Hypoparathyroidism
- Overview
- Theory
- Diagnosis
- Management
- Follow up
- Resources
Treatment algorithm
Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer
severe symptomatic hypocalcaemia (albumin-corrected serum total calcium <1.88 mmol/L [<7.5 mg/dL])
intravenous calcium
Calcium gluconate should be administered slowly via a large-bore intravenous line, preferably a central venous catheter, to minimise pain.[1]Khan AA, Bilezikian JP, Brandi ML, et al. Evaluation and management of hypoparathyroidism summary statement and guidelines from the Second International Workshop. J Bone Miner Res. 2022 Dec;37(12):2568-85. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4691 http://www.ncbi.nlm.nih.gov/pubmed/36054621?tool=bestpractice.com [27]Gafni RI, Collins MT. Hypoparathyroidism. N Engl J Med. 2019 May 2;380(18):1738-47. http://www.ncbi.nlm.nih.gov/pubmed/31042826?tool=bestpractice.com [30]Chang WT, Radin B, McCurdy MT. Calcium, magnesium, and phosphate abnormalities in the emergency department. Emerg Med Clin North Am. 2014 May;32(2):349-66. http://www.ncbi.nlm.nih.gov/pubmed/24766937?tool=bestpractice.com The initial infusion can be repeated.
Intravenous insertion site should be checked for signs of local infiltration and extravasation. Subcutaneous extravasation of calcium can cause tissue necrosis and should be avoided.
Continuous ECG monitoring is required. Albumin-corrected serum total calcium or serum ionised calcium should be monitored frequently. Serum magnesium and serum phosphate levels should be checked, as well as arterial blood gases (ABGs), to rule out alkalosis.
The treatment goal is relief of acute symptoms and attaining 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).
Transition to an oral regimen allows for safe discharge from hospital.
Primary options
calcium gluconate: 90 mg intravenously over 10 minutes initially (can be repeated), followed by 0.5 to 1.5 mg/kg/hour infusion
More calcium gluconateDose expressed as elemental calcium.
93 mg (4.65 mEq) elemental calcium = 1 g calcium gluconate.
Available as 10% solution (1 g calcium gluconate/10 mL).
parenteral magnesium
Treatment recommended for ALL patients in selected patient group
Intravenous or intramuscular magnesium can be administered if deficiency is severe. Continuous ECG monitoring is recommended for intravenous magnesium supplementation.
Frequent monitoring of serum magnesium, serum total calcium (and albumin), or ionised calcium is recommended.
The treatment goal is relief of acute symptoms and restoration of magnesium to normal range.
Transition to an oral regimen allows for safe discharge from hospital.
Primary options
magnesium sulfate: 1 g intravenously/intramuscularly every 6 hours
treatment for respiratory alkalosis
Treatment recommended for ALL patients in selected patient group
Alkalosis 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.
asymptomatic temporary postoperative hypocalcaemia
oral calcium
Routine calcium replacement is given after thyroid or parathyroid surgery even when parathyroids are expected to recover after an initial period of decreased or absent activity.[24]Edafe O, Mech CE, Balasubramanian SP. Calcium, vitamin D or recombinant parathyroid hormone for managing post-thyroidectomy hypoparathyroidism. Cochrane Database Syst Rev. 2019 May 22;(5):CD012845. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012845.pub2/full http://www.ncbi.nlm.nih.gov/pubmed/31116878?tool=bestpractice.com
Serum total calcium and albumin are checked periodically and shortly after any dosage changes. Serum phosphate, calcium, and creatinine should all be measured periodically.
If the patient remains symptom-free and is only on a prophylactic dose of calcium, the calcium supplementation can be stopped 2 weeks postoperatively.
The treatment goal is to maintain: albumin-corrected total serum calcium in the low normal range (2.00 to 2.13 mmol/L [8.0 to 8.5 mg/dL]), or up to the normal range while avoiding hypercalcaemia; and a calcium x phosphate product of <4.4 mmol²/L² (<55 mg²/dL²).
Calcium carbonate should be given with meals; calcium citrate can be administered at any time of the day.
Primary options
calcium carbonate: 500 mg orally initially, followed by 500-1000 mg twice to three times daily
More calcium carbonateDose refers to elemental calcium.
OR
calcium citrate: 500 mg orally initially, followed by 500-1000 mg twice to three times daily
More calcium citrateDose refers to elemental calcium.
low-dose calcitriol
Treatment recommended for ALL patients in selected patient group
Low-dose calcitriol is added if serum calcium is low in the first 24 hours post-operation.
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.
Serum calcium, albumin, phosphate, and creatinine are monitored regularly.
