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HYPERCALCEMIABabak Tamizi Far MD.Assistant professor of internal medicineAl-zahra hospital, Isfahan university ofmedical sciences
Babak Tamizi Far MD.Assistant professor of internal medicineAl-zahra hospital, Isfahan university ofmedical sciences
ESSENTIALS OF DIAGNOSIS
Serum calcium level > 10.5 mg/dL Serum ionized calcium > 5.3 mg/dL Primary hyperparathyroidism and malignancy-
associated hypercalcemia are the most commoncauses
Hypercalciuria usually precedes hypercalcemia Most often, asymptomatic, mild hypercalcemia (
11 mg/dL) is due to primaryhyperparathyroidism, whereas the symptomatic,severe hypercalcemia ( 14 mg/dL) is due tohypercalcemia of malignancy
Serum calcium level > 10.5 mg/dL Serum ionized calcium > 5.3 mg/dL Primary hyperparathyroidism and malignancy-
associated hypercalcemia are the most commoncauses
Hypercalciuria usually precedes hypercalcemia Most often, asymptomatic, mild hypercalcemia (
11 mg/dL) is due to primaryhyperparathyroidism, whereas the symptomatic,severe hypercalcemia ( 14 mg/dL) is due tohypercalcemia of malignancy
GENERAL CONSIDERATIONS
Primary hyperparathyroidism and malignancyaccount for 90% of cases
Chronic hypercalcemia (over 6 months) orsome other manifestations such asnephrolithiasis suggests a benign cause
Tumor production of PTH-related proteins(PTHrP) is the most common paraneoplasticendocrine syndrome, accounting for mostcases of hypercalcemia in inpatients
Primary hyperparathyroidism and malignancyaccount for 90% of cases
Chronic hypercalcemia (over 6 months) orsome other manifestations such asnephrolithiasis suggests a benign cause
Tumor production of PTH-related proteins(PTHrP) is the most common paraneoplasticendocrine syndrome, accounting for mostcases of hypercalcemia in inpatients
Granulomatous diseases, such assarcoidosis and tuberculosis, causehypercalcemia from production of activevitamin D3 (1,25 dihydroxyvitamin D3) bythe granulomas
Milk-alkali syndrome has had aresurgence related to calcium ingestionfor prevention of osteoporosis
GENERAL CONSIDERATIONS
Granulomatous diseases, such assarcoidosis and tuberculosis, causehypercalcemia from production of activevitamin D3 (1,25 dihydroxyvitamin D3) bythe granulomas
Milk-alkali syndrome has had aresurgence related to calcium ingestionfor prevention of osteoporosis
Etiology
Increased intake or absorption Milk-alkali syndrome Vitamin D or A excess
Endocrine disorders Primary and secondary hyperparathyroidism Acromegaly Adrenal insufficiency Pheochromocytoma Thyrotoxicosis
Increased intake or absorption Milk-alkali syndrome Vitamin D or A excess
Endocrine disorders Primary and secondary hyperparathyroidism Acromegaly Adrenal insufficiency Pheochromocytoma Thyrotoxicosis
Neoplastic diseases Tumor production of PTHrP (ovary, kidney,
lung) Multiple myeloma (osteoclast-activating
factor) Lymphoma
Etiology
Neoplastic diseases Tumor production of PTHrP (ovary, kidney,
lung) Multiple myeloma (osteoclast-activating
factor) Lymphoma
Miscellaneous causes Thiazide diuretics Granulomatous diseases Paget bone disease Hypophosphatasia Immobilization Familial hypocalciuric hypercalcemia Complications of kidney transplantation Lithium intake
Etiology
Miscellaneous causes Thiazide diuretics Granulomatous diseases Paget bone disease Hypophosphatasia Immobilization Familial hypocalciuric hypercalcemia Complications of kidney transplantation Lithium intake
Clinical FindingsSYMPTOMS AND SIGNS
May affect gastrointestinal, kidney, andneurologic function
Mild hypercalcemia is oftenasymptomatic
Symptoms usually occur if the serumcalcium is > 12 mg/dL and tend to bemore severe if hypercalcemia developsacutely
May affect gastrointestinal, kidney, andneurologic function
Mild hypercalcemia is oftenasymptomatic
Symptoms usually occur if the serumcalcium is > 12 mg/dL and tend to bemore severe if hypercalcemia developsacutely
SYMPTOMS AND SIGNS
Constipation and polyuria Polyuria is absent in hypocalciuric
hypercalcemia Polyuria from hypercalciuria-induced
nephrogenic diabetes insipidus canresult in volume depletion and acutekidney injury
Constipation and polyuria Polyuria is absent in hypocalciuric
hypercalcemia Polyuria from hypercalciuria-induced
nephrogenic diabetes insipidus canresult in volume depletion and acutekidney injury
Other abdominal symptoms include
Nausea Vomiting Anorexia Peptic ulcer disease Renal colic Hematuria from nephrolithiasis
Nausea Vomiting Anorexia Peptic ulcer disease Renal colic Hematuria from nephrolithiasis
Neurologic manifestations may rangefrom mild drowsiness to weakness,depression, lethargy, stupor, and comain severe cases
Ventricular ectopy and idioventricularrhythm occur and can be accentuated bydigitalis
Neurologic manifestations may rangefrom mild drowsiness to weakness,depression, lethargy, stupor, and comain severe cases
Ventricular ectopy and idioventricularrhythm occur and can be accentuated bydigitalis
DiagnosisLABORATORY TESTS
Serum calcium level > 10.5 mg/dL Serum ionized calcium > 5.3 mg/dL The highest serum calcium levels ( 15 mg/dL)
generally occur in malignancy A high serum chloride concentration and a low
serum phosphate concentration (ratio > 33:1)suggest primary hyperparathyroidism becausePTH decreases proximal tubular phosphatereabsorption
