Hypercalcemia secondary to

Primary
Hyperparathyroidism
Emily Kingsley, MD
Med-Peds II
 90% of cases of hypercalcemia are due to
hyperparathyroidism and malignancy
– HyperPTH: asymptomatic with chronic hypercalcemia,
postmenopausal woman, normal physical examination, family
history of hyperparathyroidism, and evidence of multiple
endocrine neoplasia
– Malignancy: Higher
H concentrations of and more rapid increases
in serum calcium and subsequently are more symptomatic

 Ambulatory: Healthy patients, usually due to primary

hyperparathyroidism
 Hospital: Usually due to malignancy
 Primary Hyperparathyroidism
 Usually due to parathyroid adenoma
 Typically have only small elevations in
serum calcium concentrations (less than
11 mg/dL) and sometimes values are
high-normal
– May require multiple measurements
– Parathyroid crisis: uncommon but acute
onset of severe, symptomatic hypercalcemia
 Secondary HyperPTH
 Seen in severe chronic kidney disease
 Usually low or normal serum calcium
values
 Few with hypercalcemia have decreased
bone turnover
 Tertiary HyperPTH: Parathyroid
hyperplasia to autonomous overproduction
of PTH
 Malignancy
 Mechanism of increased bone resorption
depends on the cancer
– Bony mets: direct induction of osteolysis by tumor
cells through the use of cytokines (TNF, IL-1)
– Nonmetastatic solid tumors: PTHrP
– Lymphoma: PTH-independent extrarenal production
of calcitriol from mononuclear cells

 Hypercalcemia with values above 13mg/dL

– Unusual in hyperparathyroidism
 Other causes of hypercalcemia
 Thyrotoxicosis: usu. mild hypercalcemia
 Immobilization
 Paget disease of bone
 Hypervitaminosis A
 Hypervitaminosis D
– Calcitriol used with renal failure has short half life
– Calcidiol has longer half life so symptomatic pts.
may need steroids and bisphosphonate
 Sarcoidosis, Wegener’s granulomatosis
 Milk Alkali Syndrome: can occur in the setting of excess
calcium carbonate supplementation to treat osteoporosis
or dyspepsia
 Lithium: increased secretion of PTH due to an increase
in the set point at which calcium suppresses PTH release
 Thiazide diuretics
 Pheochromocytoma
 Adrenal insufficiency
 Theophylline toxicity
 Familial hypocalciuric hypercalcemia: loss-of-function
mutation in the calcium-sensing sensor on the
parathyroid cells and in the kidneys
 Clinical Manifestations
 Ranges from asymptomatic to obtundation and coma
 Mild hypercalcemia (calcium <12 mg/dl):
Asymptomatic or nonspecific symptoms (constipation,
fatigue, and depression)
 Moderate hypercalcemia (calcium 12 to 14 mg/dL):
– may be well-tolerated chronically
– Acute rise to these concentrations may cause marked symptoms:
polyuria, polydipsia, dehydration, anorexia, nausea, muscle
weakness, and changes in sensorium.
 Severe hypercalcemia (calcium >14 mg/dL):
progression of symptoms
…Bones, stones, moans, and groans
 NEURO/PSYCH  CARDIAC
– Anxiety – Shortening of the QT interval
– Depression
– Bradycardia
– Cognitive dysfunction
– Lethargy – Hypertension
– Stupor
– Coma

 GI  RENAL
– Constipation – Polyuria: decr. concentration in distal tub.
– Anorexia – Nephrolithiasis
– Nausea – Acute/Chronic renal insuffic.
 Serum calcium of 12 to 15 mg/dL can lead
– Pancreatitis to a reversible fall in GFR from direct renal
– Peptic ulcer disease vasoconstriction
 Long-standing hypercalcemia and
hypercalciuria: Calcification, degeneration,
 MSK and necrosis of the tubular cells →Tubular
atrophy and interstitial fibrosis and
– Bone pain calcification (nephrocalcinosis).
– Profound muscle weakness
 Assessment
Normal or
Primary HyperPTH
PTHrP
Calcium PTH Malignancy Vitamin D levels
Vit D intoxication TSH
Granulomatous dis. SPEP/UPEP
Vitamin A levels

 Correction for the measured calcium concentration in

hypoalbuminemia

Ca = Serum Ca + 0.8 * (Normal Albumin – Pt

Albumin)
Haden, ST, Brown, EM, Hurwitz, S, et al. The effects of age and gender on parathyroid hormone dynamics.
Clin Endocrinol 2000; 52:329.
 25-OH Vitamin D: Usually due to ingestion
 1,25-OH Vitamin D: Ingestion, granulomatous diseases,
lymphoma, primary hyperparathyroidism
– Increased: Recommend CXR → Sarcoidosis, Lymphoma

