What are the evaluation and treatment options for patients with concerns related to parathyroid and calcitonin, such as hyperparathyroidism or osteoporosis?

Parathyroid and Calcitonin: Evaluation and Treatment

Overview of Parathyroid Hormone (PTH) Monitoring

PTH levels should be monitored when GFR falls below 60 mL/min/1.73 m² (CKD Stage 3), as secondary hyperparathyroidism begins at this threshold and progressively worsens with declining kidney function. 1

Monitoring Frequency by CKD Stage

• CKD G3a-G5 not on dialysis: Evaluate patients with progressively rising or persistently elevated intact PTH above the upper normal limit for modifiable factors including hyperphosphatemia, hypocalcemia, high phosphate intake, and vitamin D deficiency 1

• CKD G5D (dialysis patients): Maintain intact PTH levels in the range of approximately 2 to 9 times the upper normal limit for the assay 1

• Post-kidney transplant monitoring intervals 1:

  • CKD G1T-G3bT: PTH once, then based on baseline and progression
  • CKD G4T: PTH every 6-12 months
  • CKD G5T: PTH every 3-6 months

Primary Hyperparathyroidism: Diagnostic Approach

In patients with osteoporosis, screening with total serum calcium alone will miss many cases of primary hyperparathyroidism—ionized calcium and intact PTH are significantly superior for diagnosis. 2

Key Diagnostic Pitfalls

• Normocalcemic hyperparathyroidism occurs in approximately 23% of osteoporotic patients with primary hyperparathyroidism 2

  • 95% of these patients have elevated ionized calcium despite normal total calcium 2
  • 87% have elevated intact PTH levels 2

• Measure 25-OH Vitamin D levels to exclude hypovitaminosis D as a concomitant secondary cause before diagnosing primary hyperparathyroidism 3

Preoperative Imaging

• Ultrasound and/or dual-phase 99mTc-sestamibi scintigraphy with SPECT/CT are highly sensitive for localizing parathyroid adenomas before surgery 3, 4

Surgical Indications for Hyperparathyroidism

Parathyroidectomy is the only definitive cure for primary hyperparathyroidism and should be performed for symptomatic disease, including recurrent renal stones, bone disease, and neurocognitive disorders. 3, 4

Primary Hyperparathyroidism Indications 3, 4:

• Symptomatic disease (renal stones, bone disease, neurocognitive symptoms)
• Nephrolithiasis or nephrocalcinosis
• Impaired renal function (GFR < 60 mL/min/1.73 m²)
• Asymptomatic disease meeting surgical criteria

Secondary Hyperparathyroidism Indications 4:

• Refractory and/or symptomatic hypercalcemia
• Refractory hyperphosphatemia
• Persistent intact PTH > 800 pg/mL with hypercalcemia despite medical therapy 1, 4
• Severe intractable pruritus
• Calciphylaxis
• Serum calcium × phosphorus product persistently exceeding 70-80 mg/dL

Surgical Approaches

• Minimally invasive parathyroidectomy (MIP): Preferred for single adenoma with confident preoperative localization, offering shorter operating times and faster recovery 3, 4

• Bilateral neck exploration (BNE): Required for discordant/nonlocalizing imaging or suspected multigland disease 4

• Subtotal or total parathyroidectomy with autotransplantation: Recommended for secondary and tertiary hyperparathyroidism 4

Medical Management of Secondary Hyperparathyroidism

Initial treatment includes dietary phosphate restriction, phosphate binders, correction of hypocalcemia, and vitamin D supplementation, with vitamin D supplementation targeting 25-OH vitamin D levels >20 ng/mL (50 nmol/L). 3

Treatment Algorithm

• Restrict calcium-based phosphate binders in adult patients with CKD G3a-G5D receiving phosphate-lowering treatment 1

• Calcitriol and vitamin D analogs should not be routinely used in adult patients with CKD G3a-G5 not on dialysis 1

