Diabetes insipidus (DI) is a condition that arises either due to the body’s inability to produce sufficient quantities of the hormone known as antidiuretic hormone (ADH) or the body’s inability to effectively use this hormone.
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DI is not related to either type of diabetes mellitus (DM), which are metabolic diseases with elevated blood sugar levels. As a consequence of DI, the body struggles to regulate its fluid content. It is a rare condition and is seen in about 1 in every 25,000 people. It may occur at any age, but it is most prevalent in adults.
Symptoms of DI
The key features of DI are excessive urination or polyuria, and excessive thirst, also known as polydipsia. In comparison to the average adult, who may pass anywhere up to 2.6 quarts of urine per day, an individual affected by DI may pass up to 16 quarts of urine a day.
Sleep is disturbed due to having to get up frequently during the night to urinate. In some instances, bedwetting may also occur. Owing to the large volumes of urine lost, affected individuals may easily become dehydrated, and subsequently, have alterations in alertness.
Causes of DI
Diabetes insipidus is caused by either inadequate production of ADH or malfunction of the body’s ability to use ADH. ADH is also known as vasopressin, and it is essential for regulating body fluid levels. ADH is produced in the area of the brain known as the hypothalamus and it is subsequently stored in the pituitary gland until the necessity arises for its release.
Under normal physiological conditions, ADH is released from the pituitary gland when body fluids are running low. The hormone ensures a cascade of events that prevent the kidneys from making more urine and thus further depleting the body of fluid.
With DI, there are two primary ways in which the normal series of events may be disrupted. These are cranial diabetes insipidus (CDI), and nephrogenic diabetes insipidus (NDI), which are based on where the location of the problem is.
Cranial DI
CDI arises either due to the absolute or partial deficiency of ADH. The deficiency of ADH leads to an inability of the kidneys to retain sufficient levels of water that the body needs to function properly.
As a result, the body is driven to rely on alternatives means to increase water intake, which is the activation of the thirst center that then in turn leads to increased intake. This is the reason why people with CDI constantly feel thirsty. The body is compelling them to replace the water that they are losing via urination.
CDI may occur in isolation or it may be accompanied by several other signs and symptoms due to the loss of other hormones from the hypothalamus-pituitary axis. CDI can be caused by inborn problems of the pituitary gland, a tumor, or as a consequence of an accident or injury through iatrogenic cause during surgery. In the latter case, CDI may be temporary, but sometimes it can be permanent.
Nephrogenic DI
In NDI, the problem lies within the kidneys, where they are unable to respond to ADH. As a consequence, the kidneys are unable to absorb and retain water that passes through. The symptoms of NDI are the same as those with CDI and the body relies on the same alternative means to maintain fluid homeostasis.
Inherited NDI (INDI) is due to mutations in the genes responsible for coding the ADH receptors in the kidneys. INDI may be already seen in the neonatal period. These infants fail to thrive and are often irritable with poor appetite.
In contrast, acquired NDI (ANDI) is more common than INDI and may present at any point during one’s lifetime. ANDI is usually as a consequence of pharmacotherapy with medications such as lithium, gentamicin, colchicine, loop diuretics, and other nephrotoxic drugs. In addition to medications, certain conditions like chronic renal failure and electrolyte deficiencies may also give rise to ANDI.
Diagnosis and treatment of diabetes insipidus
To diagnose DI, patients with excessive urination should have a 24-hour measurement of urine, plasma osmolality test, a water deprivation test, or a trial of desmopressin where the therapeutic response is gauged.
During the water deprivation test, a patient is deprived of any fluids for at least 6 hours and urine output is monitored to see if there is a corresponding decrease. Under normal circumstances, urine output should not only decrease, but also become more concentrated. Patients with DI will continue to pass large volumes of dilute urine.
There is no cure for DI. For mild cranial diabetes insipidus, no treatment may be required and simply drinking enough water may compensate for excessive urination. In more severe cases, a synthetic version of ADH called desmopressin may be prescribed. It acts on the kidneys just like physiological ADH does, however, its effects are longer, and it is a lot more resistant to metabolism.
Another medication that can treat DI is thiazide diuretics, which reduce the amount of urine produced by the kidneys.
Sources
Updated on 21st July 2020 by Dr. Damien Jonas Wilson
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