2. ⢠Commonly encountered in Practice
⢠Diagnosis often is made incidentally
⢠The most common causes are primary
hyperparathyroidism and malignancy
⢠Diagnostic work-up includes measurement
of serum calcium, intact parathyroid
hormone (I-PTH), h/o any medications
⢠Hypercalcemic crisis is a life-threatening
emergency
2
3. ⢠Most often asymptomatic â Incidental Dx
⢠Mild Hypercalcemia is asymptomatic
⢠Most important cause is hyper parathyroid
⢠DD is needed to decide the treatment
⢠Optimal step by step evaluation is a must.
3
4. ⢠98% of the body calcium is in the skeleton
⢠Only 2% is circulation and only half of this
is free calcium (ionized Ca++)
⢠This only is physiologically active
⢠The reminder 1% is bound to proteins
⢠Direct measurement of free Calcium ??
4
8. Hormone Effect Bone Gut Kidney
PTH ď¨ Ca ďŠ Po4
Increases
Osteoclasts
Indirect
via Vit. D
Ca reab
Po4 exr.
Vitamin D3 ď¨ Ca ď¨ Po4
No direct
action
ď¨ Ca ď¨ Po4
absorption
No direct
effect
Calcitonin ďŠ Ca ďŠ Po4
Inhibits
Osteoclasts
No direct
effect
Ca & Po4
excretion
8
9. Corrected total calcium (mg%) =
[(Measured total calcium mg%) +
{(4.4 - measured albumin g%) x 0.8}]
Example:
[12.0 + {(4.4 â 2.4) x 0.8}] =
[ 12.0 + (2 x 0.8)] = 12.0 + 1.6 = 13.6
mg%
9
11. Second hydroxylation in the Kidney at first position
1,25 dihydroxy Cholecalciferol Active Vitamin D (Calcitriol)
Successive hydroxylations of Cholecalciferol
25 hydroxylation in the Liver 25 hydroxy Cholecalciferol
Vitamin D is a steroid hormone
From dietary sources Action of Sunlight on skin
11
12. PTH
⢠4 PT glands
⢠84 AA
hormone
⢠Low Ca
stimulates it
Calcitriol (D)
⢠Active bone
formation
⢠Main effect is
on the Gut
⢠PTH ď¨ Vit. D
Calcitonin
⢠Para follicular
C of Thyroid
⢠34 AA hormone
⢠On Kidney
12
13. 13
Critical - > 14 mg %
Moderate - 12 to 14 mg %
Mild â 10.4 to 11.9 mg %
Normal â 8.5 to 10.3 mg %
16. ⢠More than 90 percent of hypercalcemia cases are
Primary hyperparathyroidism and malignancy
⢠These conditions must be differentiated early
to provide optimal treatment & accurate prognosis
⢠Humoral hypercalcemia of malignancy implies a
very limited life expectancy â only a matter of
weeks
⢠Primary hyperparathyroidism has a benign course.
16
17. ⢠Primary hyperparathyroidism
⢠Sporadic, familial, associated with
Multiple Endocrine Neoplasia (MEN I or II)
⢠Tertiary hyperparathyroidism
⢠Associated with chronic renal failure
⢠PTH ď due to Vitamin D deficiency
17
18. ⢠Vitamin D intoxication
⢠Iatrogenic Vitamin D injections
⢠Usually 25-hydroxyvitamin D2 in
over-the-counter supplements
⢠Granulomatous disease â
Sarcoidosis, Berylliosis, Tuberculosis
⢠Hodgkinâs lymphoma
18
19. ⢠Humoral hypercalcemia of malignancy
(mediated by PTHrP) â common cause
⢠Solid tumors, especially lung, head and
neck squamous cancers
⢠Renal Cell Carcinoma (RCC)
⢠Local osteolysis (mediated by cytokines)
⢠Multiple Myeloma
⢠Breast cancer
19
20. ⢠Thiazide diuretics (usually mild) - common
⢠Lithium for depressive illnesses
⢠Milk-alkali syndrome (calcium + antacids)
⢠Vitamin A intoxication (including
analogs used to treat acne)
20
30. Medications
> 10.3 mg% I-PTH
High/Normal Pri ďPTH
Suppressed
Vit D Toxicity
Milk Alkali
Cancers/
Lymphoma
Suppressed PTHrP
30
31. PTHrP
Low or
Normal
Low or
Normal
1, 25 Vit. D
If Low
Cancer
If High
Lymphoma
High
24 hr. urine
calcium
Low â FHH
N or ď¨
Sestamibi
31
Endocrine
33. 33
⢠Increased screening for serum Ca++ and
⢠Wider availability of I-PTH assay
⢠80% of cases single parathyroid adenoma
⢠Usually benign adenoma or hyperplasia
⢠Rarely parathyroid cancer
⢠High PTH in the setting of hypercalcemia
⢠Slowly progressive â Sestamibi N-scan
⢠25% require surgery â RLN paralysis
34. 34
64 yrs male - âhyper parathyroid stormâ
with a serum calcium level of 16.4 mg%
35. ⢠Serum calcium level > 12 mg % at any time
⢠Episodes of hyper parathyroid crisis
⢠Marked hypercalciuria (urinary Ca++ > 400 mg /day)
⢠Nephrolithiasis; Impaired renal function
⢠Osteitis fibrosa cystica â Thinning of cortical bone
⢠Reduced bone density by DEXA scan (Z score < 2)
⢠Classic neuromuscular symptoms, Proximal muscle
weakness and atrophy, Hyper reflexia and ataxia
⢠Age younger than 50 years
35
36. 36
⢠25 OH - Vitamin D2 is the supplemental Vit D
⢠Level of 25 OH â Vitamin D3 is to be measured
⢠Macrophages in the granulomas, lymphomas
cause extra renal conversion of 25 OH form to
the1,25 hydroxy derivative âthe active Calcitriol
⢠PTH levels are suppressed; Calcitriol levels ď
⢠Stop the offending use of Vitamin D
⢠Glucocorticoids â for over one month or more
⢠Manage hypercalcemia vigorously
37. 37
⢠Most commonly mediated by systemic PTHrP
⢠Humoral Hypercalcemia of malignancy
⢠PTHrP mimics the bone & renal effects of PTH
⢠Normal Calcitriol and suppressed PTH levels
⢠Excessive bone lysis due to primary or bone
secondaries can cause hypercalcemia
⢠MM and metastatic Br Ca present in this way.
