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PA31.{4,6} | Thyroid Tumors & Parathyroid Disease — SDL Guide (Part 4)

Morphologic Features: Parathyroid Adenoma, Hyperplasia, and Skeletal Changes

Parathyroid Adenoma — Morphology:

• Gross: Solitary, oval, reddish-brown gland, typically 0.5–5 g (normal gland: 35–40 mg). Other glands are normal or atrophic (suppressed by hypercalcemia).
• Microscopic:
• Predominantly chief cells (principal cells) — small polygonal cells with round nuclei, pale eosinophilic cytoplasm; the workhorse PTH-secreting cell
• Rim of compressed normal parathyroid tissue at edge (key feature — absent in carcinoma and hyperplasia)
• Absent fat cells within the adenoma (intracellular fat is lost in hyperfunctioning chief cells)
• May contain water-clear cells or oxyphil cells (non-functional large eosinophilic cells)

Primary Chief Cell Hyperplasia — Morphology:
• All four glands enlarged — asymmetrically
• Diffuse or nodular proliferation of chief cells
• No rim of normal tissue at periphery (distinguishes from adenoma)
• Requires intraoperative assessment of all four glands at surgery

Skeletal changes of hyperparathyroidism:

Osteitis fibrosa cystica (von Recklinghausen disease of bone) — severe, prolonged hyperparathyroidism:
1. Osteoclastic bone resorption — peritrabecular fibrosis, "dissecting osteitis"
2. Brown tumor — localized collections of osteoclasts and reactive giant cells with hemosiderin deposition (hemorrhage → hemosiderin → brown color). Not a true neoplasm — these resolve after parathyroidectomy. May be mistaken for giant cell tumor of bone on X-ray.
3. "Salt and pepper" skull on X-ray — diffuse subperiosteal bone resorption
4. Subperiosteal resorption of radial aspect of middle phalanx — pathognomonic radiologic sign of hyperparathyroidism
5. Rugger jersey spine — alternating dense/lucent bands on vertebrae (in secondary HPT)

Parathyroid Adenoma: H&E Histology — Chief Cells and Rim of Normal Parathyroid Tissue

Subperiosteal Bone Resorption in Hyperparathyroidism — Hand X-ray and Phalanx Cross-sections

Secondary and Tertiary Hyperparathyroidism

Secondary Hyperparathyroidism:

• Cause: Chronic kidney disease (CKD) is by far the most common cause in clinical practice
• Mechanism in CKD:
1. ↓ GFR → phosphate retention → ↑ serum phosphate
2. ↑ Phosphate → directly suppresses serum calcium
3. ↓ GFR → ↓ 1-α-hydroxylase → ↓ calcitriol (1,25-D₃) → ↓ intestinal calcium absorption
4. Low calcium + low calcitriol → parathyroid gland stimulation → appropriate ↑ PTH
5. Chronic stimulation → all four glands enlarge (chief cell hyperplasia)

• Lab: Ca²⁺ low or normal, PO₄³⁻ elevated, PTH elevated, calcitriol low — the opposite of primary HPT phosphate pattern
• Treatment: Dietary phosphate restriction, oral calcium + vitamin D supplements, phosphate binders, cinacalcet (calcimimetic that mimics calcium at the parathyroid calcium-sensing receptor)

Tertiary Hyperparathyroidism:

• Mechanism: After prolonged secondary HPT (especially in CKD or post-renal transplant), the hyperplastic parathyroid glands develop autonomous function — they no longer respond to feedback from corrected calcium levels
• Result: Hypercalcemia despite correction of the original stimulus (e.g., after successful renal transplant)
• Histology: Nodular hyperplasia of all four glands → some nodules become clonal (adenoma-like autonomous secretion)
• Treatment: Surgical parathyroidectomy (3.5-gland removal or total with autotransplantation)

Memory scaffold:
- Primary: Problem is in the parathyroid → PTH ↑, Ca ↑, PO₄ ↓
- Secondary: Problem is outside (kidney/gut) → PTH ↑ as compensatory response, Ca low/normal, PO₄ ↑ (in CKD)
- Tertiary: Secondary that escaped feedback → now acts like primary

H&E Histology: Parathyroid Chief Cell Hyperplasia vs. Adenoma