(6.16) Graves’ Disease hyperthyroidism management in a patient with a medical history of chronic idiopathic neutropenia: a therapeutic challenge - case report

Introduction : Hyperthyroidism is a clinical state resulting from inappropriate high thyroid hormone action in tissues. In the U.S., the prevalence of hyperthyroidism is approximately 1.2% (0.5% and 0.7% subclinical). Graves’ disease (GD) is the most common etiology.
Antithyroid drugs (ATD), including propylthiouracil (PTU) and methimazole, Radioactive Iodine (RAI) therapy, or thyroidectomy, are an effective and safe therapy for GD hyperthyroidism. One of the side effects of ADTs is agranulocytosis, a rare but severe complication that occurs in 0.2-0.5% of patients with GD receiving antithyroid drugs. The mechanism behind this side effect is related to an alteration in the proliferative potential of hematopoietic progenitor cells and an immune-mediated response from ATDs. The American Thyroid Association (ATA) suggests having a baseline blood test before initiation of ATD therapy. There is no evidence that a previous diagnosis of neutropenia increases the risk of complications from ATDs. Still, it is recommended to reconsider the initiation of ATD in patients with baseline absolute neutrophil count (ANC) < 1000/mm3 (normal range: 2500-8000/mm3). It is essential to mention that blood neutrophil counts are not as stable as other blood cell counts. Neutrophil counts may vary considerably over short periods, associated with activity, exercise, eating, or just the time of day. What could be the implications of starting an ATD in patients with a high risk of severe neutropenia development?

Case(s) Description : Our case concerns a 33-year-old female diagnosed with Chronic Idiopathic Neutropenia (CIN) at two years old. She developed severe neutropenia with a brain abscess requiring antibiotics for over one year. The patient received filgrastim intermittently, with an appropriate response until age seven. The last flare was at 16 years old. At age 23, she was evaluated for amenorrhea and tachycardia. Thyroid-stimulating hormone (TSH) was 0.002 mIU/ml, free T4 was 2.3 ng/dl, and free T3 was 6.39 pg/ml. Thyroid stimulating immunoglobulin (TSI) was elevated. Thyroid ultrasound was normal, and 24-hour thyroid uptake was 62.2%. Therefore, GD was diagnosed. RAI therapy was considered the best option for her. Since stress can cause ANC decline, it was monitored every three days after RAI therapy. ANC did not drop enough to warrant filgrastim. After three months, the patient presented with TSH 190.64 and free T4 0.4, for which levothyroxine was started.

Discussion : The coexistence of GD and CIN with the risk of severe neutropenia continues to be a therapeutic challenge. Treating hyperthyroidism in a patient with a history of CIN requires careful consideration and coordination between an endocrinologist and a hematologist. ATD contraindications and adverse reactions may limit their use, including severe neutropenia, so before starting ATDs, a complete blood count, including ANC, must be done. Therefore, the recent diagnosis of hyperthyroidism in a patient with risk or severe chronic neutropenia represents a therapeutic dilemma, and further research is needed.