Parathyroid adenoma


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Parathyroid adenoma

  1. 1. Parathyroid Adenoma Chou Chien-Wen M.D. Endocrine & Metabolism Section Chi-Mei Medical Center 10 Jan 2003
  2. 2. Case Report  病歷號碼 : 14347945  姓名 : 黃 X 芷  出生日期 : 29-10-16  性別 : 女
  3. 3. Present Illness & Past History  62-year-old female, general twitching, painful sensation bothered her for months.  Gout (+), HTN (+)  Operation history: • (1)R't renal stone s/p ESWL (1993 Sep) • (2)Fail back surgery syndrome with HIVD with stenosis of L4-5 s/p disectomy of L5-S1 & laminectomy of L4-5 & L5-S1 (91-07-17) • (3)HIVD with lumbar stenosis of L4-5, left s/p disectomy with laminectomy of L4-5 (91-08-28)
  4. 4. Laboratory Data:  BUN/Cr: 22.8/1.17 (91-12-12)  Na/K: 138.1/4.72 (91-12-12)  Serum Ca: • 13.7 (91-11-18) • 11.6 (91-12-14) • 12.3 (91-12-30) • 8.8 (92-01-02) postoperation  Free-Ca: 5.6 (91-12-18)  P: 2.7 (91-12-3)  Alk P-tase: 216 (91-12-3)  i-PTH 223.7 pg/ml (91-12-2)
  5. 5. Operation & Pathology  Operation • Parathyroidectomy, right • Partial central LNs dissection  Pathology • Parathyroid adenoma, right lower parathyroid gl &, parathyroidectomy • Nodular goiter, bilateral thyroid, bilateral subtotal thyroidectomy
  6. 6. Introduction  The estimated incidence is 1 case per 1000 men & 2 to 3 cases per 1000 women.  The severe complications of hyperparathyroidism, osteitis fibrosa cystica & nephrocalcinosis, are rarely seen today.  Distinguishing primary hyperparathyroidism from malignancy, the next most common cause of hypercalcemia,  Minimally invasive surgery is now available, in addition to standard bilateral neck exploration, as curative therapy for primary hyperparathyroidism. (Mayo Clinic Proceedings Volume 77(1) January 2002 pp 87-91)
  7. 7. Etiologic Factors & Pathogenesis (1)  Sporadic, benign parathyroid adenomas 80%-85% • Postmenopausal women, average age of 55 years  External neck irradiation  Lithium therapy 5% • Multiple parathyroid glands may be abnormal, & hyperparathyroidism may persist after discontinuation of the drug.  Hereditary disorders 10%, including familial hyperparathyroidism or MEN type 1 & 2A & hyperparathyroidism-jaw tumor syndrome.  MEN 1 95% • present at a younger age, more severe disease • Associated tumors include pancreatic (30%-80%) & pituitary (15%-50%) adenomas. • The gene responsible for MEN 1, menin (chromosome 11), has been identified & cloned with tumor suppressor function.
  8. 8. Etiologic Factors & Pathogenesis (2)  MEN 2A • A milder form, resection of only enlarged glands compared to subtotal resections in patients with other forms of multigland disease. • MCT is a universal component of this syndrome. • Pheochromocytoma 50% & primary hyperparathyroidism 10%. • Mutations of the ret proto-oncogene.  Hyperparathyroidism-jaw tumor syndrome • Early, relatively severe hypercalcemia in teenagers or young adults is the common presentation. • The pathologic finding is usually a single adenoma. Bone lesions of the jaw appear as cystic punched-out regions on x-ray films. • Frequent association with Wilms tumors or renal cysts. • A familial disorders
  9. 9. Etiologic Factors & Pathogenesis (3)  Parathyroid carcinoma < 0.5% of cases • Severe hypercalcemia, extremely high PTH levels, a palpable neck mass.  Benign familial hypocalciuric hypercalcemia (FHH) • an autosomal dominant disorder, hypercalcemia & relative hypocalciuria. • The degree of hypercalcemia is generally mild. Normal PTH levels but in 5% to 10% of patients, modestly elevated. • Most kindreds have an inactivating mutation of Ca sensing receptor, resulting in a mild increase in the set point for Ca suppression of PTH secretion. • The Ca clearance-Cr clearance ratio with a cutoff of .01 distinguishing from primary hyperparathyroidism. • This disorder results in hypercalcemia at birth • Surgery or further medical evaluation is not indicated because it is a benign condition without progressive complications.
