Endocrine Abstracts

Introduction: The use of haematopoietic stem cell transplantation (HSCT) as a curative therapy for life threatening immunodeficiency signalled a paradigm shift in clinical outcomes. However, a subset of patients may experience Thyroid Immune Reconstitution Inflammatory Syndrome (IRIS) following immune reconstitution. This is recognised in the adult population but has received little attention in the paediatric literature. We present, what we believe to be, the first case series describing the clinical, biochemical and cytological course of Graves’ IRIS following HSCT in the paediatric population.

Case Series: Four children (median age 3.5 yrs, range 11 months-12 years) developed Graves IRIS (out of 395 HSCT conducted over a 25 year period). The median time interval between HSCT and Graves’ disease (GD) was 20.5 months (range 9–25 months). The diagnosis of GD was made on the basis of clinical and biochemical parameters: suppressed TSH, raised FT4 and TSH receptor antibodies. 3 patients were hypothyroid initially (suggestive of a Th1 profile) prior to GD (suggestive of a Th2 profile). In some instances, the clinical picture changed rapidly with hypothyroidism quickly followed by profound thyroid hormone excess. Importantly, the onset of Graves IRIS coincided with a rapid expansion in naïve CD₄ T cells.

Discussion: There are several potential pathogenic mechanisms that may contribute to IRIS although all of our patients had a rapid expansion in naïve and total CD4 cell counts coinciding with the onset of GD. This suggests that a combination of immunological dysregulation and an inability to delete cells with the capability to produce TSH reactive autoantibodies (loss of tolerance) was responsible for Graves IRIS in our patients. Clinicians need to be aware that HSCT-engendered immune recovery may result in a particularly aggressive form of autoimmune thyroid disease with a rapid change in thyroid status. Careful surveillance of thyroid function post HSCT is essential.