The treatment goal is to: avoid hypercalcaemia and hyperphosphataemia; maintain albumin-corrected total serum calcium in the low normal range (2.00 to 2.13 mmol/L [8.0 to 8.5 mg/dL]), or up to the normal range while avoiding hypercalcaemia; maintain calcium x phosphate product of <4.4 mmol²/L² (<55 mg²/dL²).
Primary options
calcitriol: 0.25 micrograms orally once or twice daily
chronic hypoparathyroidism
oral calcium plus calcitriol
For outpatient management of permanent hypoparathyroidism, the patient should be referred to an experienced endocrinologist for ongoing care.
The treatment goal is to maintain the blood calcium level near the lower end of normal range, while preventing symptoms of hypocalcaemia.[27]Gafni RI, Collins MT. Hypoparathyroidism. N Engl J Med. 2019 May 2;380(18):1738-47. http://www.ncbi.nlm.nih.gov/pubmed/31042826?tool=bestpractice.com Treatment requirements are highly individualised, as serum calcium levels may fluctuate without obvious reasons.
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]Gafni RI, Collins MT. Hypoparathyroidism. N Engl J Med. 2019 May 2;380(18):1738-47. http://www.ncbi.nlm.nih.gov/pubmed/31042826?tool=bestpractice.com [30]Chang WT, Radin B, McCurdy MT. Calcium, magnesium, and phosphate abnormalities in the emergency department. Emerg Med Clin North Am. 2014 May;32(2):349-66. http://www.ncbi.nlm.nih.gov/pubmed/24766937?tool=bestpractice.com
Patients who have severe, symptomatic hypocalcaemia may require intravenous calcium therapy. (See Severe symptomatic hypocalcaemia treatment section.)
Urinary calcium and creatinine, and serum calcium, albumin, phosphate, and creatinine are monitored regularly.
Periodic renal imaging for calcifications and stones is recommended.
The treatment goals are to: avoid hypercalcaemia, hypercalciuria, and hyperphosphataemia; maintain albumin-corrected total serum calcium in the low normal range (2.00 to 2.13 mmol/L [8.0 to 8.5 mg/dL]), or up to the normal range while avoiding hypercalcaemia; maintain total 24-hour urinary calcium at <300 mg (<7.5 mmol); and maintain calcium x phosphate product of <55 mg²/dL² (<4.4 mmol²/L²).
Serum calcium, albumin, phosphate, and creatinine are monitored regularly.
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]Gafni RI, Collins MT. Hypoparathyroidism. N Engl J Med. 2019 May 2;380(18):1738-47. http://www.ncbi.nlm.nih.gov/pubmed/31042826?tool=bestpractice.com [30]Chang WT, Radin B, McCurdy MT. Calcium, magnesium, and phosphate abnormalities in the emergency department. Emerg Med Clin North Am. 2014 May;32(2):349-66. http://www.ncbi.nlm.nih.gov/pubmed/24766937?tool=bestpractice.com
Calcium carbonate should be given with meals; calcium citrate can be administered at any time of the day.
human recombinant PTH (1-84) + adjustment of calcium and/or calcitriol doses
Additional treatment recommended for SOME patients in selected patient group
May be considered as adjunctive therapy in patients with an unsatisfactory response to calcium supplements and calcitriol, if available.
Human recombinant PTH (1-84) is only available in some countries.[32]Mannstadt M, Clarke BL, Vokes T, et al. Efficacy and safety of recombinant human parathyroid hormone (1-84) in hypoparathyroidism (REPLACE): a double-blind, placebo-controlled, randomised, phase 3 study. Lancet Diabetes Endocrinol. 2013 Dec;1(4):275-83. http://www.ncbi.nlm.nih.gov/pubmed/24622413?tool=bestpractice.com [33]Watts NB, Bilezikian JP, Bone HG, et al. Long-term safety and efficacy of recombinant human parathyroid hormone (1-84) in adults with chronic hypoparathyroidism. J Endocr Soc. 2023 Mar 6;7(5):bvad043. https://academic.oup.com/jes/article/7/5/bvad043/7103305 http://www.ncbi.nlm.nih.gov/pubmed/37091306?tool=bestpractice.com 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]Khan AA, Bilezikian JP, Brandi ML, et al. Evaluation and management of hypoparathyroidism summary statement and guidelines from the Second International Workshop. J Bone Miner Res. 2022 Dec;37(12):2568-85. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4691 http://www.ncbi.nlm.nih.gov/pubmed/36054621?tool=bestpractice.com Palopegteriparatide (a PTH [1-34] prodrug) has been approved for hypoparathyroidism. See Emerging treatments.
Oral doses of calcium and/or calcitriol can be lowered when PTH (1-84) is started (while following serum calcium levels and symptoms closely).
Dose can be adjusted approximately every 2-4 weeks with close biochemical and clinical monitoring. Biochemical monitoring should include serum calcium, albumin, phosphate, and creatinine, and urinary calcium and creatinine, along with periodic renal imaging for calcifications and stone formation.
