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
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 PTH
- Essential 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 levels
- Associated with hypothyroidism and hypogonadism
Genetics:
- Congenital absence
- DiGeorge syndrome:
  - Hypoparathyroidism
  - Thymic dysplasia
  - Severe immunodeficiency
- Wilson disease:
  - Destruction of gland owing to copper deposition
- 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)

Etiology

Failure of parathyroid gland:
- Autoimmune destruction
- Surgical interruption of blood supply or gland removal
- Radiation damage
- Hypomagnesemia (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:
- Weakness
- Malaise
Neuromuscular:
- Paresthesias (especially circumoral and extremities)
- Carpal pedal spasm
- Latent 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/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
Cardiovascular:
- Prolonged QT interval (owing to ST-segment prolongation)
- Heart block
- CHF
- Ventricular fibrillation (VFib)
- Vasoconstriction
Psychiatric:
- Impaired memory
- Confusion
- Hallucinations
- Dementia
Dermatologic:
- Brittle hair and nails
- Psoriasis
Hyperpigmentation:
- Lenticular cataracts

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 deficiency
- Elevated 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 deficiency
- Metastatic 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 disease
- Resistance to vitamin D
- Malabsorption or dietary deficiency
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

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 OR
- Calcium gluconate 10% (9 mg elemental Ca2+/mL):
  - For life-threatening conditions: 20-30 mL (2-3 g) over 3-5 min
- 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)
Replace magnesium if low
Bind phosphorus:
- Aluminum hydroxide-containing antacids (Maalox, Mylanta, or Gelusil) if creatinine <2
- Calcium acetate (Phoslo) or calcium carbonate when concurrent renal failure if creatinine >2
- Sevelamer 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 adults
- Calcium 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 Î¼g daily; titrate to 0.5-2 Î¼g/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.

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)

Home

Erectile Dysfunction

Doctor123.org