Endo-CalciumVitD

Question 1

Describe the vitamin D pathway

Answer 1

Regardless of the method of ingestion, vitamin D3 and D2 are both inactive forms that must be hydroxylated twice before becoming active. The first occurs in the liver and converts vitamin D to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. The second occurs primarily in the kidney and forms the physiologically active 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol

Question 2

What does vitamin D act on to increase calcium secretion?

Answer 2

Active vitamin D acts on three organ systems to achieve and maintain normal serum calcium: bone, intestine, and kidney. With adequate vitamin D, bone resorption is increased, intestinal uptake of dietary calcium is increased, and excretion of calcium through the kidney is decreased. PTH is secreted to increase the calcium in the blood in response to even the slightest degree of hypocalcemia; it acts on the kidney to increase production of active vitamin D and promote calcium reabsorption in the distal convoluted tubule and loop of Henle, and increased resorption in bones, thereby increasing release of calcium into the blood

Question 3

What are the symptoms of hypercalcemia?

Answer 3

Classic symptoms of hypercalcemia are polyuria, polydipsia, anorexia, nausea, abdominal pain, constipation, and mental status changes; as serum calcium levels increase and/or the rate of change increases, symptoms become more severe, with profound mental status changes, obtundation, and acute kidney injury.

Question 4

What is the best test for vitamin D deficiency?

Answer 4

25-Hydroxyvitamin D has a relatively long half-life of several weeks, is the best indicator of whole body vitamin D status, and is the recommended test for vitamin D deficiency.

Question 5

If high calcium is noted… then what?

Answer 5

1. Recheck calcium, if still high..

2. Determine if PTH dependent or independent, measure serum calcium and PTH

Question 6

What is the most common cause of PTH mediated hypercalcemia?

Answer 6

Elevated serum calcium level, with an inappropriately normal or elevated intact PTH level

• Due to single parathyroid adenoma (most common)
• multigland hyperplasia due to ESRD or MEN syndromes
• parathyroid gland carcinoma

Question 7

Once primary hyperparathyroidism is diagnosed, then what do you do?

Answer 7

Measure:

• serum phosphorus
• 24-hour urine calcium
• serum 25-hydroxyvitamin D levels
• serum phosphorous levels will usually be low, often normal or elevated urine calcium levels
• elevated 1, 25-vitamin D levels

Question 8

What is the treatment for primary hyperparathyroidism?

Answer 8

SURGICAL INTERVENTION IN PTS WHO:

• Cr >1 or low creatinine clearance
• T-score on DEXA of less than -2.5
• Age 50 or younger

Question 9

In patients who are not good surgical candidates, how is primary hyperparathyroidism managed?

Answer 9

In patients who do not meet the criteria for surgery, surveillance is recommended. Patients should have annual measurement of serum calcium and creatinine levels. A three-site dual-energy x-ray absorptiometry (DEXA) scan should be performed every 1 to 2 years to evaluate bone mineral density of the lumbar spine, hip, and distal radius. The frequency of DEXA scanning should increase to yearly when any treatment has been initiated for bone health or other medications have been added that may affect bone health (antiandrogen, antiestrogen, antiseizure medications, or glucocorticoids).

Question 10

How do you manage someone with asymptomatic hyperparathyroidism?

Answer 10

• replete vitamin D for low levels

- Adequate physical activity to prevent bone resorption and adequate hydration to prevent kidney damage are imperative.

Question 11

Describe how tertiary hyperparathyroidism happens?

Answer 11

Tertiary hyperparathyroidism is the result of the prolonged PTH stimulation needed to maintain normocalcemia resulting from decreased 1,25-dihydroxyvitamin D levels from kidney impairment.

This prolonged stimulation results in increased calcium levels and severe hyperparathyroid hyperplasia and elevated PTH levels that do not respond to phosphate binders and calcitriol therapy. Severe bone loss and other symptoms make surgical resection the treatment of choice.

Question 12

What is normocalcemic primary hyperparathyroidism?

Answer 12

Normocalcemic primary hyperparathyroidism is defined as increased PTH levels in the absence of elevated calcium levels.

This is a diagnosis of exclusion used in patients being evaluated for low bone density in which all secondary causes have been ruled out, including vitamin D deficiency. Approximately 20% of these patients will develop hypercalcemia within 3 years, so they should be monitored closely.

Question 13

What medications cause hypercalcemia?

