What are the symptoms and treatment options for primary hyperparathyroidism?

Symptoms of Primary Hyperparathyroidism

In countries with routine biochemical screening (United States, Canada, most of Europe), primary hyperparathyroidism (PHPT) predominantly presents as an asymptomatic disorder discovered incidentally, while in countries without routine screening, it presents with symptoms of target organ involvement including bone demineralization, fractures, nephrolithiasis, nephrocalcinosis, muscle weakness, and neurocognitive disorders. 1

Clinical Presentation by Geographic Region

Asymptomatic Presentation (Western Countries)

• Most patients (up to 80%) in Western countries present with mild, nonspecific symptoms or are completely asymptomatic, detected through routine serum calcium screening 1, 2, 3
• Common nonspecific symptoms include:
  • Fatigue and weakness 4, 2
  • Mood disturbances and mental depression 4, 2
  • Cognitive impairments 4
• Less than 5% of patients in modern series present with renal stones or hyperparathyroid bone disease, compared to 57% with renal stones and 23% with bone disease in historical cohorts 2

Symptomatic Presentation (Non-Screening Countries)

When PHPT presents symptomatically, manifestations relate to target organ damage 1:

Skeletal manifestations:

• Bone demineralization and osteoporosis 1, 3
• Pathological fractures 1
• Generalized bone disease 3

Renal manifestations:

• Nephrolithiasis (kidney stones) 1, 3
• Nephrocalcinosis 1, 3

Neuromuscular manifestations:

• Muscle weakness 1, 3
• Neuromuscular symptoms 3

Neuropsychiatric manifestations:

• Neurocognitive disorders 1
• Neuropsychiatric symptoms 3

Gastrointestinal and cardiovascular manifestations:

• Gastrointestinal symptoms 3
• Arterial hypertension 2
• Cardiovascular symptoms 3

Diagnostic Approach

PHPT is diagnosed by biochemical testing showing elevated or high-normal intact parathyroid hormone (PTH) levels in the setting of elevated total or ionized calcium levels 1, 4

Key diagnostic points:

• Serum calcium and serum PTH are the essential biochemical tests 1
• Imaging has no utility in confirming or excluding the diagnosis of PHPT 1
• Conditions that can mimic PHPT must be excluded before establishing the diagnosis 4

Treatment Options

Surgical Management

Parathyroidectomy is the definitive treatment for PHPT and is typically indicated even when asymptomatic, given potential negative effects of long-term hypercalcemia 1

Two accepted surgical approaches exist 1:

• Minimally invasive parathyroidectomy (MIP): Offers shorter operating times, faster recovery, and decreased perioperative costs; requires confident preoperative localization of a single adenoma and intraoperative PTH monitoring 1
• Bilateral neck exploration (BNE): Necessary for discordant/nonlocalizing imaging or suspected multigland disease 1

Medical Management

For patients unable to undergo parathyroidectomy, medical management options include:

Cinacalcet (calcimimetic agent):

• FDA-approved for hypercalcemia in adult patients with primary HPT for whom parathyroidectomy would be indicated but who are unable to undergo surgery 5
• Starting dose: 30 mg twice daily, titrated every 2-4 weeks to normalize serum calcium 5
• Effectively lowers serum calcium and PTH levels 6
• Monitor serum calcium within 1 week after initiation or dose adjustment 5
• Common adverse reactions include nausea (30%), vomiting, muscle spasms (18%), and headache 5

General medical management:

• Optimize calcium intake (500-800 mg/day) and vitamin D 6, 7
• Maintain adequate hydration 7
• Avoid immobilization 7
• Use diuretics with caution 7

Skeletal protection:

• Antiresorptive therapy (bisphosphonates) may be used for patients with increased fracture risk 6
• Bisphosphonates lower serum and urinary calcium but lack long-term fracture data 7

Important Caveats

• The effect of medical treatment on fracture risk reduction is unknown and requires further research 6
• Patients with asymptomatic PHPT not meeting surgical criteria can generally be safely monitored 4
• The clinical spectrum has evolved dramatically over 25 years due to improved screening technology and changing demographics 2
• PHPT is more common in women (66 per 100,000 person-years) than men (25 per 100,000 person-years) 1