This document defines hypercalcemia and discusses its causes, evaluation, clinical presentation, and management. The main causes are parathyroid hormone dependent (primary hyperparathyroidism, tertiary hyperparathyroidism) and independent (malignancy, vitamin D related, endocrinopathies). Evaluation involves history, exam, and labs. Acute management is rehydration and medications to increase calcium excretion. Long term management depends on the underlying cause and may involve surgery, bisphosphonates, glucocorticoids, or ketoconazole.

1. By
Hazem Samy Hussein
Ass. Lecturer of internal medicine

2. Defination
 Hypercalcemia is defined as total serum calcium
> 10.5 mg/dl or ionized serum calcium > 5.6
mg/dl.

4. Hormone Effect on bones Effect on gut Effect on
kidneys
Parathyroid
hormone
increase Ca++,
decrease PO4
levels in blood
Supports
osteoclast
resorption
Indirect effects
via increase
calcitriol from 1-
hydroxylation
Supports Ca++
resorption and
PO4 excretion,
activates 1-
hydroxylation
Calcitriol
(vitamin D)
Ca++, PO4
levels increases
in blood
No direct effects
Supports
osteoblasts
Increases Ca++
and PO4
absorption
No direct effects
Calcitonin
causes Ca++,
PO4 levels
decrease in
blood when
hypercalcemia is
present
Inhibits
osteoclast
resorption
No direct effects Promotes Ca++
and PO4
excretion

6. Clinical picture

7. Causes of Hypercalcemia
A. Parathyroid hormone-dependent
B. Parathyroid hormone-independent

8. A.Parathyroid hormone-dependent
hypercalcemia
1. Primary hyperparathyroidism
2. Tertiary hyperparathyroidism
3. Familial hypocalciuric hypercalcemia
4. MEN syndromes
5. Lithium therapy

9. B.Parathyroid hormone-
independent hypercalcemia
Malignancies
Vitamin-D related
Endocrinopathies
Other causes

10. Evaluation
Evaluation of a patient with hypercalcemia should
include a careful history and physical
examination focusing on
 clinical manifestations of hypercalcemia,
 risk factors for malignancy,
 causative medications,
 and a family history of hypercalcemia-
associated conditions

11. Primary hyperparathyroidism
 Most common cause of PTH-dependent
hypercalcemia.
 Adenoma(80%) ,four glands hyperplasia or carcinoma.
• May be part of MEN syndromes(1 or 2a).
• Typically : ↑PTH , ↓phosphorus ,↑ urine
Ca excretion.

12. Familial Benign Hypocalciuric
Hypercalcemia
 Far less common cause of PTH-dependent
hypercalcemia.
 Autosomal-dominant ,Caused by a calcium sensor
defect that ↑the set point for serum Ca.
 N. or Mild ↑ PTH,mild ↑Ca (10.5-12 mg/dL) and ↓urine
calcium excretion (<50 mg/24 h).
 asymptomatic and benign, the most important role of
diagnosis is to distinguish it from primary
hyperparathyroidism and avoid an unnecessary
parathyroidectomy.

13. Malignancy-Associated
Hypercalcemia
 Humoral hypercalcemia of malignancy,Caused by
PTHrP (solid tumors, adult T-cell leukemia syndrome)
 Caused by 1,25(OH)2D (lymphomas)
 Caused by ectopic secretion of PTH (rare,carcinoma of
lung,thymus and ovary)
 Local osteolytic hypercalcemia (multiple myeloma,
leukemia, lymphoma)

14. Vitamin-D related
hypercalcemia
 Vitamin D intoxication.
 Granulomatous diseases: due to increased conversion
of 25(OH)D to 1,25(OH)2D by macrophages
e.g.sarcoidosis, wagner’s granulomatosis ,T.B.,
lymphomas,etc.

15. Endocrinopathies
 Thyrotoxicosis : ↑bone turnover.
 Adrenal Insufficiency: volume contraction.

16. Other causes
 Immobilization due to ↑ bone resorption
 Acute renal failure precipitated by rhabdomyolysis .
 Other drugs: thiazides.

18. Acute management of
hypercalcemia
1)Serum Ca level <12mg/dl :usually asymptomatic
,monitor and treat underlying cause.

19. Acute management of
hypercalcemia
2) Serum Ca level ˃12mg/dl :
a)Normal Saline 2-4 L IV daily for 1-3 days
 Enhances filtration and excretion of CA++.
 Indication: Ca > 14 mg/dl, moderate Calcium with
symptoms.
 Caution: may exacerbate heart failure in elderly
patients. Lowers Calcium by 1-3 mg/dl

20. Acute management of
hypercalcemia
b)Furosemide: as necessary
 Inhibits calcium resorption in distal renal tubule.
 Indication: following aggressive hydration
 Caution: worsens hypercalcemia,hypokalemia,
dehydration if used before intravascular volume is
restored.

21. Acute management of
hypercalcemia
C)hemodialysis:if oliguric or anuric or severe
symptoms hemodialysis aginist low calcium bath.
d) synthetic salmon CT :
 may be administered at a dose of 4 to 8 IU/kg
subcutaneously every 12 hours.
 In patients with severe hypercalcemia and in those
with renal insufficiency that is refractory to
rehydration
 but most patients become totally refractory to CT
within days to weeks, so it is not suitable for chronic
use.

22. Long term management of severe
hypercalcemia
1)Primary hyperparathyroidism:
Clinical indications for surgery in patients with
primary hyperparathyroidism
 Significant symptoms of hypercalcemia.
 Nephrolithiasis.
 Low bone mineral density(T-score ≤2.5) at any site.
 Serum Calcium > 12 mg/dl.
 Age< 50 years.
 Infeasibility of longterm follow up.

23. Long term management of severe
hypercalcemia
2) Malignancy-Associated Hypercalcemia :
a)Intravenous bisphosphonates
 act by inhibiting osteoclastic bone resorption.
 pamidronate is 60 to 90 mg by intravenous
infusion over 1 hour or zoledronic acid is 4 mg
infused over 15 minutes.
 Fever is most common side effect and renal
toxicity is most serious.

24. Long term management of severe
hypercalcemia
b) Other agents besides bisphosphonates may be
considered (eg, plicamycin or gallium nitrate), but
their toxicity and lack of superior efficacy discourage
their use. Both agents act to inhibit osteoclastic bone
resorption.
c)Glucocorticoids: hematologic malignancies (40-60
mg daily).

25. Long term management of severe
hypercalcemia
3)Other causes of hypercalcemia:
a)Glucocorticoids:
first-line treatment for hypercalcemia in patients
with multiple myeloma, lymphoma, sarcoidosis, or
intoxication with vitamin D or vitamin A.
b)ketoconazole: useful alternative or adjunctive to
glucocorticoids in granulomatous diseases or
vitamin-D intoxication.