Autonomous PTH oversecretion (most often a single adenoma) producing hypercalcemia.
Also known as: primary hyperparathyroidism, parathyroid adenoma, PHPT, hyperparathyroidism
Overview
Inappropriately elevated or non-suppressed PTH in the setting of hypercalcemia. Most commonly due to a solitary parathyroid adenoma (~85%); less often hyperplasia of all four glands (~10-15%), double adenoma (~4%), or parathyroid carcinoma (<1%).
Epidemiology
Most common cause of outpatient hypercalcemia. Prevalence ~1 in 1000; up to 1 in 500 women >50. Female-to-male ratio ~3:1. Peak incidence 50-60 years. Most cases now detected on routine chemistry panels (mild, asymptomatic).
Try two board-style Primary Hyperparathyroidism questions
Real questions from the FirstPassPA bank, with the full explanation. Pick an answer — no signup, no email.
Question 1EndocrineMedium
A 35-year-old woman is evaluated after passing a kidney stone and is found on bone densitometry to have osteoporosis. Laboratory studies show serum calcium 11.8 mg/dL, phosphorus 2.1 mg/dL, intact parathyroid hormone 145 pg/mL (elevated), and a 24-hour urine calcium of 320 mg. Which of the following is the most likely diagnosis?
ATertiary hyperparathyroidism
BPrimary hyperparathyroidism
CMalignancy-associated hypercalcemia
DFamilial hypocalciuric hypercalcemia
ESecondary hyperparathyroidism
Reveal answer & full explanation
Correct answer: B — Primary hyperparathyroidism
ATertiary hyperparathyroidism
BPrimary hyperparathyroidism✓
CMalignancy-associated hypercalcemia
DFamilial hypocalciuric hypercalcemia
ESecondary hyperparathyroidism
Why Primary hyperparathyroidism is correct
Hypercalcemia (11.8 mg/dL) with an inappropriately elevated PTH (145 pg/mL) defines PTH-dependent hypercalcemia, and a parathyroid adenoma is the cause in roughly 85% of cases.
Excess PTH drives renal phosphate wasting (hypophosphatemia 2.1 mg/dL), increased bone resorption (osteoporosis), and hypercalciuria (urine calcium 320 mg/24h), producing this patient's stone and bone disease.
Why the others are wrong
Familial hypocalciuric hypercalcemia — also shows hypercalcemia with non-suppressed PTH but is defined by LOW urine calcium (calcium-to-creatinine clearance ratio typically <0.01); the elevated 24-hour urine calcium refutes it, a confused-with trap on 'high calcium, normalish PTH.'
Malignancy-associated hypercalcemia — PTHrP-mediated hypercalcemia suppresses PTH, so an elevated PTH excludes it; it is the premature-closure pick for any hypercalcemia.
Secondary hyperparathyroidism — a compensatory PTH rise to chronic hypocalcemia (renal failure, vitamin D deficiency) that presents with low or normal calcium, not hypercalcemia; buzzword-matching on 'high PTH.'
Tertiary hyperparathyroidism — also produces hypercalcemia with an elevated PTH, but it reflects autonomous parathyroid hyperplasia after long-standing secondary hyperparathyroidism, typically in chronic kidney disease or after kidney transplant; without that history, PTH-dependent hypercalcemia in a young woman with stones and osteoporosis is primary disease (confused-with trap on 'high calcium, high PTH').
Question 2EndocrineMedium
A 66-year-old woman presents with fatigue, constipation, and depression for 6 months. BP 142/86. Labs: Na 138, K 3.2, Ca 11.8 mg/dL, albumin 4.0, parathyroid hormone (PTH) 98 pg/mL (normal 10–65), creatinine 1.0. 24-hour urine calcium is elevated. DEXA shows T-score -2.3 at the lumbar spine. She is asymptomatic regarding renal symptoms. Which of the following is the most appropriate management?
