Endocrine Abstracts

Graves' disease appears to be the clinical result of an autoimmune attack on thyroid tissue however the immune defect and triggering events remain unclear. The inflammatory process in multiple sclerosis (MS) is mediated by CD4 T lymphocytes. Campath-1H, a monoclonal antibody against the CD52 antigen of CD4 T cells, improves disease activity in MS and is associated with development of Graves' disease in one-third of patients. Thus Campath-1H provides an interesting insight into the aetiology of autoimmune thyroid disease.

We report two cases of Graves' disease following treatment with Campath-1H for relapsing MS.

Case 1: A 23 year old female with MS presented to the neurology department with a 12 month history of progressive weakness and blurred vision. She was treated with intravenous Campath-1H 0.3mg/kg for five days. Baseline thyroid function tests (TFTs) were normal; free T4 14.3 pmol/l, TSH 1.1 miu/l and negative thyroptropin (TPO) antibodies. 13 months after treatment she developed symptomatic thyrotoxicosis with free T4 54.7 pmol/l, free T3 21.7 nmol/l and TSH <0.01 miu/l. TPO antibodies were now positive. She was treated with high dose carbimazole.

Case 2: A 54 year old female with MS was admitted with a spastic paraparesis and treated with pulsed methylprednisilone 1gm daily for 3 days followed by Campath-1H 0.3mg/kg intravenously for 5 days. Baseline TFTs were normal; free T4 11.4 pmol/l, TSH 2.83 miu/l and negative TPO antibodies. 11 months later she developed biochemical thyrotoxicosis; free T4 24.5 pmol/l, free T3 6.0 nmol/l, TSH 0.28 miu/l and positive TPO. The TFTs normalised over four months without treatment.

The mechanism of this association is not clear. Campath-1H suppresses Th1 lymphocytes and the subsequent decrease in the ratio of Th1:Th2 lymphocytes may cause an increase in humoral antibody production against the TSH receptor. These cases highlight the need for regular monitoring of TFTs in patients with MS treated with Campath-1H.