Hidden in the back of the thyroid gland are 4 small parathyroid glands that release parathyroid hormone (PTH), which is critical for maintaining the mineral balance in the body. Low or high blood PTH levels can decrease your quality of life and cause serious health issues. Read on to learn more about PTH and how high or low levels can affect your health.
What is Parathyroid Hormone (PTH)?
Parathyroid hormone (PTH) is produced by the parathyroid glands. Most people have 4 pea-sized parathyroid glands embedded in the back of the thyroid gland, but variations in their location and number sometimes occur.
PTH controls calcium, phosphorus, and magnesium levels in the blood.
Because calcium balance plays a critical role in many bodily functions, including muscle movement and nerve impulses, calcium levels are tightly controlled to stay within a narrow range in the blood.
PTH’s main function is to increase calcium levels when they are too low. It [1]:
- triggers the release of calcium from the bones to the blood
- decreases the loss of calcium in the urine
- increases calcium absorption from food
Measuring parathyroid hormone levels can help uncover the cause of abnormal calcium levels and can be used to monitor the progression of some diseases.
PTH Increases Blood Calcium
1) Via Bones
Bones act as a calcium reservoir, releasing calcium into the bloodstream when blood levels are low and taking up calcium when they are high. PTH communicates to bone cells what action is needed [2].
Parathyroid glands have calcium sensors. When calcium is low, the glands release more PTH. High PTH levels signal the bones to release more calcium into the blood [2].
When calcium levels in the blood are high, parathyroid glands release less PTH. Low PTH levels signal bones to take up calcium from the blood [2].
2) Via Kidneys
As blood is filtered through the kidneys, some amount is returned to the blood and some removed from the body in the urine. Parathyroid hormone influences the net balance of how much calcium and phosphorus are removed and how much is retained during that process [3].
When PTH is high, the kidneys retain more calcium. When PTH is low, more calcium is eliminated in the urine, decreasing the calcium concentration in blood [3].
3) Via Intestines
Parathyroid hormone triggers the kidneys to convert vitamin D from its inactive to its active form (1,25-dihydroxy vitamin D or calcitriol). In its active form, vitamin D increases the absorption of calcium in the intestines [4, 5, 6].
Higher PTH levels lead to an increase in active vitamin D, which leads to an increase in intestinal calcium absorption, which leads to a higher calcium concentration in the blood [5].
PTH vs. Calcitonin
Calcitonin is produced in the thyroid gland and helps maintain calcium blood levels. If calcium levels are too high, then calcitonin reduces them [7].
Calcitonin is produced in response to high calcium levels in the blood [8].
Basically, calcitonin has the opposite effect of PTH. Both hormones are responsible for maintaining healthy levels of calcium in the blood [9].
Parathyroid Hormone Test
Parathyroid hormone levels can be measured by a blood test. PTH normally ranges from 14 to 64 ng/L [10]. However, different testing methods may be used by different laboratories, which is why the normal ranges may vary.
Therefore, while labs will provide the range of normal values for their methodology, direct comparison of values from different labs may be inappropriate [11].
Normal Biological Variation
Normally, PTH is released both at low levels throughout the day and at pulses of higher levels a few times per hour [12].
An analysis of 3.6 million blood tests showed that both vitamin D and PTH levels vary seasonally. When vitamin D levels decrease, PTH levels increase, following about 4 weeks behind vitamin D levels [13].
On average, men’s vitamin D levels are lower and PTH levels are higher than women’s levels [13].
Parathyroid hormone levels can also increase during and following exercise, depending on its duration and intensity [14].
Levels May Differ Between Populations
In one study, Mexican- and African-Americans were found to have higher PTH than whites. However, both black and white Americans were found to have a higher incidence of primary hyperparathyroidism (abnormally high PTH) than Mexican-Americans in another study [15, 16].
Also, vitamin D deficiencies impacted PTH levels differently in African-Americans than in the other two groups. While PTH levels continued to decline with levels of vitamin D greater than 20 ng/ml in whites and Mexican-Americans, they did not follow the same pattern with vitamin D greater than 20 ng/ml in blacks [15].
Levels Are Higher with Obesity
As total body fat increases, parathyroid hormone levels increase. The effect of obesity on PTH levels is seen even when controlling for the decrease in vitamin D levels associated with more body fat [17].
Increasing waist size in women carries an increased risk of developing hyperparathyroidism (abnormally high PTH) [18].
One study found that both leptin and PTH levels increase with increasing body mass. However, it was only in people with higher leptin levels (greater than 10 ng/ml) that a decrease in vitamin D was associated with an increase in PTH. Leptin seems to affect PTH levels and both leptin and PTH regulate the conversion of vitamin D to its active form [19].
