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In a post-operative patient who has undergone craniotomy and is exhibiting extreme thirst along with a high urine output of over 1000 mL in two hours, Diabetes Insipidus should be suspected. This condition is often characterized by a deficiency of the hormone vasopressin (antidiuretic hormone or ADH), which leads to an inability to concentrate urine, resulting in large volumes of dilute urine and consequent extreme thirst.

The craniotomy could have impacted the pituitary gland or hypothalamus, where ADH is produced and regulated, leading to transient or permanent diabetes insipidus. The significant urine output in conjunction with excessive thirst aligns with the classic symptoms of this condition, warranting further evaluation and management.

In contrast, while Diabetes Mellitus can also lead to polyuria and polydipsia, it typically involves high glucose levels and may not be specifically indicated following a craniotomy. Hyperglycemia is associated with elevated blood sugar levels and does not directly explain the extreme thirst and output without considering other symptoms, such as increased appetite or fatigue. Acute Kidney Injury, although it can cause changes in urine output, is more often associated with oliguria (reduced urine output) rather than the significant polyuria observed in this