Graves' orbitopathy in a patient with adrenoleukodystrophy after bone marrow transplantation

Abstract

Objective: For many years, the treatment of X-linked childhood cerebral adrenoleukodystrophy (XALD) consisted of hydrocortisone replacement and a mixture of short chain-fatty acids, known as 'Lorenzo's oil'. Recently, bone marrow transplantation (BMT) has also been used. Case report: We report the case of a patient affected by XALD who developed Graves' hyperthyroidism (GH) and Graves' orbitopathy (GO) after BMT and who we could follow-up for 6.5 years afterwards. Evidence synthesis: A boy affected by XALD was treated at the age of 6 years, with a whole BMT from his sister. One year after BMT, the transplanted patient presented TSH at the lower normal value and 3 years later he developed thyrotoxicosis. After a further 2 years, the patient developed GO, which showed clinical evidence of reactivation 5 years after its onset as a consequence of an attempt to treat thyrotoxicosis by means of I 131 (300 MBq). Seven years after BMT, the donor showed alterations of thyroid autoimmunity and 1 year thereafter she developed GH. She never presented GO during a subsequent 5 year follow-up. Conclusions: This case illustrates that autoimmunity originating from a pre-symptomatic donor can be transferred into the host during allogeneic stem cell transplantation. In cases where autoimmune phenomena are recognized in the donor prior to donation, alternative donors or T-cell manipulation of the graft might be considered.

Graves' disease following immune reconstitution or immunomodulatory treatment: should we manage it any differently?

“…One donor has been reported in whom the only evidence of thyroid disease in retrospect was the presence of thyroid peroxidase (TPO) antibodies; in another, no evidence at all for thyroid disease was found. In one bone marrow recipient with adrenoleukodystrophy, Graves' disease started 3 years after transplantation and was followed by the appearance of eye signs, whereas his donor sister only developed Graves' disease without eye signs 7 years after donation.…”

Graves’ orbitopathy after allogeneic bone marrow transplantation in a patient with Fanconi anemia – side effect of alemtuzumab therapy?

“…In contrast, after the BMT, both occurrence and remissions of GD have been reported. According to Weetman, most cases of GD which follow BMT are probably the result of adoptive immunity , in which clones of autoreactive T cells from a donor with G expand in the recipient , but there is also some evidence that link disordered immunoregulation due to chronic GVHD with expansion of clinically silent autoreactive donor lymphocytes to produce autoimmune disease in the recipient .…”

“…We found one case of GO in the literature in a patient with GD following BMT that appeared to be a consequence of radioiodine treatment (I131–300 MBq) for GD. The patient was treated with oral glucocorticoids; in a few months, the orbitopathy became inactive, all the soft tissue signs disappeared, while the increased exophthalmos persisted . However, this case was not related to alemtuzumab administration.…”

Management of endocrino-metabolic dysfunctions after allogeneic hematopoietic stem cell transplantation

“…Hyperthyroidism The donor-recipient transfer of B and T lymphocytes may favor the occurrence of hyperthyroidism (Graves disease, sometimes preceded by a hypothyroid episode related to blocking anti-TSH receptor antibodies or immune reconstitution syndrome). However, the disappearance of an autoimmune disease has also been reported [ 25 ]. Iodine overload can also promote hyperthyroidism and stress may trigger the appearance of Basedow’s disease.…”