  • Reserve for patients with CKD G4-G5 with severe and progressive hyperparathyroidism 1

• For CKD G5D requiring PTH-lowering therapy: Use calcimimetics, calcitriol, or vitamin D analogs, or a combination 1

Dose Adjustments 3:

• If PTH remains elevated on oral phosphate and active vitamin D: Increase active vitamin D dose and/or decrease oral phosphate supplements
• For severe hyperparathyroidism despite normocalcemia or hypercalcemic hyperparathyroidism unresponsive to other treatments: Consider calcimimetics

Calcitonin in Hyperparathyroidism and Osteoporosis

Calcitonin has limited clinical utility in hyperparathyroidism, as patients demonstrate normal-to-blunted calcitonin responses and decreased calcitonin reserve, with hypercalcitonemia actually suggesting against the diagnosis of hyperparathyroidism. 5, 6

Calcitonin Physiology in Hyperparathyroidism

• Fasting plasma calcitonin levels are normal in primary hyperparathyroidism 5
• Only 0.5% of hyperparathyroid patients have calcitonin values exceeding normal limits 6
• Calcium infusion induces less increase in serum calcitonin in hyperparathyroid patients compared to normal persons 5, 6
• This diminished responsiveness persists postoperatively 5, 6

Calcitonin for Acute Hypercalcemia

Calcitonin can be used for emergency treatment of severe hypercalcemia, producing rapid calcium lowering and clinical improvement, making successful parathyroidectomy possible without complications. 7

• Effective in lowering serum calcium in primary hyperparathyroidism and malignancy-associated hypercalcemia 7
• Quick action with lack of toxic effects 7
• May improve creatinine clearance during treatment 7

Calcitonin-Salmon Nasal Spray for Postmenopausal Osteoporosis

Calcitonin-Salmon Nasal Spray is FDA-approved for postmenopausal osteoporosis but should be reserved for patients who refuse or cannot tolerate estrogens, or in whom estrogens are contraindicated. 8

FDA-Approved Indications and Dosing 8:

• Treatment of postmenopausal osteoporosis in females >5 years postmenopause with low bone mass
• Dose: 200 IU (one spray) daily, alternating nostrils
• Must be used with adequate calcium (≥1000 mg elemental calcium/day) and vitamin D (400 IU/day)

Evidence of Efficacy 8:

• Increases lumbar vertebral bone mineral density (BMD) relative to baseline and placebo
• Statistically significant increases in lumbar vertebral BMD as early as 6 months, persisting up to 2 years
• No effects on cortical bone of forearm or hip demonstrated

Important Limitations

Long-term studies suggest calcitonin may not provide additional benefit beyond calcium and vitamin D supplementation for preventing bone loss in osteoporosis. 9

• A 15-month study found calcium with or without vitamin D decreased PTH levels and reduced bone resorption, but adding calcitonin did not change these effects 9
• Neither treatment resulted in change of bone mass 9
• Calcitonin's predominant effect of causing hypocalcemia may stimulate PTH secretion and bone resorption 9

Postoperative Management After Parathyroidectomy

Monitor ionized calcium every 4-6 hours for the first 48-72 hours after surgery, then twice daily until stable, with immediate calcium gluconate infusion if levels fall below normal. 3, 4

Postoperative Protocol 3, 4:

• Initiate calcium gluconate infusion for hypocalcemia
• Provide calcium carbonate and calcitriol when oral intake is possible
• Adjust phosphate binders based on serum phosphorus levels

Management of Osteoporosis in CKD

In patients with CKD G1-G2 with osteoporosis and/or high fracture risk, manage as for the general population; in CKD G3a-G3b with normal PTH range, treat as for the general population. 1

• CKD G3a-G5D with biochemical abnormalities of CKD-MBD and low BMD/fragility fractures: Treatment choices should account for magnitude and reversibility of biochemical abnormalities and CKD progression, with consideration of bone biopsy 1