High PTH (Hyperparathyroidism)
Hyperparathyroidism is the condition of having abnormally high blood parathyroid hormone levels.
Causes of Abnormally High PTH
Causes listed below have been associated with higher PTH. An abnormal PTH test can indicate there is a problem, but can’t pinpoint the cause. Your doctor will usually follow this result with additional testing to investigate why your PTH is high. Work with your doctor or another health care professional to get an accurate diagnosis.
1) Primary Hyperparathyroidism
Primary hyperparathyroidism occurs when the parathyroid glands produce too much PTH despite normal or even high blood calcium levels. It is the third most common hormonal disorder after diabetes and thyroid disease. Benign tumors (adenomas) in the parathyroid gland are responsible for 80-85% of primary hyperparathyroidism cases [20].
Primary hyperparathyroidism usually results in high calcium and low phosphorus levels in the blood, which can lead to kidney stones, low bone density (osteopenia and osteoporosis due to more bone being broken down), and even depression [20, 21].
2) Chronic Kidney Disease
Secondary hyperparathyroidism occurs when low blood calcium levels caused by certain conditions and diseases stimulate the parathyroid glands to produce too much PTH. It is commonly caused by chronic kidney disease and results in high phosphorus levels in the blood [22].
Chronic kidney disease can impair kidney function, which can decrease the amount of calcium reabsorbed by kidneys during blood filtration. The resulting low blood calcium levels signal the parathyroid glands to release more PTH, causing abnormally high levels of the hormone in the blood [23, 22].
3) Dietary Deficiencies of Calcium and Vitamin D
Abnormally low levels of calcium in the blood increase parathyroid hormone levels. Dietary deficiencies in calcium or vitamin D are the most direct causes of low blood calcium levels [24].
4) Malabsorption
Poor absorption of nutrients by the intestines can lead to low blood calcium levels, which could trigger more PTH release [25].
5) High Aldosterone Levels
Primary aldosteronism (high aldosterone levels) can cause high PTH levels. High aldosterone levels cause the kidneys to release more calcium into the urine, lowering blood calcium levels and triggering the parathyroid glands to release more PTH [26, 27, 28].
6) Some Drugs
Drugs that can increase PTH include:
- Lithium treatment for bipolar disorder [29]
- Water pills (diuretics) [30, 31]
- Calcium-channel blockers such as amlodipine (Norvasc) and nifedipine (Adalat CC, Afeditab CR, Procardia), used to treat high blood pressure [31]
7) Radiation Therapy
Radioactive iodine treatment for thyroid disease can increase PTH levels [32].
8) Genes
Increased PTH levels have been associated with genetic variations in or near genes involved in vitamin D production and calcium and phosphate transport, including these SNPs [33]:
- rs6127099 (upstream of CYP24A1)
- rs4074995 (within RGS14)
- rs219779 (adjacent to CLDN14)
- rs4443100 (near RTDR1)
- rs73186030 (near CASR)
Hyperparathyroidism has also been associated with mutations in:
Health Effects of High PTH
High calcium in the blood and low calcium in the bones can lead to [20, 21]:
- kidney stones
- low bone density (osteopenia and osteoporosis) due to more bone being broken down
Higher PTH levels have been associated with heart disease [36, 37, 38].
Symptoms of high PTH levels include [20]:
- Kidney stones
- Depression
- Anxiety
- Fatigue
- Mood and sleep disorders
- Memory loss and difficulty concentration
- Irritability
Decreasing PTH
The most important thing is to work with your doctor to find out what’s causing your high PTH levels and to treat any underlying conditions. High PTH levels are often caused by underlying diseases that require medical attention and can’t be fixed by lifestyle changes or supplements.
Discuss the complementary strategies listed below with your doctor. None of these strategies should ever be done in place of what your doctor recommends or prescribes!
Ways to decrease PTH levels or reduce the risk of developing hyperparathyroidism include:
- Losing weight if overweight [18]
- Getting regular exercise [39]
- Getting more sunlight in order to raise your vitamin D levels, if you are deficient [40]
- Eat a well-balanced diet that includes calcium-rich foods, such as dairy, salmon, and kale [41, 42, 43]
If you are deficient in vitamin D or calcium, your doctor may prescribe supplements.
Low PTH (Hypoparathyroidism)
Hypoparathyroidism is the condition of having low or inappropriately normal blood parathyroid hormone levels.
If blood calcium levels are low, the parathyroid glands normally release extra PTH. So, PTH levels in the normal range are considered inappropriate when blood calcium levels remain low.
It is estimated that, in the US, 60,000 to 80,000 people have hypoparathyroidism [44].
