(21.12) Treatment refractory hyperthyroidism in an elderly patient and pre-operative management with therapeutic plasma exchange

Introduction : The prevalence of hyperthyroidism in the US is estimated to be 1.3% (0.5% clinical and 0.7% subclinical). Most common causes include Graves’ disease, toxic multinodular goiter, toxic adenoma and less common causes include TSH secreting pituitary tumors, struma ovarii, thyroiditis and excess iodine from medications and contrast.

Case(s) Description : We are presenting the case of a 94-year-old female who presented with A.Fib with RVR. Chest CT showed a large 8.6 cm left retrosternal goiter with significant mass effect on the trachea & esophagus. Pertinent history was significant for right thyroidectomy for benign goiter 30 years ago. Cardiac arrhythmias were treated with amiodarone.

Patient represented a few months later with A.Fib with RVR, heart failure and was found to be severely hyperthyroid, but not in thyroid storm. Thyroid antibodies were all negative. She was started on MMI but it was changed to PTU due to ineffectiveness and was given steroids due to presumed diagnosis of type 2 amiodarone induced thyrotoxicosis. Despite maximum medical therapy with PTU, prednisone & SSKI, the patient continued to be hyperthyroid (T4: 6.14 ng/dl). She underwent 6 procedures of therapeutic plasma exchange when her serum free T4 decreased to 2.74 ng/dl. Within 24 hours of the last session, she underwent left thyroidectomy/excision of substernal goiter without any immediate complications. Given the massive size of the goiter and significant substernal extension, partial sternotomy was necessary.

Discussion : Our patient likely had a mix of type I AIT and type II AIT with the underlying history of very large goiter. She also received multiple iodinated contrast studies which likely contributed to severe thyrotoxicosis. AIT develops in about 3-10% of amiodarone treated patients. 
Table 1 Differences between Type 1 & Type II Amiodarone Induced Thyrotoxicosis (AIT)

	AIT Type I	AIT Type II
Mechanism	Over-production	Destructive thyroiditis
Underlying Grave’s or MNG	Yes	No
Positive autoantibody	Yes	No
Elevated Beta-glucuronidase	No	Yes
Thyroid U/S	Increase vascularity	Normal vascularity
Nuclear Uptake Scan	Increase	Low/normal
Response to antithyroid	Yes	No
Response to steroids	No	Yes

Despite getting very high doses of PTU (1350mg/day), steroids (60mg daily) and SSKI (150mg/day), she remained hyperthyroid. American Thyroid Association guidelines suggest thyrotoxic patients should be rendered euthyroid before undergoing surgery to prevent precipitating thyroid storm. Per American Society for Apheresis 2023 guidelines, TPE is a category II indication for thyroid storm. Few observational studies have demonstrated efficacy of TPE in the pre-operative management of patients with treatment resistant thyrotoxicosis, who do not have thyroid storm. Hence, no specific guidelines exist about the use of TPE in such patients.

TPE works by reducing protein-bound thyroid hormones, autoantibodies and cytokines and removing 5′ mono-deiodinase, converting T4 to T3 from the circulation. However, these effects last for 24–48 hours and surgery is preferred within 24 hours after TPE. Further studies are needed to evaluate the role of TPE in the pre-operative management of such patients.