In hypernatremia, the differential diagnosis most notably includes which pairing?

• A. SIADH
• B. Adrenal insufficiency
• C. Hypothyroidism
• D. Nephrogenic DI vs central DI

Answer: (D)

Hypernatremia typically signals a deficit of free water relative to sodium, so the most important differential is a diabetes insipidus–type problem that causes free-water loss. There are two forms: central diabetes insipidus, due to insufficient release of antidiuretic hormone, and nephrogenic diabetes insipidus, due to the kidney not responding to ADH. Distinguishing these two is crucial because their management differs: central DI may respond to desmopressin and treating the underlying pituitary issue, while nephrogenic DI requires addressing the kidney’s insensitivity and any contributing factors. Diagnostic clues come from urine studies and response to desmopressin: DI shows high-volume, dilute urine with low urine osmolality; after desmopressin, central DI typically shows a marked increase in urine osmolality, whereas nephrogenic DI shows little or no response. Other conditions like SIADH cause hyponatremia with concentrated urine, and adrenal insufficiency or hypothyroidism more commonly lead to hyponatremia as well, so they are not the classic pairing for hypernatremia.