Abnormally high parathyroid hormone (PTH) levels causing disrupted calcium–phosphate homeostasis. Classified into primary (excess PTH from parathyroid gland disease, causing hypercalcemia), secondary (reactive PTH elevation due to chronic hypocalcemia, e.g. in CKD), and tertiary (autonomous PTH secretion after prolonged secondary hyperparathyroidism).
Primary HPT is the most common outpatient cause of hypercalcemia, leading to kidney stones, osteoporosis, and neuropsychiatric disturbances if untreated. Secondary HPT is a key complication of CKD (renal bone disease) and contributes to fractures and vascular calcifications. Distinguishing primary vs secondary vs tertiary hyperparathyroidism by lab profile (PTH and calcium levels) is a classic exam challenge.
Primary HPT: often asymptomatic hypercalcemia on routine labs (esp. in older adults); severe cases show stones, bones, groans, thrones, psychiatric overtones (kidney stones, bone pain/fractures, abdominal pain/constipation, polyuria, confusion/depression).
Secondary HPT: typically in CKD patients with renal osteodystrophy (bone pain, calcifications); labs show high PTH with low/normal Ca and high phosphate (in CKD). Can also occur in vitamin D deficiency (malabsorption), causing bone pain and high PTH.
Tertiary HPT: seen in ESRD patients after long-standing secondary HPT (e.g. post-kidney transplant) – parathyroids become autonomous, causing high PTH with hypercalcemia. Presents with recurrent kidney stones or hypercalcemic symptoms despite resolved initial cause.
Evaluate PTH in any hypercalcemic patient: high PTH indicates PTH-mediated hypercalcemia (primary or tertiary HPT) whereas low PTH suggests non-parathyroid causes (malignancy, etc).
Differentiate primary vs tertiary HPT: both have ↑Ca and ↑PTH, but tertiary occurs in patients with a history of long-term CKD/dialysis (all glands hyperplastic).
Rule out familial benign hypercalcemia (FHH): check 24-hour urine Ca – FHH will have very low urine calcium excretion, whereas primary HPT has high urine Ca excretion.
If PTH is high with normal/low Ca, it's secondary HPT – look for chronic kidney disease (check GFR) or vitamin D deficiency (25-OH vitamin D level) as the cause.
Imaging: for primary/tertiary HPT, perform localization studies (sestamibi scan, neck ultrasound) only if surgery is planned (not needed for secondary HPT since all glands enlarged).
Vitamin D excess (intoxication or granulomatous disease)
↑Ca from high calcitriol; PTH is suppressed
Primary/tertiary HPT: parathyroidectomy is definitive if criteria met (symptoms or Ca/bone criteria); if not surgical, use calcimimetics (cinacalcet) to suppress PTH and treat hypercalcemia, and address osteoporosis (bisphosphonates).
Secondary HPT: treat the underlying cause – in CKD, control phosphate with binders, give active vitamin D (calcitriol) to raise Ca and suppress PTH, and add cinacalcet if PTH remains high. Optimize calcium and vitamin D intake in deficiency states.
Monitor labs regularly: avoid over-suppression of PTH in CKD (to prevent adynamic bone). Tertiary HPT often requires surgery (partial/total parathyroidectomy) once PTH is autonomous.
Mnemonic for hypercalcemia: stones, bones, groans, thrones, psychiatric overtones (kidney stones, bone pain, abdominal pain, polyuria, neuropsychiatric symptoms).
PTH = 'phosphate trashing hormone': primary/tertiary HPT cause renal phosphate wasting (low serum phosphate), whereas in CKD (secondary HPT) phosphate tends to be high.
Primary HPT is the most common cause of hypercalcemia in outpatients, whereas malignancy is the most common cause in hospitalized patients.
Hypercalcemic crisis: very high Ca (>14 mg/dL) causing dehydration, confusion, arrhythmias – requires emergency IV fluids, calcitonin, bisphosphonates.
Calciphylaxis (calcific uremic arteriolopathy): in severe secondary/tertiary HPT, high Ca×P product can cause skin ischemia with necrotic ulcers – life-threatening, may require urgent parathyroidectomy.
Hypercalcemia detected → check PTH level.
If ↑Ca + ↑PTH → PTH-dependent hypercalcemia (primary or tertiary HPT). If ↑PTH but Ca normal/low → secondary HPT (look for CKD or vit D deficiency).
High PTH + high Ca: differentiate primary vs tertiary by history (no CKD vs long-standing CKD). Check 24h urine Ca to distinguish FHH if familial pattern.
Primary/tertiary: consider parathyroidectomy if symptomatic or meeting guidelines (Ca >1 mg/dL above normal, T-score ≤ -2.5, kidney stones, age <50, etc). Localize adenoma(s) with imaging if surgery planned.
Secondary: manage CKD-MBD (dietary phosphate restriction, phosphate binders, vitamin D analogs, calcimimetics). Refer for surgery if PTH remains extremely high (>800) with refractory hypercalcemia or calciphylaxis.
