VITAMIN D DEFICIENCY

VITAMIN D DEFICIENCY - Frank J. Domino, MD; Samir Malkani, MD
BASICS
This topic covers the commonly acquired vitamin D Deficiency and not type II vitamin D-resistant rickets or type I pseudo-vitamin D resistant rickets (both rare autosomal recessive disorders).
DESCRIPTION
• Vitamin D is both a hormone and a vitamin. Cholecalciferol (D3) is synthesized in the skin by exposure to ultraviolet B (UVB) radiation. Ergocalciferol (D2) and D3 are present in foods.
• D2 and D3 are hydroxylated in the liver to 25 vitamin D (calcidiol), which is the major circulating form.
• This is further hydroxylated in the kidney to the active metabolite 1,25 vitamin D (calcitriol). Any insult to this production can result in deficiency.
GENERAL PREVENTION
• Adequate exposure to sunlight and dietary sources of vitamin D (plants, fish). Many foods are fortified with D2 and D3.
• Higher intake of vitamin D recommended for ages >50.
• For age 51-70, recommended intake is 400 IU/day; for 71, 600 IU/day.
ALERT
Pediatric Considerations
The American Academy of Pediatrics recommends all breast-fed babies receive 200 I.U. of vitamin D per day.
EPIDEMIOLOGY
• Unclear in general population.
• In the community, a cohort study of asymptomatic adolescents in Boston found 24.1% were deficient, with 4.6% severely deficient. (1)
• A study of hospitalized patients in Massachusetts found 57% vitamin D deficient. (2)
• Women with history of osteoporosis or osteoporotic fracture have high prevalence of vitamin D deficiency. (3)[A]
• A cross-sectional study of patients with persistent, nonspecific pain in an urban Minneapolis primary care clinic found 93% deficient and 28% severely deficient. (4)
RISK FACTORS
• Inadequate sun exposure
• Female
• Dark skin
• Immigrant populations
• Low socioeconomic status
• Latitudes higher than 38
• Elderly
• Institutionalized
• Medications (phenobarbital, phenytoin)
Genetics
Numerous rare genetic disorders can induce hypoparathyroidism (DiGeorge syndrome)
PATHOPHYSIOLOGY
• Insufficient dietary intake of vitamin D and/or lack of UVB exposure results in low levels of vitamin D; this limits calcium absorption, causing excess parathyroid hormone (PTH) to be released.
• PTH stimulates osteoclast activity, which raises calcium and phosphorous, but results in osteomalacia.
ETIOLOGY
• Dietary deficiency
- Inadequate vitamin D intake
- Macrobiotic diet
• Inadequate sunlight exposure
- Institutionalized patients
- Hospitalized patients
- Chronic illness
- Liver or kidney disease
- Malabsorptive states
ASSOCIATED CONDITIONS
• Osteomalacia, osteoporosis
• Rickets
• Celiac disease
• Gastric bypass
• Chronic renal disease

DIAGNOSIS
SIGNS AND SYMPTOMS
• Nonspecific musculoskeletal complaints
• Weak antigravity muscles
History
• Renal disease
• Gastrointestinal (malabsorption) disorders
• Liver dysfunction
• Immigration from tropical to colder climates
Physical Exam
• Numerous neurologic signs: Numbness, proximal myopathy, paresthesias, muscle cramps, laryngospasm
• Chvostek sign: Contraction of the muscles of the eye, mouth or nose, by tapping along the facial nerve
• Trousseau phenomenon: Carpal spasms and paraesthesia produced by pressure upon nerves and vessels of the upper arm
• Tetany
• Seizures
TESTS
Lab
• 25 vitamin D (most sensitive vitamin D status)
• Vitamin D Insufficiency
- 25 D is 15-40 ng/mL
• Vitamin D deficiency
- 15 ng/mL
• PTH elevation (normal in early vitamin D deficiency)
• Low calcium and phosphorous
• Elevated alkaline phosphatase (in later disease)
Imaging
• Plain radiographs: If atypical fracture, radiographs may show osteomalacia (pseudofractures or Looser zones) in pelvis, femur, and fibula.
• Osteoporosis Screen (5)[C]
- Women 65 years with no risk factors
- Women 60 years at risk: Body weight 70 kg (best predictor); less evidence smoking, low body mass index (BMI), family history, decreased activity, alcohol, or caffeine use.
- African American women have higher bone density than Caucasians; thus, rarely screen 65
TREATMENT
GENERAL MEASURES
Diet
• Fatty fish (tuna, salmon)
• Fortified milk, cereal, and foods
Activity
Weightbearing exercise
SPECIAL THERAPY
Aggressive calcium in ICU patients with ionized calcium 3.2 mg/dL or if symptomatic (tetany, seizures, QT prolongation, bradycardia, or hypotension, or ventilated patient with decreased diaphragmatic function)
MEDICATION (DRUGS)
First Line
• Vitamin D Insufficiency
- Vitamin D 800 IU/d plus
- Elemental calcium 1,200 mg/d Or
• Ergocalciferol 50,000 IU/wk for 8 weeks plus
• Elemental calcium 1,200 mg/d
Second Line
Vitamin D deficiency
• Ergocalciferol 50,000 IU daily for 3 weeks, followed by 50,000 IU/week plus
• Elemental calcium 1,200 mg/d
• Patients with no sun exposure, malabsorption syndromes, and antiepileptic drugs may require more replacement
FOLLOW-UP
Repeat abnormal 25 vitamin D and other abnormal labs at 8 weeks.
DISPOSITION
Admission Criteria
• Symptoms of severe hypocalcemia or
• Malabsorption syndromes
Issues for Referral
Endocrinology if no response to treatment
REFERENCES
1. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med.
2. Hypovitaminosis D in medical inpatients. N Engl J Med. 1998;338:777-783.
3. QJM. 2005;98(9):667-676. Epub 2005 Jul 8.
4. Mayo Clin Proc. 2003;78(12):1463-1470. 2004;158:531-537.
5. www.ahrq.gov
ADDITIONAL READING
Undiagnosed vitamin D deficiency in the hospitalized patient: http://www.aafp.org/afp/20050115/299.html