7 - HYPERcalcemia Flashcards by Karlo Sison

Normal Serum Calcium

8.5 - 10.5
mg/dL

Half calcium is protein bound
15% bound to anions
40% bound to albumin

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Normal Ionized Serum Calcium

4.4-5.5
mg/dL

~1/2 of total serum Ca

does NOT vary with ALBUMIN

Free Ca+

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Corrected Calcium Claculation

Corrected Ca+ =

( Total Measured Ca+ ) + 0.8 (4 - Measured Serum Albumin )

Normal Serum Albumin = 4 mg/dL

This can OVERestimate Ca+,

*Ionized Ca+** should be obtained if patient is
*critically ill** or if total is low <7.5mg/dL

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Relationship between
Calcium & PTH

Calcium has a NEGATIVE feedback on PTH
via Calcium sensing Receptor

*LOW CALCIUM* –> PTH SERGE ^^

Bones
Stim Osteoclast –> bone REsorption
inhibits osteoBlasts & bone formation

Kidneys
INCREASE reabsorption of calcium, less calcium clearance
Stimulates hydroxlase –> INCREASE Vitamin D production

Gut
indirectly increases calcium absorption via stim of VITAMIN D production

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Relationship Between
Calcium & Calcitonin

High Calcium** –> **High CALCITONIN

Hormone that INHIBITS osteoclastic bone resorption (breakdown)

Mechanism to return calcium levels to NORMAL, when too HIGH

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Relationship between
Calcium & VITAMIN D

High phos / Low Ionized Ca+ leads to:
Active Vitamin D (Calcitriol)
VVVV
INHIBITS PTH Release
VV
INCREASE SERUM CALCIUM by:

Stimulating Calcium RELEASE from bones

Enhance Ca+ absorption in GI tract

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HYPERcalcemia

Value?

Total Serum Calcium
> 10.5 mg/dL

Ionized Calcium
> 5.4 mg/dL

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Etiology of HYPERcalcemia

Calcium in Circulation > Excretion of Ca+ (Urine / Bone desposition)
Caused by:
Accelerated Bone Resorption
Excessive GI absorption
Decreased Renal Excretion of Calcium

PRIMARY or SECONDARY HYPERthyroidism // MALIGNANCY
= 90% of HYPERcalcimia Cases

Drug Induced

Endocrine Disorders
Addison’s / Acromegaly / Throtoxicosis

Granulomatous Disorders
Sarcoidosis / Tuberculosis

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Primary HYPERparathyroidism

MAJOR Cause of HYPERcalcemia

Caused by:
Parathyroid ADENOMA
innapropriate increase in PTH Secretion –> HIGH Ca+

High Normal Values <11mg/dL
w/ intermittent HYPERcalcemia

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Secondary HYPERparathyroidism

MAJOR Cause of HYPERcalcemia

Associated with:
HYPERplasia of GLANDS

Observed in patients with CKD

Adaptive disease in the Setting of CKD:
Inability to activate VITAMIN D + Increased PHOS

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Tertiary HYPERparathyroidism

Advanced RENAL failure –> Parathyroid Hyperplasia

May resolve after kidney transplant

Parathyroidectamy might be needed to help PTH levels

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HIGH PTH EFFECTS
HYPEParathyroidism

KIDNEY
INCREASE renal absorption of CALCIUM
INCREASE renal EXCRETION of PHOS
Stimulate synthesis of calcitriol

INTESTINE
indirectly INCREASES absorption of Ca/P in Small Intestine

BONE
Stimulates osteoclast to RESORB bone –> ↑Ca+
inhibits osteoblast & bone absorption

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Malignancy
effects on Calcium

Also accounts for ~90% of HYPERcalcemia

Calcium Levels > 13mg/dL

Solid Tumors + Leukemia

VVVV
INCREASED
Bone RESORPTION&GI ABSORPTION

high Ca

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Drug Induced HYPERcalcemia

DISCONTINUE OFFENDING AGENTS

THIAZIDE DIURETICS
most common –> increase renal tubular reabsorption of CA
block NA rabsorption –> INCREASE Ca reabsorption

