Hypercalcemia
Download
Report
Transcript Hypercalcemia
Hypercalcemia
Case
56 Y O F with generalized body pain for 1 day
Also decreased PO intake
Expressive aphasia due to CVA, cannot give further
history
PMH to de discussed later…
PE:
Vitals stable
Moderate respiratory distress
Somnolent but arousable
Breath sounds only in R chest
Case, Continued
Labs:
Chem: 138/3.5/94/33/40/0.5 <114 – baseline BUN 7
Ca 19.8 – 11.9 one week prior
CXR: complete opacification of L hemi-thorax.
Volume loss, scarring and bronchiectasis in R lung
Next: What’s the first test you would order?
And what’s the diagnosis?
Answers
PTH < 3 when repeat Ca 18.6
History of NSCLS, squamous cell carcinoma, with
intrabronchial invasion
Important concepts in endocrine:
1- Two labs values are better than one; 3 is even better!
2- Timing
3- Inappropriately “normal” values
Synthesis and Metabolism of Vitamin D in the Regulation of Calcium, Phosphorus, and Bone
Metabolism.
Holick MF. N Engl J Med 2007;357:266-281.
Diagnostic Work Up
PTH
PTH-dependent
•Primary Hyperparathyroidism
•Familial Hypocalciuric
Hypercalcemia
•Lithuim Toxocity
•Tertiary Hyperparathyroidism
PTH-independent
•Hypercalcemia of Malignancy
•Vit D Intoxication
•Granulomatous Disease
•Hyperthyroidism
•Vit A Intoxication
•Adrenal Insufficiency
•Milk-Alkali Syndrome
•Thiazide Diuretics
•Immobilization
Why is PTH so important?
General Rules
PHPT is at least twice as common as all other causes
combined
Specially if pt seems well, hyperCa was found incidentally or is
mild, stable or known to be of long duration
More than 90% of pts referred to endocrine have PHPT
Among ill or hospitalized pts, malignancy is the cause in more
than 50% of cases
Confirm elevated Ca levels by repeating test and checking
ionized Ca
History, PE, prior lab values, ….
Primary Hyperparathyroidism
Primary abnormality of parathyroid tissue
Inappropriate secretion of PTH
What is appropriate hypersecretion of PTH in response
to hypocalcemia?
Excessive PTH
Increased renal Ca reabsorption
Phosphaturia
1,25-OH2-Vit D synthesis
Bone resorption
Primary Hyperparathyroidism
Etiology
One or more parathyroid adenomas (75-80%)
Diffuse hyperplasia of all glands (20%)
Parathyroid carcinoma (1-2%)
“Classic” manifestations
Bone: increased resorption
Renal: recurrent Ca stones, nephrocalcinosis, impaired
concentrating ability, renal failure
GI: nausea, vomiting, constipation, abd pain, pancreatitis
Neuropsychiatric symptoms *
“Contemporary” PHPT
Many pts are incidentally found, asymptomatic
Some have nl Ca and elevated PTH, found during work up of
osteopenia
Natural course variable: bone loss, kidney disease, mortality
Management: observation vs. surgery
Hypercalcemia of Malignancy
Most malignancies produce hyperCa only when far advanced
Pts usually die 1-2 months after hypercalcemia is discovered
Polydipsia, polyuria, constipation, nausea, vomiting, but
especially dramatic changes in mental status
Mechanism
Local osteolytic hypercalcemia: bone mets, most often in MM
and breast cancer
Humoral hypercalcemia of malignancy: mediated by PTHrP,
mimics all actions of PTH. Squamous cell cancers (lung, H&N,
esophagus, cervix), breast cancer, RCC, bladder.
