Understanding and treating vitamin D toxicity

Vitamin D is a vital prohormone (a physiologically inactive precursor of a hormone) that’s needed to maintain healthy bones and balanced calcium levels.^[]

Deficiencies in vitamin D result in hypocalcemia as well as defects in bone mineralization, and have been associated with increased risks of complications such as cancer, metabolic syndrome, autoimmune diseases, and chronic obstructive pulmonary disease.

While vitamin D deficiency is a global public health concern (rickets/osteomalacia), a related condition, hypervitaminosis D (also known as vitamin D toxicity), is also on the rise.

Defining hypervitaminosis D

Hypervitaminosis D is a serious health condition characterized by severe hypercalcemia (above-normal calcium in the blood). Vitamin D is a fat-soluble vitamin, meaning that it is stored in the body’s fatty tissues and liver and can be toxic when levels are too high. It can be classified as either exogenous (external factors) or endogenous (caused from within the body) vitamin D toxicity.

Endogenous vitamin D toxicity occurs when Individuals develop hypervitaminosis D due to excess production of 1,25 (OH)2D as a result of granulomatous disorders, lymphomas, or during idiopathic infantile hypercalcemia.

Exogenous vitamin D toxicity

While vitamin D is typically associated with sun exposure, exogenous vitamin D toxicity is not caused by excessive sun exposure, as the human body can regulate the concentration of previtamin D produced in the skin from ultraviolet radiation.

Exogenous vitamin D toxicity is diagnosed in individuals who have elevated levels of 25(OH)D, severe hypercalcemia (calcium in the blood) and hypercalciuria (calcium in the urine), and low parathyroid hormone levels.

Prevalence of vitamin D toxicity

In a 2016 article published in Human and Experimental Toxicology, researchers performed a retrospective analysis of data obtained from the National Poison Data System (NPDS) on exposures to vitamin D.^[] The study examined data from January 1, 2000 through June 30, 2014.

The average number of cases per year reported to NPDS between 2000 and 2005 was 196. This increased to 4,535 exposures per year between 2005 and 2011.

Vitamin D toxicity signs

While the symptoms associated with vitamin D toxicity vary, they are mostly related to hypercalcemia and can include the following:

• Neuropsychiatric symptoms—difficulty concentrating, confusion, depression, psychosis, apathy, and drowsiness

• Gastrointestinal symptoms—abdominal pain, vomiting, constipation, excessive thirst, peptic ulcers, and pancreatitis

• Cardiovascular symptoms—hypertension, bradycardia, ST segment elevation, and shortened QT interval

• Renal symptoms—dehydration, excessive thirst, frequent urination, renal failure, and nephrocalcinosis

A common saying among medical students in relation to vitamin D toxicity/hypercalcemia is "painful bones, renal stones, abdominal groans, and psychiatric moans." Patients may also experience hearing loss, band keratopathy (calcium deposits in the cornea), and periarticular calcinosis (calcium tumors within the joints).

Treatment options

First-line options consist of the following:

• Stopping vitamin D supplements and decreasing calcium intake

• Encouraging patients with granulomatous diseases, lymphoma, and idiopathic infantile hypercalcemia to decrease sun exposure

• Possibly recommending isotonic sodium chloride solution to restore kidney function and remedy dehydration

• Treatment with glucocorticosteroids, which can decrease plasma calcium levels. However, long-term use of glucocorticosteroids is linked to negative outcomes such as muscle weakness and secondary osteoporosis.

• Antiresorptive therapy with calcitonin or bisphosphonates (or both), which can be recommended in severe cases of hypercalcemia. These medications help reduce bone breakdown, which decreases calcium levels while also increasing calcium loss through the kidneys, thereby decreasing levels of calcium in the blood.