Unregulated overproduction of parathyroid hormone by the parathyroid glands, causing hypercalcemia. In ~85% of cases it's due to a single parathyroid adenoma; less often multigland hyperplasia (e.g. in MEN1/MEN2A) or rarely parathyroid carcinoma.
Primary HPT is the most common cause of hypercalcemia in outpatients. It can lead to significant complications: kidney stones, osteitis fibrosa cystica (bone resorption with fractures), peptic ulcers (from high Ca), and neuropsychiatric symptoms. Many cases are asymptomatic and caught by routine labs, so recognizing it can prevent long-term organ damage.
Often detected incidentally: mild hypercalcemia on routine blood tests in a middle-aged or older adult (especially postmenopausal women). Many have no obvious symptoms.
Classic symptomatic presentation: stones, bones, abdominal groans, and psychiatric overtones – i.e., kidney stones (nephrolithiasis), bone pain (fractures, osteitis fibrosa), gastrointestinal ulcers/constipation, and neuropsychiatric issues (fatigue, depression). May also see polyuria/polydipsia ("thrones") from hypercalcemia-induced nephrogenic DI.
May be part of a familial syndrome (MEN): MEN1 (Parathyroid, Pituitary, Pancreas tumors) or MEN2A (Medullary thyroid carcinoma, Pheochromocytoma, Parathyroid hyperplasia) – suspect if patient is young or has family history of endocrine tumors.
Confirm true hypercalcemia and elevated PTH (inappropriately high or mid-normal despite high Ca) to diagnose primary HPT.
Obtain a 24-hour urine calcium to differentiate from familial hypocalciuric hypercalcemia (FHH – which has low urine Ca and generally doesn't require surgery).
Evaluate end-organ effects: DEXA scan for osteoporosis (primary HPT causes preferential cortical bone loss), and renal imaging for nephrolithiasis/nephrocalcinosis.
Check serum 25-OH vitamin D – deficiency is common and should be corrected (vitamin D insufficiency can exacerbate PTH release). Also check kidney function to ensure hypercalcemia isn't from tertiary HPT.
If considering surgery, perform localization (neck ultrasound or sestamibi scan) for adenoma, although surgical exploration of all glands may be done regardless.
Condition
Distinguishing Feature
Familial hypocalciuric hypercalcemia
Benign inherited Ca-sensing receptor mutation; high Ca, high/normal PTH but very low urinary Ca excretion
Hypercalcemia of malignancy
High Ca, low PTH (e.g., PTHrP from squamous cell cancer, or metastatic bone lesions)
Lithium-associated hypercalcemia
Lithium therapy can raise PTH set-point: mild ↑Ca and ↑PTH in patients on lithium (resolves if drug stopped)
Parathyroidectomy is the only curative treatment and is recommended for all symptomatic patients. For asymptomatic patients, guidelines (e.g. Fifth Int'l Workshop) advise surgery if any one criterion is met: Ca >1.0 mg/dL above normal, T-score ≤ -2.5 or fragility fracture, GFR <60, nephrolithiasis or nephrocalcinosis on imaging, or age <50.
If surgery is not done (mild cases or high-risk patients): monitor labs and bone density regularly. Cinacalcet (calcimimetic) can be used to lower calcium/PTH levels (does not improve bone density). Treat osteoporosis with bisphosphonates or estrogen modulators if needed.
Conservative measures: keep patients well hydrated (to reduce stones), avoid thiazide diuretics or lithium (worsen Ca), ensure moderate calcium intake (avoid excessive Ca which can further raise levels but also avoid deficiency which raises PTH). Vitamin D should be repleted if low.
85-15-1 rule: ~85% single adenoma, ~10–15% multi-gland hyperplasia, <1% carcinoma in primary HPT.
Lithium can cause reversible primary HPT – always review medications in hypercalcemia workup.
Primary HPT can be subtle – patients might attribute fatigue or depression to aging. Many report feeling notably better (more energetic, improved mood) after curative parathyroidectomy.
Parathyroid carcinoma (rare) is suspected when Ca is extremely high (>14–15) and PTH is very high (>5× normal) – presents with a palpable neck mass and vocal cord paralysis in some cases.
Hungry bone syndrome: after parathyroidectomy, suppressed PTH can cause acute hypocalcemia as bones avidly uptake calcium – monitor Ca closely post-op and provide calcium/vitamin D supplements.
Hypercalcemia confirmed → measure PTH.
If PTH high/inappropriately normal → primary HPT likely (if no CKD). Check urine Ca to exclude FHH.
Assess need for surgery: apply guideline criteria (Ca, bone density, kidney stones, age). Obtain localization studies if proceeding to surgery.
If parathyroidectomy performed: remove the adenoma or perform 4-gland exploration (if hyperplasia). Watch for postoperative hypocalcemia (hungry bone).
If managing without surgery: regular surveillance of Ca, creatinine, DEXA; use cinacalcet to control Ca, and treat osteoporosis medically.
Woman in her 60s with osteoporosis and a history of kidney stones is found to have high calcium and high PTH → primary hyperparathyroidism (likely parathyroid adenoma).
Patient with "stones, bones, groans": recurrent kidney stones, bone fractures, abdominal pain, and psychiatric symptoms, plus ↑Ca and ↑PTH → classic primary HPT presentation.
Young adult with kidney stones and very high calcium, plus family history of endocrine tumors (pituitary or thyroid) → MEN1 or MEN2A causing primary hyperparathyroidism.
Case 1
A 65‑year‑old woman is evaluated after her blood calcium is found to be 11.0 mg/dL during routine testing. She notes mild fatigue but no major symptoms.
Case 2
A 30‑year‑old man has recurrent kidney stones and a history of two episodes of acute pancreatitis. His father had kidney stones and a pituitary tumor.
X-ray of the hands showing multiple lytic "brown tumors" (subperiosteal bone cysts) in advanced primary hyperparathyroidism.
