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Parathyroid SurgeryParathyroid Surgery

David Goldenberg MD, FACS David Goldenberg MD, FACS Professor of Surgery and OncologyProfessor of Surgery and Oncology

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AAO-HNSF/AHNS SISSON SYMPOSIUM

Review Course for Residents & Fellows

September 28th 2013

•• HistoryHistory

•• Anatomy and embryologyAnatomy and embryology

•• Calcium physiology Calcium physiology

•• HyperparathyroidismHyperparathyroidism

•• Diagnosis and clinical Diagnosis and clinical

featuresfeatures

•• Localization techniquesLocalization techniques

•• SurgerySurgery

•• Complications and followComplications and follow--

up up

•• Questions you may see on Questions you may see on

teststests

HistoryHistory• In 1852, Sir Richard Owen first described the parathyroid

glands while performing necropsy on an indian rhinoceros

• In 1879, Sandström described human parathyroids(glandulaeparathyroidae ))

• In 1891, von Recklinghausen described osteitis fibrosacystica, but its association with hyperparathyroidism (HPT) was not reported until 1904, when Ashkanazy described the bony lesions in a patient with a parathyroid tumor

• Calcium measurement possible in 1909 and association with parathyroids established

• In 1925, Mandl performed the first parathyroidectomy in Vienna. (38 yr old man with severe bone pain secondary to osteitis fibrosa cystica)The patient was initially symptom free but developed recurrent bone problems 6 years later

• In 1926, the first parathyroidectomy in the United States was performed at Massachusetts General Hospital in a patient who had 5 subsequent surgeries, including a thyroidectomy, until an ectopic gland was removed from the superior mediastinum

• In 1934, Albright reported on the association between parathyroid disease and chronic renal failure

• 1977 Nobel prize for sequencing of parathyroid hormone

AnatomyAnatomy

•• Usually Usually derive most of blood derive most of blood

supply from branches of inferior supply from branches of inferior

thyroid artery, although branches thyroid artery, although branches

from superior thyroid supply at from superior thyroid supply at

least 20% of upper least 20% of upper glandsglands

•• Glands drain Glands drain ipsilaterallyipsilaterally by by

superior, middle, and inferior superior, middle, and inferior

thyroid thyroid veinsveins

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•• The superior parathyroid glands are The superior parathyroid glands are

most commonly located in the most commonly located in the

posterolateralposterolateral aspect of the superior aspect of the superior

pole of the thyroid gland at the pole of the thyroid gland at the

cricothyroidalcricothyroidal cartilage junction. cartilage junction.

•• They are most commonly found 1 cm They are most commonly found 1 cm

above the intersection of the inferior above the intersection of the inferior

thyroid artery and the recurrent thyroid artery and the recurrent

laryngeal nerve laryngeal nerve

•• The inferior parathyroid glands are The inferior parathyroid glands are

more variable in location and are most more variable in location and are most

commonly found near the lower commonly found near the lower

thyroid pole of the thyroid.thyroid pole of the thyroid.

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Superior glands usually dorsal to the

RLN at level of cricoid cartilage

Inferior glands located ventral to nerve

Parathyroid Embryology Parathyroid Embryology

•• The The PTH glands PTH glands develop at 6 weeks develop at 6 weeks and migrate caudally at 8 and migrate caudally at 8 weeksweeks

•• The The superior superior PTH glands develop PTH glands develop with the thyroid gland from the with the thyroid gland from the fourth fourth branchialbranchial pouch and are pouch and are generally consistent in position, generally consistent in position, residing lateral and posterior to the residing lateral and posterior to the upper pole of the thyroid at the upper pole of the thyroid at the level of the level of the cricothyroidcricothyroid cartilagecartilage

•• The The inferior inferior PTH glands descend PTH glands descend with the thymus from the third with the thymus from the third branchialbranchial pouchpouch

HistologyHistology

•• The four The four PTH glands are composed PTH glands are composed mostly of chief cells mostly of chief cells

and and oxyphiloxyphil cells within an adipose cells within an adipose stromastroma

•• Chief Chief cells in the cells in the PTH glands PTH glands secrete PTH, an 84secrete PTH, an 84––amino amino

acid protein, whenever serum calcium levels acid protein, whenever serum calcium levels fallfall

•• Almost all of the Almost all of the PTH PTH is synthesized and secreted by is synthesized and secreted by

the chief cells. The function of the the chief cells. The function of the oxyphiloxyphil cells is cells is

uncertain uncertain (modified or depleted chief cells that no longer

secrete PTH??)

