The Thionamide Paradox: Thyrotoxicosis With Neutropenia as Initial Presentation of Grave’s Disease

Hyperthyroidism typically presents with symptoms such as tremors, palpitations, weight loss, heat intolerance and anxiety. Although rare, anemia, leukopenia or thrombocytopenia may develop as an unusual manifestation of thyrotoxicosis. Hematologic derangements have been reported as a side effect of antithyroid drugs (ATD) as well, and while ATD associated agranulocytosis is uncommon, it is a life-threatening condition. A 49-year-old Hispanic female with history of iron deficiency anemia came to the emergency department (ED) with a chief complaint of palpitations. Also reported fatigue, myalgias, headache and anxiety of 1 week duration. Upon​ arrival to the ED she was tachycardic, appeared anxious and diaphoretic. Physical examination revealed a very discrete, non-tender goiter. Bloodwork showed hemoglobin 9.1 g/dL (12.0-16.0), WBC 2.30 c/µ​L (4.8-10.8),​ ANC 1.04 c/µ​L​ (1.80-7.20), ALC 0.88 c/µ​L​ (1.20-4.0), PLT 209 c/µ​L​ (150-450). TFTs were pertinent for TSH 0.007 UIU/mL (0.35-3.74), free T4 5.11 ng/dL (0.76-1.46) and total T3 555 ng/dL (60-181). She received initial treatment with hydrocortisone 300 mg and PTU 300 mg. She was admitted and started on propranolol 40 mg TID and prednisone 20 mg daily, but further doses of ATD were initially held due to concerns for her marked leukopenia. She subsequently became acutely psychotic with psychomotor agitation, visual and auditory hallucinations. CT of the brain revealed no acute abnormalities. She was started on olanzapine 2.5 mg daily for hyperthyroidism induced psychosis, along with methimazole 20 mg daily, KI (Lugol solution) 0.35 mL BID and cholestyramine 4g BID. Further workup of leukopenia showed no dysplastic​ cells on​ peripheral smear, normal vitamin B12 and folate levels, and negative HIV. She displayed marked improvement, denied ongoing hallucinations after 72 hours of initiating ATD, and WBC subsequently normalized. Thyroid workup was diagnostic for GD with positive TRAB and TSI. She was discharged in stable condition on methimazole 40 mg daily. Agranulocytosis is a rare side effect of ATD (prevalence ~0.5%) and average time of onset is usually within 2-3 months after starting therapy. Although the majority of cases of hematologic alterations in GD are seen as a complication of ATD, our patient presented with the peculiarity that leukopenia (with both neutropenia and lymphopenia) was associated to untreated hyperthyroidism. This case illustrates the fact that in patients presenting with hyperthyroidism and leukopenia, treatment with ATD has proven to result in achievement of euthyroid state along with a sustained improvement in blood cell levels. Despite its rarity, agranulocytosis has become essentially ingrained to ATD amongst medical professionals. Clinicians should be aware that neutropenia is an uncommon feature of uncontrolled hyperthyroidism and feel confident with initiating ATD in this setting.