My parathyroid hormone (PTH) level is 75 pg/mL—what does this indicate and what initial evaluation and management steps should be taken?

PTH 75 pg/mL: Evaluation and Management

A PTH level of 75 pg/mL sits at the upper limit of normal and requires immediate measurement of serum calcium, phosphorus, 25-hydroxyvitamin D, and kidney function to determine whether this represents primary hyperparathyroidism, secondary hyperparathyroidism, or a normal variant. 1

Immediate Diagnostic Workup

Obtain the following laboratory tests simultaneously:

• Corrected serum calcium (total and ionized if available) – this single test distinguishes primary from secondary hyperparathyroidism 1
• Serum phosphorus – typically low-normal (2.7–4.6 mg/dL) in primary hyperparathyroidism 1
• 25-hydroxyvitamin D – deficiency (<20–30 ng/mL) is the most common cause of secondary hyperparathyroidism 1, 2
• Serum creatinine and eGFR – PTH rises when eGFR falls below 60 mL/min/1.73 m² 1, 2
• 24-hour urine calcium or spot urine calcium/creatinine ratio – helps identify hypercalciuria (>300 mg/24h) 1

Interpretation Algorithm

If Calcium is Elevated (>10.2 mg/dL):

This confirms primary hyperparathyroidism because PTH should be suppressed by hypercalcemia, yet it remains inappropriately normal or elevated. 1, 2 The autonomous parathyroid glands continue secreting PTH despite elevated calcium. 3

Immediate actions:

• Refer to endocrinology and an experienced high-volume parathyroid surgeon 1, 2
• Order pre-operative localization imaging (neck ultrasound and/or 99mTc-sestamibi SPECT/CT) only after biochemical confirmation 1, 2
• Do not order imaging before confirming the diagnosis biochemically 1

Surgical indications include any of the following: 1

• Corrected calcium >1 mg/dL above upper limit (≈>11.2 mg/dL)
• Age <50 years
• eGFR <60 mL/min/1.73 m²
• Osteoporosis (T-score ≤-2.5 at any site)
• History of kidney stones or nephrocalcinosis
• 24-hour urine calcium >300 mg
• Symptomatic disease (bone pain, fractures, neurocognitive impairment, depression, "brain fog")

If Calcium is Normal (8.6–10.2 mg/dL):

Systematically exclude all secondary causes before diagnosing normocalcemic primary hyperparathyroidism: 1, 4

1. Vitamin D deficiency – supplement to ≥30 ng/mL and recheck PTH after 3 months 1, 4
2. Chronic kidney disease – eGFR <60 mL/min/1.73 m² indicates secondary hyperparathyroidism 1, 2
3. Inadequate dietary calcium – ensure intake of 1,000–1,200 mg/day 1
4. Low urinary calcium (<100 mg/24h) – suggests calcium malabsorption or inadequate intake 1
5. Medications – thiazide diuretics, lithium, and others can elevate PTH 1

Only after excluding all of the above can normocalcemic primary hyperparathyroidism be diagnosed. 1, 4 This condition carries a risk profile comparable to hypercalcemic disease, including osteoporosis, kidney stones, and neurocognitive symptoms. 1

Critical Assay Considerations

PTH assays vary by up to 47% between different generations and laboratories – always apply your laboratory's specific reference range rather than generic cut-offs. 1, 2, 5 The normal range for healthy adults is roughly 15–65 pg/mL, but this varies by assay. 1, 6

Biological variation of PTH is substantial (≈20%) – a change of >54% between measurements is required to be clinically meaningful. 3, 5 PTH is most stable when measured in EDTA plasma kept at 4°C. 1, 3, 5

Factors that influence PTH levels include: 6, 5

• Race – PTH concentrations are higher on average in Black individuals 3, 6
• Age – PTH increases with age, largely due to declining GFR 3, 6
• BMI – higher body mass index correlates with higher PTH 3, 6
• Vitamin D status – PTH reference values are 20% lower in vitamin D-replete individuals 1

Management Based on Final Diagnosis

Primary Hyperparathyroidism (Hypercalcemic):

Surgery is definitive treatment. 1, 2 If the patient is not a surgical candidate or declines surgery:

• Monitor serum calcium and phosphorus every 3 months 1
• Annual bone mineral density assessment 1
• Annual renal ultrasound to screen for stones or nephrocalcinosis 1
• Maintain 25-OH vitamin D >20 ng/mL with supplementation 1
• Ensure dietary calcium 1,000–1,200 mg/day (do not exceed 2,000 mg/day total) 1, 3
• Ensure adequate hydration and avoid thiazide diuretics 2

Secondary Hyperparathyroidism (Vitamin D Deficiency):

Supplement with ergocalciferol or cholecalciferol to achieve 25-OH vitamin D ≥30 ng/mL. 1, 2 Monitor calcium and phosphorus every 2 weeks for the first month after initiating therapy, then monthly. 1, 2 Discontinue vitamin D immediately if calcium rises above 10.2 mg/dL. 1, 2, 3

Secondary Hyperparathyroidism (CKD Stage 3, eGFR 30–59):

Target PTH: 2–9× the assay's upper normal limit (≈70–110 pg/mL for Stage 3). 2 A PTH of 75 pg/mL may be appropriate for this stage. Initial therapy includes dietary phosphate restriction, non-calcium phosphate binders (if calcium >10.2 mg/dL), correction of vitamin D deficiency, and adequate calcium intake. 2 If PTH remains >110 pg/mL despite these measures, add calcitriol or vitamin D analogs. 2

Common Pitfalls to Avoid

• Do not assume an isolated elevated PTH indicates primary hyperparathyroidism; calcium level is essential for classification 1
• Do not supplement vitamin D when calcium >10.2 mg/dL to avoid worsening hypercalcemia 1, 2, 3
• Do not order parathyroid imaging before confirming the biochemical diagnosis 1, 2, 3
• Recognize that biotin supplementation interferes with PTH immunoassays and can produce spurious results 3
• In CKD, do not suppress PTH below 150 pg/mL in dialysis patients, as this predisposes to adynamic bone disease 3

Urgent Referral Criteria

Refer urgently if any of the following are present: 1

• Serum calcium >12 mg/dL (severe hypercalcemia)
• Symptomatic hypercalcemia (confusion, nausea, polyuria, weakness)
• eGFR <45 mL/min/1.73 m² combined with hypercalcemia
• Severe hypercalciuria (>400 mg/24h) with risk of irreversible nephrocalcinosis
• Disabling neurocognitive symptoms (significant depression, memory loss, functional impairment)