Serum calcium level > 10.5 mg/dL Serum ionized calcium > 5.3 mg/dL The highest serum calcium levels ( 15 mg/dL)
generally occur in malignancy A high serum chloride concentration and a low
serum phosphate concentration (ratio > 33:1)suggest primary hyperparathyroidism becausePTH decreases proximal tubular phosphatereabsorption
LABORATORY TESTS
Urinary calcium excretion > 200 mg/day suggests hypercalciuria < 100 mg/day suggests hypocalciuria
Hypercalciuria from malignancy or fromvitamin D therapy frequently results inhypercalcemia when volume depletion occurs
Measurements of PTH and PTHrP levels helpdistinguish between hyperparathyroidism(elevated PTH) and malignancy-associatedhypercalcemia (suppressed PTH and elevatedPTHrP)
Serum phosphate may or may not be low,depending on the cause
LABORATORY TESTS
Hypercalciuria from malignancy or fromvitamin D therapy frequently results inhypercalcemia when volume depletion occurs
Measurements of PTH and PTHrP levels helpdistinguish between hyperparathyroidism(elevated PTH) and malignancy-associatedhypercalcemia (suppressed PTH and elevatedPTHrP)
Serum phosphate may or may not be low,depending on the cause
IMAGING STUDIES
Chest radiograph: to exclude malignancy orgranulomatous disease
DIAGNOSTIC PROCEDURE ECG: shortened QT interval
Chest radiograph: to exclude malignancy orgranulomatous disease
DIAGNOSTIC PROCEDURE ECG: shortened QT interval
Treatment: MEDICATIONSEmergency treatment
Establish euvolemia to induce renal excretionof Na+, which is accompanied by excretion ofCa2+
In dehydrated patients with normal cardiac andrenal function, infuse 0.45% saline or 0.9%saline rapidly (250–500 mL/h)
Furosemide intravenously is oftenadministered but its efficacy and safety werequestioned in one meta-analysis
Establish euvolemia to induce renal excretionof Na+, which is accompanied by excretion ofCa2+
In dehydrated patients with normal cardiac andrenal function, infuse 0.45% saline or 0.9%saline rapidly (250–500 mL/h)
Furosemide intravenously is oftenadministered but its efficacy and safety werequestioned in one meta-analysis
Emergency treatment
Thiazides can actually worsenhypercalcemia (as can furosemide ifinadequate saline is given
In the treatment of hypercalcemia ofmalignancy
Bisphosphonates are the mainstay,although they may require up to 48–72hours before reaching full therapeuticeffect
Calcitonin may be helpful to treathypercalcemia before the onset of actionof bisphosphonates
Bisphosphonates are the mainstay,although they may require up to 48–72hours before reaching full therapeuticeffect
Calcitonin may be helpful to treathypercalcemia before the onset of actionof bisphosphonates
THERAPEUTIC PROCEDURES
In emergency cases, dialysis with low orno calcium dialysate may be needed
In emergency cases, dialysis with low orno calcium dialysate may be needed
Table 347-2 Guidelines for Parathyroid Surgery inAsymptomatic Primary Hyperparathyroidisma
Measurement Guidelines, 1990 Guidelines, 2002
Serum calcium (aboveupper limit of normal)
0.3–0.4 mmol/L(1–1.5mg/dL) above normal
0.3 mmol/L (1.0mg/dL) above normal
24-h urinary calcium >400 mg >400 mg24-h urinary calcium >400 mg >400 mg
Creatinine clearance Reduced by 30% Reduced by 30%
Bone mineral density Z-score <-2.0 (forearm) T-score <-2.5 at anysite
Age <50 <50
OutcomeFOLLOW-UP
Monitor serum calcium at least every 6months during medical therapy ofhyperparathyroidism
COMPLICATIONS
Pathologic fractures Renal calculi Chronic kidney disease Peptic ulcer disease Pancreatitis Precipitation of calcium throughout the
soft tissues Gestational hypercalcemia produces
neonatal hypocalcemia
Pathologic fractures Renal calculi Chronic kidney disease Peptic ulcer disease Pancreatitis Precipitation of calcium throughout the
soft tissues Gestational hypercalcemia produces
neonatal hypocalcemia
PROGNOSIS
Depends on the underlying disease Poor prognosis in malignancy Depends on the underlying disease Poor prognosis in malignancy
PREVENTION
Prevent dehydration that can furtheraggravate hypercalcemia
WHEN TO REFER
Patients with malignancy-relatedhypercalcemia should be referred to anoncologist
Patients with endocrine disorders should bereferred to an endocrinologist
Patients with granulomatous diseases (eg,tuberculosis and other chronic infections,Wegener granulomatosis, sarcoidosis) mayrequire consultation with infectious diseasespecialists, rheumatologists, or pulmonologists
Patients with malignancy-relatedhypercalcemia should be referred to anoncologist
Patients with endocrine disorders should bereferred to an endocrinologist
Patients with granulomatous diseases (eg,tuberculosis and other chronic infections,Wegener granulomatosis, sarcoidosis) mayrequire consultation with infectious diseasespecialists, rheumatologists, or pulmonologists
WHEN TO ADMIT
Patients with symptomatic or severehypercalcemia require immediatetreatment
Unexplained hypercalcemia withassociated conditions, such as acutekidney injury or suspected malignancy,may also require hospitalization fortreatment and expedited evaluation
Patients with symptomatic or severehypercalcemia require immediatetreatment
Unexplained hypercalcemia withassociated conditions, such as acutekidney injury or suspected malignancy,may also require hospitalization fortreatment and expedited evaluation
The End