AAnnual monitoring with labs
BThiazide diuretic therapy
CCinacalcet therapy
DParathyroidectomy
EBisphosphonate therapy
Reveal answer & full explanation
Correct answer: D — Parathyroidectomy
AAnnual monitoring with labs
BThiazide diuretic therapy
CCinacalcet therapy
DParathyroidectomy✓
EBisphosphonate therapy
Why Parathyroidectomy is correct
This is primary hyperparathyroidism: elevated calcium (11.8 mg/dL) with an inappropriately elevated parathyroid hormone (PTH) of 98 pg/mL (normal 10–65)
Surgical indications (Fifth International Workshop 2022) include: age <50, serum calcium >1 mg/dL above upper limit of normal, T-score ≤-2.5 (osteoporosis) or vertebral fracture, 24-hour urine calcium >250 mg/day (women) or >300 mg/day (men), glomerular filtration rate (GFR) <60, or nephrolithiasis or nephrocalcinosis on imaging
This patient has calcium 11.8 mg/dL (>1 above upper limit of normal of ~10.5) and elevated 24-hour urine calcium; the T-score of -2.3 does not quite meet the ≤-2.5 threshold, but the calcium criterion alone is sufficient — multiple criteria are met
Parathyroidectomy is indicated and is curative
Why the others are wrong
Annual monitoring with labs — observation is appropriate only when no surgical criteria are met; this patient meets multiple criteria
Bisphosphonate therapy — does not correct the underlying disease
Cinacalcet therapy — reserved for patients who are not surgical candidates
Thiazide diuretic therapy — the elevated 24-hour urine calcium and BP of 142/86 make a thiazide look attractive, since it lowers urinary calcium excretion, but thiazides increase renal calcium reabsorption and can raise serum calcium further, can worsen her hypokalemia, and do nothing for the underlying parathyroid disease in a patient who meets surgical criteria
That's 2. Get 7,700+ more.
Unlock the full FirstPassPA bank: 7,700+ board-style questions, flashcards, and an AI tutor that explains every answer. Your 7-day free trial includes everything, and there's no credit card required.
You've read your 2 free diagnosis previews. Create your free account to unlock the full Primary Hyperparathyroidism outline — plus all 514 diagnoses, 7,700+ board-style questions, flashcards, and an AI tutor. Your 7-day free trial includes everything, and there's no credit card required.
Chronic vitamin D deficiency (can mask presentation)
Pathophysiology
Loss of calcium-sensing regulation in one or more parathyroid glands → autonomous PTH secretion despite normal or elevated serum calcium. PTH increases bone resorption (osteoclast activation), enhances renal calcium reabsorption and phosphate excretion, and stimulates 1-alpha-hydroxylation of vitamin D (boosting intestinal calcium absorption). Net effect: hypercalcemia, hypophosphatemia, and skeletal/renal pathology.
Band keratopathy (rare), brown tumors (rare advanced disease)
Hypertension, sometimes bradyarrhythmia
DEXA: cortical bone loss (distal radius > spine), fractures
Classic findings
Postmenopausal woman with kidney stones, mild fatigue, osteoporosis, and incidentally elevated calcium on routine labs.
Differential diagnosis
Secondary hyperparathyroidism — Compensatory PTH elevation from hypocalcemia or vitamin D deficiency; calcium normal/low, phosphate often elevated (CKD)
Tertiary hyperparathyroidism — Autonomous PTH after prolonged secondary HPT (long-standing CKD); calcium elevated; usually requires parathyroidectomy
Familial hypocalciuric hypercalcemia (FHH) — AD inactivating CaSR mutation; mild lifelong hypercalcemia with LOW urinary calcium (Ca/Cr clearance ratio <0.01); DO NOT operate
Malignancy-associated hypercalcemia — PTH suppressed; PTHrP elevated (squamous cell, renal, breast) or osteolytic mets, or 1,25-OH vitamin D from lymphoma
Vitamin D toxicity — Elevated 25-OH vitamin D, suppressed PTH
Granulomatous disease (sarcoidosis, TB) — Elevated 1,25-OH vitamin D from macrophage activity, suppressed PTH
Milk-alkali syndrome — Large calcium carbonate ingestion; suppressed PTH, alkalosis, AKI
Hyperthyroidism, thiazides, lithium — Drug or hormonal causes; review medication list
Diagnostic workup
Diagnostic criteria
Hypercalcemia + inappropriately elevated or non-suppressed PTH; normal or high urinary calcium (calcium/creatinine clearance ratio usually >0.02) argues against FHH, which has LOW urinary calcium (ratio usually <0.01).