  10. 10. Etiologic Factors & Pathogenesis (4)  Insufficient Vit D &/or insufficient Ca intake • Mild secondary hyperparathyroidism • Normal serum Ca level & an elevated PTH level • Measurement of 25-hydroxyvitamin D & 24-hour urinary Ca level is helpful • Such patients often have intermittent elevations of ionized Ca levels with documented stone disease &/or osteoporosis.  ESRD • most common cause of secondary hyperparathyroidism. • PTH secretion is stimulated by hypocalcemia, which results from low concentrations of 1,25-dihydroxy-vitamin D due to decreased renal production, & by hyperphosphatemia. • Prevention with supplementation with 1,25-dihydroxyvitamin D & Ca & control of hyperphosphatemia  Tertiary hyperparathyroidism • Prolonged abnormalities can evolve into a state of autonomous PTH secretion & hypercalcemia,
  11. 11. Evaluation  The total Ca level can be "corrected" by adding 0.8 mg/dL for every 1.0 g/dL by which the serum albumin concentration is lower than 4.0 g/dL.  All patients will have increased ionized Ca levels.  Hypercalcemia, an elevated or inappropriately high-normal PTH level is diagnostic  Malignancy is associated with suppressed levels of PTH.  Modern intact PTH assays have no cross-reactivity with PTH-related protein.  FHH: in young patients with mild hypercalcemia & normal or slightly elevated PTH levels.  The urinary Ca clearance-Cr clearance ratio, previous Ca levels, & family history are helpful.  Evaluation for other endocrine disorders associated with one of the MEN syndromes  Appropriate genetic testing for MEN  BMD is usually measured, cortical sites such as the distal one-third radius.  A 24-hour urinary Ca measurement & radiological evaluation for the presence of kidney stones
  12. 12. Radiographic manifestations of PHP. A=subperiosteal resorption of radial side of middle phalanges & distal turfs; B="Brown tumour" (arrow) in the proximal tibia; C=resorption & tapering of distal clavicle D=cystic changes in head of humerus
  13. 13. Technetium-99m sestamibi/iodine scans in planar (A), coronal (B), & sagittal (C) views. A=increased uptake of the radiotracer in right lower parathyroid adenoma & thyroid in early image (after 20 min) B=after 2 h, concentration of radiotracer in parathyroid adenoma with disappearance of thyroid uptake C=confirms concentrations in parathyroid adenoma
  14. 14. Management (1)  Institution of therapy for hypercalcemia depends on the degree of hypercalcemia & the presence or absence of clinical symptoms.  Mild hypercalcemia usually have no symptoms, require no Ca-lowering agents  Moderate hypercalcemia & symptoms probably benefit from hypocalcemic agents.  Severe hypercalcemia require hospitalization & therapy.  The combination of altered mental status, anorexia, nausea, & defective urine-concentrating ability results in dehydration. Iv fluids are the initial therapy for severe hypercalcemia.  Diuretic therapy with furosemide (20 mg) should not be instituted until euvolemia is achieved.  Correction of fluid deficits alone can produce a decrease in the Ca level but rarely restores normocalcemia
  15. 15. Management (2)  Hypocalcemic agents, calcitonin (4-8 IU/kg im or sc q 6-8 hrs) has the most rapid onset of action.  Resistance to its hypocalcemic effects develops & limits its use to 24 to 48 hrs of therapy.  Calcitonin alone rarely normalizes serum Ca levels but is useful in addition to bisphosphonates.  Iv bisphosphonate therapy with pamidronate (60-90 mg)  The onset of action for pamidronate is 24 to 48 hours after infusion, with nadir Ca at about 7 days.  Duration of treatment effect varies from weeks to months.  Plicamycin, gallium nitrate, & etidronate, used in the past to treat severe hypercalcemia are rarely used today.  H/D in severe hypercalcemia with impaired renal function.
