🏈Secondary and Tertiary Hyperparathyroidism

Question 1

What is Renal Hyperparathyroidism

Answer 1

Secondary Hyperparathyroidism (sHPT)

Excessive PTH secretion secondary to chronic biochemical stimulus such as:

• CRF (> 1/2 of the patients with CKD 3 or 4 and > 90% of those with ESRF)
• Vitamin D deficiency.

Usually MGD

• ↓ GFR → ↓ PO4 clearance → Hyperphosphatemia (main cause of 2⁰ PTH) → Ca2+ PO4 binding → ↓ Ca2+ → stimulate PTH gland & ↓ Vit D production → hyperplasia → ↑ PTH → bone loss,
  Late - FC, calciphylaxis.

Tertiary Hyperparathyroidism (tHPT)

Autonomous (unregulated) hypersecretion of PTH in chronic Secondary HPT patient. Usually seen in:

• Post renal transplant
• Long term RRT

Question 2

Presentation of sPTH and tPTH

Tumoral Calcinosis

Answer 2

Renal failure history (duration, RRT, Cause of renal failure) – usually > 7 years.

Plan for renal transplant.

Phosphate control (medication & diet compliance). Will help decide on auto transplantation.

Early disease:

• Minimal symptoms. Vessel calcification → HPT, AMI
• Present commonly with diffuse bone and joint pain with spontaneous fractures of the ribs, spine and hips, itching, soft tissue calcifications, and vascular calcifications leading to an increased cardiovascular risk and mortality

Late disease:

• Tumoral calcinosis – a rare, hereditary metabolic dysfunction of phosphate regulation associated with development of massive periarticular calcinosis in the extra-capsular soft tissues. Patients most commonly present with palpable lesions around the hip and shoulder.
• Calciphylaxis (Calcific uremic arteriolopathy)- Calcification of media of small to medium size arteries resulting in ischemic damage in dermal & epidermal structure.
• Renal osteodystrophy – metabolic bone disease seen in patients with chronic renal insufficiency characterized by bone mineralization deficiency present with osteoporosis, osteomalacia, OFC (osteitis fibrosa cystica), adynamic bone disease (low turnover bone disease due to PTH resistance / bisphosphonate)

Tumoral Calcinosis

Question 3

Calciphylaxis

Answer 3

Question 4

Renal Osteodystrophy

Answer 4

Question 5

Management ( medical) for tertiary Hyperparathyroidism

Answer 5

Divided into:
medical
Surgery

Medical treatment (first line)
- ↑ Ca
- Hemodialysis
- Calcium supplement

• ↓ PO4
  
  • Patients should be instructed to begin controlling dietary phosphate as soon as GFR is reduced. Dietary phosphate should be restricted to 800–1,000 mg/day to keep serum phosphorus levels below 4.6 mg/dl (1.49 mmol/l) in stage 3 and 4 CKD and 5.5 mg/dl (1.78 mmol/l) in stage 5
  • Phosphate binder (CaCO3, Ca Acetate, Sevelamer, Lanthanum)
• ↓iPTH
  
  • Vit D analogue that suppress PTH secretion.
• Improve skeletal turnover & treat osteoporosis.

Question 6

Management ( Surgical option)

Answer 6

Surgical Management

Indications:

Tertiary Hyperparathyroidism

• Worsening disease despite 6 months of optimal medical treatment
• PTH > 80 pmol/L
• Persistent hyper Ca2+ (>2.6 mmol/l)
• Persistent hyper PO4
• Renal osteodystrophy, Osteitis fibrosa cystica, osteomalacia & adynamic bone disease, Osteodystrophy, Osteoporosis (T-score > -2.5 SD below mean), pathologic bone fracture. Calciphylaxis with documented elevated PTH levels (Absolute indication), Metastatic calcifications.
• Large parathyroid on USG > 500mg.
• Anaemia resistant to EPO
• Symptoms and signs – Intractable Pruritus, Bone pain, Severe vascular calcifications, Myopathy

Other indication:
- Subacute severe hypercalcemia (Ca2+ > 12.5mg/dl)
- Persistent hypercalcemia 2 years after transplantation associated with:
- Renal function decline without graft rejection
- Osteodystrophy
- Pancreatitis
- Nephrolithiasis

Adynamic bone disease (ABD) is a variety of renal osteodystrophy characterized by reduced osteblasts and osteoclasts, no accumulation of osteoid and markedly low bone turnover. It has been found in a relatively high percentage of patients on dialysis, either peritoneal or hemodialysis, but also in CKD patients on conservative treatment.

Question 7

Preoperative workout for sPTH and tPTH

Answer 7

As for pHPT.

Preoperative localization

• not necessary renal HPT (sHPT & tHPT) because all glands are hyperplastic, need to explore all 4 glands.
• Pre-operative imaging indicated in pts with previous parathyroidectomy & persistent or recurrent parathyroidectomy.

Low Sensitity of Sesatimibi for parathyroid Hyperplasia! , only sensitive for adenoma

Question 8

Surgical options for sPTH or tPTH

Answer 8

DIvided into:
- 🔥Patient planning for future renal transplant
- 🔥Patient not planning for renal transplant

(Patient Planning for Future Renal Transplant)

Total Parathyroidectomy + Auto transplantation with or without Cervical Thymectomy

• For patient awaiting renal transplant.
• Persistent growth stimulus can lead to recurrent HPT of auto transplanted parathyroids.
• Recurrence risk 4.8%. Hypoparathyroidism risk 1.6%.
• Intrathymic parathyroid glands are found in up to 44.5% of patients undergoing parathyroidectomy for rHPT

Total Parathyroidectomy with or without Auto transplantation

• 3 years follow-up, 8.3% with auto transplantation and no patient without auto transplantation had recurrent rHPT.

