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Hypoparathyroidism, Emergency Medicine

Basics

Description

- Hypoparathyroidism occurs secondary to a deficiency in parathyroid hormone (PTH) - Pseudohypoparathyroidism occurs secondary to end-organ unresponsiveness to PTH - PTH: - Decreases urinary Ca2+ loss - Increases urinary PO4 loss - Stimulates vitamin D conversion from 25(OH)-D to 1,25(OH)2-D in kidney - Liberates Ca2+ and PO4 from bone

- Genetics: - Congenital absence - DiGeorge syndrome: - Hypoparathyroidism - Thymic dysplasia - Severe immunodeficiency

- Autoimmune polyglandular syndrome type I - Hypoparathyroidism - Adrenal insufficiency - Mucocutaneous candidiasis

- Albright syndrome (hereditary osteodystrophy): - Short stature - Obesity - Round face - Short neck - Short 4th and 5th metacarpals and metatarsals (type I pseudohypoparathyroidism)

- Failure of parathyroid gland: - Autoimmune destruction - Surgical interruption of blood supply or gland removal - Radiation damage - Hypomagnesemia (PTH cofactor)

- Laryngospasm/bronchospasm - Blepharospasm - Muscle cramps - Tetany - Seizures (presenting symptom of 1/3 with hypoparathyroidism) - Increased intracranial pressure (ICP) with papilledema - Parkinson syndrome and other extrapyramidal disorders - Myelopathy

- Psychiatric: - Impaired memory - Confusion - Hallucinations - Dementia

- Dermatologic: - Brittle hair and nails - Psoriasis

- Gram-negative sepsis - Renal failure or nephrotic syndrome - Chelation: - Pancreatitis (fatty acids chelate calcium) - Ammonium bifluoride (tire cleaner spray) - Hydrofluoric acid - Citrated blood - Acute hyperphosphatemia: - Fleet enemas - Rhabdomyolysis - Acute renal failure

- For non-life-threatening conditions, administer calcium via slow infusion of 500-1,000 mg elemental Ca2+ over 6-24 hr (peds: 100 mg elemental Ca2+/kg/24 hr) - Continuous cardiac monitoring - Stop infusion if bradycardia develops - Perform frequent checks of serum Ca2+ levels - Calcium administration may precipitate digitalis toxicity - Supplement to lowest possible Ca2+ level keeping the patient asymptomatic, then switch to oral replacement: - Soft tissue calcification may occur with calcium/phosphorus product of 60 (Ca — PO4)

  • Hypoparathyroidism occurs secondary to a deficiency in parathyroid hormone (PTH)
  • Pseudohypoparathyroidism occurs secondary to end-organ unresponsiveness to PTH
  • PTH:Decreases urinary Ca2+ lossIncreases urinary PO4 lossStimulates vitamin D conversion from 25(OH)-D to 1,25(OH)2-D in kidneyLiberates Ca2+ and PO4 from bone
  • Hypocalcemia is the major metabolic derangement
  • Calcitonin:Promotes deposition of Ca2+ and PO4 into bone (produced primarily in C cells in thyroid)
  • Magnesium:Cofactor in production of PTHEssential for action of PTH in target tissues
  • Hypoparathyroidism:Primary failure of the parathyroid gland (may have associated Addison disease)
  • Pseudohypoparathyroidism:Tissue unresponsiveness with elevated PTH levelsAssociated with hypothyroidism and hypogonadism
  • Genetics:Congenital absenceDiGeorge syndrome:HypoparathyroidismThymic dysplasiaSevere immunodeficiencyWilson disease:Destruction of gland owing to copper depositionAutoimmune polyglandular syndrome type IHypoparathyroidismAdrenal insufficiencyMucocutaneous candidiasisAlbright syndrome (hereditary osteodystrophy):Short statureObesityRound faceShort neckShort 4th and 5th metacarpals and metatarsals (type I pseudohypoparathyroidism)

Etiology

  • Failure of parathyroid gland:Autoimmune destructionSurgical interruption of blood supply or gland removalRadiation damageHypomagnesemia (PTH cofactor)
  • End-organ unresponsiveness to PTH

Diagnosis

Signs and Symptoms

The most common symptomatic presentation is postoperatively after parathyroidectomy.

