Table 4.
Studies evaluating prevalence of normocalcemic hyperparathyroidism
| Study | Population | No. of NPHPT Patients (%); Mean Age, y;Sex | Definition of NPHPT | Comments/Limitations |
|---|---|---|---|---|
| Marques et al Brazil (referral center) (15) | Analyzed records of 156 postmenopausal women referred to hospital to be screened for osteoporosis | 14 (8.9); 60.6; 100% female | At least 2 samples of adjusted Ca and PTH. Excluded: 25(OH)D < 30 ng/mL, GFR < 40 mL/min, medications (bisphosphonates, diuretics, anticonvulsants, lithium), metabolic bone diseases, GI diseases with malabsorption, liver disease, incomplete records | Lower cutoff for eGFR |
| Šiprová et al Czech Republic (referral center) (16) | 15 343 referrals to endocrine center. PTH measured in 1180 (patients with pathological or marginal levels of total Ca, ionized Ca, serum phosphate, patients with reduced BMD, and with possible PHPT diagnosis from medical history) | At baseline: 187 (1.2); 61.1; 81% female; at follow-up: 151 | Normal total and ionized Ca and high PTH at first visit. 25(OH)D ≥ 20 ng/ml (patients with low vitamin D were treated, and PTH had to be elevated after retest at 3 mo). Excluded cases with renal insufficiency, Ca malabsorption, hypercalciuria, medications (PPI, thiazides, lithium) | Not clear if they excluded people on bisphosphonates, GFR cutoff not given |
| Berger et al Canada (community) (17) | Population-based Canadian Multicentre Osteoporosis Study: prospective cohort of 9423 community-dwelling women and men living within 50 km of 9 Canadian cities. 566 men and 1306 women (n = 1875) age ≥ 35 y with available PTH | 62 (3.31); NA; NA | Normal total Ca and high PTH, 25(OH) D ≥ 50 nmol/L, eGFR ≥ 60 mL/ min/1.73 m2 | 85% users of antiresorptives and diuretics. Not clear if they checked persistence or other causes of secondary hyperparathyroidism |
| Cusano et al US (community) (18) | DHS: population-based cohort study. Evaluated 3450 individuals age 18 to 65 y with Ca and PTH values.2122 patients had follow-up data 8 y later | At baseline: 108 (3.1); 41.3; 38% female; at follow-up: 13 (0.6%) | Normal albumin-adjusted Ca and high PTH. Excluded renal insufficiency (GFR < 60 mL/min), 25(OH)D ≤ 20 ng/ mL, thiazide, or lithium use | Only single laboratory values and did not check persistence.Lack of data regarding medical history and parathyroid surgery.Not clear if they excluded patients on bisphosphonates or with hypercalciuria |
| Cusano et al US (community) (18) | Osteoporotic Fractures in Men, an unselected community-based study in age ≥ 65 y. Evaluated 2364 men with calcium and PTH values | 9 (0.4); 70.0; 0% female | Normal albumin-adjusted Ca and high PTH. Excluded renal insufficiency (GFR < 60 mL/min), 25(OH)D ≤ 20 ng/ mL, thiazide use | Same as DHS |
| García-Martín et al Spain (community) (19) | Prospective study of 100 healthy postmenopausal women. All had follow-up 6 y later | 6 (6); 56.3; 100% female; at follow-up: 6 | Normal adjusted Ca and high PTH. 25(OH)D > 30 ng/mL, normal renal function (creatinine clearance > 70 mL/ min/1.73 m2) | Not clear if they excluded patients on medications. Not clear what they defined as “healthy.” |
