Diagnosis

The gold standard of diagnosis is the PTH immunoassay. Once an elevated PTH has been confirmed, goal of diagnosis is to determine whether the hyperparathyroidism is primary or secondary in origin by obtaining a serum calcium level:

Tertiary hyperparathyroidism has a high PTH and a high serum calcium. It is differentiated from primary hyperparathyroidism by a history of chronic kidney failure and secondary hyperparathyroidism.

Treatment

Treatment is first and foremost directed at hypercalcemia, if symptomatic patients are sent for surgery to remove the parathyroid tumor (parathyroid adenoma). (see hypercalcemia) Most experts now believe that almost all patients with hyperparathyroidism should be evaluated for surgery. Watching and waiting has been falling out of vogue since it is being realized that the disease will rarely stay the same. It will almost always progress as the tumor grows.

Calcium regulation is critical for normal cell function, neural transmission, membrane stability, bone structure, blood coagulation, and intracellular signaling. The essential functions of this divalent cation continue to be elucidated, particularly in head injury/stroke and cardiopulmonary effects. Depending on the cause, unrecognized or poorly treated hypocalcemic emergencies can lead to significant morbidity or death.

Hypocalciemia Pathophysiology

Metabolic and endocrine emergencies require an understanding of normal physiology.

Calcium regulation is maintained by parathyroid hormone (PTH), vitamin D, and calcitonin through complex feedback loops. These compounds act primarily at bone, renal, and GI sites. Calcium also is affected by magnesium and phosphorus.

History

• The patient may complain of muscle cramping, shortness of breath secondary to bronchospasm, tetanic contractions, distal extremity numbness, and tingling sensations.

• Chronic manifestations include cataracts, dry skin, coarse hair, brittle nails, psoriasis, chronic pruritus, and poor dentition.

• Acute hypocalcemia may lead to syncope, congestive heart failure (CHF), and angina due to the multiple cardiovascular effects.

• The patient's past medical history should be explored for pancreatitis, anxiety disorders, renal or liver failure, gastrointestinal disorders, and hyperthyroidism or hyperparathyroidism.

• The patient may have a recent history of thyroid, parathyroid, or bowel surgeries or recent neck trauma.

• Inquire about recent radiocontrast, estrogen, loop diuretics, bisphosphonates, calcium supplements, antibiotics, and anti-epileptics.

• Evaluate for appropriate dietary intake.

Physical

Neuromuscular and cardiovascular findings predominate. Neural hyperexcitability due to acute hypocalcemia causes smooth and skeletal muscle contractions. The patient should be examined for the following:

• Dry skin and psoriasis (if long-term hypocalcemia)

• Perioral anesthesia, cataracts, papilledema, and laryngeal stridor

• Scars over thyroid region

• Recent trauma or surgery to the neck

• Cardiopulmonary effects

• • Wheezing, dysphagia, stridor, bradycardia, rales, and S₃ may be noted.

  • Acute hypocalcemia causes prolongation of the QT interval, which may lead to ventricular dysrhythmias. It also causes decreased myocardial contractility, leading to CHF, hypotension, and angina. Cardiomyopathy and ventricular tachycardia may be reversible with treatment.

  • Smooth muscle contraction may lead to laryngeal stridor, dysphagia, and bronchospasm.

• Smooth muscle contraction causes biliary colic, intestinal colic, and dysphagia.

• Diarrhea and/or gluten intolerance (celiac sprue) may result in significant malabsorption and electrolyte abnormalities.

• Preterm labor or detrusor dysfunction may result from smooth muscle contraction.

• Peripheral nervous system findings include tetany, focal numbness, and muscle spasms.

• Classic peripheral neurologic findings include the Chvostek sign and Trousseau sign.

• • Chvostek sign: Tap over the facial nerve about 2 cm anterior to the tragus of the ear. Depending on the calcium level, a graded response will occur: twitching first at the angle of the mouth, then by the nose, the eye, and the facial muscles.

  • Trousseau sign: Inflation of a blood pressure cuff above the systolic pressure causes local ulnar and median nerve ischemia, resulting in carpal spasm.

• Irritability, confusion, hallucinations, dementia, extrapyramidal manifestations, and seizures may occur.

• • Calcification of basal ganglia, cerebellum, and cerebrum may occur.

  • Seizures often occur in individuals with preexistent epileptic foci when the excitation threshold is lowered.

Causes

The causes of hypocalcemia include hypoalbuminemia, hypomagnesemia, hyperphosphatemia, multifactorial enhanced protein binding and anion chelation, medication effects, surgical effects, PTH deficiency or resistance, and vitamin D deficiency or resistance.

Prehospital Care

Standard advanced cardiac life support (ACLS) procedures should be initiated in the patient whose condition is unstable. No specific therapy, other than supportive care, is recommended.

Emergency Department Care

Most hypocalcemic emergencies are mild and require only supportive treatment and further laboratory evaluation. On occasion, severe hypocalcemia may result in seizures, tetany, refractory hypotension, or arrhythmias that require a more aggressive approach.

• Mild hypocalcemia (when symptoms are not life threatening)

• • Confirm ionized hypocalcemia and check other pertinent laboratory tests.

  • If the cause is not obvious, send for a PTH level.

  • Depending on the PTH level, the endocrinologist may do further laboratory workup, particularly an evaluation of vitamin D levels.

  • Oral repletion may be indicated for outpatient treatment; patients requiring intravenous (IV) repletion should be admitted. (Recommended dose of elemental calcium in healthy adults is 1-3 g/d.)

• Severe hypocalcemia (life-threatening symptoms)

• • Supportive treatment often is required prior to directed treatment of hypocalcemia (ie, IV replacement, oxygen, monitoring). Be aware that severe hypocalcemia often is associated with other life-threatening conditions.

  • Check ionized calcium and other pertinent screening laboratory tests.

  • IV replacement is recommended in severe cases. Doses of 100-300 mg of elemental calcium (calcium gluconate – 10 mL contains 90 mg elemental calcium; calcium chloride – 10 mL contains 272 mg elemental calcium) should be given over 5-10 minutes. This dosage raises the ionized level to 0.5-1.5 mmol and should last 1-2 hours. Caution should be used when giving CaCl intravenously (see Medication).

  • Calcium infusion drips should be started at 0.5 mg/kg/h and increased to 2 mg/kg/h as needed, with an arterial line placed for frequent measurement of ionized calcium.

Consultations

Depending on the clinical situation, multiple consultations may be necessary, including internist, endocrinologist, intensivist, surgeon, oncologist, nephrologist, dietitian, and/or toxicologist.

Addison's disease

(also known as chronic adrenal insufficiency, hypocortisolism or hypocorticism) is a rare endocrine disorder in which the adrenal gland produces insufficient amounts of steroid hormones (glucocorticoids and often mineralocorticoids). It may develop in children as well as adults, and may occur as the result of a large number of underlying causes. The condition is named after Dr Thomas Addison, the British physician who first described the condition in his 1855 On the Constitutional and Local Effects of Disease of the Suprarenal Capsules. The adjective "Addisonian" is used for features of the condition, as well as patients with Addison's disease.^[1]

The condition is generally diagnosed with blood tests, medical imaging and additional investigations.^[1] Treatment is with replacement of the hormones (oral hydrocortisone and fludrocortisone). If the disease is caused by an underlying problem, this is addressed. Regular follow-up and monitoring for other health problems is necessary.^[1]