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Primary hyperparathyroidism

Oberger Marques JV1Moreira CA2.

Best Pract Res Clin Rheumatol. 2020 Apr 23:101514. doi: 10.1016/j.berh.2020.101514. [Epub ahead of print]



Primary hyperparathyroidism (PHPT) is a condition that affects calcium metabolism due to parathyroid hormone (PTH) hypersecretion leading to hypercalcemia. Manifestations have changed over time, from a symptomatic disease with bone pain, fractures, nephrolithiasis, and muscle weakness, to a condition that is mainly asymptomatic (80-90%). Typical symptoms and signs occur in the bones and kidneys and atypical manifestations are cardiovascular, neuropsychiatric and cognitive, neuromuscular, rheumatological, and gastrointestinal. Diagnosis occurs, in most cases, in asymptomatic patients by a routine calcium measurement with corrected high total calcium associated with high or inappropriately abnormal PTH. If indicated, a search for the location of the involved parathyroid gland should be performed with ultrasound, scintigraphy, or 4D CT. Parathyroidectomy is the gold standard treatment. If surgery cannot be performed, clinical management is indicated. Surgical indications are osteoporosis, hypercalciuria, spine fractures, age <50 years, calcemic values above 1.0 mg/dL threshold value, creatinine clearance ≤60 mL/min, and nephrolithiasis or nephrocalcinosis.


Current data demonstrate that clinical manifestation of PHPT has changed over the decades, and currently the diagnosis, most of the time, is made in asymptomatic patients (without bone and kidney diseases). However, it must be remembered that arthralgias, myalgias as well as generalized pain can also be a manifestation of HPTP, and therefore, it must be listed as a differential diagnosis of rheumatological symptoms. Similarly, cardiovascular and neuropsychiatric symptoms without any known etiology. However, these clinical manifestations are still not strong to indicate surgical treatment and therefore studies to evaluate the outcome of these specific symptoms after parathyroidectomy are necessary. In the presence of diagnostic suspicion, laboratory investigation including serum calcium and PTH as well as 24-hour urinary calcium and measurement of 25-OH vitamin D to rule out secondary hyperparathyroidism. In the management of HPTP, first, it is important to check out whether there is an indication for parathyroidectomy. Among the tools for localizing the parathyroid adenoma, 99mTc-sestamibi scintigraphy and dynamic (4D) CT imaging are the most effective. For those patients who will not have surgery for any reason, clinical treatment is indicated for controlling severe hypercalcemia (calcimimetic agent) and for avoiding bone loss (antireabsorptive drugs). In addition, diuretics such as hydrochlorothiazide can be used for reducing hypercalciuria and the probability for kidney stones. Studies evaluating the role of drugs such as denosumab in improving from rheumatological symptoms in addition to increasing the bone mineral density and preventing fractures in patients with PTHP are still lacking.

Practice points

 Most patients are diagnosed during routine checkups.

 Primary hyperparathyroidism is the most common cause of laboratory hypercalcemia.

 Some symptoms can be attributed to PHPT such as generalized pain, muscle weakness, and asthenia, which can mimic conditions like polymyalgia rheumatica and fibromyalgia.

 A new subset of the disease characterized by NPHT may show bone loss and kidney changes.

 The location of the affected gland is not indicated as part of the diagnosis, but only for surgical programming.

 Parathyroidectomy is not indicated for all patients, but only for those who have osteoporosis, hypercalciuria, age less than 50 years, nephrocalcinosis, nephrolithiasis, renal dysfunction, hypercalcemia, and spinal fractures.