Vit D Intoxication
Needs ingestion of about 100,000 IU of vit D per day
In US most often Iatrogenic
Hypercalcemia can be severe and prolonged (fat stores)
25-OH-Vit D levels dramatically elevated
1,25-OH2-Vit D normal or even low due to down regulation
of renal 1α-hydroxylase by low PTH levels
Granulomatous Disease
Sarcoidosis, TB, fungal infections, HIV-related PCP infection,
Crohn’s disease
Unregulated production of active Vit D by macrophages
Pts unusually sensitive to vit D an can become hypercalcemic
after exposure to ultraviolet light, or oral vit D intake
Misc. Causes
Hyperthyroidism
Ca rarely >11
Direct action of thyroid hormone to promote bone resorption
Vit A Intoxication
Requires ingestion of > 10x RDA (5000 IU/d)
Also Accutane (acne) and Retin-A (acute promyelocytic
leukemia)
Adrenal Insufficiency
Thiazide Diuretics: in PHPT, sarcoidosis, excessive Ca intake
Misc. Causes
Milk-Alkali syndrome
Hypercalcemia, metabolic alkalosis, renal failure
First described when milk and Na bicarb were used to treat
PUD
Now seen with increasing use of Ca bicarb for PUD and
osteoporosis
Immobilization
Spinal cord injury or excessive casting
Increased bone resorption
Peak Ca in 4 week, can last up to one year
Management
Severe hypercalcemia > 14 mg/dl
Unusual in PHPT, unless a secondary mechanism is
present
Dehydration from nausea, vomiting, diuretics
Immobilization
Large PO calcium intake
Severe acute hypercalcemia usually result of
malignancy
Should we treat?
Treatment: 1, 2, 3, …
Correct Intravascular volume depletion: NS 2-4 lit/d
Discontinue diuretics
+/_ furoemide
Bisphosphonates: first choice in management of severe
hypercalcemia caused by osteolytic bone resorption
Not in milk-alkali syndrome
Ca decreases within 24 h, reaches nadir within 1 week
Use half the dose in moderate renal insufficiency (GFR>30)
Effect lasts 1 week to several months
Treatment
Calcitonin: inhibits osteoclast function
Use with bisphosphonates for more rapid onset of
action (a few hours)
Ca decreases by 1-2 mg/dl
Effect lasts a few days
Steroids: PO or IV
Consider early in Vit D mediated hypercalcemia,
including granulomatous disease and lymphoma
Treatment
Follow Up
Ca repeated, 18.6 with PTH < 3
PTHrP 55 (15-27)
25-OH-Vit D and 1,25-OH2-Vit D <8
IV hydration
Calcitonin 200 IU q 12 (Ca 17.6 after 1st dose)
Pamidronate 60mg IV infusion
48 hours after admission Ca 12.9
Transferred to pall care, expired 6 d after admission
Case 1
49 y o F with laryngeal Ca s/p laryngectomy/chemo
and RT with resultant hypothyroidism and
hypoparathyroidism on replacement p/w weakness
Ca 15.6
PTH < 3
Cr 1.3 (baseline 0.8)
CO2 36
Dx?
Case 2
74 Y o M with colorectal Ca, dementia, dependant on
ADL’s p/w AMS
Ca 14.2 – Hgb 9 – Cr 5.1
PTH 21.4
SPEP: no M spike, UPEP not sent
PTHrP 23
25-OH-Vit D 35.7, 1,25-OH2-Vit D 16
Dx?
Ca 9.8 after hydration
Case 3
84 Y O F with Ehlers-Danlos syndrome, professor of
pediatric neurology at Einstein p/w AMS
Ca 16.2
PTH<3
SPEP, UPEP negative
25-OH-Vit D 127
Has been taking Vit D 5000 IU daily for “years”
Case 4
82 Y o f with HTN, endometrial Ca, COPD, morbid obesity
p/w inability to walk and b/l knee pain
Ca 16.9
PTH 7.7
Cr 1.6 (taking NSAIDs), Hgb 10.6
25-OH-Vit D 27.2, 1,25-OH2-Vit D < 8
SPEP: + M spike – serum free lambda >12,000
Bone survey: lucency in calvarium, b/l femur and humerus
Rx with IV hydration and steroids (semi-chemo)