Gravesí disease following several years of Primary Hypothyroidism

SN Ali, K Wynne, B Field and K Meeran

Imperial Centre for Endocrinology

We present an interesting case of a 66 year old Caucasian lady who was referred to our care recently by her GP. She had been previously fit and well, apart from being diagnosed with hypothyroidism approximately 12 years previously. This had been treated successfully by her GP with Levothyroxine 50mcg once daily since diagnosis.

Of interest, she developed thyroid eye disease several years after her diagnosis of hypothyroidism and was under the care of Ophthalmologists at another hospital. Anti-TSH receptor antibodies were not tested during this time, but she remained biochemically euthyroid on Levothyroxine throughout, without any need to titrate the dose.

Two years ago, on routine blood testing, she was noted to have a high free T4 of 43.1pmol/L (NR 9-26pmol/L) and a low TSH of 0.03mU/L (NR 0.3-4.2mU/L). The dose of Levothyroxine was titrated downwards. However, despite a reduction of dose from Levothyroxine 50mcg once daily to 25mcg twice weekly, TSH remained low (0.04mU/L) with a raised free T4 (44pmol/L).

She was seen at this point in clinic. She was symptomatic with tiredness, weight loss and palpitations and, on clinical examination she had a tremor and a small, smooth goitre. She had bilateral exophthalmos, mild proptosis and lid lag.

Blood tests confirmed hyperthyroidism: TSH <0.05mU/L, free T3 17.5pmol/L (NR 2.5-5.7pmol/L) and free T4 36.7pmol/L. Anti-TPO antibodies were positive at 257u/mL (NR 0-75u/mL), as were anti-TSH receptor antibodies (21.7u/mL; NR 0-0.4u/mL). Levothyroxine was stopped and carbimazole 10mg once daily was started. Following several weeks of carbimazole treatment, thyroid function tests show a definite improvement (free T3 8.4pmol/L, free T4 28.1pmol/L, TSH<0.05mU/L).

The development of Gravesí thyrotoxicosis following primary hypothyroidism is relatively uncommon and is likely to result from a switch in TSH receptor antibody specificity, from predominantly blocking to predominantly stimulating epitopes. The association between thyroid status and thyroid eye disease in this case is also unusual, with its onset occurring during biochemical hypothyroidism.