Subtotal Parathyroidectomy

• Remove 3 ½ glands (leaving 30-40 grams, smallest and macroscopically nodular, vascularized, is left in its anatomical position, clipped for later localization).
• For patient awaiting renal transplant.
• Poor compliance or in availability to Ca2+ & Vit D supplement, stay far from health center (logistic problem).
• Disadvantage
  
  • Difficult iPTH monitoring post op.
  • Risk of recurrent HPT requiring re exploration & ↑ risk RLN injury

(Patient not for Renal Transplant / Poor PO4 compliance)

Total Parathyroidectomy + Thymectomy & No Auto Transplantation

• Used in patients with aggressive rHPT and no chance of renal transplant

No need take iPTH intraoperative as patient already ESRF, excretion/metabolism will take long duration (days), so wont achieve the 50% reduction (Half life of PTH is around 7min) (Prof Chaon)

Question 9

Technique of auto transplant

Answer 9

Auto-transplantation

• Offer best possibility of graft viability & functionality but not all majority do not develop permanent hypoparathyroidism.
• How much to implant : 30-60mg

Technique

• Crushed parathyroid tissue - Suspended with saline, injected into pockets of muscle
• Slices - 30 pieces sliced 1x1x2mm of diffusely hyperplastic glands or 16 pieces of most normal looking parathyroid (1/2 of the gland)

Site of implantation

• Brachioradialis muscle – 30 pockets in forearm without AVF
• Tibialis anterior muscle
• Subcutaneously above the sternum or in the forearm
• Area being mark with non-absorbable suture or clip: so can be easily excised under LA.
• Confirm with frozen section before implant
• Success rate: > 80%.

Advantage

• Residual parathyroid function can be easily followed up.
• Easy to identify PTH gradients with peripheral blood.
• Recurrence can be treated by resection under LA

Disadvantage

• Autograft failure.
• Difficult re-operation.
• Interfere with HD access.
• Growth into adjacent tissue requiring radical excision.

Question 10

Cryopreservation for Parathyroid ( while awaiting for transplant)

Answer 10

Cryopreservation

• Stores parathyroid tissue & auto-transplant if patient develops permanent hypothyroidism
• Disadvantage is higher risk of graft failure & risk of graft dependent hypercalcemia.
• Procedure:
  
  • Tissue preparation : Tissue stored in sterile ice chilled saline.
  • Freezing : medium (80% of Roswell Park Memorial Institute solution- not suitable for freezing but good for short term preservation - 4 degree celcius and hours to days)
  • Dimethyl Sulfoxide (DMSO) ( Cryoprotectant for long-term freezing) added & freeze to -80⁰C
  • The most important step for this stage of the process is gradual cooling by −1 °C per minute. Once the tubes are cooled, they are put into a liquid nitrogen freezer and stored at temperatures between −170 and −196 °C
  • Thawing to 37⁰C and re-implanted.
• Shelf life: 2 years.
• However number of patients who require auto transplantation of
  cryopreserved parathyroid tissue is extremely small.

Question 11

What is Casanova Test ?

Answer 11

Modified Casanova Test

• 1st blood sample taken from non-transplant arm
• Apply Tourniquet / BP cuff on transplant arm above transplant site, inflate above systolic pressure
• Subsequent samples are taken 5 min, 10 min, 15 min after inflation.
• Deflate the BP cuff and repeat blood sample 10 mins later.
• PTH ↓
  
  • >50% - source is transplant
  • < 20% - neck or mediastinum (-VE test)
  • 20 - < 50 % - undefined source.

Question 12

In patients with renal hyperparathyroidism undergoing renal transplantation, a small part of the parathyroid gland may be transplanted (typically into a muscle, such as the forearm or sternocleidomastoid muscle) for the following reasons:

Answer 12

1. To Prevent Severe Hypoparathyroidism Post-Transplant
• Renal hyperparathyroidism occurs due to chronic kidney disease (CKD), where prolonged parathyroid hormone (PTH) overproduction leads to hyperplasia of the parathyroid glands.
• After a successful renal transplant, normal kidney function restores calcium-phosphorus balance, often leading to a rapid drop in PTH levels.
• If all parathyroid glands are removed (during parathyroidectomy), patients can develop severe hypoparathyroidism and hypocalcemia post-transplant, which can cause symptoms like muscle cramps, tetany, and neurological issues.
• Transplanting a small amount of functional parathyroid tissue ensures a controlled level of PTH to maintain calcium homeostasis.

2. Avoid Permanent Parathyroid Deficiency
• Transplanting part of the parathyroid gland allows the patient to retain some parathyroid function without needing lifelong calcium and vitamin D supplementation.
• The transplanted tissue can autoregulate PTH secretion to adapt to the body’s calcium needs.

3. Safety of Partial Transplant
• In renal hyperparathyroidism, the parathyroid glands are usually enlarged (secondary hyperplasia). Total parathyroidectomy is often performed to stop excess PTH production.
• A small fragment of the parathyroid gland is saved and transplanted to prevent complete loss of function.
• If needed, the transplanted tissue in an accessible site (e.g., forearm) can be easily removed later if it overproduces PTH.

Summary

The transplantation of a small piece of parathyroid tissue after total parathyroidectomy helps balance the risk of post-transplant hypoparathyroidism while still correcting the hyperparathyroidism caused by CKD. It provides a safety net for calcium regulation in patients undergoing renal transplantation.