Week 4: Hypercalcemia Flashcards
Causes of hypercalcemia
- Due to bone resorption
- malignancy: most common
- immobilization: loss of gravity promotes bone loss. e.g. astronauts
- hyperthyroidism - Hyperabsorption of dietary Calcium
- vitamin D intoxication
- granulmatous disease (sarcoid, e.g.): antigen binds to macrophage, stimulates 1a hydroxylase. If macrophage can’t process antigen, continued production of 1,25 VitD - Increased renal tubular calcium reabsorption
- familial hypocalciuric hypercalcemia
- thiazide diuretics
- litium: alters set point takes more Ca to turn off PTH
Epidemiology of hypercalcemia
- major cause-54%- due to primary hyperparathyroidism
- malignancy-35%
- all else 12%
Steps to evaluating hypercalcemia
- Is patient taking any drugs that raises serum Ca levels?
- Is elevated serum Ca value real? need to correct for albumin
- is hypercalemia PTH or non PTh mediated
- is patient symptomatic from high serum Ca levels?
how to calculate corrected serum Ca value?
For every 1 g less than 4 for the patient’s albumin level, add 1 (or is it 0.8) to the patient’s serum calcium that is measured
malignancy as cause of hypercalcemia
- Humoral hypercalcemia of malignancy
- PTH related protein (PTHrP) secretion
- 1,25(OH)2VitD: some lymphomas - Multiple skeletal metastasis
- growth factors released in bone breakdown attracts tumor cells. Causes tumor growth, tumors produce inflammatory response and stimulates osteoclastic bone resorption: cycle of bone resorption - Hematologic malignancy: multiple myeloma
- Il-1 and other factors stimulates osteoclast and leads to bone breakdown - coexistant primary hyperparathyroidism
Most common malignancies associated with hypercalcemia.
- lung and breast cancer metastases are most common
- then hematologic cancers such as myeloma and lymphoma
Primary hyperparathyroidism
- 80% adenoma.
- If Ca levels above 16, think carcinoma
- young individuals under 30: think familial and MEN Type I and IIa
- primary hyperparathyroidism is mostly in post menopausal women
- Increased Ca from: increased reabsorption from kidneys, increased resorption of bone, increased active Vit D to increase absorption from gut
Primary hyperPTH vs. FHH (familial hypocalciuric hypercalcemia)
-FHH is a benign condition that presents similarly to primary hyperPTH
-Do fasting spot urine and serum Ca and Cr
-Calculate a Ca/Cr ratio (U(ca)x S(Cr)/ S(ca) x U(cr)
Normal ratio-0.1
FHH ratio is less than 0.01 (stay away from surgery)
Primary hyperparathyroidism has ratio greater than 0.01
Symptoms of primary hyperparathryoidism
Mostly asymptomatic
- Gastrointestinal
- dry mouth, thirst, polydipsia: due to partial nephrogenic diabetes insidious
- anorexia, nausea, vomiting
- constipation
- rare pancreatitis - GU
- polyuria, nocturia
- renal stones and nephrocalcinosis
- uremia - metastatic calcification
- corneal and conjunctival calcification
- nephrocalcinosis
- vascular calcification - MSK
- fatigue, muscle weakness, arthralgia, bone pain, chonedrocalcinosis, osteoporosis - Neurological: at high calcium levels
- drowsines,s lethargy,stupor, coma, confusion, decreased DTRs
Osteitis fibrosa cystica
- if high alk phosphatase, look for this
- very vulnerable to fractures
- also called Brown’s tumors
- from chronic long standing hyperPTH
Tests to evaluate hypercalcemia
- serum calcium: corrected
- serum albumin
- serum parathyroid hormone
- serum 1,25(OH)2VitD: only due in case of granulomatous diseases or lymphomas
Using PTH value to determine cause of hypercalcemia
- hyperparathyroidism: PTH is inappropriately normal or high
- in malignancy: PTH is undetectable. If it is present, there’s another underlying condition.
Treatment of mild hypercalcemia
- if asymptomatic
- ambulate, avoid inactivity
- avoid salt restriction and dehydration: dehydration can increase Na along with Ca reabsorption
- avoid diuretics
- restrict dietary calcium only if hypercalcemia is mediated by active VitD
Treatment of moderate or severe hypercalcemia
- symptomatic
- rehydrate with normal saline: increasing blood volume will cause natriuresis via Na/Ca channel
- increase renal calcium excretion
- decrease bone resorption: Pamidronate and Zoledronic acid-they inhibit osteoclast activity and lower serum Ca
Indications for surgical treatment of symptomatic patients with primary hyperparathyroidism
- Bone mineral density T-score of 1mg/dl above the reference range.
- Urine calcium > 400 mg per day
- Creatinine clearance reduced by 30% or more relative to age.
