Case Presentation: An 80 year old woman with a history of disseminated tuberculosis (positive TB cultures in knee wound and pulmonary cavitary lesion in 2021) presented to the emergency room for edema and erythema of her right third DIP joint. Over the past 3 weeks, she had waxing and waning orientation, reduced energy, and reduced PO intake. Her anti-TB regimen was isoniazid, ethambutol, and pyrazinamide. She was taken off rifampin two months prior due to drug induced liver injury. Finger x-ray was consistent with osteomyelitis, cultures grew Staphylococcus epidermidis, and she was admitted for IV antibiotic therapy and subsequent amputation. One day after admission, she was found to be hypotensive to 70s/50s, bradycardic to 45-50s, and hypothermic. Her TSH was found to be 207 mcU/mL, her free thyroxine 0.22 ng/dL. Thyroid studies prior to admission (while on rifampin) showed subclinical hypothyroidism: TSH of 18.8, fT4 1.35. A diagnosis of myxedema coma was made, thought to be due to hypothyroidism from her anti-TB drug regimen exacerbated by infection. Given her hypotension and bradycardia, there was suspicion for adrenal insufficiency complicating myxedema coma, but ACTH stimulation test was normal. She was transferred to the ICU and started on IV liothyronine and IV levothyroxine. On hospital day 9, her TSH normalized to 3.5, free thyroxine to 1.4, but she continued to be minimally responsive. On day 17, she underwent LP for concern for TB CSF infiltration. CSF showed no growth on AFB culture. Her mental status gradually improved and she was ultimately discharged to home on hospital day 66.

Discussion: Myxedema coma is a rare, severe manifestation of hypothyroidism leading to altered mental status, hypotension, bradycardia, and hypothermia (1). It can occur after sustained periods of severe hypothyroidism or be precipitated by an acute event such as an infection in a hypothyroid patient (2). In this case, hypothyroidism likely secondary to anti-TB therapy with rifampin was exacerbated by S. epidermidis osteomyelitis resulting in myxedema coma. Hypothyroidism has been associated with various anti-tuberculosis drugs, particularly those used for multidrug resistant TB, including rifampin, ethionamide, and para-aminosalicylic acid (3-6). Case studies show hypothyroidism resulting from classic TB therapy with rifampin, isoniazid, pyrazinamide, and ethambutol (6). TB infiltration of the thyroid is rare but has been found in some cases to cause hypothyroidism through thyroid tissue destruction (7,8). However, this was less likely the etiology for this patient, whose disseminated TB was responding well to treatment. Reported mortality of myxedema coma varies from 30 to 60 percent (9). Older age, circulatory failure, need for ventilator support, and sepsis were associated with increased mortality (2). The main therapy for myxedema coma is T4 replacement. The benefit of additional T3 supplementation has not been studied through clinical trial but is recommended as T3 is more biologically active with more rapid onset than T4, and because hypothyroidism and concurrent illness can result in impaired T4 conversion(10,11). Clinical and lab improvements are typically seen within one week of initiating therapy (11).

Conclusions: In a patient with known history of disseminated TB presenting with altered mental status, hypotension, or hypothermia, thyroid function tests should be checked. Early diagnosis and initiation of thyroid hormone replacement is vital in minimizing mortality of myxedema coma.