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Parathyroid adenoma

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  • 1. Parathyroid Adenoma Chou Chien-Wen M.D. Endocrine & Metabolism Section Chi-Mei Medical Center 10 Jan 2003

2. Case Report : 14347945 : X : 29-10-16 : 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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. 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 tertiar

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