Answer 13

Thiazide diuretics decrease the excretion of calcium by the kidney and may result in increased serum calcium levels. Primary hyperparathyroidism, however, should also be considered if the patient remains hypercalcemic despite the discontinuation of the thiazide diuretic. In these patients, the thiazide may have been masking the PTH-mediated hypercalcemia.

Lithium decreases the parathyroid glands’ sensitivity to calcium and may also reduce urine calcium excretion.

Question 14

What are the two mechanisms of hypercalemia of malignancy?

Answer 14

There are two mechanisms of hypercalcemia of malignancy: local osteolytic and humoral.

(1) local osteolytic-lytic bone metastases are present, hypercalcemia is the result of increased mobilization of calcium from the bone
(2) humoral- less common and occurs when the tumor itself produces parathyroid-related protein (PTHrP) that binds to and activates the parathyroid receptor, raising serum calcium levels. Squamous cell carcinomas, breast cancers, and renal cell carcinomas are the tumors most commonly associated with hypercalcemia of malignancy. In multiple myeloma, the hypercalcemia is caused by the release of factors that stimulate osteoclast activity

Question 15

Labwise, how can you tell if something is non parathyroid hormone-mediated hypercalcemia?

Answer 15

In contrast to parathyroid hormone-mediated hypercalcemia, nonparathyroid hormone-mediated hypercalcemia is associated with very low parathyroid hormone levels, typically less than 10 to 15 pg/dL (10-15 ng/L).

Question 16

What is the acute treatment for hypercalcemia?

Answer 16

The acute treatment of hypercalcemia focuses on decreasing the serum calcium level by increasing calcium excretion with vigorous volume replacement, decreasing bone resorption with bisphosphonates.

Question 17

What are the symptoms of hypocalcemia?

Answer 17

symptoms may develop, including paresthesias (numbness/tingling around the mouth, tingling in fingers and toes), muscle cramping (Trousseau and Chvostek signs), decreased muscle strength, electrocardiogram changes (prolonged QT interval), tetany, and seizures.

Question 18

If you note hypocalcemia what do you check?

Answer 18

ionized calcium

then PTH… if parathyroid is responding properly and low calcium is real then PTH will be low to elevate calcium levels

Question 19

What is the most common cause of hypocalcemia?

Answer 19

The most common cause of hypocalcemia is hypoparathyroidism, which is most often due to trauma during surgery to the neck.

Question 20

What are some other causes of hypocalcemia not involving the parathyroid?

Answer 20

Other, less common causes of hypocalcemia include poor calcium intake, activating mutations in the CASR gene, PTH resistance, increased phosphate binding in vascular space (rhabdomyolysis or tumor lysis syndrome), increased citrate chelation with large volume blood transfusions, sepsis, vitamin D deficiency, and hypomagnesemia. Low levels of magnesium (due to alcohol abuse or malnutrition) activate G-proteins that stimulate calcium-sensing receptors and decrease PTH secretion.

Question 21

How do you treat hypocalcemia from hypoparathyroidism?

Answer 21

If hypoparathyroidism is the cause of hypocalcemia, correction of any coexisting hypomagnesemia to serum magnesium 2 mg/dL (0.8 mmol/L) or higher is necessary.

Question 22

How is osteopenia versus osteoporosis diagnosed?

Answer 22

The diagnosis of osteopenia is based on BMD testing. Osteoporosis, however, can be diagnosed by BMD testing or clinically in the patient with history of fragility fracture, hip fracture, or vertebral compression fracture.

Question 23

What does a DEXA do?

Answer 23

DEXA assesses the density of the vertebral and hip bones compared with healthy young-adult sex-matched reference values.

Question 24

What is the FRAX score? What does it help you decide?

Answer 24

In 2008, the World Health Organization (WHO) created the Fracture Risk Assessment Tool (FRAX) calculator that further defines the 10-year fracture risk for patients with osteopenia, defined as a T-score between −1.0 to −2.5 on DEXA. The FRAX score notes the probability of major osteoporotic fracture and hip fracture in the next 10 years. If the risk of major osteoporotic fracture is greater than or equal to 20% or the risk of hip fracture is greater than or equal to 3%, the patient’s benefit from therapy exceeds the risk, and treatment should be offered.

Question 25

What are the six types of therapy approved by the FDA for treatment of postmenopausal osteoporosis?

Answer 25

Currently there are six categories of pharmacologic agents that are FDA approved for the treatment of postmenopausal osteoporosis. These medications are bisphosphonates, calcitonin, estrogens, estrogen agonists, parathyroid hormone, and the receptor activator of nuclear factor κB (RANK) ligand inhibitor family.

