Bit · Endo
Hyperparathyroidism vs Hypoparathyroidism
Two opposite parathyroid diseases. Same hormone, opposite directions on calcium, phosphate, and PTH itself.
Mechanism
PTH does three things: raises serum calcium (bone resorption, distal tubule Ca²⁺ reabsorption, activates vitamin D), lowers serum phosphate (proximal tubule phosphate excretion), and activates 1-α-hydroxylase (converts vitamin D to active form):
- Primary hyperparathyroidism — autonomous PTH excess (most often a parathyroid adenoma; less commonly hyperplasia or carcinoma). High Ca²⁺, low PO₄³⁻, high PTH. 'Stones, bones, abdominal groans, psychic moans': nephrolithiasis, osteitis fibrosa cystica (subperiosteal bone resorption, brown tumors), constipation/pancreatitis, depression/fatigue. Often asymptomatic — found on routine labs.
- Secondary hyperparathyroidism — PTH appropriately elevated in response to low calcium (or impaired calcium handling). Most common cause: chronic kidney disease (decreased 1,25-(OH)₂ vitamin D → hypocalcemia + phosphate retention). Labs: low/normal Ca²⁺, HIGH PO₄³⁻ (different from primary!), high PTH.
- Tertiary hyperparathyroidism — long-standing secondary becomes autonomous; the parathyroid glands hyperplasia keeps secreting even when Ca²⁺ normalizes (often after renal transplant). Labs: HIGH Ca²⁺, HIGH PO₄³⁻, very high PTH.
- Hypoparathyroidism — most common cause: iatrogenic (post-thyroidectomy). Other causes: autoimmune, DiGeorge (congenital absence), Wilson, hypomagnesemia. Low Ca²⁺, high PO₄³⁻, low PTH. Symptoms of hypocalcemia: perioral numbness, tetany, Chvostek sign (facial twitch on tapping CN VII), Trousseau sign (carpal spasm with BP cuff), prolonged QT, seizures.
- Pseudohypoparathyroidism — end-organ resistance to PTH (defect in Gs α-subunit, AHO phenotype). Hypocalcemia + high PTH (PTH high because target tissue doesn't respond, so PTH keeps rising in compensation). Short stature, shortened 4th and 5th metacarpals, round facies.
Differentiator Table
| Primary hyperPT | Secondary hyperPT | Tertiary hyperPT | HypoPT | PseudohypoPT | |
| Cause | Parathyroid adenoma (most), hyperplasia, carcinoma | Hypocalcemia from CKD or vitamin D deficiency | Autonomous after long secondary | Post-thyroidectomy, autoimmune, DiGeorge, hypomagnesemia | End-organ Gs α-subunit defect |
| Serum Ca²⁺ | ↑ | ↓ / normal | ↑ | ↓ | ↓ |
| Serum PO₄³⁻ | ↓ | ↑ (different from primary) | ↑ | ↑ | ↑ |
| Serum PTH | ↑ | ↑ | ↑↑ | ↓ | ↑ (high, but body doesn't respond) |
| Classic findings | Stones, bones, abdominal groans, psychic moans; osteitis fibrosa cystica; brown tumors | Renal osteodystrophy | After renal transplant; persistent ↑ Ca²⁺ | Tetany, Chvostek, Trousseau, ↑ QT, perioral numbness | Albright hereditary osteodystrophy (short stature, short 4th/5th metacarpals, round face) |
| Treatment | Surgical removal of adenoma; cinacalcet | Treat CKD (calcium, vitamin D analogs, phosphate binders) | Surgical resection of hyperplastic glands | Calcium + active vitamin D (calcitriol) | Calcium + calcitriol |
The Pivot
Three questions:
- What is Ca²⁺ doing? High and PTH high → primary or tertiary hyperPT. Low and PTH high → secondary hyperPT or pseudohypoPT. Low and PTH low → hypoPT.
- What is PO₄³⁻ doing? Low PO₄³⁻ + high Ca²⁺ + high PTH = primary hyperPT. High PO₄³⁻ + low Ca²⁺ + high PTH = secondary (CKD usually).
- What is the setting? Post-thyroidectomy → hypoPT. CKD → secondary hyperPT. Asymptomatic with high Ca²⁺ on routine labs → primary hyperPT.
NBME-Style Stem
A 58-year-old woman is found on routine labs to have serum calcium 11.6 mg/dL (high), phosphate 2.1 mg/dL (low), and PTH 110 pg/mL (elevated). She is asymptomatic. Renal function is normal. 25-OH vitamin D is normal. Sestamibi scan shows a focal uptake at the inferior pole of the right thyroid. Which of the following is the most likely diagnosis?
Concept Anchor
PTH raises calcium and drops phosphate. Primary hyperPT lets PTH run free (high Ca, low PO₄). Secondary is the kidney's revenge (low Ca, high PO₄, high PTH from CKD). HypoPT is the inverse (low Ca, high PO₄, low PTH). Pseudo is the receptor lying to the gland (low Ca, high PO₄, high but ignored PTH).