Neonates/infants:

  • Transient hypoparathyroidism in 1st yr of life
  • Below normal intelligence proportional to duration of hypocalcemia
  • Dental hypoplasia

History

  • Most common presentation is in the postoperative period after parathyroidectomy or thyroidectomy
  • Prolonged severe hypomagnesemia, in the alcoholic or high-dose diuretic patient, is the next most common presentation and can be slow in onset; usually less symptomatic

Physical Exam

  • Related to severity, rapidity of onset, and duration of hypocalcemia
  • General:
  • Neuromuscular:Paresthesias (especially circumoral and extremities)Carpal pedal spasmLatent spasm elicited by:Chvostek sign (twitching of circumoral muscles after tapping facial nerve in front of the tragus)Trousseau sign (spasm after inflating BP cuff 20 mm above patients systolic BP for 3 min)Laryngospasm/bronchospasmBlepharospasmMuscle crampsTetanySeizures (presenting symptom of 1/3 with hypoparathyroidism)Increased intracranial pressure (ICP) with papilledemaParkinson syndrome and other extrapyramidal disordersMyelopathy
  • Cardiovascular:Prolonged QT interval (owing to ST-segment prolongation)Heart blockCHFVentricular fibrillation (VFib)Vasoconstriction
  • Psychiatric:Impaired memoryConfusionHallucinationsDementia
  • Dermatologic:Brittle hair and nailsPsoriasis
  • Hyperpigmentation:

Essential Workup

  • If no hypocalcemic symptoms with hypocalcemia, check albumin level:If still low after correcting for hypoalbuminemia, check ionized Ca2+
  • If hypocalcemic symptoms with normal total Ca2+, check pH for alkalosis:If not alkalotic, check ionized Ca2+ (active form)Metabolic or respiratory alkalosis increases the binding to albumin reducing the ionized Ca2+
  • If hypocalcemic symptoms with low ionized Ca2+, check a PTH level:Low in primary hypoparathyroidism and in vitamin D deficiencyElevated in pseudohypoparathyroidism and hypocalcemia from renal failure

Diagnosis Tests & Interpretation

Lab

  • Calcium: Correct for albumin using formula:Corrected Ca2+ (mg/dL) = measured Ca2+ (mg/dL) + 0.8[4.0 - albumin (g/dL)]
  • Ionized Ca2+ if symptomatic with low total calcium
  • Electrolytes, BUN, creatinine, glucose
  • Magnesium
  • Arterial blood gas (ABG) if symptomatic with normal total Ca2+Elevation of 0.1 pH unit decreases the ionized Ca2+ by 3-8%.
  • Phosphorus:Elevated except when hypocalcemia caused by vitamin D deficiencyMetastatic calcification can cause hypocalcemia by tissue deposition when the calcium/phosphorus product is >60.

Diagnostic Procedures/Surgery

ECG:

  • Prolonged QT interval:Owing to ST-segment prolongation from hypocalcemia

Differential Diagnosis

  • Must differentiate from a variety of causes of hypocalcemia
  • Lab artifact:Low total calcium that is normal when corrected for albumin level with no symptoms of hypocalcemia
  • Alkalosis:Symptomatic hypocalcemia with a normal total calcium
  • Hypomagnesemia (needed for PTH secretion)
  • PTH resistance (congenital)
  • Vitamin D deficiency (low Ca2+ + low PO4):Anticonvulsant use (decreased vitamin D absorption)Liver diseaseResistance to vitamin DMalabsorption or dietary deficiency
  • Gram-negative sepsis
  • Renal failure or nephrotic syndrome
  • Chelation:Pancreatitis (fatty acids chelate calcium)Ammonium bifluoride (tire cleaner spray)Hydrofluoric acidCitrated bloodAcute hyperphosphatemia:Fleet enemasRhabdomyolysisAcute renal failure

Treatment

Pre-Hospital

  • Administer calcium in refractory VFib or status epilepticus in addition to usual medications if known hypoparathyroidism or suspected hypocalcemia
  • Stridor may herald laryngospasm

Initial Stabilization/Therapy

  • Airway, breathing, and circulation management (ABCs):Manage airway if laryngospasm
  • Administer IV calcium bolus (chloride or gluconate) if unstable cardiac rhythm or tetany:Slow infusion much safer unless patient markedly symptomatic
  • Prepare for ventricular dysrhythmias including VFib.
  • Seizure precautions

Ed Treatment/Procedures

  • Calcium replacement:Calcium chloride 10% (27.2 mg elemental Ca2+/mL):For life-threatening conditions: 10 mL (1 g) IV over 5 min ORCalcium gluconate 10% (9 mg elemental Ca2+/mL):For life-threatening conditions: 20-30 mL (2-3 g) over 3-5 minFor non-life-threatening conditions, administer calcium via slow infusion of 500-1,000 mg elemental Ca2+ over 6-24 hr (peds: 100 mg elemental Ca2+/kg/24 hr)Continuous cardiac monitoringStop infusion if bradycardia developsPerform frequent checks of serum Ca2+ levelsCalcium administration may precipitate digitalis toxicitySupplement to lowest possible Ca2+ level keeping the patient asymptomatic, then switch to oral replacement:Soft tissue calcification may occur with calcium/phosphorus product of 60 (Ca — PO4)
  • Replace magnesium if low
  • Bind phosphorus:Aluminum hydroxide-containing antacids (Maalox, Mylanta, or Gelusil) if creatinine <2Calcium acetate (Phoslo) or calcium carbonate when concurrent renal failure if creatinine >2Sevelamer HCl or carbonate (Renagel, Renvela)
  • Vitamin D supplementation
  • Avoid carbonated beverages (high in phosphorus)
  • Assess for associated endocrinopathies

