On this page, you will find answers to frequently asked questions about secondary hyperparathyroidism, how it develops in people with chronic kidney disease, how it is managed and why it should be treated early
The parathyroid glands are four pea-sized glands located inside the neck, on the back of the thyroid gland.1 The job of the parathyroid glands is to produce and release parathyroid hormone.2
Parathyroid hormone, or PTH, is a hormone that helps to control the amount of calcium in the blood.2 When the blood calcium level drops, the parathyroid glands increase the amount of parathyroid hormone they release, which increases the calcium level.2 After the blood calcium level returns to normal, the parathyroid glands reduce the amount of parathyroid hormone they release.2
Parathyroid hormone increases the amount of calcium in the blood by making the bones release calcium3 and by making the kidneys:3
- Filter less calcium from the blood
- Filter more phosphate from the blood (because phosphate tends to combine with calcium, which reduces the calcium level)
- Activate more vitamin D (because vitamin D is required by the body to absorb calcium from food)
Hyperparathyroidism is a condition in which the parathyroid glands release abnormally large amounts of parathyroid hormone.2
Primary hyperparathyroidism is a condition in which the parathyroid glands release abnormally large amounts of parathyroid hormone due to a disorder of the parathyroid glands.2
Secondary hyperparathyroidism, or SHPT, is a condition in which the parathyroid glands release abnormally large amounts of parathyroid hormone due to a disorder outside of the parathyroid glands.2 The most common cause of secondary hyperparathyroidism is chronic kidney disease.2
Tertiary hyperparathyroidism is an advanced form of secondary hyperparathyroidism in which the parathyroid glands release abnormally large amounts of parathyroid hormone because they have enlarged.2,3 The excessive release occurs even in the absence of the initial cause of the hyperparathyroidism.2
The kidneys have many important functions, including:
- Removing waste materials, drugs and toxins from the blood4,5
- Maintaining the balance of water in the blood5,6
- Controlling the acid level of the blood5
- Maintaining the balance of electrolytes (electrically charged particles) in the blood5,6
- Releasing hormones5
- Activating vitamin D5,7
Vitamin D is a group of molecules that the body needs to absorb calcium from food.7 The most basic forms are ergocalciferol (vitamin D2) and cholecalciferol (vitamin D3), which are collectively known as native vitamin D or nutritional vitamin D.7
Nutritional vitamin D is inactive, which means that it can’t be used by the body to absorb calcium from food.7 The body must first convert it into vitamin D hormone (calcitriol), which is the active form of vitamin D.7
Most nutritional vitamin D is made by the skin when it is exposed to sunlight.7 Nutritional vitamin D can also be found naturally in a small number of foods, such as:7,8
- Red meat
- Egg yolks
- Oily fish (for example, salmon, sardines and mackerel)
In some countries, such as Germany and Finland, nutritional vitamin D may be added to certain foods, including:9
- Cow’s milk
- Plant-based milks, such as soy milk, oat milk and almond milk
- Orange juice
- Breakfast cereal
Nutritional vitamin D can also be taken as a supplement.7
Nutritional vitamin D is converted into vitamin D hormone, the active form of vitamin D, in a two-step process:
- The liver turns nutritional vitamin D into vitamin D prohormone (calcifediol)7
- The kidneys and some other parts of the body convert the vitamin D prohormone into vitamin D hormone (calcitriol)7,10
When checking a person’s vitamin D level, nephrologists usually only measure the level of vitamin D prohormone (calcifediol) in the blood.11 This is because vitamin D prohormone provides the most reliable indication of how much vitamin D is stored for use in the body.11 The amount of vitamin D prohormone in the blood also indicates how much nutritional vitamin D is being obtained from food and through production in the skin.11
In the general population, the normal range of vitamin D (calcifediol) has been defined as being between 74.9 and 249.6 nmol/L (30 and 100 ng/mL).12
In people with chronic kidney disease, the normal range of vitamin D has not been defined. Many people with chronic kidney disease have low levels of vitamin D.13 Therefore, compared with people in the general population, people with chronic kidney disease may need higher levels.14
In the general population, the normal range of calcium in the blood of adults is 2.2 to 2.7 mmol/L (8.5 to 10.5 mg/dL).15
