Endocrine Abstracts

Case History: A 37 year old female underwent an elective autologous stem cell transplant (ASCT) for multiple sclerosis (MS), with cyclophosphamide and anti-thymocyte (ATG) conditioning. She had previously received two doses of alemtuzumab, with the last dose 12 months prior to ASCT. Baseline thyroid function was normal pre atemluzumab. 3 months prior to dose 2 (18 months post first dose), subclinical hyperthryoidism was present with a raised TSH antibody (0.08 unit/ml). There were no further thyroid function tests (TFTs) done in the interim before ASCT. During the ASCT the patient became persistently tachycardic, with subsequent evidence of right heart strain and peripheral oedema. These symptoms were initially thought secondary to the conditioning regimen. No other cause was detected. TFTs subsequently revealed a severely thyrotoxic state. On retrospective enquiry, the patient identified palpitations, heat intolerance and dry eyes for the month pre ASCT. Fine peripheral tremor, mild proptosis, lid lag, and mild smooth goitre were present.

Investigations: Pre alemtuzumab: Thyroid stimulating hormone (TSH) 0.4 milliunit/L, free T4 (FT4, thyroxine)15 pmol/L. 3 months prior to second dose alemtuzumab: TSH 0.08 milliunit/L, FT4 14.6 pmol/L, free T3 (FT3, tri-iodothyronine)5.3 pmol/L. TSH antibody 1.5 unit/mL. Day 7 post stem cell transplant: TSH 0.00 milliunit/L, FT4 47.9 pmol/L, FT3 46.1 pmol/L, TSH antibody >30 unit/ml, TPO (thyroid peroxidase) antibody 239 IU/mL. Thyroid ultrasound showed diffuse hypervascularity, in keeping with Graves’ disease.

Results and treatment: Carbimazole was delayed until neutrophil regeneration post ASCT. After one month of carbimazole (40 mg OD) the patient’s thyroid function was as follows: TSH <0.01 milliunit/L, FT3 10.6 pmol/L, FT4 17.5 pmol/L, TSH antibody >30 unit/ml, TPO antibody 159.

Conclusions and points for discussion: This lady presents a likely case of alemtuzumab induced autoimmune thyroid disease, with progression from subclinical hyperthyroidism to frank thyrotoxicosis within 15 months. The development of thyroid autoimmunity months or years after alemtuzumab is a frequent and unpredictable complication, which requires ongoing biochemical surveillance for a least 4 years after therapy. The use of Alemtuzumab is significant amongst the transplant community, and in patients with MS. Therefore vigilance is required. This is especially important in patients who might undergo procedures such as ASCT, where symptoms of thyroid dysfunction may be wrongly attributed to conditioning or neutropenic sepsis. In MS patients the need for full thyroid function testing pre transplant is essential.