Approach

Initial management depends on the severity and the physical manifestations of the hypocalcaemia. In the immediate postoperative period of patients with surgical hypoparathyroidism, management of acutely symptomatic patients with confirmatory biochemical determinations is directed by the surgeon, anaesthetist, or critical care physician, as the patient often needs close ongoing cardiac and biochemical monitoring, and continuous intravenous calcium infusions. To establish an outpatient regimen for discharge, consultation with an endocrinologist experienced in the management of the disorder is appropriate. For outpatient management of permanent hypoparathyroidism, the patient should be referred to an experienced endocrinologist for ongoing care.

The approach outlined below is a general guide for the clinician as to what symptoms to monitor, and what treatments might be needed if the serum calcium is in a particular target range. The final approach to treatment should involve a careful review of the clinical and laboratory findings in each individual patient.

Severe symptomatic hypocalcaemia (albumin-corrected serum total calcium <1.88 mmol/L [<7.5 mg/dL])

Any of the following clinical situations generally require emergency intravenous calcium replacement:

For the relief of acute symptoms, the treatment goal is an albumin-corrected serum total calcium of approximately 2 mmol/L (8 mg/dL), or serum ionised calcium of 1 mmol/L (4 mg/dL).

Calcium should be administered slowly via a large-bore intravenous line, preferably a central venous catheter, to minimise pain.[1][27]​​[30]​​ Continuous ECG monitoring is required; albumin-corrected serum total calcium or serum ionised calcium should be monitored frequently. Subcutaneous extravasation of calcium can cause tissue necrosis and should be avoided. Serum magnesium and phosphate levels should be checked as well as arterial blood gases (ABGs) to rule out alkalosis, which can reduce the ionised fraction of serum calcium by favouring calcium binding to albumin. Alkalosis can contribute to a worse clinical picture than the albumin-corrected serum total calcium might suggest. If the cause of alkalosis is addressed (e.g., pain, vomiting, or stress), then recovery from hypocalcaemia may be hastened.

The rate at which the hypocalcaemia has developed will influence the presence or absence of symptoms.[27]​​[30]​​[31] Rapid drops in serum calcium (e.g., to <1.88 mmol/L [<7.5 mg/dL]) generally produce symptoms, while patients may present to the outpatient clinic with levels lower than this without symptoms because they have equilibrated to this level over a long time.[27]

Oral calcium replacement is the first-line treatment, and intravenous calcium infusion is used when symptoms are severe and with appropriate precautions. Therefore, the treating clinician must exercise judgement in selecting therapy for the patient.

Asymptomatic temporary postoperative hypocalcaemia

Routine calcium replacement is often given after thyroid or parathyroid surgery. This is the case even when the parathyroids are expected to recover following an initial period of decreased or absent activity.[24] If serum calcium is low in the first 24 hours post-operation, low-dose calcitriol is added to the regimen.

These doses are temporary, and lower than those required for permanent hypoparathyroidism. Note that higher doses are advised if the parathyroids are not expected to recover.

Chronic hypoparathyroidism

When hypocalcaemia is mild to moderate, symptoms are minimal or absent, and there are no signs of hypocalcaemia present, then a maintenance regimen of oral calcium, calcitriol, vitamin D, and/or magnesium can be used.[27][30] The biologically active form of vitamin D, calcitriol (1,25-dihydroxyvitamin D), is preferred over vitamin D2 or D3 because calcitriol has a more rapid onset of action and shorter half-life, making the risk of chronic intoxication less of an issue with calcitriol.[27]​​[30]

Adjunctive therapies

Human recombinant parathyroid hormone (PTH [1-84]) as a daily injectable therapy may be considered as adjunctive therapy in patients with an unsatisfactory response to calcium supplements and calcitriol. PTH (1-84) is only available in some countries.[32][33]​​​ In the US, the Food and Drug Administration (FDA) recalled recombinant PTH (1-84) (known as Natpara®) in October 2019 due to the possible presence of rubber particles originating from the cartridge septum. However, it is still available in the US (as part of a special use programme) for patients who face life-threatening complications as a result of the discontinuation. A similar recall has not taken place in Europe.[1]​​

Oral doses of calcium and/or calcitriol can be lowered when PTH (1-84) is started. Long-term, open-label studies in adults with hypoparathyroidism indicate stable biochemical parameters and modest improvements in quality of life over time with PTH (1-84) therapy.[34][35]

If there is a deficiency of magnesium, magnesium replacement will enable the parathyroid glands to secrete PTH normally, which will restore serum calcium to normal.[1][20][27]​ Patients with hypoparathyroidism often need modest magnesium supplements to achieve normal plasma magnesium levels.

Symptoms of hypocalcaemia fluctuate such that patients with chronic hypoparathyroidism may become more acutely symptomatic. Patients who have severe, symptomatic hypocalcaemia may require intravenous calcium therapy. (See Severe symptomatic hypocalcaemia treatment section.)

Postoperative monitoring of patients

The frequency of postoperative monitoring of patients after thyroid or parathyroid surgery will depend on several factors:

  • Extent of the surgery (e.g., removal of single adenoma, uncomplicated lobectomy, or total thyroidectomy with lymph node dissection carry different risks)

  • Intraoperative PTH levels at the end of thyroid surgery (after total thyroidectomy)

  • Levels of serum calcium within several hours of surgery

  • Presence and severity of symptoms of hypocalcaemia, if any, after surgery.

If the patient stays overnight, serum calcium levels should be checked at least twice during the first 24 hours, with the last measurement taken the morning after surgery. If these serum calcium levels are normal or just mildly and transiently reduced, then the patient may be discharged with calcium supplements to be taken as needed. If the patient remains symptom-free and is only on a prophylactic dose of calcium, the calcium supplementation can be stopped 2 weeks postoperatively.

For those treated for symptomatic hypocalcaemia or required treatment with calcitriol, serum levels of calcium and PTH should be checked 4 weeks postoperatively, and the regimen tapered accordingly. Additional inpatient or outpatient monitoring may be warranted, depending on the circumstances. Calcitriol may be prescribed for outpatient use along with calcium supplements.

Underlying condition and mitigating factors

Approximately 25% of all adults with hypoparathyroidism have a non-surgical aetiology.[1][27]​​​ In these patients, concomitant medical issues should be addressed in addition to treatment of hypoparathyroidism.

For example, in patients with autoimmune polyendocrine syndrome type 1 (APS1), careful glucocorticoid replacement is mandatory, as well as regular screening and treatment for other conditions such as coeliac disease, which can affect the success of treating hypoparathyroidism.

Drugs that interfere with magnesium or calcium absorption (e.g., proton-pump inhibitors, corticosteroids) or enhance calcium excretion (e.g., loop diuretics) may be tapered or discontinued in all patients, as appropriate, to achieve more stable control of hypocalcaemia.

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