•• PTH PTH binds to its peripheral receptors and stimulates binds to its peripheral receptors and stimulates

osteoclasts to increase bone osteoclasts to increase bone resorptionresorption, to the kidney , to the kidney

to increase calcium to increase calcium resorptionresorption and renal production of and renal production of

1,251,25--dihydroxyvitamin Ddihydroxyvitamin D33 (1,25[OH](1,25[OH]22DD33), and to the ), and to the

intestine to increase absorption of calcium and intestine to increase absorption of calcium and

phosphate. phosphate.

•• All togetherAll together, these processes raise the serum calcium , these processes raise the serum calcium

levellevel

Calcium physiology Calcium physiology

• PTH-calcium feedback loop that controls calcium homeostasis

• Four organs—the parathyroid glands, intestine, kidney, and bone—together determine the parameters of calcium homeostasis

• PTH secretion also is stimulated by low levels of 1,25-dihydroxy vitamin D, catecholamines, and hypomagnesemia

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Primary HyperparathyroidismPrimary Hyperparathyroidism

•• Affects approximately 100,000 patients a Affects approximately 100,000 patients a yearyear

•• Primary Primary hyperparathyroidism occurs in 0.1 to 0.3% of the general population hyperparathyroidism occurs in 0.1 to 0.3% of the general population and is more common in women (1:500) than in men (1:2000and is more common in women (1:500) than in men (1:2000))

•• Primary hyperparathyroidism is characterized by increased parathyroid cell Primary hyperparathyroidism is characterized by increased parathyroid cell proliferation and PTH secretion which is independent of calcium proliferation and PTH secretion which is independent of calcium levelslevels

•• The The most common cause of primary hyperparathyroidism is a sporadic, single most common cause of primary hyperparathyroidism is a sporadic, single

parathyroid parathyroid adenomaadenoma resulting resulting from a clonal mutation from a clonal mutation (~85(~85--95%)95%)

•• Less Less common are parathyroid common are parathyroid hyperplasia hyperplasia (~2.5%), parathyroid carcinoma (~2.5%), parathyroid carcinoma

(malignant tumor), and adenomas in more than one gland (together ~0.5%).(malignant tumor), and adenomas in more than one gland (together ~0.5%).

•• Primary Primary hyperparathyroidism is also a feature of several familial endocrine hyperparathyroidism is also a feature of several familial endocrine

disorders: disorders: MEN MEN type 1 and MEN type type 1 and MEN type 2A, 2A, and familial hyperparathyroidism.and familial hyperparathyroidism.

Secondary Hyperparathyroidism Secondary Hyperparathyroidism

•• When HPT is seen in the setting of chronic renal failure, it is termed When HPT is seen in the setting of chronic renal failure, it is termed secondary secondary HPTHPT

•• 9090% of patients with chronic renal failure have % of patients with chronic renal failure have some evidence some evidence of secondary HPTof secondary HPT

•• Failing kidneys do not convert enough vitamin D to its active form, and they do not Failing kidneys do not convert enough vitamin D to its active form, and they do not

adequately excrete phosphate. When this happens, insoluble calcium phosphate forms adequately excrete phosphate. When this happens, insoluble calcium phosphate forms

in the body and removes calcium from the in the body and removes calcium from the circulationcirculation

•• Secondary hyperparathyroidism can also result from Secondary hyperparathyroidism can also result from malabsorptionmalabsorption (chronic (chronic

pancreatitis, small bowel disease, pancreatitis, small bowel disease, malabsorptionmalabsorption--dependent bariatric surgery) in that dependent bariatric surgery) in that

the fat soluble vitamin D can not get reabsorbed.the fat soluble vitamin D can not get reabsorbed.

•• With With prolonged stimulation of the prolonged stimulation of the parathyroidsparathyroids, a disorder termed , a disorder termed tertiary HPTtertiary HPT

chronic chronic renal failure or those with longrenal failure or those with long--standing secondary HPT who undergo kidney standing secondary HPT who undergo kidney

transplantationtransplantation. . Autonomous Autonomous hyperfunctionhyperfunction develops and the develops and the parathyroidsparathyroids no longer no longer

respond respond to to calcium calcium feedback inhibition, which results in feedback inhibition, which results in hypercalcemiahypercalcemia..