Medication

First Line

  • Calcium gluconate: 10% (9 mg elemental Ca2+/mL): 20-30 mL over 3-5 min if life-threatening condition; otherwise, slow infusion (peds: 20 mg/kg of calcium gluconate 10% or 2 mg/kg elemental Ca):Follow with slow infusion: Calcium gluconate 10 g in liter of 5% dextrose infusedat 1-3 mg/kg/h in adultsCalcium gluconate has lower risk of venous irritation or extravasational injury compared to calcium chloride
  • Magnesium sulfate: 2 g IV (peds: 25-50 mg/kg up to 2 g) over 2 hr-if severe, 6 g over 6 hr
  • Calcium chloride 10% (27.2 mg elemental Ca2+/mL): 10 mL (1 g) IV over 5 min if life-threatening condition; otherwise, slow infusion

Second Line

  • Calcium acetate: 667 mg (169 mg elemental Ca): 1 or 2 tabs TID with meals
  • Calcium carbonate: 1,250 mg (500 mg elemental Ca): 1 or 2 tabs QID (2-4 g/d) (peds: 45-65 mg elemental Ca mg/kg/d div. QID)
  • Sevelamer (Renagel, Renvela) 800 mg: 1 or 2 tabs TID with meals
  • Magnesium oxide 400 mg: 1 tab daily or BID
  • Vitamin D: 400 IU PO daily for supplement (if not responsive to standard supplement, then consider calcitriol (1,25(OH)2-D) 0.25 μg daily; titrate to 0.5-2 μg/d):Preferred over other long-acting vitamin D analogues due to patient availability and lower cost, quicker onset and offset of action
  • Thiazide diuretics: HCTZ 25 100 mg daily

Follow-Up

Disposition

Admission Criteria

  • Symptomatic hypocalcemia
  • Abnormal ECG
  • Inability to take vitamin D or calcium orally
  • Corrected calcium <5 mg/dL

Discharge Criteria

  • Asymptomatic hypocalcemia
  • Not meeting any admission criteria

Follow-Up Recommendations

  • Any patient requiring therapy or needing follow-up lab studies
  • Repeat of calcium, phosphorus, magnesium levels in 1-2 days

Pearls and Pitfalls

  • Rapid onset of symptoms following surgical excision of the parathyroid glands is the most common symptomatic presentation
  • Symptoms often confused with hyperventilation or anxiety
  • In the absence of surgery or severe hypomagnesemia, be sure that hypocalemia is not due to sepsis or rhabdomyolysis
  • With the exception of life-threatening presentations, avoid rapid IV administration of calcium salts

Additional Reading

  • Al-Azem H, Khan AA. Hypoparathyroidism. Best Pract Res Clin Endocrinol Metab. 2012;26:517-522.
  • Andreoli T, Carpenter C. Cecil Essentials of Medicine. 7th ed. Philadelphia, PA: Saunders-Elsevier; 2007.
  • Goldman L, Bennett JC, eds. Cecils Textbook of Medicine. 44th ed. Philadelphia, PA: Saunders-Elsevier; 2012.
  • Sanctis VD, Soliman A, Fiscina B. Hypoparathyroidism: From diagnosis to treatment. Curr Opin Endocrinol Diabetes Obes. 2012;19(6):435-442.
  • Shoback D. Clinical practice. Hypoparathyroidism. N Engl J Med. 2008;359:391-403.

See Also (Topic, Algorithm, Electronic Media Element)

Hyperparathyroidism

Codes

ICD9

  • 252.1 Hypoparathyroidism
  • 275.49 Other disorders of calcium metabolism
  • 279.11 Digeorges syndrome
  • 775.4 Hypocalcemia and hypomagnesemia of newborn

ICD10

  • E20.1 Pseudohypoparathyroidism
  • E20.9 Hypoparathyroidism, unspecified
  • D82.1 Di Georges syndrome
  • E20.8 Other hypoparathyroidism
  • E20.0 Idiopathic hypoparathyroidism
  • E20 Hypoparathyroidism
  • E89.2 Postprocedural hypoparathyroidism
  • P71.4 Transitory neonatal hypoparathyroidism

SNOMED

  • 36976004 Hypoparathyroidism (disorder)
  • 58976002 Pseudohypoparathyroidism (disorder)
  • 77128003 DiGeorge sequence
  • 75316000 Autoimmune hypoparathyroidism (disorder)
  • 190455009 Post-surgical hypoparathyroidism (disorder)