⢠In Osteolytic hypercalcemia, SAP is markedly ď
⢠Hodgkinâs lymphoma â ď production of Calcitriol
38. ⢠Thiazide diuretics increase renal calcium
resorption and cause mild hypercalcemia
⢠Resolves after discontinuing the drug
⢠Thiazide unmasks hyperparathyroidism
⢠Milkâalkali syndrome â Ca + Antacids
⢠Lithium â ď the set point for PTH ď
⢠Excess Vitamin A - ď bone resorption and
causes hypercalcemia.
38
39. ⢠FHH â Familial Hypocalciuric Hypercalcemia
⢠AD â 100% penetrance â Ca-R gene mutation
⢠Moderate hypercalcemia with normal/ ď¨ PTH
⢠24 hour urinary calcium is very low
⢠No benefit from parathyroidectomy
⢠High bone turnover in Pagetâs disease or
prolonged immobilization
⢠Recovery phase of Rhabdomyolysis
39
40. ⢠Ca <12 but > 10.3 mg% â no appreciable
clinical benefit â they need evaluation
⢠Any patient with Serum Ca > 12 mg%
should be aggressively treated
⢠Ca > 14 mg% is Hypercalcemic crisis
⢠Always correct the Ca value for Sr
Albumin
40
42. ⢠Vigorous I.V. Nacl Diuresis â N Saline
⢠Adequate hydration â urine out put must be
maintained 200 ml/hour = 5 L /day
⢠The safest and most effective treatment of
Hypercalcemic crisis is saline rehydration
⢠Once the urine out put is maintained â give I.V.
Furosemide â a loop diuretic in low doses of 10
to 20 mg
⢠ERT - might be beneficial in PMW â new RCT
42
43. ⢠In severe hypercalcemia refractory to
saline diuresis
⢠Calcitonin (Zycalcit, Miacalcin) 6 -8 U/kg
IM/SC (400 i.u) given every six hours.
⢠This treatment has a rapid onset but short
duration of effect
⢠Patients develop tolerance to the calcium-
lowering effect of Calcitonin.
43
44. ⢠Zoledronic acid (Zometa) - 4 mg IV diluted in
100 ml of N Saline - over at least 15â once a
M
⢠Pamindronate (Pamidria) - 60 mg IV infusion
over 4 h initial â repeated after a month
⢠Etidronate (Didronel) - 7.5 mg/kg IV over 4 h
daily for 3-7 d; dilute in at least 250 ml of
sterile N Saline
⢠They inhibit bone resorption, inhibit the
Osteoclastic activity. 44
45. ⢠Dialysis for refractory Hypercalcemic crisis
⢠Parathyroidectomy for adenomas
⢠Rx. of the underlying cause â Eliminate drugs
⢠Plicamycin (Mithracin) 25 mcg/kg/d IV for 4 d
⢠Gallium nitrate (Ganite) 100 mg/m2/d IV for 5
days in 1 L of NS or 5% Dextrose
⢠Cinacalcet (Sensipar) - 30 mg PO od â
(increases sensitivity of calcium sensing
receptor) 45
46. ⢠Hypercalcemia is often asymptomatic
⢠Screen all suspected by doing Sr Calcium
⢠If elevated, do I-PTH and follow algorithm
⢠90% Hyperparathyroidism and malignancy
⢠Vitamin D toxicity is an important cause
⢠Thiazide diuretics common cause, Vitamin A
⢠Adequate hydration - N Saline + Furosemide
⢠Calcitonin + Zoledronic acid main stay of Rx.
46