*Lithium**
*Resets PTH** hormone –> increased PTH

Vitamin A
INCREASE bone resorption (stim osteoclasts)

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Moderate + Chronic HYPERcalcemia

Levels / Symptoms

12-14

GI:
Anorexia / N+V / Constipation

Renal:
PolyUria / PolyDipsia

MUSCLE WEAKNESS

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Severe / Life-Threatening (ACUTE)
HYPERcalcemia

Levels / Symptoms

>14** or **RAPID INCREASE IN Ca
Any level can be considered ACUTE, as long as there is:
Rapid/Substantial Rise in Ca and S/Sx present

the ACUITY of the RISE in Calcium –> determines therapy

Profound DEHYDRATION

Renal Failure / CV+Neuromuscular Dysfunction / COMA

Signs / Symptoms of
CHRONIC HYPERcalcemia

Long Standing HYPERcalcemia:
HYPERparathyroidism / Sarcoidosis / CKD

Calcium Desposition in BV & organs
deposits in artherosclerotic lesions –> heart disease
deposit in skin –> calciphylaxis
deposit in kidney –> nephrocalcinosis (permanent kidney dmg)

HYPERCalcemia TREATMENT

CHART

Treatment for MILD+Asymptomatic
HYPERcalcemia

<12 mg/dL

Reduce dietary Calcium
<400 mg/day
by avoiding food/diet high in calcium

AVOID:
Thiazides / Lithium / Vitamin D

Stay well hydrated

Avoid IMMOBILIZATION –> precipitation

*Moderate +**
*HYPERcalcemia Treatment**

12-14 mg/dL

ASYMPTOMATIC –> treat like MILD

ACUTE RISE IN CA –> TREAT as SEVERE

Treatment for SEVERE
HYPERCalcemia

*>15 mg/dL**
*Symptomatic // ACUTE RISE**

PARENTERAL THERAPY

NS 0.9% + Loop Diuretic
Volume Expansion // Increase Ca+ EXCRETIOn

Calcitonin
used in SYMPTOMATIC patients –> rapidly DECREASES serum Ca+

Bisphosphonates
provides a sustained effect in lowering calcium

*Dialysis**
*last resort**, make sure there is NO CA in dialysis fluid

SALINE
Dose / MoA / ADR

Severe HYPERcalcemia Treatment

given with LOOP DIURETICS to help increase Ca excretion

Normal Saline 0.9%
corrects volume depletion –> euvolemia

200-300 ml/hr
adjusted to maintain UOP = 100-150 ml/hr

ADR:
Fluid Overload / Edema / Electrolyte abnormalities

Considerations:
Severity / age / comordities / no diuretics with renal/heart failure

CALCITONIN

Severe HYPERcalcemia Treatment

Works VERY RAPIDLY –> deceease serum calcium

Used for:
Acute + SYMPTOMATIC patients

Hormone from Thyroid

INHIBITS Osteoclatic Bone Resorption
(bone breakdown)

Plasma concentrations are
INCREASED when ionized Ca is HIGH

CALCITONIN

Dose / MoA / ADR

Severe HYPERcalcemia Treatment

SYMPTOMATIC PATIENTS

Antagonizes PTH* // Decrease Bone Resorption
*Increase calcium EXCRETION**

4 IU/k_g** **IM/SC**
works very RAPIDLY ↓**Ca 1-2 mg/dl within 4-6 hours**
–> DOSE AGGRESIVELY
**If Responsive –> REPEAT q6-12 hours** **@4-8IU/kg_

ADR:
Nausea / HYPERsensitivity / Tachyphylaxis

**BISPHOSPHONATES** **Severe HYPERcalcemia Treatment**

Adsorb to surface of **bone hydroxyapatitie** ***INHIBIT* calcium release** --\> inhibit osteoclasts resorption Most effective in HYPERcalcemia from: **Excessive Bone Resorption** (vs other etiology) **_MORE POTENT than Calcitonin + Saline_** **_LAST LONG_** = **2-4 WEEK duration** **Drug specific Dosing: Zolendronic Acid / Pamidronate / Ibandronate**

