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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

- Genetics: - Associated with multiple endocrine neoplasia type 1: - Hyperparathyroidism - Pancreatic islet disease - Pituitary disease

- Neonate: - Hypotonia, weakness, and listlessness - Following delivery to hypoparathyroid mothers

- Hypercalcemic infants: - Broad forehead - Epicanthal folds - Underdeveloped nasal bridge - Prominent upper lip

- 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)

- 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

- 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)

- 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

  • Parathyroid hormone (PTH) excess with symptoms owing to PTH actions:Decreases urinary Ca2+ lossIncreases urinary PO42- lossStimulates vitamin D conversion from 25(OH)-D to 1,25(OH)-D in kidneyLiberates Ca2+ and PO42- from boneHypercalcemia 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 PTHEssential for action of PTH in target tissues
  • Genetics:Associated with multiple endocrine neoplasia type 1:HyperparathyroidismPancreatic islet diseasePituitary diseaseAssociated 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, vomitingMental obtundation

History

Depends on the severity and rapidity of hypercalcemia

  • Neonate:Hypotonia, weakness, and listlessnessFollowing delivery to hypoparathyroid mothers
  • Hypercalcemic infants:Broad foreheadEpicanthal foldsUnderdeveloped nasal bridgeProminent upper lip

Physical Exam

  • Dehydration
  • Cardiac:Hypertension (even in the face of dehydration)Cardiac conduction abnormalities (not proportional to degree of hypercalcemia)BradydysrhythmiaBundle branch blocksComplete heart blockAsystoleShort QT interval (shortened ST segment)Potentiation of digitalis effects (Hypercalcemia +digoxin = digitalis toxicity)
  • Neurologic:HeadachesDecreased reflexesProximal muscle weaknessDementiaLethargyComa
  • Psychiatric:Personality changesDepressionInability to concentrateAnxietyPsychosis
  • GI:Anorexia, nausea, vomitingConstipationPeptic ulcer diseasePancreatitis
  • General:FatigueWeight lossPolyuria and polydipsia
  • Musculoskeletal:Gout/pseudogoutBone pain, bone cysts (osteitis cystica)ArthralgiasChondrocalcinosis
  • Renal:Kidney stonesNephrocalcinosisDecreased renal concentrating ability

Essential Workup

  • Calcium level
  • Albumin:Elevated albumin-falsely elevated calcium levelLow 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:AsymptomaticNormal ECGCalcium 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 calciumChest radiograph (for CHF/malignancy)PhosphorusElectrolytes, BUN, creatinineSedimentation rateAlkaline phosphataseMagnesiumThyroid-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 hyperparathyroidismUsually high in secondary hyperparathyroidismNormal or high in malignancy-related hypercalcemia
  • Chloride/PO42- ratio:>33-hyperparathyroidism<30-malignancy
  • Alkaline phosphatase:Increased in 50% of patients with hyperparathyroidismNormal with vitamin D excess
  • Erythrocyte sedimentation rate (ESR):Normal in hyperparathyroidismElevated in malignancy or granulomatous diseases
  • Anemia:Present with malignancy or granulomatous diseaseAbsent in hyperparathyroidism
  • Magnesium:
  • 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 hydrationGranulomatous 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 hyperparathyroidismFamilial 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 diureticsLithiumAluminum-containing antacidsTamoxifenEstrogensAndrogensVitamin A

Treatment

Pre-Hospital

May present as a primarily psychiatric disorder

Initial Stabilization/Therapy

  • Cardiac monitor if:Symptomatic hypercalcemiaCa2+ 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 hrAchieve urine output 100 mL/hrAdminister furosemide or other loop diuretic (calciuric) after adequate volume replacement or in the presence of CHF:Common error: Administration of furosemide before adequate hydrationIf urinary sodium losses exceed replacement sodium, then renal conservation measures impede calcium excretionAvoid 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 diseasesStart bisphosphonates (pamidronate or etidronate) in conjunction with primary physician (inhibits calcium mobilization from bone)
  • Treat cardiac dysrhythmias in standard fashion:
  • 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 contraindicatedTest dose: Intradermal 0.1 mL of 10 U/mL solution recommendedInitial dose: 4 U/kg SC q12h
  • Pamidronate:If albumin-corrected Ca2+ level 12-13.5 mg/dL: 60 mg IV infused over 2 hrIf albumin-corrected Ca2+ level > 13.5 mg/dL: 90 mg IV over 4 hrDosage 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.

See Also (Topic, Algorithm, Electronic Media Element)

Hypoparathyroidism

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)