This leads to symptoms and biochemistry of an overactive thyroid (feels hot, trembly, anxious, loses weight, fast heart rate, sweaty, greasy hair), with raised free T3 and free T4, and a suppressed thyroid stimulating hormone (TSH) value. The damaged cells will no longer be able to take up iodine in order to manufacture further supplies of thyroid hormone, and thus in due course the patient comes to experience the symptoms of an underactive thyroid (feels cold, tired, depressed, gains weight, dry skin and hair) with low free T3 and free T4, and eventually increased TSH. Diagnosis
With the standard overactive thyroid, iodine uptake into the thyroid is avid, whereas if the cells are damaged, then uptake is poor. In this way, if there is doubt about whether the patient has too much thyroid hormone because of de Quervains thyroiditis, then measuring radio-iodine uptake or technetium uptake gives a clear cut answer as it will be higher than normal in standard thyrotoxicosis and lower than normal in de Quervains. Treatment
Treatment is beta blockers, aspirin, and NSAIDs (or corticosteroids if NSAIDs are ineffective). Eponym
It is named for Fritz de Quervain. It should not be confused with De Quervain syndrome. Terminology
It is sometimes called subacute thyroiditis, but there are other forms of subacute thyroiditis, subacute lymphocytic thyroiditis, postpartum thyroiditis, and autoimmune thyroiditis all of which, in contrast to de Quervains, are typically painless or "silent". It is also sometimes called "painful subacute thyroiditis". This is in contrast to subacute lymphocytic thyroiditis, which is also sometimes called "painless thyroiditis".
The biological half-life is 41 hours for the tablets and 5.6 to 11.5 weeks for the injection.Elimination has only been studied for oral administration: Most of the drug is eliminated via the faeces in unchanged form (47%). It is not known how much of this amount comes from the bile, and how much was not absorbed in the first place. (The bile actually contains the glucuronide, but this could be broken up again in the gut lumen to give the parent substance that is observed in the faeces.) To a lesser extent it is excreted via the urine (27%), almost exclusively as the glucuronide. Pharmacogenomics
UGT1A1 poor metabolizers have 1.3- to 1.5-fold increased cabotegravir concentrations in the body. This is not considered clinically significant. Chemistry
Cabotegravir is a white to off-white, crystalline powder that is practically insoluble in aqueous solutions under pH 9, and slightly soluble above pH 10. It is slightly acidic with a pKa of 7.7 for the enolic acid and 1.1 (calculated) for the carboxamide. The molecule has two asymmetric carbon atoms; only one of the four possible configurations is present in the medication. Formulation
In studies, the agent was packaged into nanoparticles (GSK744LAP) conferring a biological half-life of 21 to 50 days following a single dose. The marketed injection achieves its long half-life not via nanoparticles but with a suspension of the free cabotegravir acid. The tablets contain cabotegravir sodium salt. History
Cabotegravir was examined in the clinical trials HPTN 083 and HPTN 084.