Before reading further, please be aware that these reports are few in number and spread extremely thinly around the world and in time.
We see a steady stream of people who appear intolerant of levothyroxine. Quite often they are desperate to stop taking levothyroxine - but the hypothyroid state that results of course takes its own toll. Some of these people feel that changing to a regime of liothyronine (T3) has been beneficial.
The mention of antibodies to T4 in the second paper is interesting. These (and also antibodies to T3 and to TSH) have been mentioned in the literature but we never see anyone being tested for them.
(Note: The first paper appears to have a bit of a problem in the underlined bit. I *think* it means that the powder form does not have any Fe2O3 but the tablet form does.)
Fe2O3 is Iron(III) oxide also known as ferric oxide.
Endocr J. 2015 May 19. [Epub ahead of print]
Occurrence of thyroxine tablet (Thyradin S®) - induced liver dysfunction in a patient with subclinical hypothyroidism.
Kang S1, Amino N, Kudo T, Nishihara E, Ito M, Hirokawa M, Miyauchi A, Tamada D, Yasuda T.
1Department of Internal Medicine, Kuma Hospital, Kobe, Japan.
A 54-year-old woman with subclinical hypothyroidism developed liver dysfunction after increasing dose of levothyroxine (L-T4) in tablet form (Thyradin S®) from 25μg to 50μg. Viral hepatitis, autoimmune hepatitis and NASH were ruled out with examinations. After cessation of levothyroxine in 50μg tablet form, liver enzymes gradually returned to normal. She was diagnosed levothyroxine-induced liver injury, based on criteria proposed in DDW-J 2004 workshop. Thyradin S® powder 0.01% (here in after referred to as L-T4 in powder form) was tried as an alternative, and liver enzymes have remained within normal range. As for Thyradin S® tablet, additives are different for each type of levothyroxine sodium content. The difference of additive is whether Fe2O3 is contained or not: it is not included in Thyradin S® 50μg tablet and powder form. Although there are two case reports in the Japanese literature and three case reports in the English literature of liver dysfunction suspected due to L-T4, we cannot find past reports about cases of drug induced liver dysfunction due to Fe2O3 free levothyroxine tablet form. This is a rare case report of drug induced liver injury due to Fe2O3 free levothyroxine tablet form, and administration of L-T4 in powder form may be useful for treatment of cases similar to this one.
PMID: 25994001 [PubMed - as supplied by publisher]
Endocr J. 1999 Aug;46(4):579-83.
Levothyroxine-induced liver dysfunction in a primary hypothyroid patient.
Ohmori M1, Harada K, Tsuruoka S, Sugimoto K, Kobayashi E, Fujimura A.
Here we report a case of levothyroxine-induced liver dysfunction. T4 (levothyroxine) has been more commonly used for the treatment of hypothyroidism than T3 active hormone (triiodothyronine), because with the former drug a stabler plasma concentration is obtained after oral administration. Although there are few reports on levothyroxine-induced liver dysfunction, we treated a primary hypothyroid patient with high serum aminotransferase after administration of levothyroxine. Liver dysfunction was improved after cessation of the drug administration. Antibody to T4 was found in the serum of the patient after this event. From clinical course and laboratory data of the patient, the episode of liver damage was considered to be induced by levothyroxine. We then administrated triiodothyronine, and it did not induce liver dysfunction. Changing levothyroxine to triiodothyronine resulted in a successful clinical course in this case, as re-administration of the doubtful drug is strictly limited.
PMID: 10580751 [PubMed - indexed for MEDLINE]
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Intern Med. 2007;46(14):1105-8. Epub 2007 Jul 17.
Liver injury induced by levothyroxine in a patient with primary hypothyroidism.
Kawakami T1, Tanaka A, Negoro S, Morisawa Y, Mikami M, Hojo M, Yamamoto T, Uegaki S, Aiso M, Kawasaki T, Ishii T, Kuyama Y, Fukusato T, Takikawa H.
We report a patient with primary hypothyroidism, who developed hepatocellular injury due to levothyroxine, synthetic thyroxine. A 63-year-old male was admitted to our hospital due to elevation of liver enzymes. The patient was diagnosed as having hypothyroidism and had been treated with levothyroxine for almost two months until admission. Drug-induced liver injury induced due to levothyroxine was suspected and liver enzymes were rapidly decreased after discontinuation of levothyroxine and dried thyroid powder, also containing thyroxine. Synthetic triiodothyronine, the deiodinated form of levothyroxine was administered instead, and was well tolerated by the patient. The drug-induced lymphocyte stimulation test (DLST) using levothyroxine was negative. Since triiodothyronine which structurally resembles levothyroxine did not cause liver injury, and DLST using levothyroxine was negative, it is unlikely that levothyroxine itself was targeted by the immune system. Rather, we assume that the complex of levothyroxine as the hapten and liver-related macromolecules in the body as the carrier might have acquired antigenicity in this patient and subsequently resulted in liver injury.
PMID: 17634708 [PubMed - indexed for MEDLINE]
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