Hypoparathyroidism usually leads to low calcium and high phosphate levels in the blood [45].
Causes of Low PTH
Causes listed below have been associated with low PTH. An abnormal PTH test can indicate there is a problem, but can’t pinpoint the cause. Your doctor will usually follow this result with additional testing to investigate why your PTH is low. Work with your doctor or another health care professional to get an accurate diagnosis.
1) Surgery
About 75% of hypoparathyroidism cases are the result of neck surgery, such as for the removal of the thyroid or parathyroid glands [46].
Hypoparathyroidism resulting from surgery can cause a quick drop in calcium levels that requires immediate attention. Generally, post-surgical hypoparathyroidism is defined as having blood calcium less than 8.0 mg/dL and PTH less than 15 ng/L [45].
About 75% of the hypoparathyroidism cases following surgery are transient (temporary) and PTH levels return to normal in less than 6 months [47].
Low vitamin D levels prior to surgery can increase the risk for post-surgical hypoparathyroidism. To minimize risk, it is recommended that pre-surgery vitamin D levels in the blood are at least 20 ng/dL [44].
2) Autoimmune Disease
Autoimmune disease is the second most common cause of low PTH [48, 49].
3) Damage To the Parathyroid Gland
Damage to the parathyroid gland due to radiation, iron or copper deposition, or cancer metastasis can decrease PTH [49].
4) Magnesium Deficiency
Low levels of magnesium decrease blood PTH levels [45].
5) Some Drugs
Drugs that can decrease PTH levels include:
- Digoxin (Lanoxin, Digox, Lanoxin Pediatric, and Digitek), used to treat irregular, rapid heart rate (atrial fibrillation) [50]
- Thiazide diuretics such as hydrochlorothiazide (Microzide) and metolazone (Zytanix and Zaroxolyn), used to treat fluid retention [31]
- Calcimimetics that mimic the action of calcium, including cinacalcet (Sensipar, Mimpara) and etelcalcetide (Parsabiv) [51]
6) Genetic Disorders
These genetic disorders and their related genes are associated with hypoparathyroidism [45]:
- Autoimmune polyendocrinopathy syndrome type 1 (AIRE)
- DiGeorge syndrome types 1 (TBX1) and 2 (NEBL)
- Hypoparathyroidism-deafness-renal dysplasia syndrome (GATA3)
- Kenny-Caffey syndrome type 1 (TBCE) and 2 (FAM111A)
- CHARGE syndrome (CHD7, SEMA3E)
- Bartter syndrome, type 5 (CASR)
Mutations in these genes have been associated with hypoparathyroidism [52, 53, 54]:
Health Effects of Low PTH
The low calcium levels caused by hypoparathyroidism most commonly lead to problems with muscles and the nervous system [45].
The high calcium intake used to treat low PTH levels can cause kidney stones and increase the risk of developing chronic kidney disease [45].
Bone mass density is usually higher in patients with chronic hypoparathyroidism. Whether that is due to treatment with calcium and vitamin D supplements or low PTH levels reducing bone restructuring, or whether it is a combination of the two is unclear [45].
Many people with hypoparathyroidism report a reduced quality of life, including fatigue, depression, anxiety, and cognitive difficulties [44].
Symptoms of low PTH levels include [55, 48]:
- Muscle pains
- Muscle cramps and spasms
- Fatigue
- Chronic headaches
- Insomnia
- Tingling fingers and feet
Increasing PTH
The most important thing is to work with your doctor to find out what’s causing your low PTH levels and to treat any underlying conditions. Low PTH levels are often caused by underlying diseases which require medical attention and can’t be fixed by lifestyle changes or supplements.
Hypoparathyroidism is most commonly treated with calcium (1,000 to 9,000 mg/day) and vitamin D (0.25 to 2.0 ug/day of calcitriol) supplements. The goal is to maintain blood calcium levels at 8.0 to 9.0 mg/dL while avoiding high levels of calcium in the urine [44].
A synthetic parathyroid hormone (Natpara) was approved by the FDA as a treatment in 2015. However, long-term complications from its use are still being evaluated [56, 44].
Make sure your magnesium levels are in balance. If they are on the low end, you may benefit from taking magnesium supplements [45]. Always consult your doctor before taking supplements.
Use of Parathyroid Hormone to Treat Osteoporosis
Because parathyroid hormone is a key controller of bone building, it is an important factor in many bone disorders.
A synthetic parathyroid hormone analog (teriparatide) has been used for treating severe osteoporosis. It is effective at building bone when given in intermittent, low doses [57, 58, 59].
In 2017, another parathyroid hormone-like medication, abaloparatide, was approved by the FDA for treating severe osteoporosis [60, 61].
