parathyroid-adenoma2719

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Parathyroid Adenoma

Chou Chien-Wen M.D.

Endocrine & Metabolism Section

Chi-Mei Medical Center10 Jan 2003


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Case Report : 14347945

:X

: 29-10-16

:


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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)


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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)


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Operation & Pathology

Operation

Parathyroidectomy, right

Partial central LNs dissection

Pathology

Parathyroid adenoma, right lower parathyroid

gl &, parathyroidectomy

Nodular goiter, bilateral thyroid, bilateral

subtotal thyroidectomy


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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 ofhypercalcemia,

Minimally invasive surgery is now available, in addition to

standard bilateral neck exploration, as curative therapyfor primary hyperparathyroidism.

(Mayo Clinic Proceedings Volume 77(1) January 2002 pp 87-91)


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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 maypersist after discontinuation of the drug.

Hereditary disorders 10%, including familial hyperparathyroidism orMEN 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 beenidentified & cloned with tumor suppressor function.


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Etiologic Factors & Pathogenesis (2) MEN 2A

A milder form, resection of only enlarged glands compared tosubtotal resections in patients with other forms of multiglanddisease.

MCT is a universal component of this syndrome.

Pheochromocytoma 50% & primary hyperparathyroidism 10%.

Mutations of the retproto-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


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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 fromprimary 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.


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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 withdocumented stone disease &/or osteoporosis.

ESRD

most common cause of secondary hyperparathyroidism.

PTH secretion is stimulated by hypocalcemia, which results from lowconcentrations 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 PTHsecretion & hypercalcemia,


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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 isdiagnostic

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 elevatedPTH levels.

The urinary Ca clearance-Cr clearance ratio, previous Ca levels, & familyhistory are helpful.

Evaluation for other endocrine disorders associated with one of the MENsyndromes

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 thepresence of kidney stones


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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


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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


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Management (1)

Institution of therapy for hypercalcemia depends on the degree ofhypercalcemia & the presence or absence of clinical symptoms.

Mild hypercalcemia usually have no symptoms, require no Ca-loweringagents

Moderate hypercalcemia & symptoms probably benefit fromhypocalcemic agents.

Severe hypercalcemia require hospitalization & therapy.

The combination of altered mental status, anorexia, nausea, &defective urine-concentrating ability results in dehydration. Iv fluids arethe initial therapy for severe hypercalcemia.

Diuretic therapy with furosemide (20 mg) should not be instituted untileuvolemia is achieved.

Correction of fluid deficits alone can produce a decrease in the Calevel but rarely restores normocalcemia


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Management (2)

Hypocalcemic agents, calcitonin (4-8 IU/kg im or sc q 6-8 hrs) has themost rapid onset of action.

Resistance to its hypocalcemic effects develops & limits its use to 24to 48 hrs of therapy.

Calcitonin alone rarely normalizes serum Ca levels but is useful inaddition 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 treatsevere hypercalcemia are rarely used today.

H/D in severe hypercalcemia with impaired renal function.


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Management (3)

Glucocorticoids: hypercalcemia due to lymphoma orgranulomatous diseases but have no role in managinghypercalcemia due to hyperparathyroidism.

Treating the underlying cause of hypercalcemia is necessary.

Ca sensing receptor agonists (calcimimetics) have been studiedin a small number of patients but are not available clinically.

Estrogen replacement therapy for postmenopausal women canattenuate bone resorption & results in modest reduction inserum Ca levels.

Older bisphosphonates did not sustain reductions in serum Calevels.

Surgery is the only curative therapy for primaryhyperparathyroidism


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Management (4)

Up to 25% of patients develop an indication for surgery during medicalobservation.

Increases in BMD of both the hip & the spine after surgical cure ofhyperparathyroidism

Avoidance of drugs that could worsen hypercalcemia, especiallythiazides.

Modest Ca intake is generally recommended because low Ca intakecould 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, & maintainingCa levels to decrease stimulation of PTH secretion & parathyroidgland growth.


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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-dihydroxyvitaminD2 (paricalcitol), & 1-alpha-hydroxyvitamin D2 (doxercalciferol), have theadvantages 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 inplace of Ca-based phosphate binders to decrease hyperphosphatemia inpatients with hypercalcemia.