| Kontogeorgos et al Sweden (community) (20) | Random population sample of 2400 men and women age 25 to 64 years from World Health Organization MONItoring of trends and determinants for CArdiovascular disease project. Investigation in 1995, data on 608, including all women age 45 to 64 y, every fourth woman age 25 to 44 y, and every fourth man in all age groups (25-64 y), n = 410. | 12 (2.0%); 53.3; NA; at follow-up: 1 (0.2%) | Normal total Ca and high PTH, 25(OH) ≥ 50 nmol/L, normal renal function | Patients on bisphosphonates and diuretics. Only one blood measurement at baseline |
| Lundgren et al Sweden (community) (21) | Population-based mammography screening in 5202 women age 55 to 75 years | 28 (0.5); no data on age; 100% female | Normal ionized Ca. Creatinine < 160 μmol/L and either a) serum Ca < 2.50 mmol/L + PTH > 55 ng/L or b) serum Ca 2.50 to 2.60 mmol/L + PTH ≥ 35 ng/L. Checked for persistence (≥ 3 occasions). Excluded malabsorption and family history of hypercalcemia | Did not exclude patients on medications known to cause secondary hyperparathyroidism. No vitamin D check |
| Palermo et al Five European cities in UK, France, Germany (community) (11) | Recruited 2419 women (age 55-79 y) and 258 women (age 30-40 y) for Osteoporosis and Ultrasound Study. Follow-up after 6 y in 1416 patients | 1 (0.1); no information on age; 100% female; at follow-up: none | Mahalanobis distance used: NPHPT anyone outside ellipse with normal adjusted Ca, high PTH, 25(OH) D ≥ 50 nmol/L, GFR ≥ 60 mL/min | Unclear if they excluded patients with other causes of secondary hyperparathyroidism (diseases, medication) |
| Rosário et al Brazil (community) (22) | Prospectively recruited adults ≥ 18 y to undergo thyroidectomy for nodular disease. Excluded patients who had ultrasound because of PHPT, patients with a history of nephrolithiasis, nephrocalcinosis, and pathological fracture, personal or family history of multiple endocrine neoplasia, or diagnosis of medullary thyroid cancer. N = 676 | Criterion 1: 46 (6.8%). Only 8.7% had altered parathyroid glands (adenoma) during gland exploration (0.6% of cohort) Criterion 2: 30 (4.4%). Confirmed pathology: 13.3% Criterion 3: 12 (1.8%). Confirmed pathology: 33.3% Criterion 4: 5 (0.74%). Confirmed pathology: 80% | Criterion 1: Normal adjusted and ionized Ca and high PTH, confirmed at 2 measurements, 25(OH)D ≥ 20 ng/ dL, eGFR ≥ 40 mLl/min/1.73 m2. Excluded: those on diuretics, lithium, bisphosphonates, denosumab, recombinant PTH, corticosteroids; patients with primary aldosteronism, suspicion or known diagnosis of malabsorption, hyperphosphatemia, Ca/urinary creatine ratio ≥ 0.25, or thyroid dysfunction. Screened for celiac disease and excluded patients with positive antibodies Criterion 2: same as criterion 1 but 25(OH)D ≥ 20 ng/dL, eGFR ≥ 60 mL/ min/1.73 m2 Criterion 3: same as criterion 1 but 25(OH)D ≥ 30 ng/dL, eGFR ≥ 40 mL/ min/1.73 m2 Criterion 4: same as criterion 1 but 25(OH)D ≥ 30 ng/dL, eGFR ≥ 60 mL/ min/1.73 m2 | |
| Vignali et al Italy (community) (23) | Residents of village in Southern Italy in 2010 (685 with full data) | 3 (0.4); 47; 0% female | Normal adjusted Ca and high PTH, 25(OD)D ≥ 30 ng/mL, eGFR ≥ 60 mL/ min/1.73 m2. Excluded people on bisphosphonates and thiazides, overt GI and metabolic bone diseases | Did not check persistence and could not check urine Ca |
Abbreviations: 25(OH)D, 25-hydroxyvitamin D; BMD, bone mineral density; Ca, calcium; DHS, Dallas Heart Study; eGFR, estimated glomerular filtration rate; GI, gastrointestinal; NA, not available; NPHPT, normocalcemic hyperparathyroidism; PHPT: primary hyperparathyroidism; PPI, proton pump inhibitor; PTH, parathyroid hormone.