Hyperparathyroidism, Emergency Medicine

Basics

Description

Parathyroid hormone (PTH) excess with symptoms owing to PTH actions:
- Decreases urinary Ca2+ loss
- Increases urinary PO42- loss
- Stimulates vitamin D conversion from 25(OH)-D to 1,25(OH)-D in kidney
- Liberates Ca2+ and PO42- from bone
- Hypercalcemia is the primary metabolic finding
Hypercalciuria from hypercalcemia (despite decreased urinary loss) produces increased magnesium loss in urine
Magnesium (negative feedback to prevent hypercalcemia causes hypomagnesaemia):
- Cofactor in the production of PTH
- Essential for action of PTH in target tissues
Genetics:
- Associated with multiple endocrine neoplasia type 1:
  - Hyperparathyroidism
  - Pancreatic islet disease
  - Pituitary disease
- Associated with multiple endocrine neoplasia type 2:
  - Hyperparathyroidism (type 2A, rare in 2B)
  - Medullary carcinoma of the thyroid (type 2A and 2B, less virulent in type 2A)
  - Pheochromocytoma (type 2A and 2B)
  - Mucosal neuroma (type 2B)

Etiology

Excess secretion of PTH owing to:
- Primary hyperparathyroidism (adenoma 85%, hyperplasia 14%, carcinoma <1%)
- Secondary hyperparathyroidism (response to vitamin D deficiency or chronic renal failure with hyperphosphatemia):
  - Calcium is low or normal, but PTH levels are elevated

Diagnosis

Signs and Symptoms

Stones, bones, abdominal groans, and psychiatric moans

Hypercalcemic crisis:
- Anorexia, nausea, vomiting
- Mental obtundation

History
Depends on the severity and rapidity of hypercalcemia

Neonate:
- Hypotonia, weakness, and listlessness
- Following delivery to hypoparathyroid mothers
Hypercalcemic infants:
- Broad forehead
- Epicanthal folds
- Underdeveloped nasal bridge
- Prominent upper lip

Physical Exam

Dehydration
Cardiac:
- Hypertension (even in the face of dehydration)
- Cardiac conduction abnormalities (not proportional to degree of hypercalcemia)
- Bradydysrhythmia
- Bundle branch blocks
- Complete heart block
- Asystole
- Short QT interval (shortened ST segment)
- Potentiation of digitalis effects (Hypercalcemia +digoxin = digitalis toxicity)
Neurologic:
- Headaches
- Decreased reflexes
- Proximal muscle weakness
- Dementia
- Lethargy
- Coma
Psychiatric:
- Personality changes
- Depression
- Inability to concentrate
- Anxiety
- Psychosis
GI:
- Anorexia, nausea, vomiting
- Constipation
- Peptic ulcer disease
- Pancreatitis
General:
- Fatigue
- Weight loss
- Polyuria and polydipsia
Musculoskeletal:
- Gout/pseudogout
- Bone pain, bone cysts (osteitis cystica)
- Arthralgias
- Chondrocalcinosis
Renal:
- Kidney stones
- Nephrocalcinosis
- Decreased renal concentrating ability

Essential Workup

Calcium level
Albumin:
- Elevated albumin-falsely elevated calcium level
- Low albumin-falsely lowered calcium level
Evaluate for symptoms of hypercalcemia, especially impending parathyroid storm (hypercalcemic crisis-anorexia, nausea, vomiting, obtundation progressing to coma).
Review history for medication ingestion (see Differential Diagnosis below)
No further ED workup if:
- Asymptomatic
- Normal ECG
- Calcium level <14 mg/dL when corrected for albumin
If symptomatic with Ca2+ <14 mg/dL or any patient with Ca2+ ≥14 mg/dL, check:
- Ionized calcium
- Chest radiograph (for CHF/malignancy)
- Phosphorus
- Electrolytes, BUN, creatinine
- Sedimentation rate
- Alkaline phosphatase
- Magnesium
- Thyroid-stimulating hormone (TSH)
- CBC