Labs
Serum calcium (corrected for albumin) and ionized calcium — confirm hypercalcemia
PTH (intact) — elevated or inappropriately normal
Phosphate (low), magnesium, alkaline phosphatase (elevated in bone disease)
25-OH vitamin D (replace if deficient before final assessment), 1,25-OH vitamin D
24-hour urine calcium and creatinine — calculate calcium/creatinine clearance ratio to exclude FHH (<0.01 = FHH)
BUN, creatinine, eGFR
DEXA scan (lumbar spine, hip, AND distal third of radius)
Consider genetic testing for MEN1/MEN2 if young, family history, or multigland disease
Imaging
Renal ultrasound or CT (assess for stones, nephrocalcinosis)
Not all guidelines require localization — surgeon-dependent
Diagnostic algorithm
Diagnosis
Ca
PTH
Phosphate
Urine Ca
Key feature
Primary HPT
High
High / inappropriate
Low
High / normal
Most often single adenoma
FHH
Mildly high
High / inappropriate
Normal
LOW (Ca/Cr <0.01)
AD, lifelong; do not operate
Secondary HPT (CKD)
Low / normal
High
High
Variable
Compensatory; treat underlying
Tertiary HPT
High
High
Variable
Variable
After long-standing 2°; parathyroidectomy
Malignancy (PTHrP)
High
LOW (suppressed)
Low
High
Squamous, renal, breast cancer
Vitamin D toxicity
High
Low
High
High
Elevated 25-OH vitamin D
Differentiating causes of hypercalcemia by calcium, PTH, phosphate, and urinary calcium.
Treatment
First-line
Parathyroidectomy is definitive — minimally invasive single-gland resection if localized adenoma; bilateral neck exploration if not localized or multi-gland disease
Intraoperative PTH monitoring (>50% drop and normal range within 10 min of resection confirms cure)
Indications (any one; Fifth International Workshop 2022): symptomatic disease; OR asymptomatic with serum Ca >1 mg/dL above ULN, age <50, eGFR or creatinine clearance <60 mL/min, 24-h urine calcium >250 mg/day (women) or >300 mg/day (men), nephrolithiasis or nephrocalcinosis on imaging, T-score ≤−2.5 at lumbar spine, total hip, femoral neck, or distal 1/3 radius, or vertebral fracture
Medical (non-surgical candidates)
Calcimimetic — cinacalcet (activates CaSR; lowers PTH and calcium): for patients not surgical candidates or with parathyroid carcinoma
Surgical: recurrent laryngeal nerve injury, hypoparathyroidism (especially after subtotal/total parathyroidectomy)
Hungry bone syndrome post-op: profound hypocalcemia and hypophosphatemia
Persistent or recurrent hyperparathyroidism (missed gland, ectopic location)
PANCE pearls
Always check a 24-h urinary calcium to exclude FHH before parathyroidectomy — operating on FHH does NOT cure hypercalcemia.
Lithium and thiazide diuretics elevate calcium and PTH — stop if possible and re-test.
Always measure DEXA at distal third of radius — primary HPT preferentially affects cortical bone.
Intra-operative PTH should drop >50% within 10 min and to normal range — confirms removal of the offending gland.
Post-parathyroidectomy 'hungry bone syndrome': skeleton avidly takes up Ca and PO4, producing severe hypocalcemia — pre-treat with vitamin D and calcium.
References
Fifth International Workshop 2022 — Evaluation and Management of Primary Hyperparathyroidism: Summary Statement and Guidelines from the Fifth International Workshop (Bilezikian JP et al., J Bone Miner Res 2022;37(11):2293-2314)
AAES 2016 — American Association of Endocrine Surgeons Guidelines for Definitive Management of Primary Hyperparathyroidism (Wilhelm et al., JAMA Surg 2016)
Practice Endocrinology questions on FirstPassPA
Turn this outline into retention. 7,700+ board-style questions with an AI tutor that explains every answer — free to start, no card required.
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.