Author:
Rami A.Ahmed
Patrick G.Hughes
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
- Bartter syndrome:
- May be accompanied by hypokalemia and metabolic alkalosis
- DiGeorge syndrome:
- Hypoparathyroidism
- Thymic dysplasia
- Severe immunodeficiency
- Wilson disease:
- Destruction of gland owing to copper deposition
- Autoimmune polygland ular syndrome type I:
- Hypoparathyroidism
- Adrenal insufficiency
- Mucocutaneous cand idiasis
- Albright syndrome (hereditary osteodystrophy):
- Short stature
- Obesity
- Round face
- Short neck
- Short fourth and fifth 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
Signs and Symptoms
ALERT |
| The most common symptomatic presentation is postoperatively after parathyroidectomy |
Pediatric Considerations |
Neonates/infants:- Transient hypoparathyroidism in first 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 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
- Nail beds for fungal infection
- Psoriasis
- Vitiligo/mucocutaneous cand idiasis
- Hyperpigmentation:
Essential Workup
- If no hypocalcemic symptoms with hypocalcemia, check albumin level:
- 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
Diagnostic 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
- 1,25(OH)2-D
- 25-hydroxyvitamin D
- 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 (tyre cleaner spray)
- Hydrofluoric acid
- Citrated blood
- Acute hyperphosphatemia:
- Fleet enemas
- Rhabdomyolysis
- Acute renal failure
Prehospital
- 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/hr 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 10-20 min - 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 t.i.d with meals
- Calcium carbonate: 1,250 mg (500 mg elemental Ca): 1 or 2 tabs q.i.d (2-4 g/d) (peds: 45-65 mg elemental Ca mg/kg/d div q.i.d)
- Sevelamer (Renagel, Renvela) 800 mg: 1 or 2 tabs t.i.d with meals
- Magnesium oxide 400 mg: 1 tab daily or b.i.d
- Vitamin D: 400 IU PO daily for supplement (if not responsive to stand ard supplement, then consider calcitriol (1,25[OH]2-D) 0.25 mcg daily; titrate to 0.5-2 mcg/d):
- Preferred because PTH is important for renal conversion of 25-hydroxyvitamin D
- Preferred over other long-acting vitamin D analogs due to patient availability and lower cost, quicker onset and offset of action
- Thiazide diuretics: HCTZ 25 100 mg daily
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 d
- AbateEG, ClarkeBL. Review of hypoparathyroidism . Front Endocrinol (Lausanne). 2016;7:172.
- and reoliT, CarpenterC. Cecil Essentials of Medicine. 9th ed.Philadelphia, PA: Saunders-Elsevier; 2016.
- BilezikianJP, Brand iML, CusanoNE, et al. Management of hypoparathyroidism: Present and future . J Clin Endocrinol Metab. 2016;101(6):2313-2324.
- Brand iML, BilezikianJP, ShobackD, et al. Management of hypoparathyroidism: Summary statement and guidelines . J Clin Endocrinol Metab. 2016;101(6):2273-2283.
- GoldmanL, SchaferAI, eds. Cecil's Textbook of Medicine. 25th ed.Philadelphia, PA: Saunders-Elsevier; 2016.
See Also (Topic, Algorithm, Electronic Media Element)
Hyperparathyroidism