Tiratricol: New option for an extremely rare hereditary disease

Allan-Herndon-Dudley syndrome (AHDS) is a rare disorder characterized by a deficiency of the thyroid hormone T3 in the central nervous system (CNS) and a peripheral excess of T3 (peripheral thyrotoxicosis). It is caused by a deficiency of monocarboxylate transporter 8 (MCT8), a specific transporter for thyroid hormones. MCT8 deficiency is caused by mutations in the SLC16A2 gene, located on the X chromosome.

With only 371 documented cases, the disease is very rare. It affects exclusively men. If left untreated, ADHD is associated with, among other symptoms, hypotension, muscle weakness, and severe intellectual deficits. Thyroid hormone levels are characteristically altered: serum T3 levels are markedly elevated, with low to normal free T4 (fT4) and normal to slightly elevated TSH. A molecular genetic test that detects mutations in the SLC16A2 gene confirms the diagnosis.

Tiratricol (3,3',5-triiodothyroacetic acid) is a naturally circulating, biologically active metabolite of T3 that can enter cells independently of MCT8. It can thus replace T3 in MCT8-dependent tissues and restore normal thyroid hormone activity in these tissues. Tiratricol (Emcitate 350 µg tablets for suspension, Rare Thyroid Therapeutics International AB) is approved for the treatment of peripheral thyrotoxicosis in patients with MCT8 deficiency and AHDS from birth onward.

The recommended starting dose depends on the patient's body weight. If the patient weighs less than 10 kg, treatment is initiated at 175 µg daily (half a tablet); for a body weight of 10 kg or more, treatment is initiated at 350 µg daily. The daily dose should be gradually increased every two weeks until a maintenance dose is reached at which the serum T3 level is below the median of the normal range for the patient's age. The T3 level should be determined using liquid chromatography with tandem mass spectrometry (LC/MS/MS). In immunoassays, tiratricol cross-reacts with T3, which distorts test results.

The total daily dose should be divided into one to three doses throughout the day. The procedure for administration is as follows: In a small glass, a maximum of four tablets per single dose are dissolved in 30 ml of drinking water, stirring with a teaspoon over a period of one minute. The resulting milky white suspension is then drawn up using a 40 ml syringe and slowly administered to the patient on the inside of the cheek into the mouth. Administration via a feeding tube is also possible. A further 10 ml of drinking water is then added to the glass and stirred with a teaspoon for about five seconds. This suspension is then drawn up from the glass using the same syringe and administered to the patient.