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Diagnosis and clinical featuresDiagnosis and clinical features

Differential Diagnosis of Hypercalcemia*

ParathyroidPrimary hyperparathyroidism: Sporadic, Familial

Nonparathyroid EndocrineThyrotoxicosis

Pheochromocytoma

Acute adrenal insufficiency

Vasointestinal polypeptide hormone–producing tumor (VIPoma)

MalignancySolid tumors

Lytic bone metastases

Lymphoma and leukemia

Parathyroid hormone–related peptide

Excess production of 1,25(OH)2D3

Other factors (cytokines, growth factors)

Granulomatous DiseasesSarcoidosis

Tuberculosis

Histoplasmosis

Coccidiomycosis

Leprosy

MedicationsCalcium supplementation

Thiazide diuretics

Lithium

Estrogens, antiestrogens, testosterone in breast cancer

Vitamin A or D intoxication

OtherBenign familial hypocalciuric hypercalcemia

Milk-alkali syndrome

Immobilization

Paget's disease

Acute and chronic renal insufficiency

Aluminum excess

Parenteral nutrition

Adapted from Mulder JE, Bilezikian JP: Acute management of hypercalcemia. In Bilezikian JP, Marcus R, Levine MA (eds):

The parathyroids, ed 2, San Diego, Calif, 2001, Academic Press, p 730.

* Malignancy is the most common cause of hypercalcemia in the inpatient setting; primary hyperparathyroidism is the

most common cause in the outpatient setting.

•• Primary HPT is the third most common endocrine Primary HPT is the third most common endocrine

disorder, after diabetes mellitus and thyroid disease. disorder, after diabetes mellitus and thyroid disease.

•• MiddleMiddle--aged aged and older women are most commonly and older women are most commonly

affected by the disease. affected by the disease.

•• It It is characterized by is characterized by hypersecretionhypersecretion of PTH, leading of PTH, leading

to to hypercalcemiahypercalcemia. .

•• The diagnosis is made by demonstrating elevated The diagnosis is made by demonstrating elevated

serum calcium and intact PTH (serum calcium and intact PTH (iPTHiPTH) levels and ) levels and

normal or increased urinary calcium levels in the normal or increased urinary calcium levels in the

setting of normal renal function. setting of normal renal function.

•• A A 2424--hour urine collection can help exclude the hour urine collection can help exclude the

diagnosis of benign familial diagnosis of benign familial hypocalciurichypocalciuric

hypercalcemiahypercalcemia (BFHH(BFHH) )

•• BFHH BFHH is a generally benign condition transmitted in is a generally benign condition transmitted in

an autosomal dominant fashion that cannot be an autosomal dominant fashion that cannot be

corrected by corrected by parathyroidectomyparathyroidectomy..

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Diagnosis and clinical featuresDiagnosis and clinical features

•• Before advent of the serum channel Before advent of the serum channel autoanalyzerautoanalyzer, ,

patients with primary HPT were typically seen with the patients with primary HPT were typically seen with the

clinical manifestations of clinical manifestations of hypercalcemiahypercalcemia

THENTHEN

•• Painful Painful bones, kidney stones, abdominal groans, “psychic bones, kidney stones, abdominal groans, “psychic

moans,” and fatigue moans,” and fatigue overtonesovertones

•• Until the 1970s, 75% of patients presented with Until the 1970s, 75% of patients presented with

nephrolithiasisnephrolithiasis

NOWNOW

•• Less Less than 20% of primary HPT patients have renal than 20% of primary HPT patients have renal

symptoms symptoms

•• Less Less than 5% have evidence of than 5% have evidence of osteitisosteitis fibrosis fibrosis cysticacystica

•• Nonspecific Nonspecific complaints such as fatigue, lethargy, and complaints such as fatigue, lethargy, and

depression are most commonly depression are most commonly citedcited

•• Hypertension Hypertension --one one third of patients with third of patients with HPTHPT

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LabsLabs

•• Confirm Confirm HypercalcemiaHypercalcemia presentpresent

•• Eliminate potential causative medicationsEliminate potential causative medications

•• Obtain intact Parathyroid Hormone (PTH) LevelObtain intact Parathyroid Hormone (PTH) Level

•• PTH normal or high: Obtain 24 hour Urine PTH normal or high: Obtain 24 hour Urine

