Lab Update 66 – Parathyroid Hormone and Bone Metabolism
Authors: Dr Marita du Plessis & Dr Thanusha Reddy
Published: August 2025
Introduction
Ampath has reviewed the latest guidelines on hyperparathyroidism and developed interpretive comments for parathyroid hormone (PTH) results. These incorporate vitamin D levels, estimated glomerular filtration rate (eGFR), and calcium results.
Although the most recent calcium result (adjusted total or ionised calcium) within the past 3 days is used for interpretation, concurrent testing of calcium and PTH is recommended for confirmation.
For further reading, refer to:
- Ampath Chat 44 – Vitamin D Overview
- Ampath Chat 57 – Hypercalcaemia: A Diagnostic Approach
- Ampath Chat 69 – Primary Hyperparathyroidism
Primary Hyperparathyroidism (PHPT)
- Characterised by hypercalcaemia with modestly elevated PTH (1.5–2× upper reference limit).
- In 10–20% of cases, PTH may be inappropriately normal or minimally elevated.
- 24-hour urinary calcium helps distinguish PHPT from Familial Hypocalciuric Hypercalcaemia (FHH).
- Parathyroid carcinoma presents with severe hypercalcaemia and extremely high PTH levels (hundreds to thousands pg/mL).
Medication Effects
- Thiazide diuretics and lithium reduce urinary calcium excretion, causing mild hypercalcaemia and altering calcium-sensing receptor function.
- Discontinuation for 3 months is advised before retesting PTH and calcium. Persistent hypercalcaemia with high-normal PTH may indicate unmasked PHPT.
Familial Hypocalciuric Hypercalcaemia (FHH)
- A benign inherited condition involving the calcium-sensing receptor.
- Presents with mild hypercalcaemia, mildly increased PTH, high-normal/increased magnesium, and low urinary calcium.
- Important to differentiate from PHPT with vitamin D deficiency, as FHH does not require surgery.
Normocalcaemic PHPT
- Defined by normal calcium with elevated PTH.
- Requires exclusion of secondary causes (e.g., CKD, vitamin D deficiency).
- Diagnosis should be confirmed with repeat testing over 3–6 months and normal ionised calcium.
Urinary Calcium Excretion
Used to distinguish PHPT from FHH and assess kidney risk in asymptomatic PHPT:
- >6.2 mmol/day (females) or >7.5 mmol/day (males) supports PHPT.
- <2.5 mmol/day suggests FHH.
- Low values may also occur in PHPT with low calcium intake, lithium/thiazide use, vitamin D deficiency, or CKD.
- Intermediate values may indicate either PHPT or FHH.
- High values may result from loop diuretics or high sodium intake.
Calcium/Creatinine Clearance Ratio
Preferred test for diagnosing FHH:
- <0.01 suggests FHH (85% sensitivity, 88% specificity).
- >0.02 supports PHPT and excludes FHH (93% specificity).
- 0.01–0.02 is inconclusive; clinical evaluation and family history are needed. Genetic testing is not widely available.
Vitamin D in PHPT
- Helps differentiate mild PHPT with vitamin D deficiency from FHH.
- Also used to distinguish secondary hyperparathyroidism from normocalcaemic PHPT.
- Vitamin D repletion to 30–50 µg/L is recommended before management decisions.
- Supplementation may reduce PTH by ~33% without worsening hypercalcaemia.
- Caution is advised in patients with high-normal urinary calcium.
Non-PTH Mediated Hypercalcaemia
Characterised by low or suppressed PTH (<25 pg/mL) with hypercalcaemia. Possible causes include:
- Malignancy
- Endocrine disorders (e.g., thyrotoxicosis, Addison’s disease)
- Granulomatous diseases (e.g., TB, sarcoidosis)
- Drugs (e.g., retinoic acid, calcitriol, calcium supplements)
- Vitamin A or D intoxication
- Long-term immobilisation
Secondary Hyperparathyroidism (SHPT)
Occurs when parathyroid glands respond to low extracellular calcium:
- Biochemical profile: Elevated PTH with normal or low calcium
- Causes:
- Impaired renal function (↓ calcitriol production)
- Vitamin D deficiency
- Malabsorptive disorders
Medications contributing to SHPT:
- Calcium-lowering drugs (e.g., loop diuretics, bisphosphonates, corticosteroids)
- Drugs increasing vitamin D catabolism (e.g., phenytoin, rifampicin)
Renal Function Impact:
- SHPT is common in CKD due to calcium and vitamin D metabolism disturbances.
- PTH rises when eGFR <60 ml/min/1.73m²; ~70% of patients with eGFR <30 ml/min/1.73m² have SHPT.
- Measure PTH, calcium, phosphate, and vitamin D in all patients with eGFR <60 ml/min/1.73m².
Gastrointestinal malabsorption (e.g., post-bariatric surgery, Celiac, Crohn’s) may also cause SHPT.