SUN-308 - Hyponatremia in Severe Hypothyroidism: Lessons from a Complex Case

Background:
Severe hypothyroidism may cause hyponatremia through impaired water excretion due to increased antidiuretic hormone release from reduced cardiac output and reduced effective arterial blood volume, along with upregulation of aquaporin-2 channels, and decreased Na-K-ATPase activity. Alternative causes must be systematically evaluated, as recent evidence indicates hypothyroidism associated with hyponatremia is uncommon, and other factors frequently contribute.

Case:
A 75-year-old female with a history of ESRD s/p renal transplant (on tacrolimus and mycophenolate mofetil), CKD stage 3b, prior Hürthle cell thyroid carcinoma post thyroidectomy (on levothyroxine), and insulin-dependent type 2 Diabetes Mellitis presented with altered mental status.
The patient had a recent two-month course complicated by new-onset seizures (started on levetiracetam), critical illness requiring tracheostomy/PEG placement, and severe hypothyroidism (peak TSH 71.3 uIU/ml) managed as myxedema coma and was discharged after stabilization.
Four days post-discharge, she was readmitted with severe encephalopathy. Evaluation revealed euvolemic hypotonic hyponatremia (Na 117 mmol/L, serum Osmolality 251 mOsm/kg) and high urine osmolality (485 mOsm/kg) and urine sodium (40 mEq/L). Her TSH on readmission was 38.7 uIU/ml. Contributing medications including levetiracetam and tacrolimus were noted. Free water excess due to PEG tube free water flushes was less likely a possible cause due to high urine osmolality. An adrenal insufficiency workup was negative. Pre-admission tacrolimus levels were subtherapeutic (1.9 ng/ml).
She was treated for presumed myxedema coma with IV levothyroxine and empirical stress-dose hydrocortisone, alongside hypertonic saline for hyponatremia. Over one month, her sodium levels gradually improved to 134 mmol/L in parallel with TSH improvement (down to 15.4 uIU/ml) and her mental status improved to her baseline.

Conclusion:
Severe hypothyroidism can cause hyponatremia, though this is rare and primarily occurs in myxedema. This case shows temporal improvement of sodium with thyroid hormone replacement in a patient with multiple potential etiologies (critical illness, levetiracetam, tacrolimus). Alternative causes must always be considered. When severe hypothyroidism is identified as contributing, prompt thyroid hormone replacement is critical for effective management

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