Granulomatous dis. Milk Alkali Syndrome

Normal or Vitamin D intoxication Metastatic bone dis.
Thyrotoxicosis Immobilization

Phosphate
HyperPTH
PTHrP malignancy
-Inhibition of renal proximal tubular
Phosphate resorption
 Treatment of Hypercalcemia
 Degree of hypercalcemia and rate of rise
determine symptoms and urgency of
treatment
– Calcium >14mg/dL: Require treatment
regardless of symptoms
– Calcium 12-14mg/dL:
 Chronically maybe be tolerated
 Acutely may lead to AMS
 Ways to Correct Hypercalcemia

 Isotonic Saline
– Treats volume depletion from calcium-induced urinary salt
wasting
– Increases renal perfusion and urinary calcium clearance

– Administration: Initial rate of 200-300ml/hr adjusted for urinary

output of 100ml/h
 Limited in those with cardiac or renal disease
 Should be discontinued with development of edema
– Goal: Euvolemia
 Rarely normalizes calcium level
 Bisphosphonates
– Analogs of inorganic pyrophosphate that absorb to the
surface of bone hydroxyapatite inhibiting calcium
release by interfering with osteoclast-mediated bone
resorption
– More potent than Saline and Calcitonin

– Administration: IV Zoledronic acid preferred due to

potency and short administration time (15 min.)
 Single dose due to risk of osteonecrosis of jaw with
repeat doses
– Effect: Seen in 2-4 DAYS
 Calcitonin
– Decrease bone reabsorption by interfering with
osteoclast maturation
– Increase renal calcium excretion

– Administration: IM or subcut, nasal not effective

– Effect: Rapid with lowering within 4-6 HOURS
 Decreases the serum calcium up to a maximum of 1 to 2
mg/dL
 Efficacy limited to 48 HOURS
 Glucocorticoids
– Useful with calcidiol ingestion
– Useful with hypercalcemia from increased
calcitriol production seen in granulomatous
disease and lymphoma
 Decreases calcitriol production by activated
mononuclear cells in the lung and lymph nodes

– Administration: 20-40mg/day
– Effect: Seen in 2-5 days
 Dialysis
– Indications:
 Severe hypercalcemia (18
( to 20 mg/dL) with
neurologic symptoms
 Limited use of IV hydration:
– Renal insufficiency
– Heart failure
 In Sum…
 Mild (<12mg/dl): No therapy
– Avoid thiazide diuretic, lithium, calcium ingestion
(>1000mg/day), volume depletion, prolonged bedrest
 Moderate (12-14mg/dl): Treat if
symptomatic or an acute rise
 Severe (>14mg/dl): IV saline (immediate
effect), calcitonin (immediate effect),
bisphosphonate (delayed but most effective)

 Primary hyperparathyroidism: Parathyroidectomy

 And the calcium lived
happily ever after…

(What would a Med-Peds presentation

be without a Sponge Bob reference?!?!)
 HUNGRY BONE SYNDROME
 Develops in those with bone disease
preoperatively due to a chronic increase in bone
resorption from high levels of PTH
 Sudden withdrawal of PTH causes increased
osteoblast-mediated bone formation and marked
net increase in bone uptake of calcium,
phosphate, and magnesium
 Syndrome most likely to be present if if the
serum calcium concentration <8.5 mg/dL and
the serum phosphate concentration <3.0 mg/dL
on the 3rd postoperative day
 Hypocalcemia
– Tetany, seizures, heart failure
– Treatment:
 Oral calcium (2 to 4 g per day): Between meals to avoid phosphate binding
 IV calcium: With rapid reduction in serum calcium OR symptoms related to
hypocalcemia OR plasma calcium concentration below 7.5 mg/dL

 Hypophosphatemia: With significant bone disease

– Replacement only in severe hypoPO4 (below
( 1 mg/dL): Combines with
calcium to further reduce calcium concentration
– BUT with lack of severe bone disease: See increase in phosphate due
to reversal of PTH-induced phosphate loss in the urine

 Hypomagnesemia
– Can contribute refractory hypocalcemia by diminishing PTH secretion
and inducing PTH resistance

 Hyperkalemia
THANK YOU!
 References
 Bilezikian, J. Clinical review 51: Management of
hypercalcemia. J Clin Endocrinol Metab 1993;
77: 1445-1449.
 Haden, ST, Brown, EM, Hurwitz, S, et al. The
effects of age and gender on parathyroid
hormone dynamics. Clin Endocrinol 2000;
52:329.
 Marx, S. Hyperparathyroid and hypoparathyroid
disorders. N Engl J Med 2000; 343: 1863-1875.
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