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]Mannstadt M, Clarke BL, Bilezikian JP, et al. Safety and efficacy of 5 years of treatment with recombinant human parathyroid hormone in adults with hypoparathyroidism. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5136-47. https://academic.oup.com/jcem/article/104/11/5136/5540965 http://www.ncbi.nlm.nih.gov/pubmed/31369089?tool=bestpractice.com [35]Tay YD, Tabacco G, Cusano NE, et al. Therapy of hypoparathyroidism with rhPTH(1-84): a prospective, 8-year investigation of efficacy and safety. J Clin Endocrinol Metab. 2019 Nov 1;104(11):5601-10. https://academic.oup.com/jcem/article/104/11/5601/5532037 http://www.ncbi.nlm.nih.gov/pubmed/31310310?tool=bestpractice.com
Primary options
parathyroid hormone: consult specialist for guidance on dose
thiazide diuretic and low-salt diet
Additional treatment recommended for SOME patients in selected patient group
A low-dose thiazide diuretic will often substantially reduce the rate of urinary calcium excretion in patients with, or at risk of, hypercalciuria.
Either hydrochlorothiazide or chlortalidone, or a thiazide plus potassium-sparing diuretic combination (e.g., triamterene/hydrochlorothiazide), may be used. Diuretic therapy should be combined with a low-salt diet.
Electrolytes (serum sodium, potassium, chloride), renal function (serum creatinine and urea nitrogen), and urine calcium and creatinine should be monitored periodically, and with any dose change.
The goal of treatment is to avoid hypokalaemia, hyponatraemia, hypercalcaemia, and dehydration, and to maintain 24-hour urinary calcium at <7.5 mmol (<300 mg).
Primary options
hydrochlorothiazide: 25-50 mg orally once or twice daily
OR
chlortalidone: 25-50 mg orally once or twice daily
Secondary options
triamterene/hydrochlorothiazide: 37.5 mg (triamterene)/25 mg (hydrochlorothiazide) orally once daily, can increase to 75 mg (triamterene)/50 mg (hydrochlorothiazide) once daily according to response
oral magnesium
Additional treatment recommended for SOME patients in selected patient group
If mild to moderate hypocalcaemia is accompanied by hypomagnesaemia, consider oral magnesium supplementation.
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]Khan AA, Bilezikian JP, Brandi ML, et al. Evaluation and management of hypoparathyroidism summary statement and guidelines from the Second International Workshop. J Bone Miner Res. 2022 Dec;37(12):2568-85. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4691 http://www.ncbi.nlm.nih.gov/pubmed/36054621?tool=bestpractice.com [20]Pasieka JL, Wentworth K, Yeo CT, et al. Etiology and pathophysiology of hypoparathyroidism: a narrative review. J Bone Miner Res. 2022 Dec;37(12):2586-601. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4714 http://www.ncbi.nlm.nih.gov/pubmed/36153665?tool=bestpractice.com [27]Gafni RI, Collins MT. Hypoparathyroidism. N Engl J Med. 2019 May 2;380(18):1738-47. http://www.ncbi.nlm.nih.gov/pubmed/31042826?tool=bestpractice.com
Serum magnesium should be monitored periodically along with serum calcium, phosphate, and creatinine.
The goal of treatment is to maintain a serum magnesium level within the normal range.
Primary options
magnesium oxide: 400 mg orally once or twice daily
More magnesium oxideDose refers to elemental magnesium.
specific treatment of condition
Additional treatment recommended for SOME patients in selected patient group
Approximately 25% of all adults with hypoparathyroidism have a non-surgical aetiology.[1]Khan AA, Bilezikian JP, Brandi ML, et al. Evaluation and management of hypoparathyroidism summary statement and guidelines from the Second International Workshop. J Bone Miner Res. 2022 Dec;37(12):2568-85. https://asbmr.onlinelibrary.wiley.com/doi/10.1002/jbmr.4691 http://www.ncbi.nlm.nih.gov/pubmed/36054621?tool=bestpractice.com [27]Gafni RI, Collins MT. Hypoparathyroidism. N Engl J Med. 2019 May 2;380(18):1738-47. http://www.ncbi.nlm.nih.gov/pubmed/31042826?tool=bestpractice.com In those instances, other concomitant medical issues should be addressed in addition to treatment for the hypoparathyroidism.
For example, in patients with autoimmune polyendocrine syndrome type 1 (APS1), attention to careful glucocorticoid replacement is mandatory, as well as regular screening and treatment for other conditions that affect patients with APS1, such as coeliac disease causing malabsorption, which can affect the success of treating hypoparathyroidism.
In all patients with 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 as appropriate to achieve more stable control of hypocalcaemia.
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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer
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