PTH, Minerals, Vit D Flashcards
Pt has c/o mild fatigue and an elevated serum Ca of 11.5. What is the most likely cause of this patient’s hypercalcemia? Would you order any other lab tests?
Hyperparathyrdoidism?
PTH
PO4
A PTH of 165 is?
HIGH!
normal 15-75
A PO4 of 2.8 is?
low
normal 2.5-4.5
What is the MCC of hypercalcemia in an outpatient setting?
primary hyperparathyroidism
What are the top three causes of primary elevation of PTH?
– 85% benign parathyroid neoplasm or adenoma – 10% parathyroid hyperplasia (3% MEN)
– 2% parathyroid carcinoma
**Usually doesn’t cause serum Ca >12 mg
What percentage of patient’s with primary hyperparathyroidism have bones, stones, groans and moans?
<20%! Most people are asymptomatic
Usually in F in pts >45 yrs, otherwise similar sex diffs
In addition to PTH and PO4 what other lab tests hsould you order?
urine Ca (24 hr preferred)
How do you evaluate hypercalcemia?
Total Ca >10.5 or ionized Ca >5.6 > causative diseases vs meds > measure intact PTH level > normal/high > 24 hr urine Ca level
If 24 hr urine Ca is low….
familial hypocalciuric hypercalcemia
If 24 hr urine Ca is normal/high…
primary/tertiary hyperparathyroidism
Describe Ca equilibria in blood
High pH: Ca is bound to PROTEIN (albumin, globulins) 40-45%
Lower pH: Free (ionized)
Complexed: PO4, HCO3, Lactate (5-10%)
*All are pH dependent
What happens to free Ca in alkalemia?
HIGHER pH –> free Ca decreases, increase in Pr-bound Ca
What happens to free Ca in acidemia?
LOWER pH –> free Ca increases, Pr-bound Ca decreases
For each .1 change in pH, free Ca changes by ….
Does total Ca change?
5%
NO!
What is the major clinical utility of ionized Ca?
- Ensure maintenance of hemodyanmic fxn
- monitor pts in critical care
- higher mortality in septi pts with hypocalcemia
- neonates
- pts w/ pancreatitis/renal disease - diagnose/treat hypercalcemic/hypocalcemic conditions
What reflects TRUE Ca status, is unaffected by protein concentration and requies stringent collection/handling because its pH sensitive?
Free (ionized Ca)
What reflects (free + protein-bound + anion bound), depends on protein concentration and is not affected by pH?
Total Ca
What formula is often use to correct Ca to account for protein?
Corrected Ca (mg/dL) = Measured Total Ca (mg/dL) + 0.8*[4-Albumin (g/dL)] • Correction fails to accurately predict calcium status in individual patients
How do you correct iCa for pH changes?
Corrected iCa = Measured iCa [1-0.53(7.4-measured pH)]
- Limited range of correction (pH 7.2-7.6)
- Assumptions: patient has pH of 7.4, no variation in albumin, no additional iCa binding proteins or anions
- Preferable to avoid pre-analytical issues entirely
When should iCa be tested?
total Ca is <8 or >10.2
How can parathyroidectomies be guided by serum PTH concentrations?
• Decrease in PTH of > 50% 10 minutes post-resection signals success in removing the abnormally secreting parathyroid tissue
• Rapid turnaround time is essential
– Shorter incubation
– Compromised sensitivity
47 year old female
• 5’4, 140 lbs
• BP: 110/90
• 2-week history of fatigue and midback pain (6 out of 10)
• Described pain as aching, worse in the morning and aggravated by movement
• Laboratory tests unremarkable except for serum total calcium of 16.7 mg/dL
+ Family hx for cancer
What is the most likely cause of this pts hypercalcemia?
occult malignancy
What is the MCC of hypercalcemia in the outpatient setting when Ca < 12
hyperparathyroidism
What causes hypercalcemia by increasing synthesis of 1,25-(OH)2 vitamin D from macrophages within the granuloma?
Sarcoidosis
macrophages in the granuloma increase synthesis of vit D
What vitamin intoxication can increase Ca to 12-14 mg/dL?
vit A (50,000 to 100,000 IU)
What lab tests would you order to confirm the diagnosis of an occult malignancy causing hypercalcemia?
iPTH was 20… Suppressed
Do a sxs guided malignancy work up
What are labs to test for solid tumors?
increased PTHrP: adeno and sq cancer (lung tumor)
Increased alk phosphatase: bone lysis (breast tumor)
What are labs for hematologic malignancies?