  16. 16. Management (3)  Glucocorticoids: hypercalcemia due to lymphoma or granulomatous diseases but have no role in managing hypercalcemia due to hyperparathyroidism.  Treating the underlying cause of hypercalcemia is necessary.  Ca sensing receptor agonists (calcimimetics) have been studied in a small number of patients but are not available clinically.  Estrogen replacement therapy for postmenopausal women can attenuate bone resorption & results in modest reduction in serum Ca levels.  Older bisphosphonates did not sustain reductions in serum Ca levels.  Surgery is the only curative therapy for primary hyperparathyroidism
  17. 17. Management (4)  Up to 25% of patients develop an indication for surgery during medical observation.  Increases in BMD of both the hip & the spine after surgical cure of hyperparathyroidism  Avoidance of drugs that could worsen hypercalcemia, especially thiazides.  Modest Ca intake is generally recommended because low Ca intake could theoretically stimulate more PTH production.  Estrogen therapy can be considered in postmenopausal women.  Yearly measurement of bone density, 24-hour urinary Ca values, & serum Ca levels is advised, as is monitoring for nephrolithiasis.  Preventing tertiary hyperparathyroidism by controlling serum phosphate levels, replacing 1,25-dihydroxyvitamin D, & maintaining Ca levels to decrease stimulation of PTH secretion & parathyroid gland growth.
  18. 18. Management (5)  The doses of calcitriol needed to suppress serum PTH levels can lead to hypercalcemia or hyperphosphatemia.  New vitamin D analogues, 22-oxacalcitriol, 19-nor-1,25-dihydroxyvitamin D2 (paricalcitol), & 1-alpha-hydroxyvitamin D2 (doxercalciferol), have the advantages of suppressing PTH & a reduced tendency to increase serum Ca & phosphate levels  After tertiary hyperparathyroidism has developed, calcitriol must be used carefully because it can worsen hypercalcemia.  Sevelamer is a polymer-based phosphate binder that can be used in place of Ca-based phosphate binders to decrease hyperphosphatemia in patients with hypercalcemia.  Surgery is often necessary to control hypercalcemia in patients with tertiary hyperparathyroidism.  Indications for surgery in secondary hyperparathyroidism due to renal failure include severe metabolic bone disease (renal osteodystrophy, fractures), intractable bone pain & pruritis, & rarely necrotizing skin ulcers (calciphylaxis) not responding to dialysis & medical therapy.
  19. 19. Surgery (1)  An experienced endocrine surgeon cures > 95% undergoing initial bilateral neck exploration & incurs < 1% perioperative morbidity.  Reoperations for persistent or recurrent primary hyperparathyroidism are less successful (about 80% cure) & much higher incidence of complications.  25% of patients remained either hypercalcemic (13%) or permanently hypocalcemic (12%), a reflection of previously failed procedures.  Preoperative localization of the abnormal parathyroid gland(s) is unnecessary for initial bilateral neck exploration.  In patients who have had prior neck surgery, preoperative localization is essential because scar tissue & altered anatomy make surgical exploration more challenging.  Sestamibi imaging of the parathyroid gland has the best specificity & sensitivity (90%-95% & 80%-85%, respectively)  In sporadic cases of primary hyperparathyroidism, a single adenomatous gl & is usually found & removed.
  20. 20. A New, Practical Intraoperative Parathyroid Hormone Assay (1)  PTH measurement by immuno-chemiluminometric assay (ICMA) is a nonradioisotopic technique that is more practical for use during parathyroidectomy.  Sixteen patients had multiple samples taken during parathyroidectomy.  PTH levels measured 5 minutes after excision of a suspected abnormal gland were compared with pre- operative or preexcision samples & either confirmed complete excision or indicated the need for more exploration in each patient.  Correlation of 88 ICMA samples with standard 24-hour IRMA controls was excellent (r equals 0.9218, P <0.0001).  The sensitivity of the test in predicting postoperative Ca levels was 94 percent. (American Journal of Surgery Volume 168(5) November 1994 pp 466-468)
  21. 21. Intraoperative monitoring (with immunochemiluminometric assay ICMA) identified 11 patients with single-gland involvement by a marked decrease in intraoperative (QPTH) levels after excision. Four patients who had minimal decreases in (PTH) required excision of a second hyperfunctioning gland before an adequate decrease in PTH predicted a return to normocalcemia. One patient with an unusual tumor had a delayed (20 min) fall in QPTH.
