Case 5

• A 36-year-old woman is found to have hypercalcemia during routine

laboratory testing. She has a history of asthma.Current medications
include inhaled albuterol, and the patient takes a daily multivitamin
tablet. Her temperature is 36.7, BP is 120/70, pulse is 76, and
respirations are 14. Neurologic examination shows no focal deficits
and deep-tendon reflexes are normal. Laboratory results are as
follows:
 Labs
• Hematocrit 43% (M: 41% - 53% ; F – 36% - 46%)
• Serum calcium 11.2 mg/dL (8.4 – 10.2 mg/dL)
• Serum albumin 4.0 g/dL (3.5 – 5.5 g/dL)
• Serum creatinine 1.0 mg/dL (0.6-1.2 mg/dL)
 Case 5 - Approach
Anamnesis; Medications
Family with hypercalcemia symptoms/sequale?
Other diseases?  Bipolar? –treated? ?GERD?
 Medications  our patient  multivitamins, albuterol
Repeat lab (already done)
Baseline  1y ago  10.9

• What is the best next step to determine the cause of this patient’s
hypercalcemia?
 Intact PTH Levels
• Serum parathyroid hormone levels  61 (10-60 pg/mL)

What is the best next step?

 24-hour urinary calcium excretion!
• Elevated 24-hour urinary calcium excretion
• ≈ > 200 mg/dL  Primary hyperparathyroidism
• ≈ < 100 mg/dL  Familial hypercalcemic hypocalciuria
 Primary Hyperparathyroidism
• Epidemiology
• Most common cause of Ca
• Increased risk in MEN types 1 & 2A
• Etiology
• adenoma >> hyperplasia >>
carcinoma
• Diagnostic Findings
• Hypercalcemia
• Elevated/inappropriately
normal PTH
• Elevated 24-hour urinary
calcium excretion
 What are the
indications for
Parathyroidectomy
?
• Age < 50
• Symptomatic hypercalcemia
• Tertiary hyperparathyroidism
• Complications
• Osteoporosis (T-score < -2.5
fragility fracture)
• Nephrolithiasis/calcinosis
• CKD (GFR < 60 mL/min)
• Elevated risk for complications
• Calcium > 1 mg/dL above normal
• Urinary calcium excretion > 400
mg/day
Secondary & Tertiary Hyperparathyroidism
 What is the most common
cause of hypocalcemia with
normal/low PTH?
Iatrogenic (post-surgical) parathyroidectomy
• Commonly seen also in patient after large
goiter thyroidectomy, surgery for head &
neck cancer
• What is the differential diagnosis for
primary hypoparathyroidism?
• Autoimmune (PAS1 ± CaSR
autoantibodies)
• Primary hyperparathyroidism
+ Addison + Mucucutaneous
candidasis
• Genetic (DiGorge syndrome 
22q11 – CATCH; GCM2 mutation!
• Other rare (hemochromatosis,
Wilson disease, metastasis, HIV
infection)
 Case 6
• A 36-year-old woman comes to the office for evaluation of fatigue and
generalized weakness for the past several weeks. She has had no
appetite or weight changes, heat or cold intolerance, nausea or
vomiting, or constipation. The patient's medical and family histories
are unremarkable. Temperature is 36.7 C, blood pressure is 120/70,
pulse is 76, and respirations are 14. Physical examination shows
normal heart and lung sounds, an unremarkable abdominal
examination, and no focal neurologic deficits. Laboratory results are
as follows:
 Labs
• Calcium 7.8 mg/dL (8.4 – 10.2 mg/dL)
• Magnesium 1.7 mg/dL (1.5 – 2.0 mg/dL)
• Creatinine 0.9 mg/dL (0.6-1.2 mg/dL)
• Albumin 4.0 g/dL (3.5 – 5.5 g/dL)
• Serum parathyroid hormone 110 pg/mL (10-65 pg/mL)

What is the best next step in management of this patient?

 Serum-25-OH-
vitamin D levels!

• Inadequate sunlight  heavy skin

pigmentation, radiologist
• Malabsorption  Crohn, celiac, bariatric,
pancreatic insufficiency (CF)
• Inadequate intake  milk
avoidance/lactose intolerance, vegan
• Increased catabolism  phenytoin,
carbamazepine, INH, rifampin
• Metabolic disorders  chronic liver
failure, CKD (typically, GFR < 15)
 Other causes of
hypocalcemia with high
PTH
• Pancreatitis
• Precipitation of calcium soap
• Tumor lysis syndrome/Rhabdomyolysis
• Excess tissue/cells breakdown 
hyperphosphatemia  phosphate-calcium
binding  less free circulating calcium
• Pseudohypoparathyroidism
• Autosomal dominant GNAS1 mutation
(encodes for alpha-subunit PTH recepto = Gs)
 No activation of PTHR when PTH binds 
Resistance to PTH  persistent hypocalcemia
DESPITE high PTH levels!
 Case 7
• A 60-year-old man is brought to the emergency department by his daughter
due to a 2-day history of confusion and lethargy. According to the daughter,
he has had a constant dry cough, fatigue, anorexia, polyuria, and
constipation for several weeks. In addition, the patient has lost 9.1 kg (over
the past 3 months. He has no associated pain. The patient's medical history
is significant for hypertension treated with chlorthalidone and for
gastroesophageal reflux disease treated with over-the-counter antacids. He
smokes 2 packs of cigarettes daily and consumes alcohol occasionally. Blood
pressure is 130/90, pulse is 90/min. Temporal wasting is noted. Chest and
abdominal examinations are normal. Mental status examination shows
somnolence and disorientation to time. Neurologic examination shows
decreased deep tendon reflexes. Laboratory results are as follows:
 Labs
• Sodium 140 mEq/L (136 – 146 mEq/L)
• Potassium 4 mEq/L (3.5 – 5.0 mEq/L)
• Chloride 104 mEq/L (95-105 mEq/L)
• Bicarbonate 24 mEq/L (22-28 mEq/L)
• Creatinine 1.6 mg/dL (0.6-1.2 mg/dL)
• Calcium 14.4 mg/dL (8.4 – 10.2 mg/dL)
• Glucose 100 mg/dL (80-100 mg/dL)
• Alkaline phosphatase, serum 130 U/L (25-100 U/L)
• Phosphorus 2.2 mg/dL (25-100 U/L)

