Chapter 23 - Parathyroid Flashcards
Superior parathyroids derived from what?
4th pharyngeal pouch
Inferior parathyroids derived from what?
3rd pharyngeal pouch
Relation of superior parathyroids to surrounding structures?
- Lateral to RLNs
- Posterior surface of superior portion of thyroid
- Above inferior thyroid artery
Relation of inferior parathyroids to surrounding structures?
- Medial to RLNs
- More anterior than superior PT
- Below inferior thyroid artery
Most common ectopic location of inferior parathyroids?
Other locations?
Tail of the thymus.
Intrathyroid, mediastinal (anterior), near TE groove.
What % of patients have all 4 parathyroid glands?
90%
Blood supply to both superior and inferior parathyroids?
Inferior thyroid artery from thyrocervical trunk
Effects of PTH?
Increase serum Ca and decrease serum PO4 through kidneys and bones
- Increase kidney Ca reabsorpiton in DCT
- Decrease kidney PO4 absorption
- Increase Vit D production in kidney
- Increase osteoclasts: release Ca and PO4
How does vitamin D increase Ca?
Increases intestinal Ca and PO4 absorption by increasing Ca-binding protein
Effects of calcitonin?
Antagonistic to PTH - Decreases serum Ca
- Decrease bone Ca resorption (osteoclast inhibition)
- Increase urinary Ca and PO4 excretion
Normal PTH level?
5-40 pg/mL
Most common cause of hypoparathyroidism?
Previous thyroid surgery
What oncogene increases the risk for parathyroid adenomas?
PRAD-1
What causes primary hyperparathyroidism?
Autonomously high PTH
How is the diagnosis of primary hyperparathyroidism made?
- Increased Ca
- Decreased PO4
- Cl- to phos ratio >33
- Increased renal cAMP
- HCO3- secreted in urine
- Causes hyperchloremic metabolic acidosis
Acid-base disorder seen with primary hyperparathyroidism?
Hyperchloremic metabolic acidosis
What is the bone lesion characteristic of primary hyperparathyroidism?
Osteitis fibrosa cystica (brown tumors)
Caused by high turnover
Symptoms of primary hyperparathyroidism?
Think of hypercalcemia and hypophosphatemia symptoms
- Depression and mental status changes
- Pancreatitis
- Peptic ulcer disease
- Constipation, nausea/vomiting, anorexia
- Nephrolithiasis
- Muscle weakness and myalgia
- Bone pain and pathologic fractures
Indications for surgery for primary hyperparathyroidism?
- Ca >13 (psx w/ bone pain, AMS, GI sx)
- Decreased Cr clearance (increasing Cr on BMP), CrCL <60 ml/min
- 24 hr urinary Ca >400 (rules out FHH)
- Kidney stones (flank pain and XR findings)
- Silent nephrocalcinosis (imaging)
- Substantially decreased bone mass - osteoporosis (BMD test < -1 is osteopenia, < -2.5 is osteoporosis)
- Pathologic fracture
- Dx at age <50 yrs
% of patients with single adenoma?
80%
% of patients with multiple adenomas?
4%
% of patients with diffuse hyperplasia?
15%
MEN I or IIa pts have 4-gland hyperplasia
Treatment for parathyroid adenoma?
Resection
Inspect other glands to r/o hyperplasia or multiple adenomas
Treatment for parathyroid hyperplasia?
Do not biopsy all glands (risk hemorrhage)
Resect 3.5 glands or total parathyroidecomy and autoimplantation
Treatment for parathyroid adenocarcinoma?
Radical parathyroidectomy (with ipsilateral thyroid)
Ideal time for operation in pregnant patient for hyperparathyroid disease?
2nd trimester
Increased risk of stillbirth if not resected
Why draw intra-op PTH levels?
Helps determine if causative gland is removed
PTH should go to <1/2 the preop value
What is the half-life of PTH?
3-4 minutes
What is the most common location of a gland that was unable to be found on initial operation?
Normal anatomic position
Isthmus is MC ectopic location
What is postop hypocalcemia caused by following parathyroidectomy?
- Bone hunger (hx of osteitis fibrosa)
- Hypomagnesemia (diminishes PTH secretion, increases PTH resistance)
- Failure of parathyroid remnant or graft
Postop parathyroidectomy should have serum Ca levels monitored 2-4x/day, hypoMg corrected, PO Ca and vit D when they can swallow, IV Ca if they develop symptoms, dialysis if symptoms are severe.
What is the most common cause of persistent hyperparathyroidism?
Missed adenoma - 1%
Usually left in normal anatomic position, isthmus is MC ectopic location
Should have intraop PTH <1/2 of preop
What causes recurrent hyperparathyroidsim?
- New adenoma formation
- Tumor implants that have grown
- Recurrent parathyroid carcinoma
Bone hunger (or hungry bone syndrome) psx, dx, mgmt?
- Path: chronic bone dz (osteitis fibrosa), s/p parathyroidx
- Psx: tetany, seizures, arrhythmias, laryngeal spasm
- Dx: dec Ca - severe and prolonged; nl PTH; dec HCO3
- Tx: Vit D and Ca, fix hypoMg, avoid PO4 (can bind Ca and dec serum levels), IV Ca if symptoms, dialysis if severe
Aparathyroidism will show what lab values?
