Hypercalcemia/ Hypocalcemia

Calcium

 Neuromuscular signaling

 Cardiac contractility

 Hormone secretion

 Blood coagulation

 Level:8.9–10.1 mg/dL
Only 0.1% of the total body calcium is in the extracellular
space
99.9% is localized in bone.
 If plasma levels of albumin is low

 Adjusted total calcium (mg / dL)

= Total calcium (mg / dL) + 0.8 (4 − Albumin [g / dL] )

Normal Physiology
 Malignancy

 Malignancy is the most common cause of hypercalcemia.

 Hypercalcemia result from

(1) direct invasion of bone by metastatic disease (local osteolytic

hypercalcemia, or LOH)

(2) production of circulating factors that stimulate osteoclastic

resorption of bone (PTHrP)

(3) increased production of calcitriol, which stimulates gastrointestinal

absorption of calcium
 Primary hyperparathyroidism

 Caused by a benign adenoma of a single parathyroid

gland that autonomously secretes PTH.

 The disorder may be sporadic, familial, or inherited as a

component of the constellation of multiple endocrine

neoplasia (MEN).
 A solitary parathyroid adenoma is present in 80% to 85%

of cases.
 Primary hyperparathyroidism

 Elevation in PTH results:

– increased intestinal reabsorption of calcium through stimulation of
the production of calcitriol,
– increased osteoclastic bone resorption,

– increased renal tubular reabsorption of calcium.

– filtered load of calcium exceeds the ability of the kidney to reabsorb

calcium, leading to hypercalciuria and potentially to nephrolithiasis.
 Secondary hyperparathyroidism

 Decrease S. Ca increase PTH secretion

 Caused by diffuse hyperplasia of all 4 glands due to ongoing
stimuli such as hypocalcemia or hyperphosphatemia.
 Once circulating PTH is elevated, calcium may return to normal or
remain low.
 Correction of the underlying calcium abnormality will return serum
PTH concentrations to normal.
 Causes :CKD, vitamin D deficiency, intestinal malabsorption, and
severe dietary inadequacy
 Tertiary hyperparathyroidism

 Prolonged secondary hyperparathyroidism causes

hyperplasia or neoplasia of glands.

 Glands become adenomatous

 No longer respond to the change in calcium

 Hypercalcemia via increased bone resorption

 Stage often called tertiary hyperparathyroidism

 Lithium therapy

 Can change the set point for the calcium-sensing

receptor such that a higher serum calcium

concentration is needed to inhibit PTH secretion.
 Familial hypocalciuric hypercalcemia (FHH)

 Also known as benign familial hypercalcemia

 Inactivating mutations of CaSR

 Hereditary disease

 Calcium is unable to activate the mutant receptor,

leading to increased renal reabsorption of calcium

causing hypocalciuria,
 Hypercalcemia Classification

 Severity of symptoms and signs: depends on the degree

& velocity of its development

 Hypercalcemia may be classified based on total serum

calcium concentrationas follow:

 Mild: Ca concentration = 10.4 to 11.9 mg/dL

 Moderate: Ca concentration = 12.0 to 13.9 mg/dL

 Severe (hypercalcemic crisis): = 14.0 to 16.0 mg/dL

 Clinical Manifestations Of Hypercalcemia
General
Malaise, tiredness, weakness
Neuropsychiatric
Impaired concentration, loss of memory, headache, drowsiness, lethargy, disorientation,
depression, hallucinations, ataxia, speech defects, visual disturbances, stupor, coma
Neuromuscular
Muscle weakness, hyporeflexia or absent reflexes, hypotonia, myalgia, arthralgia, bone pain, joint
effusion, chondrocalcinosis,
Gastrointestinal
dry mouth, thirst, polydipsia, nausea, vomiting,Constipation, abdominal pain, weight loss, peptic
ulcer
Renal
Polyuria, nocturia, nephrocalcinosis, nephrolithiasis, renal failure
Cardiovascular
Arrhythmia, heart block, short QT interval, HTN, vascular Calcification

Metastatic Calcification
Band keratopathy, red eye syndrome, conjunctival calcification, Nephrocalcinosis,vascular
calcification, pruritus
 Laboratory Investigations

 iPTH

 Protein electrophoresis: to exclude myeloma

 Serum TSH: hyperthyroidism

 Serum ACE: sarcoidosis

 X-rays: renal calculi or nephrocalcinosis.

 Parathyroid imaging: high-resolution CT scan or MRI

 Radioisotope scanning - of the parathyroid tissue

 Fractional excretion of calcium

 Treatments for Hypercalcemia
AGENT MODE OF ACTION DOSE
IV hydration with saline Increases tubular flow and Hydration based on patient’s
excretion of calcium cardiovascular and renal status;
200-500 mL/hr

IV furosemide or loop diuretics Block NKCC2 channel in loop of 20-40 mg after rehydration;
Henle thus reducing positive dose may need to be adjusted
electrochemical gradient for based on kidney function level
calcium reabsorption

IV bisphosphonates Inhibit osteoclastic activity Pamidronate, 60-90mg in 4 hr

Zoledronate, 4 mg over 15 min

Calcitonin Inhibits bone resorption and 4-12 IU IM/SQ every 12 hr

enhances calcium excretion

Glucocorticoids Inhibit conversion of 25(OH)D to Hydrocortisone, 200 mg/day IV

1,25(OH)2D for 3 days
Prednisone, 60 mg PO for 10
days
Cinacalcet Allosteric activator of CaSR, 30 mg qd to bid, to a maximum
mimicking increased calcium to dose of 90 mg bid; give with
reduce PTH food to reduce nausea
Hypocalcemia
 Clinical Features of Hypocalcemia
Neuromuscular Irritability
General fatigability and muscle weakness
Paresthesias, numbness, Circumoral and peripheral extremity tingling
Muscle twitching and cramping, Tetany, carpopedal spasms, Chvostek’s
sign, Trousseau’s sign ,Laryngeal and bronchial spasms

Altered Central Nervous System Function

irritability, depression Altered mental status, coma Seizures: tonic-clonic
Papilledema, pseudotumor cerebri ,Cerebral calcifications
Cardiovascular Features
Lengthening of the QTc interval, Dysrhythmias, Hypotension
Congestive heart failure
Dermatologic and Ocular Features
Dry skin, coarse hair, brittle nails, Cataracts
 Tapping over the facial nerve anterior to the ear can induce

facial muscle spasm (Chvostek’s sign).

 Chvostek’s sign may occur in 10% of normal people and

was absent in 29% of patients with mild hypocalcemia.

 Trousseau’s sign of main d’ accoucheur : elicited by inflation

of a sphygmomanometer cuff placed on the upper arm to

10 mm Hg above SBP for 3 minutes, has greater than 90%
sensitivity and specificity.
 Lab Investigation

 serum and urine creatinine

 PTH levels absent or inappropriately low in

hypoparathyroidism, high in other causes of hypocalcaemia

 Parathyroid antibodies (present in idiopathic

hypoparathyroidism)
 25-hydroxy vitamin D serum level (low in vitamin D

deficiency)
 Treatment

 Acute, symptomatic hypocalcemia: calcium gluconate,

 Continuing hypocalcemia: constant i/v infusion

 Chronic hypocalcemia due to hypoparathyroidism is

treated with calcium supplements, calcitriol

 Vitamin D deficiency is treated using vitamin D

supplementation.
 Treatment goal: S. calcium into the low normal range and

to avoid hypercalciuria, which may lead to nephrolithiasis

Thank you