Abstract

Background: Anterior pituitary dysfunction is a known, time and dose dependent effect of cranial radiotherapy but central diabetes insipidus (CDI) has been rarely reported. We present a patient with partial CDI (PCDI) and adipsia, months after subtotal resection and radiation therapy for a large anterior cranial fossa meningioma. Clinical Case: A 53-year-old woman with history of subtotal resection of a 7 cm meningioma ~2 years ago and radiation therapy (54 Gy, completed 15 months ago), was admitted to the ICU with obtundation, tachycardia (120/min), hypotension (87/52 mmHg, on vasopressors in the first 24 hours), severe hypernatremia (serum Na 170 mmol/L), and acute kidney injury (creatinine 2.11 mg/dL; baseline 1.0 mg/dL). Plasma osmolality (pOSM) was 385 mOsm/kg and urine osmolality (uOSM) was 982 mOsm/kg. MRI brain 3 months ago showed frontal lobe encephalomalacia, residual meningioma at the planum sphenoidale (1.8x3.5x2.8 cm) with cavitary lesion compatible with post-radiation necrosis. After receiving 4 litres (L) isotonic fluids and 5 L hypotonic fluids in the first 38 hours, serum Na was 168 mmol/L, creatinine 1.35 mg/dl and uOSM 386 mOsm/kg. Urine output was 2.6 L on day-1 and 1.9 L during first 7 hours on day-2. After an IV dose of 2 mcg DDAVP, uOSM increased to 784 mOsm/kg, and Na decreased to 164 mmol/L, supporting CDI diagnosis. ACTH stimulation test was normal. Levothyroxine 50 mcg daily was started for central hypothyroidism. By day-6, her mental status returned to baseline (alert only to person). DDAVP dose adjustment was challenging due to frequent fluctuation in her serum Na (130s to 150s), adipsia and urinary incontinence. On day-44, she was discharged on subcutaneous (subQ) DDAVP 0.25 mcg every 36 hours, with a serum Na of 145 mmol/L. She was readmitted 3 days later with serum Na of 164 mmol/L, followed by another prolonged hospitalization complicated by acute kidney injury and popliteal DVT. On day-64, she was discharged to a nursing facility on DDAVP 0.25 mcg subQ twice daily. Clinical Lesson: Delayed PCDI with adipsia is an exceedingly rare but challenging complication of cranial radiation therapy. The initial uOSM (twice as high as pOSM) in our case caused a delay in diagnosis. This could reflect enhanced antidiuretic response to low circulating ADH levels, possibly due to lower rate of solute extraction in dehydration, upregulation of ADH receptors due to chronic hormone deficiency, and to a fall in glomerular filtration rate. Decrease in uOSM after hydration could be due to ADH exhaustion.

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