Hypothyroidism to Graves' disease and late appearance of pretibial myxoedema

[ling]

Case study to share.

Rare case of autoimmune hypothyroidism switching to Graves, caused by TSH receptor stimulating antibodies

thelancet.com/journals/lanc...

A 57-year-old man attended our clinic complaining of orbital pain, anxiety, and a tremor. On examination, he had oedema and retraction of his eyelids and an obvious tremor. 6 months earlier, he had been diagnosed with autoimmune hypothyroidism after he began to gain weight and complained of feeling tired: his thyroid-stimulating hormone (TSH) concentration was raised at 83 mIU/L (normal range 0·3–4·6), free thyroxine (T4) concentration was 5·9 pmol/L (normal range 10–23), and the antithyroid peroxidase antibody concentration was markedly elevated at 1488 IU/mL (normal level <101). The thyroid gland was recorded as being minimally enlarged. At that stage the patient had been started on levothyroxine.

When we saw him, his TSH concentration was 0·02 mIU/L and his free T4 concentration was 35 pmol/L, and we concluded that he was hyperthyroid because of treatment with excessive levothyroxine; we reduced the dose and arranged to see him 1 month later. At that time, his serum TSH concentration remained suppressed (0·01 mIU/L) and the concentration of TSH receptor antibodies (TRAb) was high at more than 20 IU/mL (normal level <1). We made a diagnosis of Graves' disease and treated the patient with block and replace therapy—giving him thiamazole 30 mg daily followed by levothyroxine 75 μg daily. We also made an urgent referral to an ophthalmologist: the patient had progressive retraction of both eyelids and a scleral show of 1 mm, and was diagnosed as having Graves' opthalmopathy.

1 year after starting the block and replace treatment, the patient visited a dermatologist, complaining of large, red-orange plaques on both shins. They were not painful or itchy (figure). On examination, he had sharply demarcated, waxy, peau d'orange texture, firm, non-pitting plaques. He was euthyroid and continued with the block and replace therapy. Histological examination of a skin biopsy specimen showed mucopolysaccharide deposition localised to the reticular dermis and attenuation of collagen fibres such that they were frayed, fragmented, and widely separated, confirming a diagnosis of pretibial myxoedema. Our patient was treated with topical corticosteroids and compression stockings. After 6 months, the skin was less firm, but there was no significant improvement in his condition; we advised him to only continue with the compression stockings. A blood test taken after a trial of stopping block and replace therapy showed a serum TSH concentration of 0·01 mIU/L, free T4 concentration greater than 100 pmol/L, and TRAb concentration greater than 20 IU/L (see appendix for complete blood results). An ultrasound—2 years after the initial diagnosis of Graves' disease—showed diffuse enlargement of the thyroid.

Conversion of Graves' disease to hypothyroidism is not uncommon. However, the reverse is rare: in our patient, autoimmune hypothyrodisim switched to hyperthyroidism, caused by TSH receptor stimulating antibodies. Pretibial myxoedema or Graves' dermopathy is an infrequent, but classic, sign of Graves' disease that should be recognised as an extrathyroidal manifestation. It can develop years after the hyperthyroidism and as a result may present to a dermatologist rather than an endocrinologist. Although pretibial myxoedema is a relatively benign condition, it is often resistant to treatment and can cause a great deal of distress—as in our patient—for cosmetic reasons.

[TSH110]

Very interesting, thanks for posting