A 43-year-old male patient who has been on HD for 10 years, underwent parathyroidectomy 18 months ago due to severe hyperparathyroidism. The histopathology confirmed parathyroid adenoma. For one year after parathyroidectomy, the patient had normal PTH and calcium levels. However, the patient showed abnormally high serum calcium and PTH levels in his last routine labs.
The patient labs are shown in table 1
Test
Value
S. Creatinine
4.8 mg/dL
S. corrected Calcium
11.6 mg/dL
S. Phosphorus
6.8 mg/dL
iPTH
610 pg/mL
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
B. How would you approach this case?
29 Comments
Radwa Ellisy
– This lab is consistent with tertiary hyperparathyroidism, hypercalcemia and hyperparathyroidism and hyperphosphatemia
this might be as a result of subtoatal parathyroidectomy and the loss of the inhibitory mechanisms by removal of the adenoma, so hyperplasia or adenoma by the remaining parathyroid gland
– First, imaging by neck US and radioisotope scan to localize the pathlogy part and further parathyroidectomy for the remaining parts.
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH? After initial parathyroidectomy, some patients develop recurrent PHPT (>6 months from initial exploration).
B. How would you approach this case? If the diagnosis of recurrent PHPT is suspected:
confirmed biochemically
indications for operation considered. High risks of complications such as recurrent laryngeal nerve injury, permanent hypoparathyroidism, and nontherapeutic re-exploration are higher.
major manifestations of hypercalcemia: ● Nephrolithiasis ● Osteoporosis ●Serum calcium level >12 mg/dL ● Hypercalciuria ● 30% decrease in renal creatinine clearance
two concordant imaging studies for localisation be obtained prior to re-exploration.
ultrasound-guided fine needle aspiration of a suspected gland(s) with both histology and PTH assay performed on the aspirate
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?Patient is having tertiary hyperparathyroidism due to hyperplasia of parathyroid gland with one single autonomus pituitary adenoma. This adenoma suppressed other glands. Ocne the single adenoma is removed. The suppression effect is lifted and other glands start to be active and hypersecrete PTH leading to hypercalcemia.
B. How would you approach this case?This patient will need three and a half Parathyroid glands removal.
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
Recurrent primary hyperparathyroidism which is due to activation of remaining parathyroid gland tissue leading to high levels of calcium and PTH
B. How would you approach this case?
Do imaging studies to evaluate the adenoma recurrence or not
A.What are the possible mechanisms underlying the recurrent increase of calcium and PTH?possible mechanism could include recurrent of the diseases
in some studies also discussed the patients who had larger tumour might have high PTH levels after surgery B. How would you approach this case?first would do imaging to evaluate if adenoma reoccur ,,
give active vitamin d , and sevelamer
if no response after 3 months , may operate again
What are the possible mechanisms underlying the recurrent increase of calcium and PTH?recurrent adenoma after subtotal parathyroidectomy or ectopic adenoma
How would you approach this case?single-radioisotope scintigraphy with technetium-99m (99mTc) combined with single-photon emission computed tomography (SPECT) imaging Four-dimensional CT and MRI may have a more beneficial role in localizing ectopic glands after failed parathyroidectomy.
Trial of calcimimitics and non calcium containing phosphate binders then add vitamin d and vitamin d receptor activators after normalisation go serum phosphorus for 3 months
if no response, surgical intervention
If secondary hyperpara; add active vitamin D and 25(OH) vitD and cinacalcet with sevelamer, then check the lab regularly for follow up and adjustment of the doses.
It seems this patient has another source may be another site adenoma, so we need to localize by scintigraphy or SPECT PET, and intervene surgically. If not on cinacalcet, I will add it, if on a low dose, I will increase and reevaluate.
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH? subtotal parathyroidectomy with recurrent adenoma in the remaining glands or ectopic gland . B. How would you approach this case?subtotal parathyroidectomy with recurrent adenoma in the remaining glands .
