Symptoms of Hyperparathyroidism
Hyperparathyroidism presents differently depending on whether it is primary (most commonly asymptomatic in screened populations) or secondary (symptomatic with severe manifestations), with symptoms ranging from bone pain and kidney stones to neuropsychiatric disturbances and intractable pruritus.
Primary Hyperparathyroidism Symptoms
Asymptomatic Presentation
- In countries with routine biochemical screening (United States, Canada, most of Europe), up to 80% of patients present asymptomatically or with mild, nonspecific symptoms discovered incidentally on laboratory testing 1
- This represents a dramatic shift from the classic symptomatic presentation seen 20-30 years ago 2
Symptomatic Manifestations (When Present)
- Skeletal manifestations: Bone demineralization, osteoporosis, pathological fractures, and bone/joint pain 1
- Women report bone and joint pain significantly more frequently than men (44.2% vs 20%) 3
- Renal manifestations: Nephrolithiasis (kidney stones) and nephrocalcinosis 1
- Men experience nephrolithiasis significantly more often than women (36.7% vs 16.8%) 3
- Neuromuscular symptoms: Muscle weakness 1
- Neuropsychiatric manifestations: Neurocognitive disorders, depression, and psychological disturbances 1
- Women report depressive episodes significantly more frequently than men (32.6% vs 10%) 3
- Other symptoms: Fatigue, gastritis, and cardiovascular disease 3
Secondary Hyperparathyroidism Symptoms
Moderate Elevation (PTH 500-800 pg/mL)
- Progressive skeletal and articular pain 1
- Bone pain with elevated alkaline phosphatase 1
- Early renal complications 1
- Intractable pruritus becomes debilitating and often requires surgical intervention at these levels 1
Severe Elevation (PTH >800-1000 pg/mL)
- Persistent hypercalcemia causing progressive renal damage 1
- Severe bone disease with pathological fractures and skeletal deformities (when PTH exceeds 10 times upper normal limit) 1
- Calcium-phosphate product exceeding 70 mg²/dL² with extraskeletal calcifications 1
- Intractable pruritus refractory to medical management 4
- Generalized bone pain 4
Additional Manifestations
- Neurocognitive disorders and psychological disturbances with chronic disease 1
- Calciphylaxis in severe cases 4
- Progressive calcification of vessels and soft tissues 4
Treatment Options
Primary Hyperparathyroidism
- Parathyroidectomy is the definitive curative treatment and is indicated even for asymptomatic disease given the potential negative effects of long-term hypercalcemia 1
- Specific surgical indications include: presence of symptoms, age ≤50 years, serum calcium >1 mg/dL above upper limit of normal, osteoporosis, creatinine clearance <60 mL/min/1.73 m², nephrolithiasis, nephrocalcinosis, or hypercalciuria 5
- Minimally invasive parathyroidectomy (MIP) is preferred when preoperative imaging confidently localizes a single adenoma, offering shorter operating times, faster recovery, and decreased costs 6
- Bilateral neck exploration (BNE) remains necessary for discordant/nonlocalizing imaging or suspected multigland disease 6
- For patients unable to undergo surgery, cinacalcet 30 mg twice daily (titrated up to 90 mg 3-4 times daily) can normalize serum calcium levels 7
Secondary Hyperparathyroidism
- Initial medical management: Dietary phosphate restriction, phosphate binders, correction of hypocalcemia, and vitamin D sterols (calcitriol, paricalcitol, doxercalciferol) 6
- For peritoneal dialysis patients: Oral calcitriol 0.5-1.0 μg or doxercalciferol 2.5-5.0 μg given 2-3 times weekly 6
- Calcimimetics (cinacalcet) starting at 30 mg once daily may be considered for persistent disease, though caution is warranted due to hypocalcemia risk and QT interval prolongation 6, 7
- Parathyroidectomy is recommended for severe hyperparathyroidism (persistent iPTH >800 pg/mL) with hypercalcemia and/or hyperphosphatemia refractory to medical therapy 6
Critical Monitoring Requirements
- For patients on cinacalcet: Measure serum calcium within 1 week of initiation/dose adjustment; monitor monthly once stable for dialysis patients, every 2 months for primary hyperparathyroidism 7
- For patients on vitamin D sterols: Monitor serum calcium and phosphorus every 2 weeks for 1 month after initiation, then monthly; monitor PTH monthly for 3 months, then every 3 months 6
- Postoperative monitoring: Check ionized calcium every 4-6 hours for first 48-72 hours, then twice daily until stable 6
Important Caveats
- Cinacalcet is contraindicated if serum calcium is below the lower limit of normal and is not indicated for CKD patients not on dialysis due to increased hypocalcemia risk 7
- Total parathyroidectomy should be avoided in patients who may receive kidney transplant due to problematic calcium control 6
- Life-threatening hypocalcemia with paresthesias, muscle spasms, tetany, seizures, QT prolongation, and ventricular arrhythmia can occur with cinacalcet treatment 7