Central diabetes insipidus is an uncommon disease caused by a deficiency in vasopressin (antidiuretic hormone [ADH]) from the posterior pituitary.
Primary central diabetes insipidus (without an identifiable lesion noted on MRI of the pituitary and hypothalamus) accounts for about one-third of all cases of diabetes insipidus. Familial diabetes insipidus occurs as a dominant genetic trait with symptoms developing at about 2 years of age. Diabetes insipidus also occurs in Wolfram syndrome, a rare autosomal recessive disorder that is also known by the acronym DIDMOAD (diabetes insipidus, type 1 diabetes mellitus, optic atrophy, and deafness). Although DIDMOAD manifestations usually present in childhood, they may not occur until adulthood, along with depression and cognitive problems. Central diabetes insipidus may also be idiopathic or due to autoimmunity against hypothalamic arginine vasopressin (AVP)-secreting cells. Reversible central diabetes insipidus can occur during chemotherapy with temozolomide and in the myelodysplastic preleukemic phase of acute myelogenous leukemia.
Secondary central diabetes insipidus is due to damage to the hypothalamus or pituitary stalk by tumor, hypophysitis, infarction, hemorrhage, anoxic encephalopathy, surgical or accidental trauma, infection (eg, encephalitis, tuberculosis, syphilis), or granulomas (sarcoidosis or Langerhans cell granulomatosis). Cancer immune therapy with the anti-PD-L1 monoclonal antibody avelumab has been reported to cause reversible central diabetes insipidus. Metastases to the pituitary are more likely to cause diabetes insipidus (33%) than are pituitary adenomas (1%).
The symptoms of the disease are intense thirst, especially with a craving for ice water, with the volume of ingested fluid varying from 2 L to 20 L daily, and polyuria, with large urine volumes and low urine specific gravity (usually less than 1.006 with ad libitum fluid intake). The urine is otherwise normal. Partial diabetes insipidus presents with less intense symptoms and should be suspected in patients with enuresis. Most patients with diabetes insipidus are able to maintain fluid balance by continuing to ingest large volumes of water. However, in patients without free access to water or with a damaged hypothalamic thirst center and altered thirst sensation, diabetes insipidus may present with hypernatremia and dehydration. Diabetes insipidus is aggravated by administration of high-dose corticosteroids, which increases renal free water clearance.
Diagnosis of central diabetes insipidus is a clinical one; there is no single diagnostic laboratory test. Evaluation should include a 24-hour urine collection for volume and creatinine. A urine volume of less than 2 L/24 h (in the absence of hypernatremia) rules out diabetes insipidus. The patient can be tested during ad libitum fluid intake. A random urine is tested for osmolality. Blood testing includes plasma vasopressin and serum glucose, urea nitrogen, calcium, potassium, sodium, and uric acid.