A- subtotal parathyroidectomy with recurrent adenoma in the remaining glands
B- sestamebi scan of parathyroid glands to exclude adenoma – pan CT to exclude malignancy – PTH related peptide level – 25 (OH) vit D assay
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
May be recurrence & hyperfunction of the remaining parathyroid gland recurrent hyperparathyroidism are: Dormant (sleeping) second parathyroid adenoma, also known as subordinate adenoma. B. How would you approach this case? Use U/S , sestemba scan, use calcimimetic drugs VDRA and and total parathyroidectomy surgery again if no improvement. Monitoring of s.ca and PTH.Control hyperphosphatemia by diet restriction and enhanced dialysis (increase time and high flux dialyser )
A.What are the possible mechanisms underlying the recurrent increase of calcium and PTH? Subtotal or Total with re-implantation of part of the gland into either the forearm or sternocleidomastoid muscle
B.How would you approach this case? calcimimetics and VDRA, Re-consider surgery again if no improvement
THIS PATIENT HAS RECURENT HYPERPARATHYROIEDIM WITH HYPERCALCIMIA AND HYPERPHOSPHATEMIA , WE NEED TO GO FOR SESTAMIBI SCAN TO CONFIRM THE DIAGNOSES OF HYPERPARATHYROIDISM , WE CAN START PATIENT ON CALCIMEMETIC , NONCALCIUM BASED PHOSPHATE BINDER , DIALYSIS WITH LOW OR FREE CALCIUM IF POSSIBLE , MAY HE WILL NEEDS FOR SURGICAL INTERVENTION , BIPHOSPHANATE IV , CHECK FOR VIT D ALSO
A- the possible mechanism if underlying condition mostly recurrant parathyroid adenoma or hyperplasia in remnant parathyroid gland.
B- approach in these case we need sistamibi scan to detect the site of active gland .start cinacalcite and non ca containing po4 binder
the patient has recurrent hyperparathyroidism:
1- inadequet exploration and res,ection, 2- ectopic or supernumerary gland
3- parathyromatosis:occurs due to rupture of the capsule and escape of parathyroid cells
approach: 1st is localization of the lesoin by non-invasive methods or less likely invasive
non-invasive methods includde:us,Sestamibi scans. CT, AND MRI
THIS should be followed by redo parathyroidectomy
A. Disease recurrence in other Parathyroid tissues.
B. Nuclear studies, sonography. First , conservative treatment for 6 months with cincalcet and if failure then parathyreoidectomy
A-
may be the recurrence of parathyroid adenoma of remaining parathyroid gland
B-i will order neck USS and sestamibi scan
review medications and hold alfacalcidol and calcium suplementations and use low calcium dialysate 1.25 mmol/l
control hyperphosphatemia by diet restriction and enhanced dialysis (increase time and high flux dialyser ) ,use non calcium based phosphate binder
surgical review .
a- possible mechanisms underlying the recurrent increase of calcium and PTH
over activity of the remaining parathyroid tissue post parathyroidectomy
start conservative medication
for suppression pth as cinacalcet
and re-assessment the condition
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
autonomous secretion of parathyroid adenoma due to tertiary hyperparathyroidism. successful surgery was done as there was normal serum calcium and PTH for 1 year. However, the patient developed a disease recurrence due to overgrowth of the remaining parathyroid tissue.
B. How would you approach this case?
Sestamibi scan for detection of any active parathyroid tissue.
Subtotal resection of the remaining tissue with intra-operative monitoring of PTH to guide the size of removal.
A-Patient may have recurrence of hyperparathyroidism because surgery was subtotal, other parathyroid glands may have been suppressed by the active one, so it is difficult to see then during surgery, once the active one removed other PT glands can become active and hypertrophied
A) -hyperplasia of remaining gland tissue if the surgery was sub total or hyperplasia of the implant
-missed retrosternal gland hyperplasia.
B)Re scan of the neck and retrosternal
consider cinacalcet as a line of treatment with non ca binding phosphate binder
What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
The recurrence of hyperparathyroidism and hypercalcaemia is a manifestation of recurrence/regrowth of parathyroid tissue
Parathyroid surgery in patients with end-stage kidney disease is an effective therapy for normalisation of calcium and parathyroid hormone metabolism in patients with renal osteodystrophy. Medical therapy still remains the initial treatment in these patients, and the following is indications for parathyroidectomy:
Patients with refractory hyperparathyroidism as well as associated signs and symptoms
Hypercalcaemia and refractory hyperphosphataemia
Bone pain
Pruritus
Myopathy
Calciphylaxis
The current techniques for parathyroid surgery includes:
Targeted parathyroidectomy
Sub- or near-total parathyroidectomy
Total parathyroidectomy with autotransplantation
Total parathyroidectomy without autotransplantation
Most end-stage kidney disease patients has multi-gland hyperplasia, for which a subtotal, near-total, total parathyroidectomy is typically performed as initial surgery. Targeted parathyroidectomy is an option for the rare post renal transplant patients who presented single or double adenomas.
How would you approach this case?