In the general population, the normal range of phosphate in the blood of adults is 0.81 to 1.45 mmol/L (2.5 to 4.5 mg/dL).16
The most common causes of secondary hyperparathyroidism are:2
- Prolonged low levels of vitamin D
- Chronic kidney disease
Chronic kidney disease, or CKD, is a condition in which the kidneys gradually lose their ability to function properly.17 Often caused by diabetes or high blood pressure,18 chronic kidney disease can eventually lead to kidney failure, wherein the kidneys can’t do their jobs well enough for survival.17 In this instance, dialysis or a kidney transplant is required.18
Nephrologists divide the progression of chronic kidney disease into six grades or stages, as defined in Table 1.17 The higher the stage is, the more advanced the chronic kidney disease will be.17
Table 1. Stages of chronic kidney disease17
Secondary hyperparathyroidism affects up to:19
- 40% of patients with stage 3 chronic kidney disease (kidney function 30–59% of normal)
- 82% of patients with stage 4 chronic kidney disease (kidney function 15–29% of normal)
Secondary hyperparathyroidism can develop as early as stage 2 chronic kidney disease (kidney function 60–89% of normal).19
In the early stages of secondary hyperparathyroidism, there may be no symptoms.20 However, as secondary hyperparathyroidism progresses, some people may experience tiredness, muscle soreness, bone pain and joint pain.20 These symptoms may gradually increase in severity.20
Secondary hyperparathyroidism is diagnosed through a blood test.17
Secondary hyperparathyroidism is monitored through blood tests.17 Regular blood tests are used to keep track of how the parathyroid hormone level is changing.17 Blood tests are also required to monitor changes in vitamin D, calcium and phosphate levels.17 The regularity of the blood tests depends on how advanced the chronic kidney disease is, with more advanced cases requiring more frequent monitoring.17
Secondary hyperparathyroidism is managed with medications, such as vitamin D therapies and calcimimetics (both of which are described below).21 The goal of treatment of secondary hyperparathyroidism is to control the parathyroid hormone level by restoring the balance of the vitamin D hormone, calcium and phosphate levels.17,22
The vitamin D therapies used for the treatment of secondary hyperparathyroidism are presented in Table 2.
Table 2. Vitamin D therapies used to treat secondary hyperparathyroidism, and their availabilities
Vitamin D therapies help to reduce the amount of parathyroid hormone being released by the parathyroid glands by increasing the vitamin D hormone level.21
Nutritional vitamin D is the most basic form of vitamin D.7 Two types are available over the counter and on prescription: ergocalciferol (vitamin D2)23 and cholecalciferol (vitamin D3).24 After nutritional vitamin D is taken, the body must convert it first into vitamin D prohormone and then into vitamin D hormone.7
Vitamin D prohormone, also known as calcifediol, is the precursor of vitamin D hormone.7 It is sometimes available on prescription.25 After vitamin D prohormone is taken, the body must convert it into vitamin D hormone.7
Vitamin D hormone, also known as calcitriol, is the active form of vitamin D.7 It is available on prescription.26
Vitamin D hormone analogues are artificially made forms of vitamin D hormone.28 One example is paricalcitol.27 Vitamin D hormone analogues are available on prescription.27
Calcimimetics are medications that mimic calcium.29 They are available on prescription30 but are usually used for the treatment of secondary hyperparathyroidism only in people on dialysis.17,30
Calcimimetics help to reduce the amount of parathyroid hormone being released by the parathyroid glands by indicating to the parathyroid glands that the calcium level in the blood has increased.29
Treatment of secondary hyperparathyroidism early in the course of chronic kidney disease is essential to reduce the risk of complications.22,31
Without early and effective treatment of secondary hyperparathyroidism:
- All or some of the parathyroid glands may grow, allowing them to produce even more parathyroid hormone and make the condition worse3,21
- The enlarged parathyroid glands may become less sensitive to medications, making secondary hyperparathyroidism more difficult to treat3,32,33
- The risk of bone disease may increase34–38
- The risk of heart disease may increase37–40
If the parathyroid glands are under constant pressure to release large amounts of parathyroid hormone, they will grow by increasing in the number of cells.3 Having more cells makes it easier for them to meet the demand of releasing large amounts of parathyroid hormone.
