Sporadic primary hyperparathyroidism: medical and surgical updates

Abstract

This review discusses recent findings on the clinical presentation, evaluation, medical and surgical management of primary hyperparathyroidism. Medical management includes the use of cinacalcet and bisphosphonates for bone loss and correction of vitamin D deficiency. Surgical updates reviewed recent studies on the preoperative localization of the disease, specifically, sestamibi scans, 4DCT and MRI. Focused parathyroidectomy continues to be the preferred surgical approach for a select group of patients, guided by intraoperative use of PTH and new technology, such as endoscopic and robotic platforms; however, there appears to be no difference in long-term success compared to the traditional approach.

Keywords::

• bisphosphonates
• bone loss
• cinacalcet
• hypercalcemia
• normocalcemic primary hyperparathyroidism
• parathyroidectomy
• primary hyperparathyroidism
• vitamin D deficiency

Financial & competing interests disclosure

P Camacho is a PI for a multicenter osteoporosis trial sponsored by Amgen. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Mild, asymptomatic untreated primary hyperparathyroidism (PHPT) is associated with increased all-cause mortality, and fatal and non-fatal cardiovascular disease.

• In addition to genetic mutations, factors that are implicated in the pathophysiology of PHPT include radiation exposure and prolonged parathyroid gland stimulation by vitamin D or calcium deficiency.

• Although PHPT is asymptomatic in 80% of the cases, it is associated with a higher prevalence of cardiovascular risk factors such as type 2 diabetes mellitus, hypertension and hyperlipidemia, and a higher prevalence of coronary artery disease compared to the general population. It is also associated with depression, anxiety, poor sleep, impaired cognitive function and decreased quality of life. Normocalcemic PHPT, a new phenotype of the disease, is defined by elevated parathyroid hormone (PTH) levels with the presence of persistently normal total and ionized serum calcium levels, and the absence of other causes of PTH elevation such as vitamin D or calcium deficiency, renal impairment, hypercalciuria and medications.

• Although less is known about normocalcemic PHPT compared to hypercalcemic PHPT, it might be associated with similar complications and should be approached in a similar manner.

• The indications for surgical referral in patients with asymptomatic include serum calcium more than 1 mg/dl above the upper limit of normal, creatinine clearance less than 60 ml/min, T-score less than −2.5 at any site and/or previous low-trauma fracture, age less than 50 years and cases where medical surveillance is neither desired nor possible.

• Preoperative localization for parathyroid surgery using ultrasound, 99mTc-sestamibi scan and four-dimensional computed tomography (4DCT), as well as intraoperative PTH monitoring allow surgeons to perform a focused operation through a smaller incision with a greater than 95% cure rate.

• Referral to a highly experienced parathyroid surgeon is a key factor in successful surgical treatment of PHPT.

• For patients with PHPT who cannot or will not undergo surgery, targeted medical therapy includes the use of the calcimimetic cinacalcet for significant hypercalcemia, and the use of bisphosphonates to treat bone loss.

• 25-hydroxyvitamin D should be routinely measured in patients with PHPT, and deficiency or insufficiency should be corrected with close monitoring of 24-h urine calcium levels.

Notes

Data taken from [2].