STEPTRACKERENDOCRINE | PATHOLOGY + PHYSIOLOGY + GENETICS | HIGH-YIELD REVIEW

Parathyroid & Calcium Disorders

Calcium too high or too low — read PTH, phosphate and urine calcium together to find the cause.

FOCUS ON
Primary hyperparathyroidism (adenoma): ↑ Ca²⁺, ↓ PO₄³⁻, ↑ PTH — stones, bones, groans, psychiatric moans. FHH: mild ↑ Ca²⁺ with low urine calcium — don't operate. Malignancy: PTHrP (squamous cancers, RCC), calcitriol (lymphoma, granulomas), lytic bone. Hypoparathyroidism: post-thyroidectomy, DiGeorge, low Mg²⁺ → tetany. Pseudohypopara: ↑ PTH, resistance (GNAS).
DISORDER
MECHANISM
LABS · FEATURES
CLUE · TREATMENT
Primary hyperparathyroidism
Adenoma (~85%), hyperplasia (MEN1, MEN2A), carcinoma
↑ Ca²⁺, ↓ PO₄³⁻, ↑ PTH, ↑ ALP, ↑ urine Ca²⁺ and cAMP; often found on routine labs
Parathyroidectomy · cinacalcet if not a surgical candidate
Hyperparathyroidism — features
Bone resorption + hypercalcemia effects
Kidney stones, polyuria; osteitis fibrosa cystica (subperiosteal resorption of phalanges, brown tumors, salt-and-pepper skull); constipation, pancreatitis, PUD; depression, fatigue
"Stones, bones, groans, thrones, psychiatric overtones"
Familial hypocalciuric hypercalcemia
Loss-of-function CaSR (AD) → higher calcium set point
Mild ↑ Ca²⁺, normal/mildly ↑ PTH, ↓ urine Ca²⁺ (Ca/Cr clearance < 0.01)
Benign — no surgery
Humoral hypercalcemia of malignancy
PTHrP acts on PTH receptor
↑ Ca²⁺, ↓ PO₄³⁻, ↓ PTH; squamous cell lung, head and neck, RCC, bladder, breast, ovary
Most common cause in inpatients
Calcitriol-mediated hypercalcemia
Macrophage 1α-hydroxylase (PTH-independent)
Lymphoma, sarcoidosis, TB, other granulomas; ↑ calcitriol, ↓ PTH
Glucocorticoids
Osteolytic hypercalcemia
Tumor → RANKL, IL-6 → osteoclasts
Breast cancer metastases, multiple myeloma; ↓ PTH
Bisphosphonates, denosumab
Other hypercalcemia
Excess intake, ↓ excretion, ↑ turnover
Vitamin D toxicity, milk-alkali syndrome, thiazides, lithium, immobilization, hyperthyroidism, adrenal insufficiency
Acute: IV saline, calcitonin, bisphosphonate
Hypoparathyroidism
Thyroid/neck surgery (most), autoimmune (APS-1, AIRE), DiGeorge (22q11), infiltration, hypomagnesemia
↓ Ca²⁺, ↑ PO₄³⁻, ↓ PTH; tetany, perioral numbness, Chvostek and Trousseau signs, long QT, seizures
Calcium + calcitriol; replace Mg²⁺ first
Pseudohypoparathyroidism 1A
GNAS (Gsα) mutation inherited from mother → kidney/bone resistance to PTH
↓ Ca²⁺, ↑ PO₄³⁻, ↑ PTH; Albright hereditary osteodystrophy: short stature, short 4th/5th metacarpals, round face, obesity
Pseudo-pseudo: paternal GNAS, AHO with normal labs
Vitamin D deficiency
↓ gut Ca²⁺ absorption → secondary ↑ PTH → phosphate wasting
Low/normal Ca²⁺, ↓ PO₄³⁻, ↑ PTH, ↑ ALP; rickets/osteomalacia
CKD-related HPT: see 12.10
Parathyroid carcinoma
Malignant chief cells; CDC73 (HRPT2)
Very high Ca²⁺ (> 14), palpable neck mass, severe bone and kidney disease
En bloc resection

Mechanism — what PTH does

↓ Serum Ca²⁺CaSR on chief cells
→
↑ PTH
→
BoneRANKL → osteoclasts
Kidney↑ Ca²⁺ reabsorption (DCT), ↓ PO₄³⁻ reabsorption (PCT), ↑ 1α-hydroxylase
Gut (via calcitriol)↑ Ca²⁺ and PO₄³⁻ absorption

Magnesium is needed for PTH release and action — low Mg²⁺ causes refractory hypocalcemia.

Reading the calcium panel

CONDITION
Ca²⁺
PO₄³⁻
PTH
Primary HPT
↑
↓
↑
FHH
↑ (mild)
Normal
Normal / ↑
PTHrP malignancy
↑
↓
↓
Vitamin D excess / granuloma
↑
↑
↓
Hypoparathyroidism
↓
↑
↓
Pseudohypopara
↓
↑
↑
Vitamin D deficiency
↓ / normal
↓
↑

How it's tested

COMMON CONFUSIONFHH and mild primary hyperparathyroidism look alike in the blood. Urine calcium separates them: low in FHH, normal-high in primary HPT.
THE TRAPHypocalcemia that won't correct with calcium often means low magnesium (alcoholism, diuretics, PPIs, diarrhea). Replace Mg²⁺ first.
YOUR APPROACHCalcium (correct for albumin) → PTH (high or suppressed?) → phosphate → urine calcium, PTHrP, vitamin D metabolites → cause.

If you see… think…

Asymptomatic ↑ Ca²⁺, ↓ PO₄³⁻, ↑ PTH → parathyroid adenoma
Subperiosteal resorption of the phalanges, brown tumors → osteitis fibrosa cystica
Mild hypercalcemia, normal PTH, very low urine calcium → FHH — no surgery
Smoker with central lung mass, Ca²⁺ 13.5, ↓ PTH → PTHrP from squamous cell carcinoma
Sarcoidosis with hypercalcemia → macrophage 1α-hydroxylase
Back pain, anemia, hypercalcemia, ↑ creatinine → multiple myeloma
Tetany and Chvostek sign after thyroidectomy → hypoparathyroidism
Infant with hypocalcemia, absent thymus, heart defect → DiGeorge (22q11)
Short 4th metacarpals, round face, ↓ Ca²⁺, ↑ PTH → pseudohypoparathyroidism 1A
Hypocalcemia not correcting in an alcoholic → hypomagnesemia