Show Summary Details
Page of

Parathyroid disorders and diseases altering calcium metabolism 

Parathyroid disorders and diseases altering calcium metabolism

Parathyroid disorders and diseases altering calcium metabolism

R.V. Thakker


July 30, 2015: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.


Hyperparathyroidism—expanded comment on treatment with cinacalcet.

Hypoparathyroidism—discussion of treatment by PTH replacement.

Updated on 30 Nov 2011. The previous version of this content can be found here.
Page of

PRINTED FROM OXFORD MEDICINE ONLINE ( © Oxford University Press, 2015. All Rights Reserved. Under the terms of the licence agreement, an individual user may print out a PDF of a single chapter of a title in Oxford Medicine Online for personal use (for details see Privacy Policy).

date: 28 April 2017

The control of body calcium involves a balance—chiefly under the control of parathyroid hormone (PTH)—between the amounts that are absorbed from the gut, deposited into bone and into cells, and excreted from the kidney. Under normal physiological circumstances PTH secretion from the parathyroid glands is increased by hypocalcaemia and diminished by hypercalcaemia.


Clinical presentation—this is very variable, ranging from a mild asymptomatic biochemical abnormality to (in extreme cases) a life-threatening medical emergency. Clinical manifestations can be renal (nephrocalcinosis, kidney stones), musculoskeletal (bone pain, muscular weakness), gastrointestinal (anorexia, nausea, vomiting, constipation, peptic ulceration, pancreatitis), neurological (depression, confusion, coma), and cardiac (arrhythmia).

Aetiology—primary hyperparathyroidism and malignancy account for >90% of patients with hypercalcaemia. Other causes include (1) excess vitamin D—exogenous or endogenous (e.g. granulomatous disorders); (2) drugs—e.g. thiazide diuretics, lithium, milk-alkali syndrome; (3) nonparathyroid endocrine disorders—e.g. thyrotoxicosis, immobilization; (4) inappropriate PTH levels due to altered set point—e.g. familial benign hypocalciuric hypercalcaemia.

Management—aside from appropriate treatment of the underlying condition, management of hypercalcaemia depends on its severity and the presence of symptoms. Asymptomatic patients with serum calcium less than 3.00 mmol/litre do not usually need urgent treatment. Patients with serum calcium below 3.50 mmol/litre, or above 3.00 mmol/litre with symptoms, require (1) vigorous hydration with 0.9% saline (assuming adequate renal function), with diuresis encouraged with a loop diuretic (e.g. furosemide) if necessary; (2) parenteral bisphosphonate (e.g. pamidronate, zoledronic acid); with (3) glucocorticoids—if the hypercalcaemia is mediated by the actions of 1,25-dihydroxy vitamin D, e.g. granulomatosis disease, lymphoma, myeloma; and in exceptional circumstances, (4) haemodialysis.

Specific diseases causing hypercalcaemia

Primary hyperparathyroidism—due to excessive secretion of PTH by parathyroid tumour(s); of unknown cause in most instances, but 10% of cases are associated with hereditary disorders, e.g. multiple endocrine neoplasia type 1 (MEN1, with combined occurrence of parathyroid, pancreatic islet cell and anterior pituitary tumours) and type 2 (MEN2, with association of medullary thyroid carcinoma, phaeochromocytoma and parathyroid tumours); biochemical diagnosis typically achieved by finding an elevated PTH concentration in the presence of hypercalcaemia; parathyroidectomy is the definitive cure, but cinacalcet—an allosteric activator of the calcium sensing receptor—can be effective.

Tertiary hyperparathyroidism—secondary hyperparathyroidism arises in the context of chronic kidney disease, but eventually the parathyroid cells become autonomous, secreting excessive PTH despite hypercalcaemia, which is known as tertiary hyperparathyroidism. See Chapter 21.6 for further discussion.

Malignancy—hypercalcaemia is usually due to increased bone resorption, which may either be directly due to skeletal metastases (most commonly from breast, lymphoma or multiple myeloma) or indirectly due to tumour-production of a humoral factor (usually parathyroid hormone related peptide, PTHrP, secreted from squamous carcinomas or other cancers) that stimulates osteoclastic bone resorption. Aside from measures described above, management involves reducing the tumour load by surgery, radiotherapy and/or chemotherapy.

Granulomatous disorders—hypercalcaemia is due to extrarenal synthesis of 1,25-dihydroxy vitamin D; most common diagnosis is sarcoidosis, when hypercalcaemia should respond within 10 days to treatment with glucocorticoids.

Familial benign hypocalciuric hypercalcaemia—autosomal dominant due to heterozygous inactivating mutation of the calcium sensing receptor; causes (usually) asymptomatic hypercalcaemia in association with an inappropriately low urinary calcium excretion and normal serum PTH.


Clinical presentation—this is variable, including (1) a mild, asymptomatic, biochemical abnormality; (2) in chronic cases with ectopic calcification, subcapsular cataract, papilloedema, and abnormal dentition; and (3) in severe cases with neuromuscular irritability.

Aetiology—may be associated with (1) low serum PTH—hypoparathyroidism, most often caused by autoimmune disease, surgical removal of the parathyroid glands, or hypomagnesaemia; or (2) high serum PTH—secondary hyperparathyroidism, most commonly due to vitamin D deficiency and/or renal failure.

Management—aside from appropriate treatment of the underlying condition, management of acute hypocalcaemia depends on its severity, rapidity of onset, and the degree of neuromuscular irritability. Patients with seizures or tetany may require intravenous calcium gluconate, as do asymptomatic patients with serum calcium below 1.90 mmol/litre as well as oral vitamin D.

Specific diseases causing hypocalcaemia

Pluriglandular autoimmune hypoparathyroidism—characterized by hypoparathyroidism, Addison’s disease, and candidasis in the presence of other organ-specific autoimmune diseases; autosomal recessive inheritance due to mutation of an autoimmune regulator gene, with antibodies directed against the adrenal, thyroid, and parathyroid glands sometimes present.

Hypomagnesaemia—may be caused by malabsorption or renal tubular disorder; leads to functional hypoparathyroidism because magnesium is required for the release of PTH from the parathyroid gland and also for PTH action via adenyl cyclase.

A wide range of rare syndromes may cause hypoparathyroidism, and similar functional consequences can be caused by resistance to the effects of PTH, e.g. pseudohypoparathyroidism, of which there are five variants, some with somatic features such as shortening of one or more metacarpals.

Access to the complete content on Oxford Medicine Online requires a subscription or purchase. Public users are able to search the site and view the abstracts for each book and chapter without a subscription.

Please subscribe or login to access full text content.

If you have purchased a print title that contains an access token, please see the token for information about how to register your code.

For questions on access or troubleshooting, please check our FAQs, and if you can't find the answer there, please contact us.