Diagnosis Tests & Interpretation

Lab

Calcium correction for albumin:
- Corrected Ca2+ (mg/dL) = measured Ca2+ (mg/dL) + 0.8 [4 - albumin (g/dL)]
- Acidosis:
  - Decreases affinity to albumin-increases ionized (metabolically active) Ca2+
  - Decrease of 0.1 pH unit increases the ionized Ca2+ by 3-8%
Phosphorus:
- Low in primary hyperparathyroidism
- Usually high in secondary hyperparathyroidism
- Normal or high in malignancy-related hypercalcemia
Chloride/PO42- ratio:
- >33-hyperparathyroidism
- <30-malignancy
Alkaline phosphatase:
- Increased in 50% of patients with hyperparathyroidism
- Normal with vitamin D excess
Erythrocyte sedimentation rate (ESR):
- Normal in hyperparathyroidism
- Elevated in malignancy or granulomatous diseases
Anemia:
- Present with malignancy or granulomatous disease
- Absent in hyperparathyroidism
Magnesium:
- Low or low normal
PTH:
- Elevated in primary and secondary hyperparathyroidism
PTH-related peptide:
- Secreted by squamous cell carcinomas of lung, head, neck; renal carcinomas, bladder carcinomas, adenocarcinomas, and lymphomas

Imaging

Chest radiograph:
- To assess CHF risk during IV hydration
- Granulomatous disease or malignancy if cause of hypercalcemia is uncertain

Diagnostic Procedures/Surgery
Definitive treatment is parathyroidectomy to treat and establish cause of hyperparathyroidism

Differential Diagnosis

PTH related:
- Primary or secondary hyperparathyroidism
- Familial hypocalciuric hypercalcemia
Malignancy related:
- PTH-related peptide or Ca2+ release from osteolytic tumor
Vitamin D related:
- Excess vitamin D intake or vitamin D production by granulomas
Immobilization:
- Associated with Paget disease
Drug induced:
- Thiazide diuretics
- Lithium
- Aluminum-containing antacids
- Tamoxifen
- Estrogens
- Androgens
- Vitamin A

Treatment

Pre-Hospital

May present as a primarily psychiatric disorder

Initial Stabilization/Therapy

Cardiac monitor if:
- Symptomatic hypercalcemia
- Ca2+ level >14 mg/dL
Hydrate with IV 0.9% NS.
Correct acidosis

Ed Treatment/Procedures

Treat hypercalcemia:
- Vigorous hydration with 0.9% NS at minimum of 250 mL/hr unless CHF:
  - Lowers calcium 1.5-2 mg/dL in 24 hr
  - Achieve urine output 100 mL/hr
- Administer furosemide or other loop diuretic (calciuric) after adequate volume replacement or in the presence of CHF:
  - Common error: Administration of furosemide before adequate hydration
  - If urinary sodium losses exceed replacement sodium, then renal conservation measures impede calcium excretion
- Avoid thiazide diuretics (impede calcium excretion)
- Consider glucocorticoid administration (decreases gut absorption and increases renal excretion of Ca2+); most effective with vitamin D intoxication or granulomatous diseases
- Start bisphosphonates (pamidronate or etidronate) in conjunction with primary physician (inhibits calcium mobilization from bone)
Treat cardiac dysrhythmias in standard fashion:
- Correct acidosis
Determine the cause of the hypercalcemia.
Stop all medications that may contribute to hypercalcemia
Exercise extreme caution in the use of digoxin.
Anticipate CHF and electrolyte imbalance with frequent reassessment of patient and monitoring of serum electrolytes and magnesium levels
Calcitonin if unable to use hydration
Emergent dialysis with renal failure