  22. 22. Surgery (2)  Hereditary & multigland disease, more aggressive initial surgery is performed, usually a subtotal or a total parathyroidectomy with autotransplantation.  Recurrence of primary hyperparathyroidism due to remnant gland or autotransplanted tissue is common in patients with MEN 1 & renal failure.  Because of improvements in preoperative localization imaging of the parathyroid glands with sestamibi scintigraphy & high-resolution ultrasonography coupled with intraoperative rapid PTH assay, minimally invasive techniques are feasible.  Minimally invasive parathyroidectomy refers to one of several procedures, including video-assisted or endoscopic, radioguided, & unilateral image-guided explorations.  Abnormal parathyroid gland must be located preoperatively on imaging studies, usually sestamibi imaging.  Patients with known or suspected multigland disease or prior neck surgery are not generally candidates for this procedure.  Cure rates are no better than those with traditional bilateral neck exploration.  Improved cosmetic appearance, less pain, & shorter operative time.  Procedures performed with local anesthesia are associated with fewer GI adverse effects.
  23. 23. Minimal InvasiveAdenectomy (Ann of Surgery Volume 231(4) April 2000 pp 559-565)
  24. 24. Changes in the pattern of clinical presentation of primary hyperparathyroidism
  25. 25. Indications for surgery in asymptomatic patients with hyperparathyroidism (1) serum Ca level > 1 mg/dL above reference range (2) any complications such as nephrolithiasis or bone disease (3) an episode of life-threatening hypercalcemia (4) severe hypercalciuria (>400 mg/24 h) (5) reduced bone mass, especially of distal radius (T score less than -2) (6) age younger than 50 years
  26. 26. Role of surgery in mild primary hyperparathyroidism in the elderly  The usual reasons for advising surgery in an 'asymptomatic' or minimally symptomatic patient are to prevent complications such as nephrolithiasis, deterioration in renal function, accelerated bone loss and fracture  Elderly patients with primary HPT present more often with indistinct psychiatric and musculoskeletal symptoms, and these are the symptoms most likely to be improved by operation  Morbidity and mortality rates related to neck exploration in the elderly are similar to those in younger age groups (British Journal of Surgery Volume 87(12) December 2000 pp 1640-1649)
  27. 27. Success of Cervical Exploration for Patients with Asymptomatic Primary Hyperparathyroidism  61 patients were identified. 19 (31%) had no symptoms, 21 (34%) had subjective symptoms, & 21 had associated conditions  Average preop & postop Ca levels were 11.5 mg% & 8.5 mg%, respectively.  Average PTH levels fell from 142 pg/mL to 49 pg/mL after surgery.  Preop & postop Ca & PTH levels for the three groups showed no significant differences.  The success of surgery in identifying pathology ranged from 90.5% to 95%, & again showed no difference among the three groups.  Long-term morbidity (>6 months) in all groups was 0%.  Cervical exploration & parathyroidectomy for asymptomatic primary hyperparathryoidism is safe & has similar success rates in identifying pathology & correcting biochemical abnormalities compared with patients with symptomatic disease. ( Am J Surg. 1999;177:69-74).( Am J Surg. 1999;177:69-74).
  28. 28. Ethanol Ablation  The abnormal parathyroid gland(s) must be detectable by ultrasonography & confirmed by fine-needle aspiration for cytology & PTH measurement before this approach.  Large parathyroid adenomas are difficult to cure by ethanol injection.  Patients who have undergone a subtotal parathyroidectomy for multigland disease & have recurrent hyperparathyroidism due to the remnant gland are c&idates for ethanol ablation.  Hypoparathyroidism & recurrent laryngeal nerve damage are rarely seen.  Cure rates are much lower than those with surgery.
  29. 29. Angiographic Ablation of Mediastinal Parathyroid Adenomas  3 patients with likely mediastinal parathyroid adenomas that had single feeding arteries underwent attempted arteriographic ablation with a slow continuous infusion of contrast medium.  All 3 patients were cured (follow-up 22 to 68 months) with no long-term complications. (American of medicine Volume 97(6) December 1994 pp 529-534)