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

[Outline]

• DESCRIPTION
• ETIOLOGY

SIGNS AND SYMPTOMS

ALERT

Pediatric Considerations

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 patient's 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

[Outline]

• SIGNS AND SYMPTOMS
• ESSENTIAL WORKUP
• DIAGNOSIS TESTS & INTERPRETATION
• DIFFERENTIAL DIAGNOSIS

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 infused at 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 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

[Outline]

• PRE-HOSPITAL
• INITIAL STABILIZATION/THERAPY
• ED TREATMENT/PROCEDURES
• MEDICATION

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

[Outline]

• DISPOSITION
• FOLLOW-UP RECOMMENDATIONS

• 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

ICD9

• 252.1 Hypoparathyroidism
• 275.49 Other disorders of calcium metabolism
• 279.11 Digeorge's syndrome

ICD10

• E20.1 Pseudohypoparathyroidism
• E20.9 Hypoparathyroidism, unspecified
• D82.1 Di George's syndrome

[Outline]

• ICD9
• ICD10

• 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. Cecil's 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

Rami A. Ahmed

Brad D. Gable