Updated: 10/25/2018

Hyperparathyroidism

Topic
Review Topic
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Questions
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Evidence
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Snapshot
  • 55-year-old woman has hypercalcemia discovered as an incidental finding during normal routine physical examination. A hand radiograph is shown at right.
Introduction
  • Increased parathyroid hormone (PTH) production that may be of primary, secondary or tertiary causes
  • Pathophysiology
    • PTH indirectly stimulates osteoclasts by binding to its receptor on osteoblasts, inducing RANK-L and M-CSF synthesis
  • Epidemiology
    • occurs in 0.1% of the population
    • 90% result from a single adenoma
    • remaining 10% from parathyroid hyperplasia
    • parathyroid carcinoma accounts for less than 1% of all cases
Classification
  • Primary 
    • typically the result of hypersecretion of PTH by a parathyroid adenoma/hyperplasia 
    • may result in osteitis fibrosa cystica
      • breakdown of bone
      • common involves the jaw
  • Secondary
    • secondary parathyroid hyperplasia as compensation from hypocalcemia or hyperphosphatemia
      • ↓ gut Ca2+ absorption
      • ↑ phosphorous
    • associated conditions
      • chronic renal disease
        • renal disease causes hypovitaminosis D
          • leads to ↓ Ca2+ absorption 
      • renal osteodystrophy
        • bone lesions due to secondary hyperparathyroidism 
  • Tertiary
    • parathyroid glands become dysregulated after secondary hyperparathyroidism
      • secrete PTH regardless of Ca2+ level
     
    Serum Ca
    Serum Phos
    Serum PTH
    Primary
    Secondary
    normal or ↓
    Tertiary
Presentation
  • Symptoms
    • often asymptomatic
    • weakness
    • kidney stones ("stones")
    • bone pain ("bones")
    • constipations ("groans")
Evaluation
  • Serology
    • primary
      • hypercalcemia
      • ↑ PTH
    • secondary
      • hypocalcemia/normocalcemia 
      • ↑ PTH
    • malignancy
      • ↓ PTH
    • ↑ alkaline phosphatase
    • normal anion gap metabolic acidosis
      • ↓ renal reclamation of bicarbonate
  • Urinalysis
    • primary
      • hypercalciuria (renal stones)
      • ↑ cAMP
  • Radiograph
    • cystic bone spaces ("salt and pepper")
      • often in the skull
    • loss of phalange bone mass
      • ↑ concavity (see key image of this topic)
    • subperiosteal thinning (cortical resorption) 
  • EKG
    • shortened QT
Treatment
  • Operative
    • resect adenoma/hyperplastic glands
      • indications
        • primary hyperparathyroidism with adenoma
      • outcome
        • curative if present
  • Pharmacologic
    • hydration followed by furosemide
      • ↑ excretion of calcium
    • bisphosphonates
    • cinacalcet 
      • calcium mimetic that decreases PTH production in the parathyroid glands
Complications
  • Peptic ulcer disease
    • ↑ gastrin production stimulated by ↑ Ca2+
  • Acute pancreatitis
    • ↑ lipase activity stimulated by ↑ Ca2+
  • CNS dysfunction
    • anxiety, confusion, coma
    • result of metastatic calcification of the brain
 

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Questions (6)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
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(M1.EC.75) A 54-year-old female presents to her primary care physician with complaints of fatigue, constipation, and what the patient describes as "aching in her bones." Her medical history is significant for hypertension, well-controlled on lisinopril, and two prior kidney stones that both passed spontaneously without need for surgery. Vital signs are within normal limits, and physical exam is not significant for any notable findings. Preliminary lab work is ordered and reveals: calcium 11.6 mg/dL (normal range 8.5 - 10.9 mg/dL), phosphorus 2.1 mg/dL (normal range 2.4 - 4.1 mg/dL), and an elevated parathyroid hormone (PTH) level. Which of the following findings would most likely be expected on radiographic evaluation of this patient's hands? Review Topic

QID: 106788
1

Joint space narrowing at the proximal and distal interphalangeal joints

4%

(5/127)

2

Osteoid matrix accumulation around bony trabeculae

19%

(24/127)

3

Subperiosteal cortical thinning

66%

(84/127)

4

Ulnar deviation of the metacarpophalangeal joints

2%

(2/127)

5

Dense bone filling the medullary cavity of the phalanges and metacarpals

6%

(8/127)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M1.EC.14) A 52-year-old female presents to clinic complaining of sudden onset of flank tenderness that was fluctuating and radiating into her groin. Laboratory analysis reveals a serum calcium of 12.4 (normal 8.4-10.2) and a serum phosphorous of 2.5 (normal 2.7-4.5) and a chloride:phosphorous ratio >33. You suspect primary hyperparathyroidism. Which of the following mechanisms is responsible for the patient’s current condition? Review Topic

QID: 101951
1

PTH binding to receptors on osteoclasts

46%

(6/13)

2

Parafollicular, or C-cell, synthesis of calcitonin

15%

(2/13)

3

Increased RANK-L production

31%

(4/13)

4

Decreased M-CSF production

8%

(1/13)

5

Increased synthesis of osteoid by osteoblasts

0%

(0/13)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 3

(M1.EC.21) A 65-year-old female with chronic renal failure presents with recent onset of bone pain. Serum analysis reveals decreased levels of calcium and elevated levels of parathyroid hormone. One of the mechanisms driving the elevated PTH is most similar to that seen in: Review Topic

QID: 100322
1

End stage liver failure

45%

(5/11)

2

Insufficient Ca intake

18%

(2/11)

3

Parathyroid adenoma

9%

(1/11)

4

Decreased functioning of the calcium-sensing receptor (CASR)

9%

(1/11)

5

Sarcoidosis

9%

(1/11)

M1

Select Answer to see Preferred Response

PREFERRED RESPONSE 1
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