The Grave Hematologic and Hepatic Effects of Hyperthyroidism

Abstract

Background: Hyperthyroidism can present with a myriad of symptoms including some rare, but morbid systemic manifestations. Here we present the case of a patient who presented with thyrotoxicosis, pancytopenia and cholestatic liver disease. Clinical Case: A 37 year-old Hispanic female with no significant past medical history presented with weight loss, fatigue, jaundice and irregular menstrual cycles ongoing for 10 months. Upon presentation, vitals were notable for mild tachycardia. She had significant jaundice and a visibly enlarged thyroid gland, while no thyroid eye disease was noted. The patient was found to have a hemoglobin level of 6.5 g/dL (12.0 - 16.0 g/dL), white blood cell level of 2.3 K/uL (4.5 - 11.0 K/uL) and platelet count of 82 K/uL (150 - 400 K/uL). Alkaline phosphatase was elevated to 214 U/L (34.0 - 104.0 U/L) and total bilirubin was 8.7 mg/dl (0.2 - 1.2 mg/dL) with direct bilirubin of 5.4 mg/dL (0.0 - 0.2 mg/dL). Thyroid panel revealed an undetectable TSH and a free T4 of 5.58 ng/dL (0.61 - 1.18 ng/dL). Hematological work-up was negative for malignancy but did note severe iron deficiency. Hepatitis B and C virus, parvovirus B19 serology, magnetic resonance cholangiopancreatography, and autoimmune disease work-up all returned normal. Thyroid uptake scan showed diffuse uptake without nodular disease and a 24-hour uptake of 57% (normal 7-32%). Thyroid stimulating antibodies were positive at 115 IU/L (0.00-0.55 IU/L). Since all other work up was negative, it was concluded that her pancytopenia and cholestatic pattern of liver injury were likely due to hyperthyroidism with plan to do a bone marrow biopsy if she does not have improvement in blood cell counts. Patient was treated with radioactive iodine (RAI) ablation. A week after treatment she had further elevation in total bilirubin, whereas her blood counts had improved. It was decided to initiate methimazole with close monitoring of her liver function tests. Two months after treatment, her thyroid function improved and she was eventually transitioned to levothyroxine for post-ablative hypothyroidism. Bilirubin improved to normal range and her pancytopenia resolved without additional intervention. She had complete resolution of jaundice and started having regular menses 2 months after her RAI treatment. Conclusion: The etiology of pancytopenia has been thought to be multifactorial with consumption of nutrients (including iron, manifesting as iron deficiency anemia), stimulation of erythropoiesis and sequestration of blood cells due to splenomegaly. Thyroid associated hepatic dysfunction has been proposed to be secondary to relative hypoxia in the perivenular regions and the direct toxic effect of thyroid hormone on hepatic tissue. In patients with concurrent hepatic disease and thyrotoxicosis, it is reasonable to consider treatment with thionamides with close monitoring, if other etiologies for hepatic disease are ruled out.