Question 26

When is osteoporosis prevention therapy given?

Answer 26

Prevention therapy may be used in patients with osteopenia who do not meet FRAX standards for therapy but have multiple risk factors such as high-risk medications (glucocorticoids or antiestrogen, antiandrogen, or antiseizure medications) in combination with a strong family history of osteoporosis.

Question 27

How should women be treated for osteoporosis?

Answer 27

According to updated guidelines from the American College of Physicians (ACP), women with osteoporosis should be given alendronate, risedronate, zoledronic acid, or denosumab for 5 years to reduce the risk for hip and vertebral fractures. Pharmacologic treatment with bisphosphonates may also be used to reduce the risk for vertebral fracture in men who have clinically recognized osteoporosis.

Question 28

How do bisphosphonates work?

Answer 28

They inhibit osteoclast activity

Question 29

How often are the following bisphosphonates given?

Zoledronic acid
Alendronate
Ibandronate
Denosumab

Answer 29

Zoledronic acid-1x per year
Alendronate-daily or weekly
Ibandronate-monthly or every 3 months
Denosumab-every 6 months

Question 30

When can calcitonin be used?

Answer 30

Calcitonin is FDA approved for the treatment of osteoporosis in women who are 5 or more years postmenopausal.

Question 31

When is teraperatide used for osteoporosis?

Answer 31

Teriparatide (recombinant human PTH [1-34]) has been FDA approved for the treatment of osteoporosis in postmenopausal women and men who are at high risk for fracture. “High risk” is defined as patients with a T-score of -3.0 or less or patients who have either had a fracture or decreased BMD while on bisphosphonate therapy. It is also approved for men and women at high risk of fracture due to long-time glucocorticoid use. Teriparatide has bone-building properties in addition to the antiresorptive properties of the other agents. It is the only bone-building treatment option for osteoporosis.

Question 32

Who gets Denosumab?

Answer 32

Denosumab is a receptor activator of nuclear factor κB (RANK) ligand inhibitors that is FDA approved for the treatment of osteoporosis in postmenopausal women who are at high risk of fracture. It is an antiresorptive agent, like the bisphosphonates with much the same effect and outcomes. It is also approved for treatment of osteoporosis in men and those undergoing treatment of certain cancers, such as prostate cancer, who are at high risk for fractures. Denosumab is given by subcutaneous injection (60 mg every 6 months).

Question 33

What is the guideline/consensus for Vitamin D?

Answer 33

A 25-hydroxyvitamin D level between 30 and 40 ng/mL (75-100 nmol/L) is deemed sufficient for bone health; most expert groups recommend screening all groups at least once for evidence of deficiency since U.S. incidence is 30% to 60% of the population, however, it should not be a serial, recurring screening test.

Question 34

What is the most common clinical manifestation of Paget Disease?

Answer 34

The most common clinical manifestation is asymptomatic elevated serum alkaline phosphatase levels; only 30% of patients have symptoms at diagnosis.

the dysfunctional bone structure creates expansion in the bone leading to pain, swelling, and warmth. Bones of the axial skeleton are most frequently affected, namely the pelvis (70%), femur (55%), lumbar spine (53%), skull (42%), and tibia (30%). As a result, patients tend to have headache, sensorineural hearing loss, and bowing of the long bones

Question 35

Who should the diagnosis of Paget disease be suspected in? What is the diagnostic workup?

Answer 35

1. elevated alk phos
2. bone scan
3. plain film

The diagnosis of Paget disease should be suspected in asymptomatic patients with an isolated elevation of alkaline phosphatase without evidence of liver disease.

In these patients the most sensitive test is a nuclear bone scan which will detect areas of increased metabolic activity.

Plain films of these areas should be obtained to identify pathognomonic pagetic lesions such as focal osteolysis with coarsening of the trabecular pattern and cortical thickening. In symptomatic patients with bone pain, plain films of painful areas may be the initial imaging test, although many experts recommend a baseline bone scan once the diagnosis is confirmed prior to initiating treatment.

Question 36

What is the treatment for Paget Disease? What is the indication for treatment?

Answer 36

The main therapies for Paget disease of bone are the nitrogen-containing bisphosphonate medications (alendronate, pamidronate, risedronate, and zoledronic acid).

The main indications for antiresorptive therapy are (1) pain caused by the increased metabolic activity; (2) planned surgery at site of pagetic bone disease, and (3) hypercalcemia due to multiple affected sites.

• PAIN
• SURGERY
• HYPERCALCEMIA