What is the most likely pathophysiology leading to this patient hypercalcemia?

 Answer: Elevated PTH-rP
Cause Tumor Type Mechanism Diagnostics
PTHrP Squamous cell PTH mimic Low PTH
Renal & Bladder High PTHrP
Breast & Ovarian
Bone metastases Breast Osteolysis Low PTH
Multiple myeloma High PTHrP
Low vitamin D
Calcitriol Lymphoma Increase Ca Low PTH
reabsorption High vitamin D
 Case 8
• A 65-year-old woman comes to the office for follow-up. Two months
ago, the patient was found to have low bone mineral density on
screening dual-energy x-ray absorptiometry. Her serum calcium and
vitamin D levels were within normal limits, and weekly alendronate
therapy was prescribed. After starting the bisphosphonate, the
patient has had burning epigastric discomfort and nausea, which are
controlled with daily over-the-counter antacids. She also has heart
failure, for which she takes furosemide. The patient consumes a
balanced diet and performs weight-bearing exercises regularly. Blood
pressure is 110/66 and pulse is 88/min. Physical examination is
normal. Laboratory results are as follows:
 Labs
• Sodium 143 mEq/L (136 – 146 mEq/L)
• Potassium 3.9 mEq/L (3.5 – 5.0 mEq/L)
• Bicarbonate 34 mEq/L (22-28 mEq/L)
• Creatinine 1.7 mg/dL (0.6-1.2 mg/dL)
• Calcium 12.1 mg/dL (8.4 – 10.2 mg/dL)
• Phosphorus 1.2 mg/dL (3.0-4.5 mg/dL)
• Magnesium 1.1 mg/dL (1.5 – 2.0 mg/dL)
 Case 8 - Approach
Anamnesis; Medications
Family with hypercalcemia symptoms/sequale?
Other diseases?  Bipolar? –treated? ?GERD – Never suffered from reflux
 Medications  our patient  multivitamins, albuterol
Repeat lab (already done)
Baseline  Serum creatinine was 0.8 mg/dL 2 months ago

What is the best next step in management of this patient?

STOP TAKING SO
MUCH ANTEACID
• Hypercalcemia + Metabolic alkalosis
+ AKI  Milk-Alkali Syndrome
• Type of HyperCa  HyperCa
with supressed PTH!
• Treatment
• Stop taking the causative
agent!
• Isotonic saline followed
by furosemide!
 Hypocalcemia - Treatment
• Severe and/or symptomatic hypocalcemia: e.g., tetany, seizures, prolonged QT interval, serum
calcium ≤ 7.5 mg/dL (< 1.9 mmol/L)
• IV calcium supplementation: calcium gluconate
• Continuous telemetry
• Mild and/or chronic hypocalcemia: no symptoms or only mild neuromuscular irritability (e.g.,
paresthesias), serum calcium 7.6–8.4 mg/dL (1.9–2.12 mmol/L)
• Oral calcium supplementation: calcium citrate, calcium carbonate
• Treatment of underlying cause
• Hypoparathyroidism
• Calcium supplementation
• Vitamin D supplementation
• Recombinant human PTH can reduce the amount of supplemental calcium and vitamin D required.
• Secondary to loop diuretics: consider discontinue loop diuretic and change medication to thiazides
• Vitamin D deficiency: vitamin D supplementation
• Hypomagnesemia-induced hypocalcemia: magnesium supplementation
 Hypercalcemia - Treatment
• Severe (calcium > 14 mg/dL) or symptomatic
• Short term (immediate treatment)  normal saline hydration + calcitonine
and avoid loop diuretics (unless volume overload – like HF – exist)
• Long term treatment  Bisphosphonate (zoledronic acid)
• Moderate (calcium 12-14 mg/dL)
• Usually no immediate treatment required unless symptomatic
• Treatment is similar to that of severe hypercalcemia
• Asymptomatic or mild (calcium < 12 mg/dL)
• No immediate treatment required
• Avoid thiazide, diuretics, lithium, volume depletion & prolonged bed rest (immobilization
can also cause hypercalcemia!)
References

• UpToDate
• Williams Endocrinology
• Endocrine and reproductive
physiology (MOSBY)
• Harrison's Principles of Internal
Medicine (Twenty-First Edition)
Thank You!