Calcium Metabolism

Question 1

4 ways parathyroid hormone (PTH) increases serum calcium?

Answer 1

1) Increases bone resorption (activates osteoclasts).
2) Production of Active form of Vitamin D (adds 2 hydroxy groups)
3) Increased kidney reabsorption of Ca++.
4) Increased gut absorption of Ca++ (by calcitriol)

Question 2

Mnemonic for hyperparathyroidism (hyper-PTH) effects?

What significant problem isn’t included in this mnemonic?

Answer 2

Bones, groans (GI stuff), stones, and psychic moans.

There is also kidney dysfunction (increase in urinary phosphate), and increased BP

Question 3

Most common etiology of primary hyper-PTH?

Less common causes?

Answer 3

Solitary adenoma - 85%
Diffuse hyperplasia - 15%
Parathyroid carcinoma - <1% - really rare.

Question 4

What happens to phosphate in hyper-PTH?

Answer 4

More is absorbed from bone, but even more is excreted in the kidney.
Net result: decreased serum phosphate (with decreased ECF phosphate).

Question 5

2 GI effects of hyper-PTH?

Answer 5

1) Constipation, GI distress

2) Stomach ulcers, pancreatitis

Question 6

What are the “psychic moans” of hyper-PTH?

Answer 6

Can cause depression and/or psychosis, fatigue and malaise.

Question 7

Stones of hyper-PTH?

Answer 7

Kidney stones - from increased Ca++ in urine.

Question 8

What’s the term for the pattern of bone demineralization seen in hyper-PTH? What 3 bone findings define it?

Answer 8

Osteitis fibrosa cystica.

1) Generalized demineralization of bone
2) Subperiosteal bone resorption
3) Bone cysts

Question 9

What type of bone does hyper-PTH most effect? (What’s a good place to x-ray… or DXA??… that has a lot of this type of bone?)

Answer 9

Mostly affects cortical bone.

the distal radius is often looked at - femoral neck too. Not vertebrae.

Question 10

How do most patients with hyper-PTH present?

Answer 10

With high Ca++ in screening bloodwork. They’re often caught before they’re symptomatic.

Question 11

When would you do surgery on an asymptomatic patient with hyper-PTH? (there are 4 criteria)

Answer 11

When younger than 50.
Severe hypercalcemia.
Reduced creatinine clearance (impaired kidney function).
Osteoporosis.
(also want to make sure it’s not Familial Hypocalciuric Hypercalcemia)
- Only need to meet 1 of these criteria to go to surgery

Question 12

Parathyroid adenoma looks histologically like…

Answer 12

increased cellularity… making lots of PTH.

- Clustering of cells–> can lead to atrophy of the parathyroid glands

Question 13

3 causes of secondary hyper-PTH?

Answer 13

It’s all about decreased Ca++ due to…

1) Renal insufficiency.
2) Calcium malabsorption.
3) Vitamin D deficiency.

Question 14

What is tertiary hyper-PTH?

Answer 14

Starts off as secondary PTH, but then some of the parathyroid becomes autonomous -> primary PTH.

Question 15

What is Familial Hypocalciuric Hypercalcemia (FHH)? Sequelae?

Answer 15

There’s a mutation in the calcium sensor such that the set-point for PTH is shifted: PTH is secreted at a higher level of Ca++, so serum Ca++ stays higher than normal.
It’s a completely benign condition.
They have LOW URINE CALCIUM
DON”T SEND THEM TO SURGERY

Question 16

Where is the mutated Ca++ sensor in FHH? Why does this matter?

Answer 16

In both the parathyroid and the kidney.
It matters that it’s in the kidney because excess Ca++ is NOT excreted into the urine because the kidney doesn’t think Ca++ is high.
Ca++ is kept at a higher set point both at the level of PTH and resorption in the kidney.

Question 17

How do you differentiate primary hyper-PTH from FHH?

Answer 17

In primary hyper-PTH, urine Ca++ will be elevated (also causing kidney stones).
In FHH, urine Ca++ will be normal (low)

Question 18

3 types of causes of hypoparathyroidism (hypo-PTH)?