Initiate the patient on calcimimetics and vitamin D receptor agonist
Consider the patient for the exploration of the neck
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?The explanation depends on the type of surgery:
Targeted parathyroidectomy(not all the hyperfunctioning parathyroid tissue has been removed)
Sub- or near-total parathyroidectomy(the remnant gland still active)
Total parathyroidectomy with autotransplantation(reactivation of implanted gland)
Total parathyroidectomy without autotransplantation(missing gland(s), retroesophageal and deep paratracheal spaces
B. How would you approach this case?Check the type of operation
send for alkaline phosphatase, 25-vit-D
sestamibi scan, U/S neck, possible CT scan
A.What are the possible mechanisms underlying the recurrent increase of calcium and PTH?-Approach to parathyrodiectomy may be either
Subtotal or
Total with re-implantation of part of the gland into either the forearm or sternocleidomastoid muscle
Which one is better is controversial !
However, subtotal may be associated with recurrence of secondary hyperparathyroidism and the problem with re-implantation is that, frequently the re-implanted tissue becomes fibrotic or doesn’t function or rarely develop parathroidomatosis i.e. the microscopic cells produce high levels of PTH.
B.How would you approach this case?
Trial of calcimimetics and VDRA
Re-consider surgery again if no improvement . This can be very challenging & difficult.
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH? possible causes Dormant (sleeping) second parathyroid adenoma
B. How would you approach this case?neck ultrasound .
follow PTH ,Ca
24 h.urinary Ca
– This lab is consistent with tertiary hyperparathyroidism, hypercalcemia and hyperparathyroidism and hyperphosphatemia
this might be as a result of subtoatal parathyroidectomy and the loss of the inhibitory mechanisms by removal of the adenoma, so hyperplasia or adenoma by the remaining parathyroid gland
– First, imaging by neck US and radioisotope scan to localize the pathlogy part and further parathyroidectomy for the remaining parts.
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
After initial parathyroidectomy, some patients develop recurrent PHPT (>6 months from initial exploration).
B. How would you approach this case?
If the diagnosis of recurrent PHPT is suspected:
major manifestations of hypercalcemia:
● Nephrolithiasis
● Osteoporosis
● Serum calcium level >12 mg/dL
● Hypercalciuria
● 30% decrease in renal creatinine clearance
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?Patient is having tertiary hyperparathyroidism due to hyperplasia of parathyroid gland with one single autonomus pituitary adenoma. This adenoma suppressed other glands. Ocne the single adenoma is removed. The suppression effect is lifted and other glands start to be active and hypersecrete PTH leading to hypercalcemia.
B. How would you approach this case?This patient will need three and a half Parathyroid glands removal.
-recurrent adenoma
-imaging
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
Recurrent primary hyperparathyroidism which is due to activation of remaining parathyroid gland tissue leading to high levels of calcium and PTH
B. How would you approach this case?
A.What are the possible mechanisms underlying the recurrent increase of calcium and PTH?possible mechanism could include recurrent of the diseases
in some studies also discussed the patients who had larger tumour might have high PTH levels after surgery
B. How would you approach this case?first would do imaging to evaluate if adenoma reoccur ,,
give active vitamin d , and sevelamer
if no response after 3 months , may operate again
What are the possible mechanisms underlying the recurrent increase of calcium and PTH?recurrent adenoma after subtotal parathyroidectomy or ectopic adenoma
How would you approach this case?single-radioisotope scintigraphy with technetium-99m (99mTc) combined with single-photon emission computed tomography (SPECT) imaging
Four-dimensional CT and MRI may have a more beneficial role in localizing ectopic glands after failed parathyroidectomy.
Trial of calcimimitics and non calcium containing phosphate binders then add vitamin d and vitamin d receptor activators after normalisation go serum phosphorus for 3 months
if no response, surgical intervention
Possible mechanism
Approach
It seems this patient has another source may be another site adenoma, so we need to localize by scintigraphy or SPECT PET, and intervene surgically. If not on cinacalcet, I will add it, if on a low dose, I will increase and reevaluate.
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH? subtotal parathyroidectomy with recurrent adenoma in the remaining glands or ectopic gland .
B. How would you approach this case? subtotal parathyroidectomy with recurrent adenoma in the remaining glands .
A- subtotal parathyroidectomy with recurrent adenoma in the remaining glands
B- sestamebi scan of parathyroid glands to exclude adenoma – pan CT to exclude malignancy – PTH related peptide level – 25 (OH) vit D assay
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
May be recurrence & hyperfunction of the remaining parathyroid gland recurrent hyperparathyroidism are: Dormant (sleeping) second parathyroid adenoma, also known as subordinate adenoma.
