Endocrine Abstracts

42-year-old female with relapsing Graves’ disease treated with propylthiouracil (PTU) presented to the Emergency Department with a two-week history of fevers, night sweats, transient rash, arthralgia and fatigue. Five years previously she presented with Graves’ disease, TSH <0.02 mIU/l, FT4 of 39.8 pmol/l (9–16 pmol/l) and TSH receptor antibody positive with a titre of 11.3 IU/l. Initially treated with carbimazole therapy but developed an urticarial rash, lower limb swelling and eosinophilia and was switched successfully to PTU. At the time of presentation, she had been taking PTU for 18 months. She had a family history of hypothyroidism in one sister, was a non-smoker, rarely took alcohol and was an office worker. On examination the patient had a low-grade pyrexia (37.6°C), mild diffusely enlarged non-tender goitre with no evidence of retrosternal extension or thyroid eye disease. Initial investigations revealed a neutrophil count of 0.36×10⁹/l and white cell count of 1.57×10⁹/l, haemoglobin and platelet counts were normal. Biochemistry showed normal renal, liver and thyroid function. Blood and urine cultures were repeatedly negative. Extended viral screen was also negative. Chest radiograph was normal. Urinalysis showed a small amount of blood with no proteinuria, no crystals, no casts. Serum was positive for ANCA antibodies with dual positivity for myeloperoxidase (MPO), 6.4 IU/ml (NR 0–3.4), and proteinase-3 (PR3), 42 IU/ml (NR 0–2), consistent with vasculitis. Antinuclear factor was positive. Rheumatoid factor and complement were normal. Antibodies to DNA, RNP, Smith, Ro and La were negative. There was no evidence of renal or pulmonary involvement of vasculitis.

Results & Treatment: PTU was stopped due to both the agranulocytosis and ANCA-associated vasculitis (AAV). She was treated with broad spectrum antibiotics and granulocyte colony-stimulating factor, resulting in resolution of neutropenia. PR3 and MPO titres reduced and her vasculitic symptoms resolved upon discontinuation of PTU. Management options of Graves’ disease were discussed and the patient opted for radioactive iodine (RAI). Following two doses of RAI, she became hypothyroid and was commenced on levothyroxine.

Conclusions and points for discussion: Clinicians should be cognisant of the significant risk profile of PTU. AAV is a rare side effect of PTU however, PTU is the most commonly reported medication causing drug-induced AAV. PTU-induced AAV has a better prognosis and milder course than primary AAV provided PTU is stopped, which is evident in the case outlined above. With prompt discontinuation of PTU, the patient’s symptoms resolved precluding the need for immunosuppressive therapy.