4th year pathology

1. Parathyroid Gland Disorders
By Dr Hassan Yar

2. Outlines
• Basic concepts
• Calcium homeostasis and pth
• Pathologies of pth
• Hyperparthyroidism
• Clinical correlation

3. Parathyroid Gland
• 4 small glands (Post. Thyroid)
• 2 superior, 2 inferior
• Arise from 4th and 3rd pharyngeal pouches
• Contains chief cells which secrete pth

4. Parathormone/PTH
• Major hormone in calcium/phosphate metabolism
• Regulates free ionized calcium
• Bone remodeling (osteoclastic activity)
• Vitamin D activation

5. Role of Vitamin D
• ⬆️ Ca reabsorption in duodenum
• ⬆️ Phosphorus reabsorption in small intestine
• ⬆️ Ca reabsorption in kidneys (distal tubule)

6. Serum Calcium
• 40% bound to albumin
• 13% bound to phosphorus/citrate
• 47% free ionized calcium (negative feedback with pth)

8. Common manifestation of PTH derangement
Hyperparathyroidism
• Primary HPTH
• Secondary HPTH
• Tertiary HPTH
Hypoparathyroidism
• Hypoparathyroidism
• Pseudohypoparathyroidism

9. Primary HPTH
• Most common nonmalignant cause of hypercalcemia
• Postmenopausal women
• Association with MEN I and MEN Iia
• 3 major causes:
1. Adenomas (80%)
2. Primary hyperplasia (20%)
3. Carcinoma (uncommon)

10. Pathogenesis
• Mostly unknown
• Cyclin D1 gene inversions
• MEN1 mutations (even in those not manifesting)

11. Morphology
• Glandular change (minimal and indistinguishable mostly)
1. Endocrine atypia
2. Hyperplasia of chief cells and oxyphil cells
3. Water clear cell hyperplasia
• Affected Organ specific:
Myriad of changes depending on involved structures.
1. Metastatic calcification
2. Nephrolithiasis/nephrocalcinosis
3. Subperiosteal resorption

12. Clinical features
“painful bones, renal stones, abdominal groans, and psychic moans.”
• Renal stones
• Osteitis fibrosa cystica
• PUD/constipation/acute pancreatitis
• Diastolic HTN
• Psychosis/confusion/coma
• Metastatic calcification

14. Comparison of biochemical profile

15. Treatment
• Surgical removal
• Diuretics and fluids
• Bisphosphonates
• Cincalcet

16. Secondary HPTH
• All four parathyroid Gland involved
• Physiological compensation for hypocalcemia
• Mostly secondary to CKD
• Renal osteodystrophy
• Can develop tertiary hyperthyroidism

17. Hypoparathyroidism
• Hypofunction leading to hypocalcemia
• Autoimmune hypothyroidism(most common cause)
• History of thyroid surgery (total thyroidectomy)
• Digeorge syndrome
• Hypomagnesemia
⬇️ PTH, ⬆️ phosphates, ⬇️ calcium

18. Clinical features
• Tetany
• Calcification of basal ganglia
• Cataracts
• Trousseau/chvostek sign
• Treatment include calcium and vitamin d, and
teriparatide(recombinant pth)

19. Pseudo hypothyroidism
• Autosomal dominant disease
• End organ resistance to pth
• Inability to synthesize 1-α-hydroxylase
⬇️ calcium, ⬇️ Phosphorus,⬇️ Calcitriol but normal calcidiol, normal/⬆️
pth,

20. Presentation
• Mental retardation
• Basal ganglia calcification
• “Knuckle knuckle dimple dimple” Sign

23. • A: Hypoparathyroidism
• B: Hypoalbuminemia
• C: Secondary HPTH
• D: Respiratory alkalosis
• E: Primary HPTH
• F: Hypercalcemia of neoplasm