The parathyroid glands can detect how much vitamin D hormone and calcium are in the blood because they contain vitamin D hormone and calcium receptors.21 Relative to their size, enlarged parathyroid glands have fewer vitamin D hormone and calcium receptors, making it more difficult for them to sense the effects of medications such as vitamin D therapies and calcimimetics.3,32,33
If the parathyroid glands enlarge moderately, the amount of parathyroid hormone they release can be managed with medications.21 However, if the parathyroid glands enlarge significantly, enabling them to constantly release abnormally large amounts of parathyroid hormone (a condition known as tertiary hyperparathyroidism2), the only way to reduce the amount of parathyroid hormone they release is to either completely or partially remove them through surgery.21 The surgery is called a parathyroidectomy.21
The job of parathyroid hormone is to increase the blood calcium level.2
It does this in different ways.3 One way is to make the bones release calcium.3 If secondary hyperparathyroidism is not treated and parathyroid hormone levels remain high, bone density begins to drop.34–36 The more bone density drops, the weaker the bones become, leading to a bone disorder known as high-turnover bone disease.34–36
Parathyroid hormone increases the blood calcium level.2 If secondary hyperparathyroidism is not treated and parathyroid hormone levels remain high, the calcium in the blood can combine with phosphate and become deposited in blood vessels, in the heart and on the heart’s valves, making them harden.21,41,42 This process, known as calcification, increases the risk of heart complications, such as abnormal heart rhythm,43 heart valve disease42 and heart attack.40,43
No, but you should be aware of the potential risks posed by secondary hyperparathyroidism if it is not managed,37,38 and you should take any measures that are necessary to ensure that it is managed effectively, such as:
- Take your medications as instructed
- Attend your check-ups as scheduled
Secondary hyperparathyroidism can be managed with medications, especially if it is diagnosed and treated early.22,31 If you have any concerns about secondary hyperparathyroidism, please speak to your nephrologist or nurse.
- Ramas A et al. Med Arch. 2019;73(4):249–52.
- Ilahi A et al. StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537203/ [update 2020 August 10; accessed 2021 January 29].
- Rodriguez M et al. Am J Physiol Renal Physiol. 2005;288:F253–64.
- Inui KI et al. Kidney Int. 2000;58(3):944–58.
- Traynor J et al. BMJ. 2006;333(7571):733–7.
- Kwon T et al. Kidney Res Clin Pract. 2013;32(3):96–102.
- Holick MF. N Engl J Med. 2007;357:266–81.
- Schmid A et al. Adv Nutr. 2013;4:453–62.
- Pilz S et al. Front Endocrinol (Lausanne). 2018;9:373.
- Adams JS et al. J Steroid Biochem Mol Biol. 2014;144PA:22–7.
- Ross AC et al., editors. Institute of Medicine (US) Committee to Review Dietary Reference Intakes for Vitamin D and Calcium [Internet]. Washington (DC): National Academies Press (US); 2011. Available from: https://www.ncbi.nlm.nih.gov/books/NBK56070/ [accessed 2021 March 4].
- Holick MF et al. J Clin Endocrinol Metab. 2011;96:1911–30.
- Doorenbos CRC et al. Nat Rev Nephrol. 2009;5:691–700.
- Ennis JL et al. J Nephrol. 2016;29:63–70.
- Carroll R et al. Ther Adv Endocrinol Metab. 2010;1(1):29–33.
- Martin AG et al. Endocrinol Diabetes Nutr. 2020;67(3):205–15.
- Kidney Disease: Improving Global Outcomes (KDIGO) Work Group. Kidney Int Suppl. 2017;7:1–59.
- Fraser SDS et al. Pragmat Obs Res. 2016;7:21–32.
- Levin A et al. Kidney Int. 2007;71:31–8.
- Levy AR et al. Am J Kidney Dis. 2020;75(3):373–83.
- Cunningham J et al. Clin J Am Soc Nephrol. 2011;6:913–21.
- Tomasello S. Diabetes Spectr. 2008;21:19–25.
- RPH Pharmaceuticals AB. Ergocalciferol Injection BP 300,000 IU Summary of Product Characteristics; 2019 December 06.
- Colonis Pharma Ltd. Colecalciferol 1,000 IU Capsules Summary of Product Characteristics; 2020 February 20.
- Desma Pharma. Dedrogyl 15 mg/100 mL Solution Buvable en Gouttes Résumé des Caractéristiques du Produit; 2021 March 30.
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- Locatelli F et al. Nephrol Dial Transplant. 2002;17:723–31.
- Fukuda N et al. J Clin Invest. 1993;92:1436–43.
- Gogusev J et al. Kidney Int. 1997;51:328–36.
- Rix M et al. Kidney Int. 1999;56(3):1084–93.
- Qi Q et al. Am J Kidney Dis. 1995;26(4):622–31.
- Torres A et al. Kidney Int. 1995;47:1434–42.
- Geng G et al. Osteoporos Int. 2019;30:2019–25.
- Xu Y et al. Clin Kidney J. 2021;sfab006.
- Lishmanov A et al. Int Urol Nephrol. 2012;44:541–7.
- de Boer IH et al. JASN. 2002;13(11):2762–9.
- Castro RH et al. Poster C-1002 presented at: European Congress of Radiology (ECR) 2011; 2011 March 3–7; Vienna, Austria.
- Linefsky JP et al. J Am Coll Cardiol. 2011;58(3):291–7.
- Kovesdy CP et al. Kidney Int. 2008;73:1296–302.