**BISPHOSPHONATES** **Dose / MoA** **Severe HYPERcalcemia Treatment**

***Inhibit* Calcium Release =** ***inhibits osteoclasts*** * *_*SLOW* Infusion Rate_** for patinets with **Renal Dysfunction** * *2-4 Week duration** * *_ZOLENDRONIC ACID_** * *4mg IV** over **15 minutes** * *MOST POTENT** = PREFERRED, *renal toxicity with 8mg dose* **_Pamidronate_** 60-90mg IV over 2 hours, *fever* **_Ibandronate_** 2mg IV over 2 hours, *dyspepsis / backpain*

**BISPHOSPHONATES** **ADRs** **Severe HYPERcalcemia Treatment**

**Osteonecrosis of JAW** w/ repetitive use **Acute Phase Reactions** bone pain / fever / flu like symptoms **_*AVOID* if CrCl \<30 ml/min_** // **ESRD = renal dosage**

**Preventing HYPERcalcemia Recurrance in MALIGNANCY**

***lower tumor burden*** **Metastatic BONE Disease:** Administer * *_PAMIDRONATE / ZOLENDRONIC ACID_** * *q 3-4 weeks** **_Denosumab_** for **refractory HYPERcalcemia** *no restriction* in CKD patients, effect seen in 2-4 days **60 g SC** w/ repeat dosing based on response

**Role of GLUCOCORTICOIDS** **in HYPERcalcemia**

Used in: **Chronic Granulomatous Diseases = Sarcoidosis** ***Decreased* Intestinal Calcium Absorption** ***Decreased* Calcitriol Production** by activated mononuclear cells in lungs / lumph nodes **_PREDNISONE 20-40 mg/day_** effect in **2-5 days**, can last **days - weeks**

**HYPERcalcemia in HYPERparathyroidism**

Usually **CHRONIC + Asymptomatic** Long standing consequences: **Osteoporosis** / **Calcifications** in **organ systems** Use **CALCIMEMETICS:** **_Sensipar = Cinacalcet_** **_Parsabiv = Etelcalcetide_**

**SENSIPAR** For **Hypercalcemia in Hyperparathyroidism**

**Cinacalcet** ***_Decrease PTH_*** by increasing sensitivity of calcium receptor on PT gland **30 - 60 - 90 mg** **QD WF** ADR: ***decrease in SERUM Ca+*** // **NVD** ensure **corrected Ca \> 7.5mg/dL before dose titration** titration is **q3-6 weeks** strong inhibitor of **CYP2D6**

**PARSABIV** For **Hypercalcemia in Hyperparathyroidism**

**Etelcalcetide** **Binds to Calcium Sensing Receptor** on PT gland & enhances activation by serum calcium **_5 mg IV bolus_ 3 x Week** @ end of hemodialysis Dose Adjustment: **Titrate dose in 2.5 or 5mg increments** no more than **\< q4 weeks** Conversion from Cinacalcet/Sensipar: **D/C Sensipar** for **\>7 days** prior to initiating ADR = **Serum Calcium** / **adj dose if Ca \<7.5mg/dL** **DO NOT GIVE if HEMODIALYSIS session is MISSED** If miss \>2 weeks of doses --\> **restart @ 5mg IV 3 x week**

**_Calcitriol Induced HYPERcalcemia_** **TREATMENT of HYPERvitaminosis D**

**TRIOL = TRYING = ACTIVE VITAMIN D** Lasts **1-2 days** due to **short half life** **_D/C Calcitriol_** **INCREASE FLUID INTAKE / IV HYDRATION w/ SALINE**

**_Calcidiol Induced HYPERcalcemia_** ## Footnote **TREATMENT of HYPERvitaminosis D**

**-Diol** - **Lasts LONGER** **_AGGRESIVE THERAPY_** **Glucocorticoids** **IV Bisphosphonates** if symptomatic