Hyperthyroidism As a Complication Following Myloablative Therapy and Stem Cell Transplantation for Childhood Diseases

Thyroid dysfunction is a known complication following hematopoietic stem cell transplantation (HSCT) in children.  Most reports in children describe hypothyroidism related to pre transplant conditioning regimens, especially total body irradiation (TBI).  We now report the development of post-transplant thyroid dysfunction on 8 children that developed hyperthyroidism following HSCT.  Three patients were transplanted for metabolic diseases (two with Sanfilippo Syndrome and one with Adrenal Leukodystrophy,  one for Acute Myelogenous Leukemia, one for Kostman’s Syndrome, one for Purine Nucleotide Phosphorylase Deficiency (PNP), one for Paroxysmal Nocturnal Hemoglobinuria (PNH) and one for Chronic Granulomatous Disease (CGD).  Five children were transplanted with Unrelated Umbilical Cord Blood (URCB), one with matched sibling transplant and two with adult Matched Unrelated Donor (MUD) transplant. Four of the five patients receiving cord blood transplants received myloablative therapy with Busulfan, Cytoxan and ATG; one of the URCB patients and one MUD transplant patient received Fludarabine, Busulfan, Cytoxan and ATG and the other MUD transplant received Fludarabine, Cytoxan and two doses of TBI for conditioning. The patient that received the matched sibling transplant was prepared for transplant with Busulfan and Melphalan.  The onset of hyperthyroidism ranged between 9 months and 5 years post transplant.  Five patients were off of immunosuppression when hyperthyroidism was diagnosed and 2 were being treated for chronic GvHD; one with Etanercept, Cyclosporine and Solumedrol and one with Orapred and Imuran. One patient was still on prophylactic Tacrolimus when hyperthyroidism was diagnosed 9 months after transplant.  All patients required a form of ablative therapy. Two received radioactive iodine as treatment.  Three patients received Methimazole alone.  One patient failed Methimazole, received radioactive iodine and then underwent thyroidectomy revealing follicular carcinoma. One of the patients did not receive any therapy; he had Hoshimoto’s thyroidits and went on to develop hypothyroidism. Another patient had a total thyroidectomy that revealed diffuse hyperplasia. All patients are surviving 1 to 9 years after diagnosis of thyroid disease.