Decreased PTH, normal HCO3-
What is sestamibi-technetium-99 good for?
Preferential uptake by overactive parathyroid gland.
Good for picking up adenomas (not for hyperplasia).
Best for trying to pick up ectopic glands.
What patients show secondary hyperparathyroidism?
Renal failure. Leads to interferance with vit D metabolism, leading to decreased Ca absorption from GI tract.
Other causes are sprue, chronic vit D deficiency, aluminum toxicity seen in hemodialysis.
Usually will not develop hypercalcemia.
Lab values in secondary hyperparathyroidism?
Increased PTH in response to decreased Ca.
Treatment for secondary hyperparathyroidism?
Decrease PO4, supplement the hypocalcemia
- Control diet PO4
- PO4-binding gel
- decreased aluminum
- Ca supplement
- vitamin D/Ca in dialysate
When is surgery indicated for secondary hyperparathyroidism?
Bone pain (80-90% get relief); total parathyroidecomy with autotransplantation
What is tertiary hyperparathyroidism?
Renal disease has been corrected with transplant, but still overproduces PTH. Usually after longstanding secondary hyperparathyroidism.
Treatment of tertiary hyperparathyroidism?
Subtotal or total parathyroidectomy with autoimplantation
Lab values seen in familial hypercalcemic hypocalciuria?
High serum Ca, low urine Ca.
HyperCa 2/2 hyperPTH has elevated urine Ca.
What is the cause of familial hypercalcemic hypocalciuria?
Defect in PTH receptor in distal convoluted tubule of kidney; causes increased resorption of Ca
Treatment for familial hypercalcemia hypocalciuria?
Nothing. Ca generally not that high; NO parathyroidectomy.
What is pseudohypoparathyroidism caused by?
Defect in PTH receptor in kidney, does not respond to PTH
5-year survival for parathyroid cancer?
50% 5 year survival
Lab values in parathyroid cancer?
High Ca, PTH, and alkaline phosphatase
Most common site of mets from parathyroid cancer?
Lung
% of patients with parathyroid cancer recurrence?
50% (same as 5 yr survival rate)
What are the tumors of MEN syndromes derived from?
APUD cells
Inheritance of MEN syndromes?
Autosomal dominant, 100% penetrance, variable expressivity
Tumors associated with MEN I?
- Parathyroid hyperplasia (usually 1st to become symptomatic)
- Pancreatic islet cell tumors
- Pituitary adenoma (usually prolactinoma)
- Correct hyperparathyroidism 1st (hyperCa exacerbates sx of panc NETs)
- 70% have pancreas tummors - most commonly gastrinoma (insulinoma in general population)
Tumors associated with MEN IIa?
- Parathyroid hyperplasia
- Pheochromocytoma
- Medullary cancer of thyroid (ppx resection early)
- Correct pheo first
1 cause of death in MEN IIa/IIb?
Medullary thyroid cancer
Do ppx thyroidectomy early in life
Tumors associated with MEN IIb?
- Pheochromocytoma
- Medullary cancer of thyroid
- Mucosal neuromas
- Marfan’s habitus
- Musculoskeletal abnormalities
Gene mutation associated with MEN I?
MENIN gene on chromosome 11q13
Gene mutation associated with MEN II?
RET proto-oncogene on chromosome 10
Other causes of hypercalcemia?
- Malignancy
- Hyperthyroidism
- Immobilization
- Granulomatous disease
- Excess vitamin D
- Milk-alkali syndrome
- Thiazide diuretics
MOA of midramycin?
Inhibits osteoclasts (used with malignancies or failure of conventional treatment); has hematologic, liver, renal side effects
What causes a hypercalcemic crisis? Treatment?
Usually secondary to another surgery
Excretion: furosemide and dialysis
What’s the next test after detecting hypercalcemia on routine lab testing?
PTH
What if elevated PTH is found with normocalcemia? What needs to be ruled out before establishing diagnosis of primary hyperparathyroidism?
vit D deficiency, familial hypercalcemic hypocalciuria
In a patient with parathyroid carcinoma, what is a good marker for local recurrence or metastasis?
- Recurrent hypercalcemia
- 50% recur/persist
Patients with renal hyperPTH can develop what skin condition?
Calciphylaxis - precipitation of calcium and phosphorus. Can cause necrosis leading to sepsis from infection.
How do you treat calciphylaxis?
If no emergent operation is needed (necrotic skin infection), then do parathyroidectomy.
What do you do for parathyroid carcinoma found incidentally?
Complete an en block resection, which can include thyroid, RLN.
Prophylactic neck dissection is not useful.
What is the workup once PHPT is revealed?
- serum calcium
- PTH
- ALP (demonstrates bone turnover)
- 24 hr urinary calcium (rule out FHH)
- 25-OH vit D (rule out vit def)
- US
- sestamibi scan
What is the workup for an identified MEN1 patient?
- serum calcium
- serum gastrin
- pancreatic popypeptide levels
- fasting blood glucose
- serum prolactin
- visual field testing
- head imaging
Recommendations for surgery in asymptomatich PHPT?
What do you do with local recurrence and localized distant metastasis for parathyroid carcinoma?
Surgery. Chemo and radiation is not efficacious and is only used palliatively.
