What are the clinical manifestations of hypervitaminosis D?

Clinical Manifestations of Hypervitaminosis D

Hypervitaminosis D manifests primarily through hypercalcemia-related symptoms, including fatigue, weakness, nausea, vomiting, altered mental status, polyuria, polydipsia, and constipation, typically occurring when 25(OH)D levels exceed 150 ng/mL. 1

Generalized Symptoms

• Fatigue and weakness are early manifestations resulting from elevated calcium levels impairing cellular function 1
• Confusion, apathy, and lethargy develop as hypercalcemia progresses 2
• Anorexia and dehydration commonly accompany the clinical presentation 3

Gastrointestinal Manifestations

• Nausea, vomiting, and constipation are among the most frequently noted symptoms and worsen as hypercalcemia advances 1, 2
• Recurrent vomiting and abdominal pain occur with moderate to severe hypercalcemia 1, 2

Neurological Manifestations

• Altered mental status, irritability, confusion, and encephalopathy emerge with progressive hypercalcemia 1
• Slurred speech and unstable gait may develop 4
• In severe cases, coma can occur 1
• Hypotonia has been documented, particularly in pediatric cases 3

Renal and Endocrine Manifestations

• Polyuria and polydipsia result from hypercalcemia-induced nephrogenic diabetes insipidus 1, 2
• Renal injury and kidney stones may occur with vitamin D toxicity 1
• Acute kidney injury can develop secondary to severe hypercalcemia 4
• Nephrocalcinosis may result from chronic vitamin D administration 3

Cardiovascular Effects

• Vascular (arterial) calcification can occur as a silent complication mediated by osteogenic pathways activated by excess vitamin D 1
• Bradycardia and hypotension may develop when serum calcium exceeds approximately 14 mg/dL 1
• Short QTc interval on EKG is a characteristic finding 3

Biochemical Thresholds and Laboratory Findings

• Toxicity typically occurs at 25(OH)D levels >150 ng/mL (>375 nmol/L), with acute toxicity associated with levels >200 ng/mL 1, 2
• The upper safety limit for serum 25(OH)D is 100 ng/mL, above which toxicity risk increases substantially 1
• Suppressed parathyroid hormone is a typical laboratory finding in vitamin D toxicity 1
• Hypercalcemia in generally healthy adults has been observed only if daily intake was >100,000 IU or if the 25(OH)D level exceeded 100 ng/mL 1

Important Clinical Pitfalls

• Vitamin D toxicity may occur without overt hypercalcemia because tissues expressing 25-hydroxylase can be adversely affected directly; therefore, normal calcium levels do not exclude toxicity and serum 25(OH)D should be measured when toxicity is suspected 1
• A highly variable individual response exists—most subjects with hypercalcemia present at serum concentrations of 25(OH)D <375 nmol/L, demonstrating substantial inter-individual differences in vitamin D metabolism 5, 1
• Hypervitaminosis D is related to long-term effects of vitamin D storage in adipose tissue, which can cause persistent symptomatic hypercalcemia even after discontinuation 6

High-Risk Populations Requiring Vigilance

• Patients with chronic kidney disease are at increased risk due to impaired calcium and phosphorus regulation and require monitoring of serum calcium and phosphorus at least every 3 months during supplementation 1
• Patients with sarcoidosis develop hypercalcemia in approximately 6% of cases due to unregulated extra-renal production of active 1,25-dihydroxyvitamin D by activated macrophages 7, 1
• Elderly individuals are especially vulnerable due to age-related decline in renal function, polypharmacy, and altered calcium balance 1
• Immobilized patients require dose reduction of active vitamin D formulations to prevent hypercalciuria and hypercalcemia 1