Surgery is often necessary to control hypercalcemia in patients withtertiary hyperparathyroidism.

Indications for surgery in secondary hyperparathyroidism due to renalfailure include severe metabolic bone disease (renal osteodystrophy,fractures), intractable bone pain & pruritis, & rarely necrotizing skin ulcers(calciphylaxis) not responding to dialysis & medical therapy.


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Surgery (1) An experienced endocrine surgeon cures > 95% undergoing initial

bilateral neck exploration & incurs < 1% perioperative morbidity.

Reoperations for persistent or recurrent primary hyperparathyroidismare less successful (about 80% cure) & much higher incidence ofcomplications.

25% of patients remained either hypercalcemic (13%) orpermanently hypocalcemic (12%), a reflection of previously failedprocedures.

Preoperative localization of the abnormal parathyroid gland(s) isunnecessary for initial bilateral neck exploration.

In patients who have had prior neck surgery, preoperative

localization is essential because scar tissue & altered anatomy makesurgical 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 singleadenomatous gl & is usually found & removed.


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A New, Practical Intraoperative Parathyroid

Hormone Assay (1)

PTH measurement by immuno-chemiluminometric assay(ICMA) is a nonradioisotopic technique that is more practicalfor 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 confirmedcomplete excision or indicated the need for moreexploration in each patient.

Correlation of 88 ICMA samples with standard 24-hourIRMA controls was excellent (r equals 0.9218, P


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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.


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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 orautotransplanted tissue is common in patients with MEN 1 & renal failure.

Because of improvements in preoperative localization imaging of theparathyroid glands with sestamibi scintigraphy & high-resolution

ultrasonography coupled with intraoperative rapid PTH assay, minimallyinvasive techniques are feasible.

Minimally invasive parathyroidectomy refers to one of several procedures,including video-assisted or endoscopic, radioguided, & unilateral image-guidedexplorations.

Abnormal parathyroid gland must be located preoperatively on imaging studies,usually sestamibi imaging.

Patients with known or suspected multigland disease or prior neck surgery arenot 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 GIadverse effects.


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Minimal InvasiveAdenectomy

(Ann of Surgery Volume 231(4) April 2000 pp 559-565)


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Changes in the pattern of clinical

presentation of primary hyperparathyroidism


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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


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Role of surgery in mild primary

hyperparathyroidism in the elderly

The usual reasons for advising surgery in an'asymptomatic' or minimally symptomatic patient are toprevent 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, andthese are the symptoms most likely to be improved byoperation

Morbidity and mortality rates related to neck exploration inthe elderly are similar to those in younger age groups

(British Journal of Surgery Volume 87(12) December 2000 pp 1640-1649)


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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 nosignificant differences.

The success of surgery in identifying pathology ranged from90.5% to 95%, & again showed no difference among the threegroups.

Long-term morbidity (>6 months) in all groups was 0%. Cervical exploration & parathyroidectomy for asymptomatic

primary hyperparathryoidism is safe & has similar success ratesin identifying pathology & correcting biochemical abnormalitiescompared with patients with symptomatic disease.

( Am J Surg. 1999;177:69-74).


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Ethanol Ablation

The abnormal parathyroid gland(s) must be detectable byultrasonography & confirmed by fine-needle aspiration forcytology & PTH measurement before this approach.

Large parathyroid adenomas are difficult to cure byethanol injection.

Patients who have undergone a subtotalparathyroidectomy for multigland disease & haverecurrent hyperparathyroidism due to the remnant glandare c&idates for ethanol ablation.

Hypoparathyroidism & recurrent laryngeal nerve damageare rarely seen.

Cure rates are much lower than those with surgery.


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Angiographic Ablation of Mediastinal

Parathyroid Adenomas

3 patients with likely mediastinal parathyroidadenomas that had single feeding arteries

underwent attempted arteriographic ablationwith a slow continuous infusion of contrastmedium.

All 3 patients were cured (follow-up 22 to 68months) with no long-term complications.

(American of medicine Volume 97(6) December 1994 pp 529-534)

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