Vitamin D Toxicity
Overview
Plain-Language Overview
Vitamin D toxicity occurs when there is an excessive amount of vitamin D in the body, usually from taking high doses of supplements. This condition can lead to high levels of calcium in the blood, which may cause symptoms like nausea, vomiting, weakness, and frequent urination. In severe cases, it can result in kidney problems or calcium deposits in soft tissues. Vitamin D toxicity is rare and typically happens due to overuse of supplements rather than from diet or sun exposure. Early recognition and treatment are important to prevent serious complications.
Clinical Definition
Vitamin D toxicity, also known as hypervitaminosis D, is a clinical syndrome caused by excessive intake of vitamin D leading to elevated serum levels of 25-hydroxyvitamin D. This results in increased intestinal absorption of calcium and subsequent hypercalcemia. The condition manifests with symptoms related to hypercalcemia such as polyuria, polydipsia, nausea, vomiting, muscle weakness, and neuropsychiatric disturbances. Prolonged hypercalcemia can cause nephrocalcinosis, renal failure, and vascular or soft tissue calcification. Vitamin D toxicity is most commonly due to inappropriate supplementation rather than endogenous overproduction. Diagnosis requires correlation of clinical features with elevated serum 25-hydroxyvitamin D levels, typically above 150 ng/mL, and hypercalcemia. Management involves cessation of vitamin D intake, hydration, and in severe cases, use of corticosteroids or bisphosphonates. Understanding the pharmacokinetics of vitamin D and its metabolites is essential for recognizing and treating this potentially serious condition.
Inciting Event
- Ingestion of large doses of vitamin D supplements beyond recommended limits.
- Increased endogenous production of 1,25-dihydroxyvitamin D in granulomatous diseases.
- Accidental or intentional overdose of vitamin D.
Latency Period
- Symptoms typically develop within days to weeks after excessive vitamin D intake.
Diagnostic Delay
- Non-specific symptoms such as fatigue and nausea may be attributed to other causes.
- Lack of awareness about vitamin D toxicity among clinicians.
- Failure to inquire about supplement use during history taking.
Clinical Presentation
Signs & Symptoms
- Nausea, vomiting, and anorexia are common gastrointestinal symptoms.
- Polyuria and polydipsia result from hypercalcemia-induced nephrogenic diabetes insipidus.
- Muscle weakness and fatigue occur due to neuromuscular effects.
- Confusion and altered mental status may develop in severe cases.
- Constipation is frequently reported.
History of Present Illness
- Symptoms of hypercalcemia including nausea, vomiting, polyuria, and confusion.
- Muscle weakness and bone pain may be present.
- History of recent high-dose vitamin D supplementation.
Past Medical History
- History of granulomatous diseases such as sarcoidosis or tuberculosis.
- Chronic kidney disease affecting calcium and vitamin D metabolism.
- Previous episodes of hypercalcemia or vitamin D supplementation.
Family History
- none
Physical Exam Findings
- Patients may exhibit dehydration signs such as dry mucous membranes and decreased skin turgor.
- There can be evidence of hypertension due to hypercalcemia-induced vasoconstriction.
- Muscle weakness may be observed on neuromuscular examination.
Diagnostic Workup
Diagnostic Criteria
The diagnosis of vitamin D toxicity is based on the presence of elevated serum 25-hydroxyvitamin D levels, usually exceeding 150 ng/mL, accompanied by hypercalcemia. Clinical symptoms consistent with hypercalcemia such as nausea, vomiting, polyuria, and weakness support the diagnosis. Additional laboratory findings may include suppressed parathyroid hormone levels and hypercalciuria. A history of excessive vitamin D supplementation is often present. Imaging may reveal nephrocalcinosis or soft tissue calcifications in advanced cases.
Pathophysiology
Key Mechanisms
- Excessive vitamin D intake leads to increased intestinal absorption of calcium, causing hypercalcemia.
- Elevated serum calcium results in calcification of soft tissues and renal damage.
