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)