Clinical biochemistry: disorders of calcium metabolism

This series of freely available online resources takes you through calcium and phosphate metabolism, its endocrine control, and the fundamentals of how to investigate hyper- and hypo-calcaemia. Parathyroid hormone (PTH), vitamin D, and their disorders are discussed.

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  1. The endocrine control of calcium and phosphate metabolism: this diagram and its legend outline clearly the actions of PTH and vitamin D in controlling calcium homeostasis.  It contains a little more detail than is required for medical students (who don't really need to know much about FGF ).  The full article can also be accessed through this link, and contains a good description of FGF .
  2. When investigating disorders of calcium metabolism, a number of tests should be requested.  These include calcium and phosphate, but the other key investigation is PTH.  The page from Lab Tests Online below gives an excellent overview.
  3. Vitamin D is also a commonly requested test, usually in the context of suspected metabolic bone disease, hypocalcaemia, or a raised serum alkaline phosphatase.  Vitamin D deficiency has been associated with a wide range of disorders, but it is unclear to date whether measuring vitamin D or replacing vitamin D is of benefit.  The article from Lab Tests Online indicates when it should be tested, and importantly distinguishes 25-hydroxy-vitamin D testing (this is what you would get from a lab when requesting vitamin D) from 1,25-hydroxy-vitamin D testing, the activated form, which has a much more specific use.
  4. The investigation and management of hypercalcaemia is covered in this page from Endobible.  It has a helpful section on clinical symptoms and signs to look out for that may indicate hypercalcaemia or suggest a cause.  It also has a good section on investigation, including radiology.
  5. Hypocalaemia is discussed in this entry from (professional pages).  There is also a page on hypercalcaemia, which is also good.
  6. Case reports

    In this section there are a series of case reports that emphasize some of the important points covered so far, and demonstrate how an understanding of the calcium biochemistry and homeostasis, along with relevant anatomy, are important in making sense of the clinical presentation and management.The first case (actually at the end of the linked article below) is of primary hyperparathyroidism. This is an article from the USA, so the units are different, but the basic concepts are the same. The authors are surgeons, and there is an interesting discussion of surgical management and the use of intraoperative plasma PTH measurements. There is an inaccuracy, however, as it is stated that vitamin D deficiency is a cause of hypercalcaemia - it is of course a cause of hypo calcaemia. I think the authors intention is to point out that vitamin D deficiency may cause secondary hyperparathyroidism. This occurs as vitamin D deficiency causes hypocalcaemia, which stimulates the parathyroid glands to produce more PTH (which is entirely appropriate). The pattern of results seen in this case is a low or low-normal calcium with a raised PTH and low vitamin D. That aside, it is a good article.
  7. The next case is of a condition that should be excluded before parathyroidectomy is carried out as it also causes hypercalcaemia with a raised plasma PTH: familial hypocalcuric hypercalcaemia (FHH).  This case also illustrates how difficult it can be to untangle the cause of hypercalcaemia in the presence of multiple pathologies.
  8. The final case is of osteomalacia and contains a useful clinical description. Again, the article is from the USA, so the units are different to those used in the UK.  The initial testing for coeliac disease in the UK is also different to that mentioned in the article - IgA anti-tissue transglutaminase (anti-TTG) antibodies are used first line as their sensitivity and specificity is very high.