CalciumCalcium

–– 24 hour Urine Calcium normal or high24 hour Urine Calcium normal or high

•• Primary HyperparathyroidismPrimary Hyperparathyroidism

•• Recovery from Acute Tubular NecrosisRecovery from Acute Tubular Necrosis

•• Lithium therapyLithium therapy

–– 24 hour Urine Calcium low 24 hour Urine Calcium low

•• Familial benign Familial benign hypocalciurichypocalciuric hypercalcemiahypercalcemia

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Indications for Surgery in Asymptomatic Indications for Surgery in Asymptomatic

Patient w/ Primary HPT Patient w/ Primary HPT -- NIH NIH

Consensus(1990)Consensus(1990)•• Serum calcium concentration >1Serum calcium concentration >1 mg/mg/dLdL (>0.25(>0.25 mMmM/liter) /liter)

above the upper limits of above the upper limits of normal normal (markedly elevated serum Ca++ (markedly elevated serum Ca++

or episode of lifeor episode of life--threatening threatening hyperCahyperCa++)++)

•• Reduced Reduced creatininecreatinine clearance; renal stonesclearance; renal stones

•• Bone Bone density at the lumbar spine, hip, or distal end of the density at the lumbar spine, hip, or distal end of the

radius that is >2radius that is >2 SD below peak bone mass (TSD below peak bone mass (T--score <−2.5)score <−2.5)

•• Individuals Individuals with primary hyperparathyroidism with primary hyperparathyroidism <<5050 yryr

•• Patients for whom medical surveillance is undesirable or Patients for whom medical surveillance is undesirable or

impossibleimpossible

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Preoperative localization in Patients With Primary Hyperparathyroidism

IMAGING

MODALITYSENSITIVITY SPECIFICITY COST SAFETY

Noninvasive

Sestamibi Moderate Moderate Moderate Safe

Sestamibi SPECT High High Moderate Safe

Ultrasound Moderate Moderate Low Safe

4D-CT High High High Radiation

MRI Low Moderate Moderate Safe

PET-CT ? ? High Radiation

Invasive

Angiography Moderate Moderate Very high

Hematoma,

CVA,

nephropathy*

Venous

localizationHigh High Very high

Hematoma,

nephropathy*

Ultrasound,

biopsyHigh High Moderate

Hematoma,

infection

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4D-CT, Four-dimensional CT; CVA, cerebrovascular accident (stroke); PET, positron emission tomography; SPECT, single-photon

emission CT.

SubstractionSubstraction

•• Thallium (Thallium (TlTl) scan 1st) scan 1st

–– Thyroid and parathyroidThyroid and parathyroid

–– Allow for washout Allow for washout from bothfrom both

•• Follow Follow with with Technetium (Technetium (TcTc) scan) scan

–– Thyroid onlyThyroid only

•• TcTc image (thyroid) isimage (thyroid) is

subtracted from subtracted from TlTl imageimage

((thyrthyr + + parathyrparathyr) to get) to get

parathyroid image itselfparathyroid image itself

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UltrasoundUltrasound

•• Ultrasound is effective, noninvasive, Ultrasound is effective, noninvasive,

and inexpensive, but its limitations and inexpensive, but its limitations

include operator dependency and include operator dependency and

restriction to application in the neck restriction to application in the neck

because it cannot image because it cannot image mediastinalmediastinal

parathyroid lesions parathyroid lesions

•• It It has a 48% to 74% truehas a 48% to 74% true--positive positive raterate

•• Ultrasound Ultrasound often is used in often is used in

combination with combination with sestamibisestamibi, in which , in which

case the combined truecase the combined true--positive rate positive rate

rises to 90rises to 90%%

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SestamibiSestamibi washout scanwashout scan

•• 99mTc 299mTc 2--methylmethyl--isobutylisobutyl--isonitrile radionuclide isonitrile radionuclide ((TcTc--sestamibisestamibi))

•• Discovered Discovered in 1989 to be useful in imaging of in 1989 to be useful in imaging of parathyroid glands.parathyroid glands.

•• Radioisotope uptake increases with gland weight.Radioisotope uptake increases with gland weight.

•• MIBI concentrated in tissues rich in mitochondria.MIBI concentrated in tissues rich in mitochondria.

–– HeartHeart

–– Salivary glandsSalivary glands

–– Thyroid glandsThyroid glands

–– Parathyroid glandsParathyroid glands

SPECTSPECT•• Increases the accuracy of routine Increases the accuracy of routine SestamibiSestamibi scanning by about 2 to 3 scanning by about 2 to 3

percentpercent

•• We had been using SPECT imaging for all patients in which there is a We had been using SPECT imaging for all patients in which there is a

questionable adenoma (about one in 20questionable adenoma (about one in 20--30) 30)

•• SPECT scanning can be performed at any time within the first several SPECT scanning can be performed at any time within the first several

hours after a patient is injected with the radioactive hours after a patient is injected with the radioactive SestamibiSestamibi

radiopharmaceutical. radiopharmaceutical.

