Diabetes insipidus: Clinical sciences

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Introduction 0:00–1:00

Diabetes insipidus, or DI for short, is a type of polyuria-polydipsia syndrome, meaning increased fluid intake and urination, specifically resulting in more than 3 liters per day of dilute urine.
The most common cause of polyuria-polydipsia syndrome is diabetes mellitus; but three other causes include diabetes insipidus, which can be central or nephrogenic; and primary polydipsia.
In central DI, the pituitary doesn’t make enough vasopressin, also called antidiuretic hormone or ADH for short, which normally increases water reabsorption in the kidneys; while with nephrogenic DI, the kidneys don’t respond to vasopressin.
Finally, in primary polydipsia, there’s increased fluid intake, which naturally suppresses vasopressin secretion. Now, if your patient presents with a chief concern suggesting diabetes insipidus, first, perform an ABCDE assessment to determine if they’re unstable or stable.

Unstable patient 1:00–2:21

If unstable, stabilize their airway, breathing, and circulation. Next, obtain IV access and put your patient on continuous vital sign monitoring, including blood pressure, heart rate, and pulse oximetry.
Finally, if needed, provide supplemental oxygen. Now, here’s a clinical pearl!
In most cases, patients with diabetes insipidus can compensate for the fluid loss through increased fluid intake. However, individuals who aren’t able to drink fluids, like those with impaired regulatory thirst mechanisms or impaired consciousness, can develop severe dehydration and hyperosmolality!
Severe dehydration can cause hypotension, renal hypoperfusion, subsequent tubular necrosis, and even shock. On the flip side, hyperosmolality leads to an osmotic shift of intracellular fluid toward the extracellular space, causing neurons in the brain to become dehydrated.
Eventually, this causes various neurologic manifestations, including irritability, seizures, and even coma. Now, let’s go back to the ABCDE assessment and take a look at stable patients.

Stable patient - H&P 2:21–3:15

In this case, obtain a focused history and physical examination. Most patients will compensate for the fluid loss through increased fluid intake, so the typical presentation will include a patient who reports symptoms associated with polyuria, such as urinary frequency, nocturia, and enuresis.
Additionally, they’ll report excessive thirst and increased fluid intake! In some individuals, history might reveal recent neurosurgery, head trauma, lithium use, or a family history of diabetes insipidus.
On the other hand, there are no signs of dehydration on the physical exam since patients compensate by increased fluid intake!
In other words, most of your patients will have normal skin turgor and moist mucous membranes! With these findings, you should suspect polyuria-polydipsia syndrome.

Suspect polyuria polydipsia syndrome 3:15–3:39

Your next step is to obtain a fingerstick glucose level to rule out diabetes mellitus. If that’s ruled out, obtain the patient’s 24-hour urine output on unrestricted fluid intake, and order labs, including urine and plasma osmolality, as well as serum sodium.
First, assess the 24-hour urine output. If it’s less than 50 milliliters per kilogram of body weight, you can rule out polyuria and consider alternative diagnoses.

Polyuria-Polydipsia Syndrome 3:39–4:27

On the other hand, if urine output is greater than 50 milliliters per kilogram, you are dealing with polyuria. Next, you should assess urine osmolality (Uosm), meaning how concentrated the urine is.
If urine osmolality is higher than 800 milliosmoles per kilogram, that suggests concentrated urine, so consider alternative diagnoses.
However, if urine osmolality is less than 800 milliosmoles per kilogram, that suggests dilute urine, so polyuria-polydipsia syndrome!
Next, assess serum sodium levels and plasma osmolality. If serum sodium is 135 millimoles per liter or less, and plasma osmolality is 280 milliosmoles per kilogram or less, you can diagnose primary polydipsia!

Primary polydipsia 4:27–5:01

Management involves restricting fluid intake and addressing the underlying cause. For example, if it’s associated with psychiatric conditions, you should consult your psychiatry team and consider appropriate therapies.
But, in most individuals, serum sodium and plasma osmolality are normal, so be sure to order the water deprivation test to determine the exact cause of polyuria-polydipsia syndrome!

Normal results 5:01–5:36

To perform this test, first, restrict the patient’s fluid intake over a prolonged period of time, typically up to 17 hours, and check the urine osmolality every 1 to 2 hours.
Normally, fluid restriction stimulates vasopressin secretion, increasing water reabsorption in the kidneys, which concentrate the urine and increase osmolality!
So, if upon water deprivation, urine osmolality increases over 800 milliosmoles per kilogram, the patient’s ability to concentrate urine is normal, so you can diagnose primary polydipsia.

