What is primary hyperparathyroidism?

Primary Hyperparathyroidism

Primary hyperparathyroidism (PHPT) is defined as excessive parathyroid hormone (PTH) production resulting in hypercalcemia, typically caused by autonomous overproduction of PTH from one or more parathyroid glands. 1

Pathophysiology and Causes

Primary hyperparathyroidism occurs when the parathyroid glands autonomously overproduce parathyroid hormone, disrupting normal calcium homeostasis. The etiology includes:

• Single parathyroid adenoma (80%) - most common cause 1
• Multiple adenomas or multigland hyperplasia (15-20%) 1
• Parathyroid carcinoma (<1%) - rare cause 1

Some cases are hereditary, associated with:

• Multiple endocrine neoplasia types 1 and 2A
• Familial hyperparathyroidism

However, most cases are sporadic in nature 1.

Epidemiology

PHPT demonstrates significant demographic patterns:

• More common in women (incidence of 66 per 100,000 person-years)
• Less common in men (25 per 100,000 person-years)
• Prevalence increasing significantly in recent decades 1
• Most frequently found in the 6th to 7th decade of life 2

Clinical Presentation

The presentation varies significantly based on geographic location and screening practices:

In countries with routine biochemical screening (US, Canada, Europe):

• Predominantly asymptomatic - discovered incidentally through routine blood tests showing hypercalcemia 1
• Normocalcemic variant - characterized by elevated PTH with normal calcium values, still at risk for complications 1

In countries without routine screening (China, India):

• Symptomatic presentation with target organ involvement 1

Clinical Manifestations

PHPT affects multiple organ systems:

Skeletal manifestations:

• Bone demineralization
• Increased fracture risk
• Osteoporosis 1, 2

Renal manifestations:

• Nephrolithiasis (kidney stones)
• Nephrocalcinosis
• Impaired kidney function 1

Neurocognitive manifestations:

• Muscle weakness
• Neurocognitive disorders
• Depression 1, 3

Cardiovascular manifestations:

• Potential cardiovascular complications 2

Diagnosis

The diagnosis of PHPT is established through biochemical testing:

1. Elevated or inappropriately normal PTH with hypercalcemia is the hallmark 1
2. Hypercalcemia - key diagnostic finding
3. Hypophosphatemia - often present
4. Elevated alkaline phosphatase - indicates bone involvement
5. Elevated 24-hour urine calcium - provides further confirmation 4

Important diagnostic considerations:

• Imaging has no role in confirming or excluding PHPT - diagnosis is biochemical 1
• Assay-specific reference values should be used for PTH measurement 1
• Normocalcemic PHPT is characterized by elevated PTH with normal calcium values 1, 5

Treatment

Surgical Management:

Parathyroidectomy is the only curative treatment for PHPT and is indicated for symptomatic patients and those with complications. 1, 2

Specific surgical indications include:

• Symptomatic disease
• Osteoporosis
• Impaired kidney function (GFR < 60 mL/min/1.73 m²)
• Kidney stones
• Hypercalciuria
• Age ≥ 50 years
• Calcium increased by more than 0.25 mmol/L above upper limit of normal 1

Surgical approaches:

1. Bilateral neck exploration (BNE) - traditional approach examining all parathyroid glands
2. Minimally invasive parathyroidectomy (MIP) - targeted removal of affected gland(s) 1

MIP requires:

• Confident preoperative localization of adenoma
• Intraoperative PTH monitoring 1

Medical Management:

For patients who are not surgical candidates, options include:

• Bisphosphonates
• Calcitonin
• Calcimimetics 2

Preoperative Imaging

Imaging is used to localize abnormal glands before surgery, not for diagnosis:

• CT neck without and with IV contrast (4-D parathyroid CT) - sensitivity 62-88%, PPV 84-90% 1
• Nuclear scanning with technetium-99-m sestamibi 4
• Radio-guided probes - used intraoperatively 4

Complications and Prognosis

If left untreated, PHPT can lead to:

• Progressive bone disease
• Renal complications
• Neurocognitive deterioration
• Potentially death in severe cases 6

Surgical cure rates are high with experienced surgeons, and complication rates are relatively low 6, 5.

Special Considerations

• Parathyroid crisis - rare but life-threatening hypercalcemia requiring emergency intervention 3
• Ectopic parathyroid tissue - can occur in unusual locations including intrathyroidal position 3
• Vitamin D status - affects PTH levels and should be considered in evaluation 1