• Clinical science



Hyperparathyroidism (HPT) is characterized by abnormally high parathyroid hormone (PTH) levels in the blood due to overactivity of the parathyroid glands. It is differentiated into three types based on the underlying cause: primary HPT (pHPT), secondary hyperparathyroidism (sHPT), and tertiary hyperparathyroidism (tHPT). pHPT is characterized by elevated parathyroid hormone and calcium levels and is usually caused by parathyroid adenomas (or, in rare cases, by parathyroid carcinomas). Although often asymptomatic, symptoms such as bone pain, gastric ulcers, and/or kidney stones may emerge in severe cases. sHPT is characterized by high parathyroid hormone and low calcium levels and may be caused by kidney failure, vitamin D deficiency, or malabsorption. sHPT is also called reactive HPT, as the increase in (parathyroid) hormone production is a physiological response to hypocalcemia and not caused by an abnormality of the parathyroid glands. If sHPT and elevated parathyroid hormone blood levels persist, tHPT may develop, resulting in a shift from low to high calcium blood levels. Hyperparathyroidism is diagnosed and classified by evaluating calcium, phosphorus, and parathyroid hormone levels and, in the case of sHPT, evaluating the underlying disease (e.g., creatinine in chronic kidney disease). Surgery is the primary treatment option for symptomatic patients and asymptomatic patients who meet certain criteria. Patients who are not surgical candidates are managed with either calcimimetics or, if osteoporosis is present, bisphosphonates. In sHPT, treatment of the underlying disease is the focus.


All forms of hyperparathyroidism are characterized by elevated PTH levels.



Primary hyperparathyroidism

  • Parathyroid gland adenomas (∼ 85%)
  • Hyperplasia and multiple adenomas (∼ 15%)
  • Rarely carcinomas (∼ 0.5%)
  • MEN type 1 or 2

Secondary hyperparathyroidism

Tertiary hyperparathyroidism

  • Caused by persistent sHPT



Physiological secretion of PTH

Pathologically increased secretion of PTH

pHPT develops due to hyperplasia of the parathyroid glands. sHPT develops due to decreased levels of calcium in the blood (reactive HPT)!


Clinical features

Primary hyperparathyroidism

The majority of patients are asymptomatic!

"Stones, bones, abdominal groans, thrones, and psychiatric overtones!"

Secondary hyperparathyroidism

  • Symptoms related to the underlying cause of sHPT (commonly renal failure)
  • Bone pain and increased risk of fractures



Laboratory studies of hyperparathyroidism

Calcium Phosphorus Alkaline phosphatase Parathyroid hormone (PTH)
Primary hyperparathyroidism

Secondary hyperparathyroidism

n/↓ n/↑
Tertiary hyperparathyroidism


Hypercalcemic crises may occur in primary and tertiary HPT!


  • Ultrasound/nuclear imaging (Tc99m-sestamibi scan): only performed prior to surgery to determine the exact location of the abnormal glands
  • Skeletal x-ray: decreased bone mineral density, but usually an incidental finding, as x-ray is not a routine diagnostic tool
    • Cortical thinning: especially prominent in the phalanges of the hand (acroosteolysis)
    • Salt-and-pepper skull
    • Rugger-jersey spine sign



Primary hyperparathyroidism

  • Surgical
    • Indications
      • Symptomatic patients
      • Asymptomatic patients who meet at least one of the following criteria:
        • Age < 50 years
        • Serum calcium level more than 1 mg/dL higher than the normal upper limit
        • Impaired renal function (eGFR < 60 mL/min)
        • Increased calcium excretion (> 400 mg/day) in combination with an increased risk for nephrolithiasis
        • Evidence of nephrolithiasis or nephrocalcinosis via imaging
        • Reduced bone mineral density (T-score < -2.5 at lumbar spine, total hip, femoral neck, or distal third of the radius, or preexisting asymptomatic vertebral fracture)
    • The procedure depends on the pathology:
  • Nonsurgical: in symptomatic patients who are not able to undergo surgery or asymptomatic patients who do not meet the criteria for surgical therapy

Secondary hyperparathyroidism

Tertiary hyperparathyroidism