Primary polydipsia 5:36–6:00

Even though this case is mild, management also relies on restricting free water intake and addressing the underlying cause of excessive fluid intake.
Finally, if the urine osmolality remains below 300 milliosmoles per kilogram, your patient’s ability to concentrate the urine is impaired, so diagnose diabetes insipidus.

Desmopresin test 6:00–6:36

In this case, proceed with the desmopressin test, which will help you determine if your patient has a vasopressin deficiency, meaning central DI; or a resistance to vasopressin, meaning nephrogenic DI.
To perform this test, give your patient a synthetic vasopressin analogue called desmopressin and evaluate the urine osmolality after 1 hour.
If urine osmolality increases by more than 50%, that's a clear indication of vasopressin deficiency and that the kidneys respond normally to vasopressin, so diagnose central diabetes insipidus.

Central DI types 6:36–8:29

For management, the first step is to rehydrate your patient with oral or IV fluids. Next, initiate therapeutic desmopressin and monitor sodium levels carefully as you titrate the dosage.
This is important because desmopressin can potentially cause hyponatremia, with dangerous complications like cerebral edema.
Once you initiate the management, don’t forget to determine the underlying cause of central diabetes insipidus. Start by checking for any recent history of neurosurgery or head trauma.
If present, the cause could be an injury to the pituitary gland. These types of injuries are often mild, making diabetes insipidus only transient, so management primarily relies on monitoring serum sodium and urine output and tapering the desmopressin as the polyuria subsides.
On the other hand, if your patient has not had any recent neurosurgery or head trauma, suspect a pituitary gland pathology or CNS tumor.
To confirm, order an imaging such as a brain MRI. If a structural cause is identified, like a pituitary or CNS tumor.
Management involves treating the underlying cause and, if needed, consulting your surgery team. Now, here’s a clinical pearl!
There’s a fourth type of polydipsia-polyuria syndrome, which is called gestational diabetes insipidus. In this type, the enzyme produced by the placenta called vasopressinase is breaking down the vasopressin from the bloodstream, causing similar manifestations of diabetes insipidus.
Now that we’re done with central diabetes insipidus, let’s move on to individuals who don’t respond to desmopressin, meaning their urine osmolality increases by only 50% or less.

Nephrogenic DI 8:29–10:27

In this case, diagnose nephrogenic diabetes insipidus, which can be caused by electrolyte imbalances, such as hypercalcemia and hypokalemia, and side effects of medications, like lithium.
Management includes oral or IV rehydration and addressing any electrolyte imbalances. Next, don’t forget to encourage a low-sodium, low-protein diet to help reduce solute excretion and lower urine output.
If your patient is on lithium, consider discontinuing the medication, or adding amiloride to reduce its uptake by the distal tubules.
Other treatments include high doses of desmopressin and thiazide diuretics, which induce mild hypovolemia and increase proximal sodium reabsorption.
Finally, you might consider NSAIDs as well, which work by blocking prostaglandin synthesis, eventually increasing AVP-independent water reabsorption.
Now a clinical pearl! Normally, the posterior pituitary gland cleaves the pre-pro-vasopressin into vasopressin and copeptin, to release them into the circulation!
Now, you could try to measure the patient’s vasopressin blood levels to differentiate central from nephrogenic diabetes insipidus, but the thing is, vasopressin is quickly removed from the plasma and is really hard to measure!
For that reason, it’s better to measure copeptin since this peptide mirrors the concentration of vasopressin! During the copeptin test, low copeptin levels usually point towards central diabetes insipidus and primary polydipsia, whereas high copeptin levels indicate nephrogenic diabetes insipidus.
Lastly, if the serum sodium level is greater than 145 millimoles per liter, and plasma osmolality is at least 300 milliosmoles per kilogram, you are dealing with diabetes insipidus.

Diabetes Insipidus 10:27–10:48

Again, you need to order the desmopressin test to determine the type of diabetes insipidus and the appropriate treatment.
Alright, as a quick recap… Polyuria-polydipsia syndrome is defined by excessive urination, more than 3 liters per day, and increased fluid intake.

Review 10:48–11:30

After ruling out diabetes mellitus, there are three main types of polyuria-polydipsia syndrome based on the underlying cause, which include primary polydipsia, central diabetes insipidus, and nephrogenic diabetes insipidus.
The work up for a patient with polyuria-polydipsia syndrome primarily relies on 24-hours urine output and labs, including urine and plasma osmolality, as well as serum sodium; and in most cases, you’ll need to order additional tests, like the water deprivation test and desmopressin challenge.
Diabetes insipidus: Clinical Sciences: Video | Osmosis