Diabetes insipidus and SIADH: Pathology review

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Diabetes insipidus and SIADH: Pathology review

Endocrine system


Diabetes insipidus and SIADH: Pathology review

USMLE® Step 1 questions

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A 30 year-old woman comes to her primary care physician because of muscle cramps, nausea, and fatigue. The patient endorses a history of depression and seizure disorder, both of which are currently managed with medications. Family history is notable for Addison disease in her maternal uncle. Temperature is 36.9°C (98.4°F), pulse is 75/min, respirations are 14/min and blood pressure is 115/80 mmHg. Cardiac, pulmonary, and abdominal examinations are noncontributory. Additional laboratory results are as follows:  
Laboratory value  Result 
Sodium   122 mEq/L 
 Potassium   3.7 mEq/L 
 Creatinine  0.9 mg/dL 
 Glucose  102 mg/dL 
 Serum osmolality   240 mOsm/kg 
 Urine osmolality  445 mOsm/kg 

Which of the following is the most likely explanation of the patient’s symptoms?


Okay, so two people were admitted to the Endocrinology ward. One of them is 35 year old Imre, who came in with intense polyuria and polydipsia. Imre was dehydrated and presented with dry mouth, headache, dry skin and dizziness. Several tests were done and results showed increased serum osmolality and further on, a desmopressin test was done. During the test, an ADH analogue was administered and urine osmolality increased. The other person is 45 year old Sienna who came in to do some routine tests because she started taking cyclophosphamide and wanted to make sure that there are no complications. Her lab results showed hyponatremia, decreased blood osmolality, and her urine osmolality was higher than serum osmolality.

Now, both individuals are unable to maintain normal osmolality. But to understand this we need to go over a bit of physiology first. In the brain, specifically in the hypothalamus, there are osmoreceptors which can sense the osmolality of the blood, or how concentrated it is. Osmolality is the concentration of dissolved particles in the blood plasma, or the liquid portion of blood. There are a number of dissolved particles in the blood plasma, but the major ones are glucose, sodium, and blood urea nitrogen, and a normal osmolality is between 285 and 295 milliOsmoles per kilogram.

Now, during periods of dehydration there is an increase in concentration of these particles in the blood and osmolality increases. The osmoreceptors in the hypothalamus sense the change in osmolality and this triggers the sensation of thirst. The water that we drink gets absorbed and dilutes the blood, bringing the osmolality back to normal.

In addition to osmoreceptors, the hypothalamus also contains the supraoptic and paraventricular nuclei that produce antidiuretic hormone, or ADH, which is then sent to the posterior pituitary for storage. ADH is also called vasopressin because it causes smooth muscle around the blood vessels to contract, which increases resistance and raises blood pressure.


  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "undefined" Reviews in Endocrine and Metabolic Disorders (2003)
  4. "Treatment of Lithium-Induced Diabetes Insipidus with Amiloride" Pharmacotherapy (2003)
  5. "Paraneoplastic Syndromes: An Approach to Diagnosis and Treatment" Mayo Clinic Proceedings (2010)
  6. "Syndrome of Inappropriate Antidiuretic Hormone Secretion Induced by a Single Dose of Oral Cyclophosphamide" Annals of Pharmacotherapy (2012)

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