Medication

First Line

NS hydration: Initial 250-300 mL/h depending on patients propensity to CHF
Furosemide: 40 mg IV q2-4h after assurance of adequate hydration
Prednisone: 40-60 mg PO OR Hydrocortisone: 100 mg (peds: 1-2 mg/kg) IV

Second Line

IN CONSULTATION WITH ENDOCRINOLOGIST
Calcitonin salmon 4 U/kg SC if saline hydration contraindicated
- Test dose: Intradermal 0.1 mL of 10 U/mL solution recommended
- Initial dose: 4 U/kg SC q12h
Pamidronate:
- If albumin-corrected Ca2+ level 12-13.5 mg/dL: 60 mg IV infused over 2 hr
- If albumin-corrected Ca2+ level > 13.5 mg/dL: 90 mg IV over 4 hr
- Dosage should be reduced in renal impairment and infusion time may be extended to reduce nephrotoxic potential but no formal recommendations exist (pregnancy category D - maternal benefit may outweigh fetal risk)
Zoledronic acid: 4 mg IV over 15-30 min (first-line agent due to efficacy and convenience, but less preferred due to lack of less expensive available generic)
Cinacalcet (Sensipar): 30 mg PO daily or BID (calcimimetic for secondary hyperparathyroidism or parathyroid carcinoma)

Follow-Up

Disposition

Admission Criteria

Corrected calcium >14 mg/dL
Symptomatic hypercalcemia
Evidence of abnormal cardiac rhythm or conduction

Discharge Criteria

Not meeting admission criteria
Able to maintain adequate hydration

Issues for Referral
If diagnosis is suspected, referral to check PTH levels and response to therapy

Follow-Up Recommendations

If hyperparathyroidism is suspected arrange follow-up and send a PTH level
Patient needs to be instructed to maintain hydration and stop medications associated with hypercalcemia (see the list in Differential Diagnosis)

Pearls and Pitfalls

The hypercalcemia of hyperparathyroidism is rarely symptomatic and Ca2+ level rarely >14. (Higher levels are most frequently attributable to neoplastic disease)
The importance of diagnosis is to prevent long-term complications
Calcium level should be measured as ionized Ca2+, or corrected for albumin level
Administration of loop diuretics prior to adequate saline hydration will worsen hypercalcemia; some experts suggest that loop diuretics may be no longer warranted for this indication

Additional Reading

Andreoli TE, Carpenter CCJ, Cecil RL. Andreoli and Carpenters Cecil Essentials ofMedicine. 7th ed. Philadelphia, PA: Saunders-Elsevier; 2007.
Goldman L, Bennett JC, eds. Cecil's Textbook of Medicine. 23rd ed. Philadelphia, PA: Saunders-Elsevier; 2008.
Jamal SA, Miller PD. Secondary and tertiary hyperparathyroidism. J Clin Densitom. 2013;16(1):64-68.
Khan AA. Medical management of primary hyperparathyroidism. J Densitom. 2013;16(1):60-63.
Marcocci C, Cetani F. Primary hyperparathyroidism. N Engl J Med. 2011;365:2389-2397.

Codes

ICD9

252.00 Hyperparathyroidism, unspecified
252.01 Primary hyperparathyroidism
252.02 Secondary hyperparathyroidism, non-renal
252.08 Other hyperparathyroidism
252.0 Hyperparathyroidism

ICD10

E21.0 Primary hyperparathyroidism
E21.1 Secondary hyperparathyroidism, not elsewhere classified
E21.3 Hyperparathyroidism, unspecified
E21.2 Other hyperparathyroidism

SNOMED

66999008 hyperparathyroidism (disorder)
36348003 primary hyperparathyroidism (disorder)
91478007 secondary hyperparathyroidism (disorder)
254119005 neonatal hyperparathyroidism (disorder)
19034001 Hyperparathyroidism due to renal insufficiency (disorder)
47445009 Hyperparathyroidism due to vitamin D deficiency (disorder)

Home

Erectile Dysfunction

Doctor123.org