Answer 18

1) Post-surgery following total thyroidectomy
2) Infiltrative disease.
3) Congenital.

Question 19

2 infiltrative diseases that cause hypo-PTH?

Answer 19

Hemochromatosis, Wilson’s disease.

fine details…

Question 20

2 congenital cause of hypo-PTH?

Answer 20

1) DiGeorge syndrome.

2) Autosomal recessive autoimmune polyglandular syndrome Type 1.

Question 21

2 signs of hypocalcemia?

Answer 21

1) Cardiac arrhythmias.

2) Neuromuscular irritability. (paresthesias, tingling, tetany)

Question 22

2 tetany signs associated with hypocalcemia? What is each?

Answer 22

Chvostek’s sign: tapping angle of jaw cause muscles innervated by the facial nerve to twitch.
Trousseau’s sign: carpal spasm (wrist flexion in response to prolonged brachial a. occlusion)

Question 23

Tx for hypo-PTH?

Answer 23

Replace the downstream effects of PTH:
Give Ca++
Give Vitamin D.

Question 24

What is the target calcium level for a patient with hypo-PTH? Why?

Answer 24

Low normal.
You’re not replacing PTH’s effect on kidney to reabsorb Ca++, so lots will spill into urine, and you don’t want to cause kidney stones.

Question 25

How can someone give his or herself prolonged hypercalcemia accompanied by nausea, vomiting, weakness, and altered mental status?

Answer 25

Taking too much Vitamin D (>10,000 IU/d).

Question 26

Why does Vitamin D toxicity last so long?

Answer 26

Because it’s Vit D is fat soluble.

Question 27

4 etiologies of Vitamin D deficiency?

Answer 27

1) Not enough sunlight.
2) Not enough intake / absorption.
3) Defects in metabolic activation of Vit D.
4) GI disease (Celiac, Crohn’s)
(Fun fact: Lighter-pigmented skin is thought to have evolved when early humans migrated north out of Africa to latitudes with less direct sun exposure in order to better make Vit D.)

Question 28

What’s the weird rough measure for how much Vit D you make in response to UV radiation?

Answer 28

Minimum Erythema (or something) Dose (MED) = enough UV to make your skin just a little red.
1 MED -> 10,000 to 20,000 IU Vit D in 24 hours.
…and then calculate how much Vit D you made based on how much of your skin is red….
Not very useful.

Question 29

2 disease of Vit D deficiency?

Answer 29

1) Rickets in kids.

2) Osteomalacia in adult

Question 30

What is the role of Vitamin D in bone formation/health?

Answer 30

Mineralization of the osteoblasts–> lays down calcium

Question 31

Classic presentation of Rickets?

Answer 31

Kids’ legs bowed because they can’t support weight.
Metaphyseal cupping…
Fraying of distal radius and ulna.
WIDENED OSTEOID SEAMS AND IMPAIRED MINERALIZATION

Question 32

Characteristic symptoms of osteomalacia?

Answer 32

Diffuse bone pain and tenderness (in hips/pelvis)
Proximal muscle weakness.
WIDENED OSTEOID SEAMS AND IMPAIRED MINERALIZATION

Question 33

What is the parathyroid sensitive to?

Answer 33

• Low Ca2+ levels–> works to increase serum Ca2+

- High Ca2+–> will shut down production of PTH (negative feedback loop)

Question 34

Basic difference between primary and secondary hyperparathyroidism?

Answer 34

Primary: High PTH AND HIGH calcium
Secondary: LOW calcium–> High PTH (revved up to increase serum Ca2+)
- Secondary is NOT pathological (it’s the appropriate response to low Ca2+)

Question 35

How does vitamin D cause hypercalcemia?

Answer 35

It increases calcium absorption from the gut?

Question 36

How do you TX vitamin D deficiency?

Answer 36

• TX underlying disorder (if due to malabsorption)

- Correction of hypocalcemia and low vitamin D levels with vitamin D supplements (D2 and D3)