Thyroid dysfunction (TD) frequently occurs as an autoimmune complication of immune reconstitution
therapy (IRT), especially in individuals with
multiple sclerosis treated with
alemtuzumab, a pan-lymphocyte depleting drug with subsequent recovery of immune cell numbers. Less frequently, TD is triggered by
highly active antiretroviral therapy (
HAART) in patients infected with human immunodeficiency virus (HIV), or patients undergoing bone-marrow/
hematopoietic-stem-cell transplantation (BMT/HSCT). In both
alemtuzumab-induced TD and HIV/
HAART patients, the commonest disorder is
Graves' disease (GD), followed by
hypothyroidism and
thyroiditis;
Graves' orbitopathy is observed in some GD patients. On the contrary, GD is rare post-BMT/HSCT, where
hypothyroidism predominates probably as a consequence of the associated radiation damage. In
alemtuzumab-induced TD, the
autoantibodies against the
thyrotropin receptor (TRAb) play a major role, and 2 main aspects distinguish this condition from the spontaneous form: (1) up to 20% of GD cases exhibit a fluctuating course, with alternating phases of hyper- and
hypothyroidism, due to the coexistence of TRAb with stimulating and blocking function; (2) TRAb are also positive in about 70% of hypothyroid patients, with blocking TRAb responsible for nearly half of the cases. The present guidelines will provide up-to-date recommendations and suggestions dedicated to all phases of IRT-induced TD: (1) screening before IRT (recommendations 1-3); (2) monitoring during/after IRT (recommendations 4-7); (3) management of TD post-IRT (recommendations 8-17). The clinical management of IRT-induced TD, and in particular GD, can be challenging. In these guidelines, we propose a summary algorithm which has particular utility for nonspecialist physicians and which is tailored toward management of
alemtuzumab-induced TD. However, we recommend prompt referral to specialist endocrinology services following diagnosis of any IRT-induced TD diagnosis, and in particular for pregnant women and those considering pregnancy.