PANCE Blueprint Endocrinology (7%)

Diabetes insipidus (ReelDx)

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Diabetes insipidus

6-year-old with polyuria, weight loss and recent seizures (view video)

Patient will present as → a 25-year-old male complaining of a unabated thirst that began three weeks ago. He is constantly drinking and goes to the bathroom around five times a night. He has lost five pounds over the last few weeks. The patient is on lithium for a bipolar disorder. His BP is 115/70. The patient’s labs are significant for serum Na of 145 mEq/L (normal: 135-145). Urine osmolality is 185 mOsm/kg, and urine specific gravity is 1.004 (normal: 1.012 to 1.030).

Diabetes insipidus (DI) is caused by a deficiency of or resistance to vasopressin (ADH), which decreases the kidneys' ability to reabsorb water, resulting in massive polyuria

  1. Central diabetes insipidus (no ADH production most common type): idiopathic, autoimmune destruction of posterior pituitary from head trauma, brain tumor, infection, sarcoid
  2. Nephrogenic DI: partial or complete insensitivity to ADH: caused by drugs (Lithium, Amphoterrible), hypercalcemia and hypokalemia affect the kidneys ability to concentrate urine, acute tubular necrosis

Serum osmolality (concentration) is high (unable to stop secretion of water into the kidneys so blood becomes more concentrated) and urine osmolality is low because it is so dilute

The water deprivation test is the simplest and most reliable method for diagnosing CDI but should be done only while the patient is under constant supervision. Serious dehydration may result

  • Normal response is progressive urine concentration
  • Diabetes insipidus results in continued production of dilute urine despite water deprivation

Desmopressin (ADH) stimulation test: differentiates nephrogenic from central DI Give ADH

  • Central DI - reduction in urine output indicating response to ADH
  • Nephrogenic DI - continued production of dilute urine (no response to ADH) because kidneys can't respond

Central diabetes insipidus: Desmopressin/DDAVP (synthetic ADH)

Nephrogenic diabetes insipidus: Sodium and protein restriction - hydrochlorothiazide, indomethacin

ADH

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Question 1
A 25-year-old woman presents with the sudden onset of increased thirst and increased urination. This began abruptly 1 week ago and has not abated since. She states that since then, she has been thirsty all the time. The only significant illness in her life has been the recent diagnosis of bipolar affective illness that was made 12 weeks ago. She started taking lithium carbonate and currently is taking 1200 mg/ day. Her serum lithium levels have been normal since the beginning. On examination, her blood pressure is 110/ 70 mm Hg. She has lost 5 pounds during the past week and looks somewhat dehydrated. What is the most likely diagnosis in this patient
A
diabetes mellitus type 1
B
central diabetes insipidus
C
nephrogenic diabetes insipidus
D
adverse drug reaction
Question 1 Explanation: 
This patient has nephrogenic diabetes insipidus. This has resulted from the lack of renal response to antidiuretic hormone (ADH); in this case, the diabetes insipidus is of the nephrogenic subtype and caused by the drug lithium carbonate.
Question 2
What is the treatment of choice in this patient?
A
discontinuation of lithium
B
substitution of carbamazepine for lithium carbonate
C
insulin
D
Glyburide
Question 2 Explanation: 
The treatment for central diabetes insipidus is desmopressin either intranasally or orally; nephrogenic diabetes insipidus is best treated by discontinuation of the offending drug (if the drug is the cause, as is the most common scenario). In the case of this patient, who was started on lithium carbonate for treatment of bipolar affective disorder, a switch to carbamazepine would be most appropriate.
Question 3
A 45-year-old female undergoes a transsphenoidal approach for a pituitary prolactinoma. Surgery proceeded without complications and the entire mass was removed. The patient’s urine output is 4 L on postoperative day 1, and labs are significant for serum Na of 145 mEq/L (normal: 135-145). Urine osmolality is 185 mOsm/kg, and urine specific gravity is 1.004 (normal: 1.012 to 1.030). Which of the following choices is the next best step?
A
Water restriction
Hint:
Water restriction can be used to distinguish central DI from primary polydipsia - however, in this situation, the clinical picture points toward central DI.
B
Loop diuretic
Hint:
Loop diuretics are not used in the treatment of DI
C
CT scan of the brain
Hint:
CT scan of the brain would likely reveal post-operative changes, but not help diagnose DI.
D
0.45% NaCl administered intravenously
Hint:
Administration of fluids would not be sufficient for treatment of DI.
E
Desmopressin
Question 3 Explanation: 
The patient’s history and lab results are consistent with post-surgical central diabetes insipidus. The most reasonable next step is the administration of desmopressin or chlorpropamide.
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