High Calcium

Causes of High Calcium Levels in the Blood

High calcium levels or high blood calcium levels

What to do if your blood calcium level is high
The finding of a high blood calcium level is very common, occurring in millions of Americans each year.  Sometimes, this will just be a single event related to a laboratory error or being dehydrated on the day the lab was drawn. 

However, quite frequently a high blood calcium level will mean that there is an important underlying problem.  In general, the first thing to do is re-check the level to confirm it.

Primary hyperparathyroidism is the most common cause of high blood calcium levels >

This is common sense.  For example, if you heard a strange noise in your car, you would certainly listen for it again the next time you drove to double check if it was a real problem, right?  You will see that in these pages we will frequently ask that you use common sense, as using your instincts or “gut feeling” is a good way to avoid being misled by biased or inaccurate information on the web. See Getting started: a word of caution regarding medical information on the internet.

If your blood calcium level is high on more than one occasion, then it is probably time to get more serious about finding out why this is happening.

Causes of high blood calcium levels include:

1. Primary hyperparathyroidism.  This is the most common cause of high blood calcium levels.  People with primary hyperparathyroidism usually have a benign tumor of the parathyroid glands (see What are the parathyroid glands?  Regulation of calcium in the human body) causing excessive amounts of calcium to leave the bone and enter the blood.
2. Malignancy (cancer).  This is the second most common cause of high blood calcium levels, and has nothing to do with the parathyroid glands.  Types of cancer that cause hypercalcemia of malignancy include cancers of the lung, breast, esophagus, mouth, tongue, lip, kidney, ovary, uterus, and cervix.  Blood-borne cancers such as lymphoma and multiple myeloma can also cause high calcium levels.  Thankfully, hypercalcemia of malignancy is uncommon and generally not worth worrying about in most healthy people.  (Really, please don’t worry.  Kindly read on.)
3. Thiazide diuretics.  Thiazide diuretics are a class of medicines that are commonly used to treat hypertension (high blood pressure).  They cause the kidney to “hold on” to calcium, preventing it from exiting in the urine and thereby increasing the blood calcium level slightly.  Examples of thiazide diuretics are: hydrochlorothiazide (HCTZ), chlorothiazide, chlorothalidone, indapamide, and metolazone.
4. Kidney disease, also known as renal failure or chronic renal failure.  High blood calcium levels can be found in people with slow or reduced kidney function, including those on dialysis and those who have had a kidney transplant.
5. Other rare causes, such as:

• Familial hypocalciuric hypercalcemia (FHH), also known as benign familial hypocalciuric hypercalcemia (BFHH) since it is associated with normal health.  This is a rare inherited trait characterized by a slightly high blood calcium level.
• Milk-alkali syndrome, or taking too much calcium by mouth.  Many antacids are calcium salts.  In the past, people with stomach ulcers would treat themselves by drinking lots of milk and taking lots (fistfuls) of calcium salt antacids, thereby raising the blood calcium level.  This is very rare now, since powerful non-calcium-based antacids have become available over the counter.
• Thyroid disease, such as hypothyroidism (too little thyroid hormone) and hyperthyroidism (too much thyroid hormone).  The thyroid gland is a neighbor to the parathyroid glands but has a completely separate function.  The thyroid gland governs metabolism, or how fast the cells in your body work.  In rare cases of severe thyroid disease, blood calcium levels can become imbalanced.
• Hypervitaminosis D, or too much vitamin D (See Vitamin D).  In rare circumstances, people can receive toxic levels of vitamin D leading to high blood calcium.  There have been a few interesting outbreaks of this related to errors in fortifying milk (see references below).
• There are a few more rare causes of high blood calcium levels but we have decided to leave them out because they are so very rare as to barely be worth mentioning.  So please note that this is not a complete list.

Primary hyperparathyroidism is the most common cause of high blood calcium levels (Figure 1). 

This pie chart shows the most common causes of chronically elevated blood calcium levels, meaning when the calcium test is high more than once over several months. 

Classical primary hyperparathyroidism is diagnosed when both the calcium level and the parathyroid hormone (PTH) level are above the normal range (calcium >10.5 mg/dL and PTH >65 pg/mL). 

Non-classical primary hyperparathyroidism is diagnosed when the calcium level is elevated and the PTH level remains higher than it should be, given what the calcium level is (calcium >10.5 mg/dL and PTH 21-65 pg/mL, this is also known as an inappropriately normal PTH level – see Establishing the diagnosis of primary hyperparathyroidism).  Other causes of high blood calcium are listed above and most commonly refer to hypercalcemia of malignancy (high blood calcium levels due to cancer elsewhere in the body as described above) and use of thiazide diuretics.  Patients with “possible primary hyperparathyroidism” in the pie chart are those in whom the PTH level was never checked; however all of the other causes of high calcium were ruled out.  Please note that renal failure (chronic kidney disease) can also cause high blood calcium levels but those patients were excluded from this analysis.

To summarize, about 90% of patients whose blood calcium levels are found to be high more than once have some form of primary hyperparathyroidism.  If this has happened to you or a family member, you may wish to have the parathyroid hormone (PTH) level checked.  A high or inappropriately normal PTH level will frequently establish the diagnosis of primary hyperparathyroidism (see Establishing the diagnosis of primary hyperparathyroidism).  A low PTH level will suggest other causes of high blood calcium levels.

Where does this information come from?

The pie chart contains data derived from approximately 3.5 million Americans who receive care from a vertically-integrated health maintenance organization in California.  The population studied is similar in size to the population of the state of Ohio.  Through this unique research collaboration, UCLA Endocrine Surgery has been able to study both high blood calcium levels and primary hyperparathyroidism in a completely new way, looking at large, racially diverse populations in great detail with respect to their health outcomes (see How successful is parathyroid surgery?).

References

1. Lafferty FW. Differential diagnosis of hypercalcemia. J Bone Miner Res. 1991 Oct;6 Suppl 2:S51-9; discussion S61. Review. PubMed PMID: 1763670.
2. Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005 Jan 27;352(4):373-9. Review. PubMed PMID: 15673803.
3. Varghese J, Rich T, Jimenez C. Benign familial hypocalciuric hypercalcemia.Endocr Pract. 2011 Mar-Apr;17 Suppl 1:13-7. Review. PubMed PMID: 21478088.
4. Blank S, Scanlon KS, Sinks TH, Lett S, Falk H. An outbreak of hypervitaminosis D associated with the overfortification of milk from a home-delivery dairy. Am J Public Health. 1995 May;85(5):656-9. PubMed PMID: 7733425; PubMed Central PMCID: PMC1615443.
5. Yeh MW, Haigh PI, Ituarte PH, Liu IL, Zhou H, Nishimoto S, Dell RM, Adams AL. Incidence and prevalence of primary hyperparathyroidism in a racially mixed population. Manuscript in preparation.