A study reviewed past and current research to help clarify appropriate treatment plans for patients with primary hyperparathyroidism.

The surgical removal of parathyroid glands has been shown to reduce the symptoms of primary hyperparathyroidism (pHPT) but since the condition ranges over a large spectrum it is difficult for clinicians to determine which patients would benefit the most from the procedure. An article published in JAMA Surgery reviews past and current research to attempt to clarify the indications for parathyroidectomy to treat symptoms of pHPT.

There are typically 4 parathyroid glands located within the boundaries of the thyroid, which is located in the neck, and their function is to regulate the amount of calcium in the body. This is accomplished by secretion of parathyroid hormone (PTH) when calcium levels are low. PTH acts on the bones, kidneys, and intestines to increase the levels of calcium in the blood. Conversely, when calcium levels are elevated then PTH is decreased to lessen the amount of calcium being retained in the body.

When this regulatory system is altered by a tumor or an enlargement of parathyroid tissue then more PTH is released and subsequently, more calcium is retained in the body which can lead to many serious symptoms. Many patients will present with joint aches, fatigue, and loss of appetite in the early stages of the disease. At higher levels of PTH and blood calcium, there is a higher risk of impaired kidney function with frequent urination, kidney stones, calcium deposits within the kidney as well as more intense gastrointestinal and joint symptoms. There are also neuropsychiatric symptoms such as depression and difficulties concentrating that are seen as well but are less reliable when making a diagnosis.  Left untreated this can progress to more severe symptoms such as ataxia (loss of control over muscle movement) and even coma.  This myriad of symptoms that are caused by a direct effect on the parathyroid glands are grouped into the condition of pHPT and many clinical textbooks will associate the rhyme “stones, bones, abdominal groans, thrones and psychiatric overtones” with this disease. It is most commonly seen in post-menopausal women.

The two main treatments for the treatment of pHPT are parathyroidectomy, which is the removal of the parathyroid gland, and antiresorptive therapy, which is a medication regimen aimed at flushing out the excess PTH and calcium in the body. The issue that the researchers in this review article were trying to understand was which treatment works best for each individual patient since many patients with pHPT present with a much more mild form of the disease and are usually asymptomatic, presenting only with high blood calcium. Researchers reviewed several recent clinical trials aimed at assessing the efficacy of parathyroidectomy versus antiresorptive therapy or observation alone to determine when it is best to consider surgery for pHPT.

Bone density scans are typically the most accurate way to measure whether or not treatment for pHPT is working because the majority of calcium in the body is stored in bones. pHPT is usually associated with lower bone density because of the increased PTH harvesting more calcium from the bone to be put into circulation. This increases the risk of fractures, osteoporosis and other issues with the skeletal system over time so if a surgical intervention should be used it would be most effective earlier in the progression of the disease. When assessing 3 randomized clinical trials, meaning the studies were designed so that less confounding variables could be introduced, the researchers found that patients with pHPT post-parathyroidectomy had significant increases in bone density, indicating improvement. They also included in their analysis a cohort study from 2013 of 236 patients with pHPT who underwent surgery and showed similar improvements in bone density. When compared to antiresorptive therapy, the improvements in bone density were similar in magnitude.

Although parathyroidectomy showed clear promise in restoring bone density to normal levels, psychiatric improvements were less clear. The researchers quoted some studies as providing subjective evidence in the improvement of neuropsychiatric symptoms but only one large randomized clinical trial with 191 patients that reported improvements in these symptoms. In a conference in 2008 on pHTP, researchers concluded that data so far points to improvements in neuropsychiatric symptoms but this evidence is not sufficient to justify surgery.

The researchers were able to review enough evidence from other studies that showed improved bone health post-parathyroidectomy but the exact effect on neuropsychiatric symptoms remain unclear. They concluded that since most patients with primary hyperparathyroidism present with no obvious signs or symptoms that surgical considerations should primarily include an evaluation of bone and kidney health since the two systems are interrelated and most affected by pHPT. Further, these evaluations should be carried out as early as possible to prevent progression of the disease. Further research will likely focus on more accurate ways to measure bone density as well as how to better evaluate neuropsychiatric symptoms as they relate to primary hyperparathyroidism.  In all, the evidence points towards surgery as the best option for most patients.

Written by Clifton Lewis

References: Stephen AE, Mannstadt M, Hodin RA. Indications for Surgical Management of HyperparathyroidismA Review. JAMA Surg. Published online June 28, 2017. doi:10.1001/jamasurg.2017.1721

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