HYPERCALCEMIAThe Nuts and Bolts

DEFINITION• Total S. Ca >10.3 mg/dl + Normal S. Albumin

• Ionized S. Ca > 5.2 mg/dl

CAUSES

1. Related to PTH2. Malignancy3. Vitamin D-related4. Medications5. Other endocrine6. Genetic7. Other

PTH Related• Primary hyperparathyroidism

• Adenoma(s) • MEN I or II• Carcinoma

• Familial hypocalciuric hypercalcemia

• Tertiary hyperparathyroidism• CRF• Vitamin D deficiency

Malignancy related• Humoral hypercalcemia (mediated by PTHrP)

• Solid tumors• Lung• Head and neck squamous cancers• Renal cell tumors

• Local osteolysis (mediated by cytokines) • Multiple myeloma

• Ectopic Vit D3 secretion• Hodgkin’s lymphoma

Vitamin D related• Vitamin D intoxication

• Granulomatous disease• Sarcoidosis• Berylliosis• Tuberculosis

• Hodgkin’s lymphoma

Medications• Thiazide diuretics (usually mild)

• Lithium

• Milk-alkali syndrome (from calcium antacids)

• Vitamin A intoxication (including analogs used to treat acne)

Endocrine disorders• Hyperthyroidism

• Adrenal insufficiency

• Acromegaly

• Pheochromocytoma

Genetic disorders• Familial hypocalciuric hypercalcemia

• Mutated calcium-sensing receptor

• Normal PTH in 80-85% of patients

• Benign inherited condition

Others• Immobilization

• High bone turnover• Paget’s disease, bedridden child

• Recovery phase of rhabdomyolysis

MOST COMMON• Primary hyperparathyroidism

• Malignancy• Multiple myeloma• Breast carcinoma

• Account for 90% cases

SYMPTOMS• Renal

• Musculoskeletal

• Gastrointestinal

• Neurological

• Cardiac

• Others

Renal• Nephrolithiasis

• Nephrocalcinosis

• Polyuria

• Polydipsia

Musculoskeletal• Bone pain

• Osteopenia

• Fractures

• Muscular weakness, especially proximal myopathy

Gastrointestinal• Nausea

• Vomiting

• Lack of appetite

• Constipation

• Peptic ulcers

• Pancreatitis

Neurological• Tiredness

• Lethargy

• Inability to concentrate

• Increased sleepiness

• Depression

• Confusion

• Coma

Cardiac• Bradycardia

• First-degree AV block

• Arrhythmias

• Shortened QT interval

Others• Itching

• Keratitis

• Conjunctivitis

• Corneal calcification, band keratopathy

• Carpal tunnel syndrome• Occasionally with hyperparathyroidism

DIAGNOSIS

TREATMENT EMERGENCY• Rehydrate:-

• 4–6 L of 0.9% saline on day 1• 3–4 L for several days thereafter

• Intravenous bisphosphonates:-• Hypercalcaemia of malignancy• Undiagnosed cause• Pamidronate, Zoledronate

• Prednisolone:- • Myeloma, Sarcoidosis, Vitamin D excess (ineffective usually)

• Calcitonin:-• Short-lived action

• Oral phosphate

TREATMENT MEDICAL• High fluid intake

• Avoid high calcium intake

• Avoid high vitamin D intake

• Exercise

TREATMENT SPECIFIC• Primary hyperparathyroidism – Sx

• Malignancy – Rx for malignancy

• Vit D excess – ↓ Vit D intake

• Avoid ppting drugs

• Treat endocrine disorders

• Treat CRF