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
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.
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.