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 (pHPT): Hypercalcemia results from abnormally active parathyroid glands.
- Secondary hyperparathyroidism (sHPT): Hypocalcemia results in reactive overproduction of PTH.
- Tertiary hyperparathyroidism: (tHPT): Hypercalcemia results from untreated sHPT, with continuously elevated PTH levels.
Epidemiological data refers to the US, unless otherwise specified.
- Parathyroid gland adenoma (∼ 85%): benign tumor of the parathyroid glands
- Hyperplasia and multiple adenomas (∼ 15%)
- Rarely carcinomas (∼ 0.5%)
- MEN type 1 or 2
- (most frequent cause)
- (e.g., reduced exposure to sunlight, nutritional deficiency, liver cirrhosis)
- Caused by persistent sHPT
Physiological secretion of PTH
- See .
Pathologically increased secretion of PTH
Primary hyperparathyroidism: overproduction of PTH by parathyroid chief cells
- Effect of PTH on bone → increased bone resorption → ↑ release of calcium phosphate → ↑ calcium levels
- Effect of PTH on the kidneys → ↑ phosphate excretion (phosphaturia)
- Secondary hyperparathyroidism: ↓ calcium and/or ↑ phosphate blood levels → reactive hyperplasia of the parathyroid glands → ↑ PTH secretion
- Tertiary hyperparathyroidism: chronic renal disease → refractory and autonomous secretion of PTH → hypercalcemia
- Renal disease → secondary or tertiary hyperparathyroidism → → bone lesions
- FHH) is discussed in the article . (
The majority of patients are asymptomatic!
- Cardiovascular disease
- Musculoskeletal system
- Digestive tract
- Psychological symptoms: depression, fatigue, anxiety, sleep disorders
"Stones, bones, abdominal groans, thrones, and psychiatric overtones!"
- 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)|
|Tertiary hyperparathyroidism||↑|| |
- pHPT: hypercalciuria (calcium/creatinine ratio > 0.02), and ↑ cAMP in urine
- In sHPT, diagnosis focuses on identifying the underlying disease (e.g., creatinine in chronic kidney disease).
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
- 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
- Treat the underlying condition (e.g., see treatment of treating hyperphosphatemia ) and focus on
- In case of vitamin D deficiency: substitute with ergocalciferol
- Similar to pHPT