eliminating its aetiology, e.g. by treating the tumour or, in cases of multiple hepatic hemangiomas, liver transplant.

As a potential conservative therapeutic option, especially in hemangiomas, treatment with beta-blocking agents, e. g. propranolol, has been reported to be beneficial. Unselectvie beta blockers may be effective by inhibiting certain growth factors, which are necessary for both continued existence of the hemangioma and for overexpression of type 3 deiodinase^[6][2].

6 Historic vignette

The classical form of the disease was first described by Huang et al. in 2000, who observed severe otherwise unexplained hypothyroidism in a three months old infant with multiple hepatic haemangiomas and severe and otherwise unexplained hypothyroidism^[7]. The first report of the immunogenic form dates back to 1956, when it was described by Robbins et al. in a 26-year-old female patient with papillary thyroid cancer^[8].

7 References

1. ↑ Ruppe MD, Huang SA, Jan de Beur SM. Consumptive hypothyroidism caused by paraneoplastic production of type 3 iodothyronine deiodinase. Thyroid. 2005 Dec;15(12):1369-72. PMID 16405410
2. ↑ ^{2.0 2.1 2.2} Luongo C, Trivisano L, Alfano F, Salvatore D. Type 3 deiodinase and consumptive hypothyroidism: a common mechanism for a rare disease. Front Endocrinol (Lausanne). 2013 Sep 4;4:115. doi: 10.3389/fendo.2013.00115. PMID 24027558; PMCID PMC3761349
3. ↑ Yan LH, Mo XW, Qin YZ, Wang C, Chen ZN, Lin Y, Chen JS. Consumptive hypothyroidism due to a gastrointestinal stromal tumor expressing type 3 iodothyronine deiodinase. Int J Clin Exp Med. 2015 Oct 15;8(10):18413-9. PMID 26770446; PMCID PMC4694346
4. ↑ Kappers MH, van Esch JH, Smedts FM, de Krijger RR, Eechoute K, Mathijssen RH, Sleijfer S, Leijten F, Danser AH, van den Meiracker AH, Visser TJ. Sunitinib-induced hypothyroidism is due to induction of type 3 deiodinase activity and thyroidal capillary regression. J Clin Endocrinol Metab. 2011 Oct;96(10):3087-94. doi: 10.1210/jc.2011-1172. PMID 21816788
5. ↑ Karlsson FA, Wibell L, Wide L. Hypothyroidism due to thyroid-hormone-binding antibodies. N Engl J Med. 1977 May 19;296(20):1146-8. PMID 404551
6. ↑ Vergine G, Marsciani A, Pedini A, Brocchi S, Marsciani M, Desiderio E, Bertelli S, Vecchi V. Efficacy of propranolol treatment in thyroid dysfunction associated with severe infantile hepatic hemangioma. Horm Res Paediatr. 2012;78(4):256-60. doi: 10.1159/000337253. PMID 22907522.
7. ↑ Huang SA, Tu HM, Harney JW, Venihaki M, Butte AJ, Kozakewich HP, Fishman SJ, Larsen PR. Severe hypothyroidism caused by type 3 iodothyronine deiodinase in infantile hemangiomas. N Engl J Med. 2000 Jul 20;343(3):185-9. PMID 10900278.
8. ↑ ROBBINS J, RALL JE, RAWSON RW. An unusual instance of thyroxine-binding by human serum gamma globulin. J Clin Endocrinol Metab. 1956 May;16(5):573-9. PMID 13319450.