B. How would you approach this case?
Use U/S , sestemba scan, use calcimimetic drugs VDRA and and total parathyroidectomy surgery again if no improvement. Monitoring of s.ca and PTH.Control hyperphosphatemia by diet restriction and enhanced dialysis (increase time and high flux dialyser )
A. Subtotal parathyroidectomy or ectopic pt gland
B. Use sestemba scan, use calcimimetic drugs VDRA and surgery
A.What are the possible mechanisms underlying the recurrent increase of calcium and PTH? Subtotal or Total with re-implantation of part of the gland into either the forearm or sternocleidomastoid muscle
B.How would you approach this case? calcimimetics and VDRA, Re-consider surgery again if no improvement
THIS PATIENT HAS RECURENT HYPERPARATHYROIEDIM WITH HYPERCALCIMIA AND HYPERPHOSPHATEMIA , WE NEED TO GO FOR SESTAMIBI SCAN TO CONFIRM THE DIAGNOSES OF HYPERPARATHYROIDISM , WE CAN START PATIENT ON CALCIMEMETIC , NONCALCIUM BASED PHOSPHATE BINDER , DIALYSIS WITH LOW OR FREE CALCIUM IF POSSIBLE , MAY HE WILL NEEDS FOR SURGICAL INTERVENTION , BIPHOSPHANATE IV , CHECK FOR VIT D ALSO
A- the possible mechanism if underlying condition mostly recurrant parathyroid adenoma or hyperplasia in remnant parathyroid gland.
B- approach in these case we need sistamibi scan to detect the site of active gland .start cinacalcite and non ca containing po4 binder
the patient has recurrent hyperparathyroidism:
1- inadequet exploration and res,ection, 2- ectopic or supernumerary gland
3- parathyromatosis:occurs due to rupture of the capsule and escape of parathyroid cells
approach: 1st is localization of the lesoin by non-invasive methods or less likely invasive
non-invasive methods includde:us,Sestamibi scans. CT, AND MRI
THIS should be followed by redo parathyroidectomy
A. Disease recurrence in other Parathyroid tissues.
B. Nuclear studies, sonography. First , conservative treatment for 6 months with cincalcet and if failure then parathyreoidectomy
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
disease recurrence due to overgrowth of the remaining parathyroid tissue.
B. How would you approach this case?
US and sestimibi scan to detect and gland tissue
Cinacalcit and VDRA
Monitoring of s.ca and PTH.
A-
may be the recurrence of parathyroid adenoma of remaining parathyroid gland
B-i will order neck USS and sestamibi scan
review medications and hold alfacalcidol and calcium suplementations and use low calcium dialysate 1.25 mmol/l
control hyperphosphatemia by diet restriction and enhanced dialysis (increase time and high flux dialyser ) ,use non calcium based phosphate binder
surgical review .
a- possible mechanisms underlying the recurrent increase of calcium and PTH
over activity of the remaining parathyroid tissue post parathyroidectomy
start conservative medication
for suppression pth as cinacalcet
and re-assessment the condition
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
B. How would you approach this case?
A-Patient may have recurrence of hyperparathyroidism because surgery was subtotal, other parathyroid glands may have been suppressed by the active one, so it is difficult to see then during surgery, once the active one removed other PT glands can become active and hypertrophied
B-US scan, Sestamibi scan
A) -hyperplasia of remaining gland tissue if the surgery was sub total or hyperplasia of the implant
-missed retrosternal gland hyperplasia.
B)Re scan of the neck and retrosternal
consider cinacalcet as a line of treatment with non ca binding phosphate binder
What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
How would you approach this case?
Recurrent hyperparathyroidism should also make you think about Primary Hyperparathyroidism or part of a MEN Syndrome!
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?The explanation depends on the type of surgery:
Targeted parathyroidectomy(not all the hyperfunctioning parathyroid tissue has been removed)
Sub- or near-total parathyroidectomy(the remnant gland still active)
Total parathyroidectomy with autotransplantation(reactivation of implanted gland)
Total parathyroidectomy without autotransplantation(missing gland(s), retroesophageal and deep paratracheal spaces
B. How would you approach this case?Check the type of operation
send for alkaline phosphatase, 25-vit-D
sestamibi scan, U/S neck, possible CT scan
A.What are the possible mechanisms underlying the recurrent increase of calcium and PTH?-Approach to parathyrodiectomy may be either
B.How would you approach this case?
A. What are the possible mechanisms underlying the recurrent increase of calcium and PTH?
possible causes Dormant (sleeping) second parathyroid adenoma
B. How would you approach this case?neck ultrasound .
follow PTH ,Ca
24 h.urinary Ca