HYPERCALCEMIA

ANEELA PASHA

Final year

Clinical Pharmacy.

HYPERCALCEMIA

• Serum calcium > 10.5 mg/dl

• Mild: total CA : 10.5-11.9 mg/dl

• Moderate: total CA : 12-13.9 mg/dl

• Severe: total CA: 14-16 mg/dl

• Calcium enters extra cellular fluid from intestine and bone and excreted through kidney.

• Calcium is tightly controlled by hormones (PTH, calcitriol , calcitonin).

CALCIUM and its three forms

• Ionized (physiological form) (40%)

• Protein bound (50%), mainly to albumin

• Non ionized or Complexes to citrate and phosphate (10%)

CALCIUM

ECF8.5-10.6 mg/dl

2.25-2.65 nmol/l

ICFCYTOPLASMIC FREE

50-100 nmol/l

PROTIEN BOUND

45%

DIFFUSIBLEULTRAFILTRABLE

55%

90% ALBUMIN

10% GLOBULUIN

IONIZED45%

COMPLEXED10%

FUNCTIONS

• Muscle contraction

• Neuromuscular/ nerve conduction

• Intracellular signaling

• Bone formation

• Coagulation

• Enzyme regulation

VITAMIN D

Causes of hypercalcemiaEndocrine:• Hyperparathyroidism

• MEN Type 1 (parathyroid adenoma , pituitary adenoma , pancreatic islet cell tumor)

• Familial hypocalciuric hypercalcemia

Malignancy:• Metastases

• PTHrP

• Breast caner, lung cancer , bone cancer.

Granulomatous Disease:• Sarcoidosis

• TB

Miscellaneous:• Acute kidney failure

• Milk-alkali syndrome

Medications:• Lithium therapy

• Thiazides ( inc. Na, water absorp and inc ca concentration)

• Vit D

Causes of hypercalcemia

C calcium supplements

H hyperparathyroidism

I immobilization

M MEN, milk-alkali syndrome, medication

P parathyroid hyperplasia or adenoma

A alcohol

N neoplasm (breast, lung, kidney)

Z Zollinger ellison syndrome

E excessive vit D

E excessive vit A

S Sarcoidosis

THYROTOXICOSIS

• Sever thyrotoxicosis

• Increased calcium release from bone (thyroxine acts on bone)

• PTH is normal

• Takes 4-6 weeks to resolve with antithyroid treatment

Clinical presentation

• The famous mnemonic ;• Stone• Bones• Abdominal moans• thrones• Psychic groans• Others: anorexia, n/v , weakness, renal failure cardiac

arrest , stupor or coma .• Hypocalcaemia can increase gastrin production,

leading to increased acidity so peptic ulcer may also occur.

INVESTIGATIONS

• History

• Examination

• ECG

• Blood levels.

INVESTIGATIONS

• History + PTH levels are essential for diagnosis.

• Blood tests: calcium, phosphate, magnesium, creatinine, U&E, PTH.

• CXR (bones ,lungs etc. )

• CT scan / MRI

• Mammogram

• ECG = short QT interval

MANAGEMENT

• Persistent high levels of calcium.

MANAGEMENT

• Acute management focuses on hydration the other medications

• Chronic management focuses on the underlying etiology.

• Hypercalcemia crisis = aggressive TX

MANAGEMENT

• Rehydration:

• Monitor for fluid overload if renal impairment or elderly.

• Loop diuretics rarely used and only if fluid overload develops; not effective for reducing serum calcium

• furosemide 40mg/12h PO/IV.

Intravenous 0.9% saline 4-6 litres in 24h

MANAGEMENT• After rehydration: intravenous bisphosphonates

(inhibits osteoclast. )

Or Pamidronate 30 to 90mg (depending on severity of hypocalcaemia) at 20mg/hrOr Ibandronic acid 2 to 4mg

• Give more slowly and consider dose reduction in renal impairment • Monitor serum calcium response -after at 2 to 4 days • Can cause hypocalcaemia if vitamin D deficiency or suppressed PTH• Max effects in 1W.

Zoledronic acid 4mg over 15 mins

MANAGEMENT

• Second line treatments:

• Glucocorticoids (inhibit VIT D production)

• In lymphoma, other granulomatous diseases or Vit D poisoning, sarcoidosis.

• Prednisolone 20-40mg daily

• Usually effective in 2 to 4 days

MANAGEMENT

• Calcitonin :

• Can be considered if poor response to Bisphosphonates

• Dose 4U/kg S/C or IM 12h

• Calcimimetics :

• Licensed for hypocalcaemia due to primary hyperparathyroidism, parathyroid carcinoma or renal failure.

• only cinacalcet is currently available

• DIALYSIS

• In cases life-threatening hypercalcemia, dialysis to get rid your blood of extra calcium and waste and lowering serum calcium levels.

• Only when other treatment methods not works.

MANAGEMENT

• SURGERY

• Parathyroidectomy

• Can be considered in acute presentation of primary hyperparathyroidism if severe hypercalcaemia and poor response to other measures.

• Chemotherapy in malignancy.

LIFESTYLE CHANGES

• Healthier lifestyle

• Drink plenty of water

• Exercise .

Complications (if untreated)

• Osteoporosis

• Kidney stones

• Kidney failure

• Nervous system dysfunction

• Arrhythmia

• Cardiac arrest

REFERENCE

• Society for Endocrinology, Endocrine guidance.

• Kumar and Clark medicine 2009

• Emedicine.medscape.com

• Dipiro Pharmacotherapy Handbook 8th Edition

• (Pg. 988-989)