Learning objectives
- •
Signs and symptoms of hypervitaminosis D.
- •
The management of hypervitaminosis D.
- •
Diseases that increase the risk of hypovitaminosis D and hypervitaminosis D.
The case study
Reasons for seeking medical help
- •
About 3 years ago MH was diagnosed with osteoporosis as evidenced by the lowest T-score−2.5 in her upper 4 lumbar vertebrae.
- •
At that time, she was found to also have a marginally elevated serum alkaline phosphatase (bone isoenzyme) and hypovitaminosis D (25-hydroxy): 14 ng/mL. Her only complaint was easy fatigue and generalized weakness at times. Other common diseases, including psychological and psychiatric ones, had been ruled out, and her symptoms were attributed to vitamin D deficiency.
- •
She was prescribed ergocalciferol 50,000 units daily for only 3 months and was instructed to take over-the-counter vitamin D3 (cholecalciferol) 2000 units tablets once a day. She was scheduled for a follow-up clinic visit 3 months later with repeat assay of her serum vitamin D level at that time.
- •
MH, however, showed up for neither her laboratory work-up nor follow-up appointment. She did not think she needed medical care. The medical office was unable to reach her.
- •
She continued to take OTC vitamin D3, 2000 units once a day, but then increased it to 2000 units twice a day since her last clinic visit about 2 years ago. She also increased her sun exposure in addition to ultraviolet light.
- •
Her generalized muscle weakness improved, and she had bouts of “increased energy.” This was nevertheless short-lived.
- •
She now returns to the clinic, about 2 years after her initial encounter, because she was experiencing abdominal pain, polyuria, nausea, and occasional vomiting. She also developed at least three renal calculi which she passed spontaneously. In addition, she also experienced bouts of confusion.
Past medical and surgical history
- •
Natural menopause age 47 years, 1 year of HRT, then discontinued it.
- •
Essentially healthy until this present episode.
Lifestyle
- •
Sedentary lifestyle: works as a receptionist 5 days a week. She walks with her husband on Saturday mornings for about 45 min.
- •
Suspected to have lactose intolerance.
- •
History of cigarette smoking half a pack a day for about 4 years in her 20s.
- •
Caffeine intake three cups of coffee daily.
- •
Alcohol consumption, occasionally, about once a month.
- •
No excessive sodium intake.
Medication(s)
- •
Vitamin D3 2000 units bid. Frequently, at least 3 times a week, she would double the vitamin D dose when she felt tired and weak and in need of “that bout of extra energy.” She also purchased an “ultraviolet lantern” to stimulate the cutaneous production of vitamin D. She uses it daily, sometimes twice a day during weekends.
- •
Calcium carbonate tablets, on average 4 a day.
- •
Multiple vitamin and mineral supplements, purchased over the counter, 3–4 tablets a day.
Family history
- •
Unknown; she was adopted soon after birth.
Clinical examination
- •
Weight: 152 lbs., height: 63″.
- •
Clinical examination does not reveal any significant finding.
Laboratory result(s)
- •
Serum 25-OH vitamin D: 124 ng/mL.
- •
Comprehensive metabolic profile: no abnormal findings.
Multiple choice questions
- 1.
Factors that initially may have contributed to MH’s vitamin D deficiency include:
- A.
Lactose intolerance.
- B.
Limited sun exposure.
- C.
Ethnicity.
- D.
Low daily calcium and vitamin D intake.
- E.
All of the above
Correct answer: E
Comment:
Patients who are lactose intolerant and do not use alternative sources of dietary calcium and vitamin D are at risk of developing vitamin D deficiency: hypovitaminosis D. Limited sun exposure from staying indoors can also increase the risk of vitamin D deficiency. Similarly, an increase in melanin pigments in the skin, as with African Americans, can decrease the cutaneous vitamin D production from sunlight further increasing the risk of vitamin D deficiency. A decreased vitamin D level increases the risk of diabetes mellitus and insulin resistance.
- A.
- 2.
At this stage the following laboratory tests are indicated for Ms. MH:
- A.
Vitamin D (25-hydroxy).
- B.
CMP and ionized serum calcium level.
- C.
HGB A1C.
- D.
A and B.
- E.
A, B, and C.
Correct answer: E
Comment:
MH initially was prescribed 3 months of vitamin D2 (ergocalciferol) 50,000 units once a week in addition to vitamin D3 (cholecalciferol) obtained over the counter. After 3 months, she continued taking vitamin D3, 2000 units BID, and often increased the dose, especially as she felt that the vitamin D supplements increased her “level of energy.” She also increased the amount of exposure to sun and ultraviolet rays. At this point, she needs her serum vitamin D level assayed to fine-tune the treatment regimen and tailor it to her individual circumstances.
A comprehensive metabolic profile is justified to identify the underlying cause of her renal calculi and whether she has sustained any renal impairment. Ionized serum calcium assay is also relevant. As excessive vitamin D intake increases the risk of hyperglycemia and diabetes mellitus, an assay of serum HGB A1C is therefore also justified.
- A.
- 3.
Vitamin D toxicity presents with these symptoms:
- A.
Nausea/vomiting.
- B.
Muscle weakness.
- C.
Hypercalcemia.
- D.
Decreased appetite.
- E.
All of the above.
