Parathryoid, Calcium & Vitamin D

Question 1

Calcium Fractions

Answer 1

• total calcium is the most common assay
• half of serum calcium is bound to albumin
• If low total calcium, must adjust for low albumin –> you’ll be ok if free/ionized calcium is normal

corrected Ca = measured Ca + (4.0 - albumin)

Question 2

Causes of Hypocalcemia

Answer 2

1. Failure to secrete PTH: requires magnesium
2. Failure to respond to PTH
3. Failure to produce 1,25 Vit D
4. Failure to respond to 1,25 Vit D: autosomal recessive Vit D receptor mutation
5. Calcium complexation or deposition

90% of cases due to low albumin or renal failure
- Main factor is decreased calcitriol, also causing decreased response

Question 3

Pseudohypoparathyroidism

Answer 3

• Failure to respond to PTH

- PTH levels are actually high

Question 4

Albright’s Hereditary Osteodystrophy

Answer 4

• autosomal dominant kidney unresponsiveness to PTH
• Hypocalcemia
• shortened 4th/5th digits
• short stature

Question 5

1-alpha-hydroxylase deficiency

Answer 5

• Failure to produce 1,25 Vitamin D
• This enzyme is necessary to add hydroxyl group to 25-Vit D
• autosomal recessive

Question 6

Hyperphosphatemia

Answer 6

• phosphate released into blood complexes with calcium, removing active free/ionized calcium, causing hypocalcemia
• often due to crush injury or tumor lysis

Question 7

Hungry bone syndrome

Answer 7

• Occurs after surgery for hyperparathyroidism

- With removal of PTH, the bones gobble up free calcium

Question 8

Clinical Features of Hypocalcemia

Answer 8

• PARESTHESIAS – tingling or numbness
• SEIZURES
• TETANY – painful tonic muscular contractions
• Carpospasms
• CARDIAC – delay in repolarization; long QT interval
• EYE – subcapsular cataract
• DERMATOLOGIC – dry skin and brittle nails
• CHVOSTEK’S SIGN – tap facial nerve, causing that side of the face to contract

TROUSSEAU’S SIGN – induce carpalspasm by inflate BP cuff 20 mm Hg above systolic BP and wait 3 minutes

Question 9

Activation of Vitamin D

- know the different sites

Answer 9

1. SKIN:
   - sunlight (UVB) converts pro-D3 to pre-D3
   - heat reaction converts pre-D3 to Vitamin D3
2. LIVER:
   - Vitamin D3 is hydroxylated to 25-Hydroxy-D3
3. Kidney:
   - 1-alpha-hydroxylase converts 25-(OH)-D3 to 1,25-(OH)-D3

Question 10

What do you measure for Vitamin D Deficiency?

Answer 10

25-Hydroxy-D3

Question 11

PTH

Answer 11

Source: CHIEF CELLS of the parathyroid

Function:

• BONE: increase bone resorption of calcium and phosphate
• KIDNEY:
  
  • DCT: increase calcium reabsorption
  • PCT: decrease phosphate reabsorption
  • stimulate production of 1,25-(OH)2D3

Regulation:
- decreased serum Ca2+ or Mg2+ increases PTH secretion

Question 12

Vitamin D

Answer 12

Function:

• GUT: increases dietary absorption of calcium and Phosphate
• BONE: increases bone resorption of Calcium and Phosphate

Question 13

Calcitonin

Answer 13

SOURCE: Parafollicular cells (C cells) of the thyroid

FUNCTION: decrease bone resorption of calcium (opposes actions of PTH)

Question 14

Effect of Acidemia or Alkalemia on fraction of free vs. bound calcium

Answer 14

Acidemia: More H+ ions that bind to binding proteins (albumin); artificially increases amount of free Calcium

Alkalemia: decreases amount of free calcium, and increases amount of bound calcium

Question 15

Parathyroid Hormone Related Peptide (PTHrP)

Answer 15

• Major product of fetal parathyroid
• has ability to facilitate calcium transfer across the placenta, and calcium entry into myometrial cell
• Is also critical for normal bone development, converting cartilage to bone
• Increased production of PTHrP is common cause of hypercalcemia in patients with malignancies

Question 16

PTH Assays

Answer 16

• PTH is rapidly cleaved to C-terminal fragment in circulation
• Hypercalcemia favors formation of the C-terminal fragment
• Intact PTH assays are the most reliable
• C-terminal fragment assays must be interpreted in light of plasma calcium concentration

Question 17

Urinary excretion of Calcium & Phosphate

Answer 17

• Virtually all patients with hypercalcemia will have normal or increased urinary calcium excretion
• patients with hypocalcemia will have low urine calcium
• Urine Ca > 400 mg/d indicates high
  risk of kidney stones

Question 18

familial hypocalciuric hypercalcemia

Answer 18

urinary calcium excretion is decreased, resulting in hypercalcemia

Question 19

ARTIFACTUAL HYPERCALCEMIA / Hemoconcentration

Answer 19

• produces an increase in protein-bound calcium; since free calcium is normal, there is no physiologic significance to this transient finding
• commonly caused by diuretics use, dehydration, drawing blood too soon after a person has been upright, or with prolonged tourniquet use

Question 20

Symptoms of Hypercalcemia

Answer 20

- Usually asymptomatic
- Neurologic symptoms predominate (loss of concentration, forgetfulness, coma if severe)
- Polydipsia, polyuria if severe
- Bone symptoms, kidney stones occur
in < 5% of cases

Question 21

Primary Hyperparathyroidism

Answer 21

- Inappropriate overproduction of PTH
- Majority of cases asymptomatic or have mild neurologic symptoms (40%)
- Kidney stones present in 5% of cases
- Bone disease less common now (usually only affects cortical bone vs. trabecular bone)
- Subperiosteal reabsorption in metacarpal, metatarsal, digits
- “Brown tumor”
- Osteitis Fibrosa Cystica (severe,
generalized bone reabsorption) - von Reclinghausen’s disease of bone

Tx: surgery recommended unless contraindications

Question 22

Hypercalcemia of Malignancy

Answer 22

- Most common cause overall
- Usually due to PTHrP production (squamous, breast, renal)
- Often severe hypophosphatemia
- Diabetes insipidus often accompanies
hypercalcemia
- PTH typically undetectable

Question 23

Secondary Hyperparathyroidism

Answer 23

- Appropriate overproduction of PTH
in response to low calcium/calcitriol
- Chronic renal failure is most common
cause
- Malabsorption, vitamin D deficiency
can also cause
- PTH tends to be much higher, bone
disease thus much more severe