TYPE 1 TYPE 2

Intuitive Analytic

Fast Deliberate

Experiential Rational

Pattern Recognition Careful Analysis

Matching Against Illness Scripts Consider Wider differential

Hypercalcemia: Background

Hypercalcemia: Differential PTH Primary Hyperparathyroidism – majority in outpatients Tertiary hyperparathyroidism Familial hypocalciuric hypercalcemia (FHH)

PTHrP Solid tumors malignant: lung, head/neck, esophagus, prostate, breast, lymphoma Solid tumors benign: uterine myoma, pheochromocytoma Leukemia or multiple myeloma

1,25 vitamin D Lymphoma Granulomatous disease: sarcoid, granulomatous myositis, histiocyte disordres

(Langerhans) Inflammatory – Crohn’s, Wegeners, SLE, foreign bodies, beryliosis Infections – TB, fungal disease CYP24A1 mutations

Excessive bone resorption: immobilization, hyperthyroidism Excessive calcium intake – milk alkalai syndrome Vitamin D intoxication: D2, D3, analogs Drugs: HCTZ, lithium, high dose vitamin A Adrenal insufficiency

Bilezikian JP et al JCEM 2014;99:3561

• Calcium 1 mg/dl above upper limit of normal

at lumbar spine, total hip, femoral neck or

• Vertebral fracture by VFA, radiograph, CT, or MRI

• Creatinine clearance <60 mL/min

• 24 hour urine calcium >400 mg/day

• Nephrolithiasis or nephrocalcinosis by radiograph, CT or ultrasound

Bilezikian JP et al JCEM 2014;99:3561

Measure PTH

Suppressed

Measure 1,25 OH Vit D, PTHrP, SPEP,

UPEP

Normal or high 1,25 vitamin OH D

Evaluate for 1,25 OH mediated causes

Elevated PTHrP

Evaluate for malignancy, myeloma

Elevated SPEP/UPEP

Myeloma

Normal or Elevated

24 hr urine Ca, Na, Cr, calcium clearance

Clearance <0.01

Genetic test CaSR mutation (FHH)

Clearance >0.01

Primary Hyperparathyroidism

Measure PTH

Suppressed

Measure 1,25 OH Vit D, PTHrP, SPEP,

UPEP

Normal or high 1,25 vitamin OH D

Evaluate for 1,25 OH mediated causes

Elevated PTHrP

Evaluate for malignancy, myeloma

Elevated SPEP/UPEP

Myeloma

Normal or Elevated

24 hr urine Ca, Na, Cr, calcium clearance

Clearance <0.01

Genetic test CaSR mutation (FHH)

Clearance >0.01

Primary Hyperparathyroidism

Measure PTH

Suppressed

Measure 1,25 OH Vit D, PTHrP, SPEP,

UPEP

Normal or high 1,25 vitamin OH D

Evaluate for 1,25 OH mediated causes

Elevated PTHrP

Evaluate for malignancy, myeloma

Elevated SPEP/UPEP

Myeloma

Normal or Elevated

24 hr urine Ca, Na, Cr, calcium clearance

Clearance <0.01

Genetic test CaSR mutation (FHH)

Clearance >0.01

Primary Hyperparathyroidism

Jacobs, TP et al JCEM 2014;99:708-712

Brandi ML et al. J Clin Endocrinol Metab. 2016;doi: 10.1210/jc.2015-3907

Bilezikian JP et al. J Clin Endocrinol Metab. 2016;doi: 10.1210/jc.2015-3910

Bilezikian JP et al. J Clin Endocrinol Metab. 2016;doi: 10.1210/jc.2015-3910

Bilezikian JP et al. J Clin Endocrinol Metab. 2016;doi: 10.1210/jc.2015-3910

Bilezikian JP et al. J Clin Endocrinol Metab. 2016;doi: 10.1210/jc.2015-3910

• Enhances calcium absorption, stimulates bone remodeling

• Overdosing detected early by urine calcium elevations

• Active metabolites

• Calcitriol (1,25 vitamin D3) half life 4-6 hours, peak levels 3-6 hours

• 0.25-0.5 mcg twice daily typically up to total of 2 mcg daily

• Increases calcium levels within 1-3 days

• Alfacalcidol (1α-hydroxyvitamin D3) (not in USA)

• About 2 mcg/day

• Onset 1-3 days

• Offset 5-7 days (longer half life than calcitriol)

Bilezikian JP et al. J Clin Endocrinol Metab. 2016;doi: 10.1210/jc.2015-3910

• Vitamin D3 (or D2) in addition to active metabolites

• Longer half-life 2-3 weeks (recovery from overdose can take weeks)

• Especially useful if some parathyroid function (25 to 1,25 conver

Bilezikian JP et al. J Clin Endocrinol Metab. 2016;doi: 10.1210/jc.2015-3910

Bilezikian JP et al. J Clin Endocrinol Metab. 2016;doi: 10.1210/jc.2015-3910

“How often do you see a patient with a previous DXA report interpretation that is incorrect?”

Lewiecki, EM, et al. J Clin Densitom, 9:388-392, 2006

30

25

20

15

10

5

0

Perc

en

tage

of

Re

sp

on

ders

> 1/day > 1/week 1/week 1/month <1/month never

6%

22%

17%

27% 25%

4%

WHO Definition of Postmenopausal Osteoporosis Based on T-score Classification

Post-menopausal women and older men (>50)

Lumbar spine, total hip, femoral neck and one-third radius

World Health Organization. Technical Report Series 843; WHO, Geneva.1994.

Kanis JA et al. J Bone Miner Res. 1994;9:1137.

T-score (SD)

Normal Equal to -1.0 or higher

Low Bone Mass (Osteopenia) Between -1.0 and -2.5

Osteoporosis Equal to -2.5 or lower

Severe Osteoporosis Equal to -2.5 or lower with fracture