Correct answer: E
Comment:
Excessive amounts of vitamin D can increase calcium absorption causing renal calculi, polyuria, polydipsia, nausea and vomiting, muscle weakness, dehydration, and decreased appetite. MH specifically complained of muscle weakness. Other manifestations of vitamin D toxicity include confusion, apathy, and abdominal pain.
- A.
- 4.
MH’s laboratory tests reveal:
Serum vitamin D (25-hydroxy-vitamin D) hypervitaminosis D: 145 ng/mL.
Comprehensive metabolic profile: within normal limits, except for marginal hypercalcemia (serum calcium 10.5 mg/dL: normal range 8.6–10.3 mg/dL).
HGB A1C 6.5%, within normal range.
At this stage the treatment plan for Ms. MH is:
- A.
Discontinue calcium supplementation.
- B.
Discontinue vitamin D3 and any type of vitamin D supplementation, including vitamin D2.
- C.
Recheck serum vitamin D level in 3 months.
- D.
A and B.
- E.
A, B, and C.
Correct answer: E
Comment:
Vitamin D intoxication can occur with serum concentrations above 80 ng/mL. However, concentrations are much greater with symptomatic hypervitaminosis D. MH developed several renal calculi and experienced vitamin D toxicity symptoms (muscle weakness and nausea). If she continues with vitamin D supplementation, even at a lower dose, her vitamin D level will continue to rise. The best course of action is to stop her supplementation and recheck her level in 3 months.
- A.
- 5.
Additional laboratory studies include:
- A.
Serum parathyroid hormone (PTH).
- B.
Ionized serum calcium.
- C.
24-h urinary calcium.
- D.
A and B.
- E.
All of the above.
Correct answer: E
Comment:
All of the above tests are needed to monitor MH’s condition. PTH blood levels will decrease as calcium levels increase due to hypervitaminosis D. To counteract the increase in calcium, the kidneys will increase urinary calcium excretion to try maintaining homeostasis. This, however, increases the risk of renal calculi.
- A.
- 6.
If MH continues with her vitamin D supplementation, the following may occur:
- A.
Renal calculi.
- B.
Hypercalciuria.
- C.
Decreased PTH.
- D.
A and B.
- E.
All of the above.
Correct answer: E
Comment:
As vitamin D levels increase to 150 ng/mL, calcium levels tend to increase causing a decrease in PTH to compensate for the increased calcium level, as well as an increase in calcium excreted through the urine. The patient then becomes at an increased risk of developing renal calculi.
- A.
- 7.
Three months later: MH returns. Her serum vitamin D (25-hydroxy) level is now 98 ng/mL. She no longer has muscle weakness or nausea. The treatment plan should include:
- A.
No vitamin D supplementation.
- B.
Start treatment for her osteoporosis.
- C.
Start 1000 unit vitamin D3 (cholecalciferol) daily.
- D.
A and B.
- E.
B and C.
Correct answer: D
Comment:
MH now has a vitamin D level within the normal range. At this stage, therefore she does not need any supplementation. She nevertheless would benefit from a yearly vitamin D level assay to detect early mild hypervitaminosis D while she is still in the asymptomatic phase.
With a low vitamin D level, MH may experience generalized bone pain when she starts treatment for osteoporosis, so it is important to ensure that she has a normal serum vitamin D level prior to initiating treatment for osteoporosis.
- A.
- 8.
Hypervitaminosis D typically occurs from:
- A.
Increased exposure to the sun.
- B.
Diet consisting of foods with high vitamin D content.
- C.
Exogenous sources of vitamin D as over-the-counter supplements.
- D.
A and B.
- E.
A, B, and C.
Correct answer: C
Comment:
Typically, patients take mega doses of exogenous vitamin D, readily available as supplements, obtained over the counter, with no medical prescription required, and taken each day may lead to vitamin D toxicity. Whereas the body is able to regulate the amount of vitamin D absorbed from food sources, it is sometimes not able to maintain a normal vitamin D level from large doses of vitamin D intake.
- A.
- 9.
Patients at a greater risk to develop hypervitaminosis D include:
- A.
Patients with hypocalcemic disorders, such as hypoparathyroidism, osteomalacia.
- B.
Patients with lymphomas.
- C.
Patients with Williams-Beuren syndrome.
- D.
Patients with tuberculosis.
- E.
All of the above.
Correct answer: E
Comment:
Hypersensitivity to vitamin D occurs in patients with lymphomas and granuloma disorders, such as tuberculosis and giant cell polymyositis. PTH levels are suppressed in these cases. In tuberculosis, elevated serum levels of vitamin D are due to macrophages increasing extrarenal synthesis of 1, 25(OH)2D. The pathophysiology of how patients with Williams-Beuren syndrome develop hypervitaminosis D is still obscure.
- A.
- 10.
The earliest renal sign of vitamin D toxicity is:
- A.
Hypercalciuria.
- B.
Polyuria.
- C.
Dehydration.
- D.
Renal calculi.
- E.
All of the above are early signs.
Correct answer: A
Comment:
Hypercalciuria, polyuria, dehydration, and renal calculi are signs of hypervitaminosis D. Hypercalciuria occurs first. Gastrointestinal symptoms, such as nausea/vomiting, constipation, as well as neuropsychiatric symptoms can also occur. It is important to emphasize to patients the need for regular follow-ups.
- A.
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