Lecture 2 - Clinical mineral dysfunction Flashcards
Primary vs secondary hyperthyroidism
1 - parathyroid gland itself
2 - something else is telling the PT gland to secrete more PTH
HPT: what is it, what are the types, and what does it cause?
Hyperthyroidism
- 1°HPT
- 2°HPT
Excess secretion of PTH
1°HPT: what is it, what is it caused by, and what does it cause?
Primary hyperparathyroidism - a common endocrinopathy
Generally by hyperplasia - a monoclonal parathyroid adenoma caused by:
* Mutation of Vitamin D receptor gene (VDR)
* Mutation of MEN1 (multiple endocrine neoplasia) tumour suppressor gene
* Overexpression of cyclin D1 (cell cycle regulator); implicated in 20-40% sporadic PT adenomas.
- Hypercalcaemia
- Hypophosphatemia
- Bone demineralisation
- Hypercalciuria - kidney stones
- Multiple bone cysts (osteitis fibrosa cystica)
1°HPT: what are the statistics?
Incidence in the UK is ~1/1000
Accounts for 54% of all cases of hypercalcaemia
Treatments of primary HPT: what is the main and easiest option, what is the main primary HPT complication, and what treatments are suggested for this?
Parathyroidectomy (PTx) - removing the gland with the tumour
Main complication - nephrolithiasis
- Hydration
- Moderate Ca²⁺ intake
PTx: what is it, what are the benefits, and what are the disadvantages?
Parathyroidectomy - removing the gland with the tumour
- Relatively inexpensive & curative
- Long-term medical follow-up
- Ca²⁺/vit D replacement for life.
- If all four glands need to be removed, with no PTH, there is a steady drop in serum Ca²⁺, causing hypocalcaemic tetany
Tetany after thyroid surgery: what may it be caused by?
Iatrogenic (doctor-caused) hyperparathyroidism
Parathyroidectomy: what is it and what is the standard process?
PTx - removing the gland with the tumour
- Bilateral neck exploration
- Gland visualisation
- Excision
Parathyroidectomy: what are the current employed methods and why are these methods preferred?
- Pre-operative parathyroid localisation techniques (including High-resolution neck ultrasonography (US), Radio-guided MIRP)
- Surgery to remove the localised tumour
- Most 1°HPT cases result from solitary parathyroid adenoma
- Less invasive due to pre-operative localisation
- Can be performed under local anaesthetic (+ sedative)
Parathyroidectomy video
http://www.parathyroid.com/
https://www.google.com/url?q=http://www.parathyroid.com/&sa=D&source=editors&ust=1730823065350244&usg=AOvVaw2vJTm_73AhdZm7cWCuXi3B
2°HPT: what is it, what may it be caused by, what does it cause?
Secondary hyperparathyroidism (2°HPT)
Increased PTH secretion caused by:
* Decrease in serum Ca²⁺
* Prolonged serum phosphate (Pᵢ) increase (may be due to CKD)
* Vitamin D deficiency (may be due to kidney damage) - no PTH negative feedback
CKD: what is it, what happens in it, and how does it relate to hyperthyroidism?
Chronic kidney disease
Damage to the kidneys
Renal cells fail to react to PTH, meaning the Kidney fails to excrete sufficient PO₄ or generate sufficient calcitriol, resulting in secondary HPT
Standard movement of sodium, phosphate, and PTH in the proximal tubule
- NaPᵢ brings sodium and phosphate in but is inhibited by PTH
- NHE - sodium, proton exchange pump brings Na⁺ in and H⁺ out
- 1αOHase hydroxylates calcifediol into calcitriol, stimulated by PTH
Movement of sodium, phosphate, and PTH in the proximal tubule in CKD
Proximal tubule fails to respond to PTH
- NaPᵢ brings too much sodium and phosphate in due to lack of PTH inhibition
- NHE brings less Na⁺ in and H⁺ out
- 1αOHase hydroxylates produces less calcitriol
Effects:
Acidosis, hyperphosphataemia, and hypercalcaemia, etc
2°HPT treatment
- Phosphate binders
- Vitamin D
- Calcimimetics
- Combined Vit D/Cinacalcet: