SG 6.2: Cases of Calcium and Phosphate Disorders

Question 1

57 year old male presents to your clinic for a routine check-up

he has been on lisinopril and metoprolol which have controlled his blood pressure well

you ordered a routine blood test which showed:
Calcium = 11.2 mg/dl [8.5-10.0]
Creatinine = 1.0 mg/dL [0.5-1.5]

a week later,
Calcium = 11.1 mg/dL [8.5-10.0]
Phosphorus = 2.2 mg/dL [2.5-4.5]

Answer 1

1. associated symptoms
2. family history
3. do you have any bone pain
4. kidney stones
5. PTH levels
6. recent bone fractures?

Question 2

57 year old male presents to your clinic for a routine check-up

he has been on lisinopril and metoprolol which have controlled his blood pressure well

you ordered a routine blood test which showed:
Calcium = 11.2 mg/dl [8.5-10.0]
Creatinine = 1.0 mg/dL [0.5-1.5]

a week later,
Calcium = 11.1 mg/dL [8.5-10.0]
Phosphorus = 2.2 mg/dL [2.5-4.5]

History of nephrolithiasis about 10 years ago, spontaneously passed
No history of fragility fracture, height loss or back pain
No changes in mood, memory, muscle strength, constipation, increasing thirst, or urination
No chest pain, palpitation, irregular heart rhythm or SOB
Otherwise asymptomatic
No family history of hypercalcemia, MEN, or metabolic bone disorders
P/E: largely unremarkable including neck exam with no palpable mass

what test should you order first? what is the differential diagnosis?

Answer 2

PTH

you want to see if it’s PTH dependent or independent

then 24 hr urinary calcium

Question 3

if you have an elevated PTH level, what condition does the patient have?

Answer 3

you don’t know yet!

you have to do some more testing

Question 4

if a patient has an elevated PTH level, what is your next best step?

Answer 4

order a 24 hr urinary calcium

this way you can differentiate between primary hyperparathyroidism and

familial hypocalciuric hypercalcemia

Question 5

what is primary hyperparathyroidism?

Answer 5

primary abnormality of the parathyroid leads to inappropriate secretion of PTH

there is excessive renal Ca reabsorption, phosphaturia, 1,25(OH)D synthesis and bone resorption

if untreated there are clinical consequences so a parathyroidectomy is often needed

Question 6

what is familial hypocalciuric hypercalcemia?

Answer 6

an AD disorder of mutated CaSR leading to complete or partial loss of function of the CaSR

this results in hypercalcemia at birth but most patients are asymptomatic so end organ damage doesn’t usually happen

parathyroidectomy is contraindicated!!

Question 7

what is the UCCR? what is it used for?

Answer 7

UCCR = 24hr urinare calcium x serum creatinine/serum calcium x 24 hr urine creatinine

if it’s over 0.02 then it’s 90% chance it’s primary hyperparathyroidism

Question 8

how would you console a patient with a new diagnosis of primary hyperparathyroidism?

Answer 8

further tests are needed in order to evaluate its effects especially on bones and kidneys

if they’re super damaged then maybe you’d consider parathyroidectomy but otherwise probably start calcimimetric agents

Question 9

if a patient with primary parahyperhtyroidism has a history of nephrolithiasis and T-score of -2.5 in the 1/3 distal radius what is the recommended treatment?

Answer 9

-2.5 is indicative of severe bone mineral density loss

he meets the criteria for parathyroidectomy

Question 10

how do you know if a parathyroidectomy is successful?

Answer 10

measure PTH before and after removal and it should drop 90% or back into the normal range

Question 11

how do you monitor an asymptomatic primary hyperparathyroidism that doesn’t undergo treatment?

Answer 11

x-ray every 1-2 years of the spine if there is height loss or back gain

annual GFR and serum creation

Question 12

55 year old female presents with upper and lower extremity numbness and clumsiness due to spine stenosis at the C3-4 level caused by disc herniation

admitted for surgical decompression

pre-op blood work-up showed phosphate 1.6 mg/dL (2.5-4.5)

generalized weakness, pain in the hips and legs for years, history of delayed walking as a child, BW: 43 kg, Ht: 155 cm, bowed legs, denture in her late 20’s

what additional tests would you like to order?

Answer 12

1. PTH
2. FGF23 levels

3 vitamin D

4. alkaline phosphatase
5. urine calcium/phosphate/creatinine

Question 13

what are the differential diagnoses for chronic hypophosphatemia?

Answer 13

1. vitamin d deficiency

2. x-linked hypophosphatemic rickets

Question 14

what are the causes of chronic hypophosphatemia?

Answer 14

1. inadequate intake
2. medications: insoluble aluminum or magnesium phosphate salts, antacid, niacin or diuretics
3. steatorrhea and chronic diarrhea
4. hyperparathyroidism
5. vitamin D deficiency or resistance
6. primary renal phosphate ewasting
7. Fanconi syndrome
8. osmotic diuresis like uncontrolled DM

Question 15

what are the causes of chronic hypophosphatemia?

Answer 15

1. inadequate intake
2. medications: insoluble aluminum or magnesium phosphate salts, antacid, niacin or diuretics
3. steatorrhea and chronic diarrhea
4. hyperparathyroidism
5. vitamin D deficiency or resistance
6. primary renal phosphate ewasting
7. Fanconi syndrome
8. osmotic diuresis like uncontrolled DM

Question 16

what genetic defect is responsible for x-linked hypophosphatemia?

Answer 16

inactiation mutation in PHEX leading to excess FGF23 levels

Question 17

how do you figure out what the cause is of hypophosphatemia?

Answer 17

1. figure out if it’s renal or non-renal cause by doing a 24 hr urine phosphate collection to see what the threshold of renal phosphate absorption is

if it’s renal, you need to check FGF23 levels to see if it’s FGF23 mediated or not

if it’s non-renal then check to see if there is impaired intake or GI absorption of phosphate or transcellualr shifts

Question 18

how do you manage x-linked hypophosphated?

Answer 18

phosphate and calitirol therapy

all children with XLH require therapy and surgical correction for LE deformities

adults with XLH with stress fractures and bone pain need therapy too

can use neutralizing antibodies again FGF23 too to help