Opties voor de behandeling van de ziekte van Graves

Deze review onderzoekt de voor- en nadelen van de diverse behandelingen van de ziekte van Graves, zoals schildklierremmers, radioactief jodium en operatie. Aan bod komen hier de behandeling met schildklierremmers (block en replace of titratie) en onder andere ook betablokkers, jodium (lugol), lithium en rituximab. 

Current and emerging treatment options for Graves’ hyperthyroidism
Prakash Abraham, Shamasunder Acharya

Schildklier remmende medicijnen 

De startdosering van Carbimazol (CBZ) / Strumazol (MMI) is gewoonlijk tussen 20 en 40 mg / dag, afhankelijk van de ernst van de hyperthyreoïdie. PTU wordt gestart met een dosis van 100 tot 150 mg driemaal daags. PTU 100 mg wordt beschouwd als gelijk aan ongeveer 10 mg CBZ / MMI. De hoge startdosis van de medicijnen kan na 4 tot 8 weken worden afgebouwd in het zogenaamde titratieregime. Een onderhoudsdosis van 5 tot 20 mg MMI of equivalent wordt bereikt na ongeveer 4 tot 6 maanden en dit wordt voortgezet gedurende 12 tot 18 maanden.

Het block-replace regime verwijst naar de mogelijkheid om de hoge dosis schildklierremmers te handhaven terwijl levothyroxine wordt toegevoegd om euthyreoïdie in stand te houden. Dit heeft als voordeel dat er minder schildklierfunctietesten (TFT's) zijn, maar er zijn aanwijzingen voor een hogere frequentie van bijwerkingen. Ongeveer 12 onderzoeken hebben deze regimes onderzocht. De terugvalpercentages zijn vergelijkbaar met meer dan 55%. Stoppen met de behandeling als gevolg van bijwerkingen (16% versus 9%) en complicaties, waaronder huiduitslag en agranulocytose, waren hoger bij het block-replace regime.

Other antithyroid agents

Betablockers

Many of the symptoms of hyperthyroidism such as sweating, anxiety, tremor and palpitations are caused by increased sympathetic activity and can be controlled rapidly by beta-blockers. Propranolol in relatively high doses of over 160 mg per day can mildly inhibit conversion of T4 to T3. Once daily betablockers such as atenolol 50 to 100 mg or nadolol 40 to 80 mg can be used to improve compliance. In the absence of contraindications such as asthma, betablockers are used in the first few weeks of treating hyperthyroidism while awaiting the effect of antithyroid medications. They may also be used when antithyroid medications are withdrawn for treating with RAI. Rate-limiting calcium channel blockers may be used if there are contraindications for betablockers.

Iodine and iodine-containing compounds

These are rarely used for the rapid control of hyperthyroidism in the context of thyroid storm or in the preoperative preparation for thyroid surgery. Iodide decreases thyroid hormone synthesis by blocking iodide oxidation and organification – the Wolff–Chaikoff effect. It also inhibits thyroglobulin proteolysis and release of T4 and T3. The effect is rapid and pronounced but lasts for only a few weeks with a potential for subsequent deterioration. Iodide decreases the vascularity of the thyroid but in one controlled study had no significant influence on blood loss or perioperative course. It can be given as Lugol’s solution (8 mg of saturated iodide per drop) 3 to 5 drops 3 times a day or as a saturated solution of potassium iodide (SSKI, 50 ng of iodide per drop) 1 drop 3 times a day. Oral cholecystographic agents (sodium iopanoate and sodium ipodate) have also been used for rapidly lowering thyroid hormone levels in combination with MMI74 and may be useful in thyroid storm.

Lithium

Lithium has a role in inhibiting thyroid hormone synthesis and release. Lithium can rarely be used in patients intolerant of thionamides. It has been shown to reduce the thyroid hormone increase after thionamide withdrawal and RAI therapy in Graves’ disease.

Potassium perchlorate

This is a competitive inhibitor of iodide transport but is rarely used due to its side effects, particularly the risk of aplastic anemia with long-term use. It may be used in the context of amiodarone-induced thyrotoxicosis or while awaiting RAI in patients allergic to thionamides.

Cholestyramine

Cholestyramine decreases the enterohepatic reabsorbtion of thyroid hormones. Thyrotoxic patients have an abnormal increase of thyroid hormones in their enterohepatic circulation. Cholestyramine used in combination with PTU or MMI brought about a more rapid decline of thyroid hormones during the first month of antithyroid therapy.

Rituximab

Graves’ disease is an autoimmune B-cell mediated condition in which TSH receptor antibodies (TRAb) play an important role in the pathogenesis. A few agents are being investigated but the only agent that has entered phase II clinical studies is rituximab (RTX). This is an anti-CD20 monoclonal antibody which causes B cell depletion in the circulation as well as in target organs such as the thyroid. Due to the limited experience and costs further studies are needed before these agents are considered as possible therapies in GH.