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.
- Parathyroid gland adenoma (∼ 85%): benign tumor of the parathyroid glands
- Hyperplasia and multiple adenomas (∼ 15%)
- In rare cases, carcinomas ; (∼ 0.5%) or idiopathic
- MEN type 1 or 2
- Lithium 
- (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 → ↑ 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).” (
- Nonspecific: weakness
- Cardiovascular system
- Musculoskeletal system
- Digestive tract
- Psychological symptoms: : depression, fatigue, anxiety, sleep disorders
The majority of patients are asymptomatic.
"Stones, bones, abdominal groans, thrones, and psychiatric overtones!"
Secondary and tertiary hyperparathyroidism
Laboratory studies of hyperparathyroidism
|Overview of laboratory parameters in hyperparathyroidism|
|Calcium||Phosphorus||Alkaline phosphatase||Parathyroid hormone (PTH)|
|Primary hyperparathyroidism|| || || |
| || || || |
|Tertiary hyperparathyroidism|| || || || |
- Measurement of 25-hydroxyvitamin D 
Hypercalcemic crises may occur in primary and tertiary HPT.
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: granular decalcification 
- Rugger-jersey spine sign: Alternating low and high density in the vertebrae produces a banded pattern, similar to a striped rugby jersey. 
Osteitis fibrosa cystica (OFC): a rare skeletal disorder seen in advanced hyperparathyroidism characterized by replacement of calcified bone with fibrous tissue
- Most commonly seen in primary hyperparathyroidism but can also occur in secondary hyperparathyroidism
- ↑ PTH → ↑ RANK ligand expression → activation of osteoclasts → bone resorption, cortical bone destruction, and fibrous tissue deposition
- Features include bone pain, subperiosteal thinning, and bone cysts (multiple bone cysts in the skull can demonstrate as pepper-pot appearance on x-ray)
- In advanced OFC, large, cystic, vascular cavities with a tumor-like appearance on x-ray and a brown color due to hemosiderin deposition (brown tumors) can form in long bones.
- Ultrasound/nuclear imaging (Tc99m-sestamibi scan): only performed prior to surgery to determine the exact location of the abnormal glands
- 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)
- In cases of solitary adenoma
- Only the respective gland is removed.
- Complication: hungry bone syndrome
Total parathyroidectomy ; 
- In cases of hyperplasia
- All four glands are removed. 
- Tumor resection
Calcimimetics (e.g., cinacalcet)
- Mechanism of action: modulation of calcium-sensitive receptor (CaSR) in parathyroid glands → ↑ sensitivity of the receptor to circulating Ca2+ → inhibition of PTH release
- Adverse effects
- Interactions: strong inhibition of CYP2A6
- Bisphosphonates: In patients with osteoporosis
- Avoid lithium and thiazide diuretics.
- For treatment of acute hypercalcemia, see “ .”
Treat the underlying condition (e.g., see “Treatment” in “ treating hyperphosphatemia ”) and focus on
- Dietary phosphorus restriction (e.g., no soft cheese, nuts)
- If dietary restriction alone is unsuccessful, add phosphate binders.
- In case of vitamin D deficiency: substitute with ergocalciferol
- Agent: sevelamer
- Mechanism of action: binds phosphate in the gut (sevelamer is nonabsorbable) → ↓ phosphate absorption → ↓ serum phosphate → ↓ PTH
- Indication: hyperphosphatemia caused by chronic kidney disease
- Adverse effects
- Similar to pHPT