+ myeloma screen: MM
increased calcitriol: lymphoma, granulomatous disease
What is PTHrP?
it is DISTINCT from PTH but has some N terminal homoogy so can interact with the PTH receptor and mimic PTH activity
What is the normal range for PTHrP?
1-2 pmol/L
collect and process on ice with protease inhibitors!
71 year old female referred to endocrinology clinic after several years of unresolved hypomagnesemia (NORMAL 1.7-2.5)
• Numerous hospital admissions to receive IV magnesium
• Previously presented with palpatations (x3) and once with diarrhea and vomiting
• Medical history included type 2 diabetes mellitus and hiatal hernia
• Medications: simvastatin, esomeprazole/Nexium, verapamil, pioglitazone, metformin
• Supplementation: calcium, magnesium, vitamin D
• Clinical examination unremarkable
• Normal ECG and echocardiogram
MG .52
CA 6.84
WHAT COULD BE THE CAUSE OF THIS PT’S HYPOMAGNESEMIA?
• Renal – Medication (diuretics, cisplatin, aminoglycosides, cyclosporine) – Infection (pyelonephritis, glomerulonephritis) – Osmotic diuresis • Gastrointestinal – Diarrhea, vomiting – Laxative abuse – Lack of intake or absorption of dietary Mg – Malabsorption – Malnutrition – Alcoholism – TPN • Leads to secondary hypoparathyroidism
What is PPIH?
PPI induced hypomagnesemia
- Median # of years before onset: 5.5 years
- Mechanism largely unknown
- Clinical guidelines recommend obtaining serum Mg on new patients starting PPIs and regular monitoring of patients on long-term PPI therapy
- Relatively rare complication
- Patients at greater risk: GI disorders, diuretics
12 mo M presents for pediatric WCC
- breastfed since birth
- meeting mile stones
- mild vaglus varus both legs
- CBC:normal
- iPTH:334pg/mL
- Phosphorus:2.5mg/dL • Magnesium: 2.3 mg/dL • Totalcalcium:9.7mg/dL
What is the most likely cause of this child’s elevated PTH?
Vit D def
If you suspect vit D def in a child what other tests would you order?
25-hydroxyvitamin D
What is required to convert 25 OH vit D to 1,25 OH vit D?
PTH!
D3 vs D2: syntehsized in the body
D3 (D2 plant)
D3 vs D2: synthetically derived supplement
D2 (D3 natural)
Leads to a sigfniciant increase in total 25OH vit D in body
D3 (D2 only moderate)
What form of vit D is recommended by experts for optimal bone and immune support?
D3
What lab is the best indication of a patient’s true vitamin D status?
25-OH (t1/2 2-3 weeks)
How does vit D prevent hypocalcemia?
it inhibits PTH
What biochemical changes are assocaited with vit D deficiency?
Decrease in 25OHD
Decrease urCa
INCREASE in PTH
Eventual decrase in Ca/Phos
What is Rickets?
- Originated in late 1600’s
- By 1900 > 80% children in industrialized cities in North America and Europe suffered from rickets
- 1920’s: irradiation/fortification of milk became common practice; eventually saw eradication of rickets
- C-sections increased; rate has remained the same since after WWII
What are signs of Rickets?
- Skeletal deformities (delayed fontanelle closure, bowed legs, breastbone projection)
- Weakness
- Unable to stand or walk
- Slow growth
- Bone pain and tenderness
- Seizures
- Dental deformities
Where is Rickets becoming more common now?
(children): prevalent among immigrants from Asia, Africa, and Middle Eastern countries
• Vitamin D deficiency associated with Fe deficiency; treatment with Fe can increase 25(OH)D concentrations
• More likely to follow dress restrictions limiting sun exposure
• Darker pigmented skin converts UV rays to vitamin D less efficiently than lighter skin
What sort of supplementation is required for every age?
– Birth – 1y: 400 IU
– 1-70y: 600 IU
– 71+ y: 800 IU
– Breastfed infants need supplementation!
How much vit D shoiuld you get during pregnancy?
- Current requirement: 600 IU
- Supplementation with 800-1600 IU/day
- Supplement with vitamin D3 or D2? D3 is what is quantitatively transferred in human milk
How much vit D supplementation is recommended for neonates?
400 IU
Breast milk is DEFICIENT in vit D
How much vitamin D should lactating women receive?
400 IU/day
What can be used for 25OH vit D screening?
immunoassays
What is the most accurate test used to test for vit D def and who should it be used for?
LC-MS/MS
CKD pts
pediatrics
pts on vitamin D supplementation
Where is the greatest prevalence of vit D def?
Inpatients/hospitalized adults
What indicates a vit D def?
<20 (20-60 ref range)
What vit D levels are considered toxic?
> 150