- High levels of vitamin D increase bone resorption by stimulating osteoclast activity.
| Involvement | Details |
|---|---|
| Organs | Kidneys regulate calcium excretion and are at risk of nephrocalcinosis in vitamin D toxicity. |
| Intestines absorb dietary calcium under the influence of vitamin D. | |
| Parathyroid glands regulate calcium homeostasis and reduce PTH secretion in response to hypercalcemia. | |
| Tissues | Bone tissue serves as the major reservoir of calcium and is affected by altered resorption. |
| Renal tissue is involved in calcium filtration and reabsorption, vulnerable to damage from hypercalcemia. | |
| Intestinal mucosa is the site of calcium absorption enhanced by vitamin D. | |
| Cells | Osteoclasts are responsible for bone resorption and release calcium into the bloodstream. |
| Renal tubular cells regulate calcium reabsorption and excretion in the kidney. | |
| Intestinal epithelial cells mediate calcium absorption influenced by vitamin D. | |
| Chemical Mediators | 1,25-dihydroxyvitamin D (calcitriol) is the active form of vitamin D that increases calcium absorption in the gut. |
| Parathyroid hormone (PTH) regulates calcium homeostasis and is suppressed in vitamin D toxicity. | |
| Calcitonin lowers serum calcium by inhibiting osteoclast activity. |
Treatment
Pharmacological Treatments
Hydration with intravenous fluids
- Mechanism: Dilutes serum calcium and promotes renal calcium excretion
- Side effects: Fluid overload, electrolyte imbalance
Loop diuretics (e.g., furosemide)
- Mechanism: Increases renal calcium excretion by inhibiting sodium reabsorption in the thick ascending limb of the loop of Henle
- Side effects: Hypokalemia, dehydration, ototoxicity
Bisphosphonates (e.g., pamidronate)
- Mechanism: Inhibits osteoclast-mediated bone resorption, lowering serum calcium
- Side effects: Hypocalcemia, osteonecrosis of the jaw, renal toxicity
Corticosteroids
- Mechanism: Decrease intestinal calcium absorption and reduce vitamin D activation
- Side effects: Immunosuppression, hyperglycemia, osteoporosis
Non-pharmacological Treatments
- Discontinuation of all vitamin D supplements and calcium intake.
- Avoidance of excessive sunlight exposure to reduce endogenous vitamin D synthesis.
- Monitoring and management of hydration status to prevent kidney injury.
Prevention
Pharmacological Prevention
- Avoid excessive use of vitamin D supplements beyond recommended doses.
- Monitor serum calcium and vitamin D levels during supplementation.
Non-pharmacological Prevention
- Limit sun exposure to prevent endogenous vitamin D overproduction in susceptible individuals.
- Educate patients on appropriate dietary intake of vitamin D-rich foods.
- Regular monitoring of at-risk patients to detect early signs of toxicity.
Outcome & Complications
Complications
- Acute kidney injury from hypercalcemia and volume depletion.
- Nephrocalcinosis and kidney stone formation.
- Cardiac arrhythmias due to electrolyte disturbances.
- Pancreatitis secondary to hypercalcemia.
| Short-term Sequelae | Long-term Sequelae |
|---|---|
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Differential Diagnoses
Vitamin D Toxicity versus Milk-Alkali Syndrome
| Vitamin D Toxicity | Milk-Alkali Syndrome |
|---|---|
| Hypercalcemia due to excessive vitamin D intake | History of excessive calcium and alkali ingestion |
| Metabolic alkalosis may be absent or less prominent | Hypercalcemia with metabolic alkalosis and renal impairment |
| Elevated 25-hydroxyvitamin D levels | Low or suppressed parathyroid hormone (PTH) |
Vitamin D Toxicity versus Primary Hyperparathyroidism
| Vitamin D Toxicity | Primary Hyperparathyroidism |
|---|---|
| Suppressed parathyroid hormone (PTH) due to feedback inhibition | Elevated parathyroid hormone (PTH) levels |
| Hypercalcemia with hyperphosphatemia or normal phosphate | Hypercalcemia with hypophosphatemia |
| Elevated 25-hydroxyvitamin D levels | Bone resorption and subperiosteal erosions on imaging |
Vitamin D Toxicity versus Sarcoidosis
| Vitamin D Toxicity | Sarcoidosis |
|---|---|
| Elevated 25-hydroxyvitamin D from exogenous intake | Elevated 1,25-dihydroxyvitamin D due to macrophage production |
| Absence of granulomatous inflammation on biopsy | Noncaseating granulomas on biopsy |
| Normal or mildly elevated ACE levels | Elevated angiotensin-converting enzyme (ACE) levels |