Double Whammy: Graves' Hyperthyroidism with Superimposed Non-Thyroidal Illness Syndrome (NTIS)

Introduction:
Occam’s razor tells us to look for one unifying diagnosis to explain the patient’s signs and symptoms, but it doesn’t always apply. We describe a case of two concurrent diagnoses: Graves’ hyperthyroidism and Non-Thyroidal Illness Syndrome (NTIS). NTIS, while appropriate in a euthyroid individual as a means of conserving energy, in our patient, it created the perfect storm, obscuring the diagnosis of Graves’ hyperthyroidism.

Case Description:
A 39-year-old man with a history of alcohol and IV drug use disorders, HFrEF, and hypertension presented with hypoxia requiring 6L supplemental oxygen, atrial fibrillation with heart rate 180/min. Patient required intubation and treatment of sepsis. Initial laboratory studies demonstrated mild leukocytosis WBC 12.9, undetectable TSH, and elevated free T4 of 1.6 [normal 0.6-1.3]. Despite adequate treatment for infection, the patient had persistent fevers and tachycardia, experiencing two episodes of rates to the 160s, with systolic pressures >200. Eye exam showed proptosis after initial swelling from intubation decreased. Thyroid function tests were repeated revealing undetectable TSH with further increased free T4 of 3.1. Endocrinology was consulted and additional labs were obtained. Total T3 was 1.4 [normal 0.9-1.8] and reverse T3 84.4 [normal 9.2-24.1]. Bedside ultrasound demonstrated diffuse thyroid enlargement with heterogeneous echotexture, no discrete nodules and scattered vascularity. Burch-Wartofsky score was 50, highly suggestive of thyroid storm. Methimazole 20 mg twice daily, hydrocortisone 100 mg IV 3 times daily, propranolol 2 mg every 4 hours and SSKI solution every 6 hours were started. Thyrotropin receptor antibody resulted at 2.66 [normal 0.00-1.75] & thyroid stimulating antibody later resulted at 2.07 IU/L [reference range: 0-0.05]. He was successfully extubated eight days after admission and discharged on methimazole and carvedilol. His free T4 was 1.3 ng/dL approximately two weeks later.

Discussion:
The hypothalamic-pituitary-thyroid (HPT) axis plays a key role in thermoregulation, energy expenditure & metabolism. The HPT axis is exquisitely sensitive to physiologic stress and during illness, endogenous production of thyroid hormones is altered from baseline. TSH is typically suppressed & T4 is normal to low. There is also a decrease in T3 and increase in biologically inactive reverse T3 caused by down regulation of peripheral deiodinases that shunt production from T3 to rT3.

Non thyroidal illness can incite Graves’ hyperthyroidism, either the first episode or a recurrence, and our patient’s sepsis served as the inciting non-thyroidal illness. Grave’s hyperthyroidism is characterized by markedly increased T3 production, but in our patient’s case, NTIS prevented this elevation of T3, instead driving the marked increase in rT3 via the afore mentioned deiodinase actions. The strikingly high rT3 aided in clinching the diagnosis of Graves’ hyperthyroidism. Our case illustrates that T3 levels can be deceivingly low in the face of a co-existing acute illness that has caused NTIS.