•• During the scan, 30 (typical) or more images are taken surrounding During the scan, 30 (typical) or more images are taken surrounding

the patient's head and neck. the patient's head and neck.

•• When ordinary When ordinary SestamibiSestamibi scans are inconclusive or reoperation scans are inconclusive or reoperation

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SPECT/CT fusion refers to the imaging technique that combines the functional information from SPECT with the anatomical information from CT into one set of images.

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Cross sectional imagingCross sectional imaging-- CT,MRI, 4DCT,MRI, 4D--CT scanCT scan

•• CrossCross--sectional sectional imaging imaging useful useful for visualizing for visualizing

mediastinalmediastinal tumors and glands within the tumors and glands within the

tracheoesophagealtracheoesophageal groove. groove.

•• MRI MRI -- parathyroid adenomas often appear parathyroid adenomas often appear

intense on T2intense on T2--weighted images. weighted images.

•• CT CT is less expensive and has a sensitivity of is less expensive and has a sensitivity of

70% and a specificity of nearly 10070% and a specificity of nearly 100%%

•• FourFour--dimensional CT (4Ddimensional CT (4D--CT), a novel CT), a novel

imaging modality similar to CT angiography, imaging modality similar to CT angiography,

is derived from threeis derived from three--dimensional (3D)dimensional (3D)--CT CT

scanning with an added dimension from the scanning with an added dimension from the

changes in perfusion of contrast over time. changes in perfusion of contrast over time.

•• In In a study of 75 patients with primary HPT, a study of 75 patients with primary HPT,

4D4D--CT demonstrated improved sensitivity CT demonstrated improved sensitivity

(88%) over (88%) over sestamibisestamibi (65%) and (65%) and

ultrasonography (57%) when the imaging ultrasonography (57%) when the imaging

studies were used to lateralize studies were used to lateralize

hyperfunctioninghyperfunctioning parathyroid glands to one parathyroid glands to one

side of the neck.side of the neck.

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Invasive Preoperative LocalizationInvasive Preoperative Localization

•• A subset of patients who require A subset of patients who require reexplorationreexploration will have will have

negative, discordant, or negative, discordant, or nonconvincingnonconvincing noninvasive noninvasive

localization studies. localization studies.

•• These These patients patients may undergo may undergo invasive localization in the invasive localization in the

form of selective arteriography in conjunction with form of selective arteriography in conjunction with

venous sampling for PTH venous sampling for PTH

•• This This technique requires catheterization of multiple veins technique requires catheterization of multiple veins

in the neck and mediastinum, from which blood samples in the neck and mediastinum, from which blood samples

are are obtainedobtained

•• Rapid Rapid PTH measurement is now being performed in the PTH measurement is now being performed in the

angiography suite. Results are available quickly, so angiography suite. Results are available quickly, so

interventional radiologists can obtain additional samples interventional radiologists can obtain additional samples

from a region in which a subtle, but potentially from a region in which a subtle, but potentially

significant, PTH gradient is detected. Because parathyroid significant, PTH gradient is detected. Because parathyroid

adenomas have increased vascularity, they have a adenomas have increased vascularity, they have a

characteristic blush on arteriography. Although these characteristic blush on arteriography. Although these

studies have a sensitivity of only 60%, they yield few studies have a sensitivity of only 60%, they yield few

falsefalse--positive results. positive results.

•• This This use of interventional radiology rarely causes serious use of interventional radiology rarely causes serious

complications such as visual field defects or other complications such as visual field defects or other

cerebrovascular events, but such studies are timecerebrovascular events, but such studies are time--

consuming and expensive and must be performed only at consuming and expensive and must be performed only at

centers with expertise.centers with expertise.

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Venous localization mapping PTH levels at different cervical sampling sites.

The 1049 level is consistent with a right posterior parathyroid adenoma. B, Corresponding angiogram showing the adenoma as a classic blush in the

right posterior position (arrows).

Surgery for primary Surgery for primary

hyperparathyroidisimhyperparathyroidisim

•• Bilateral Neck Bilateral Neck ExplorationExploration

•• Minimally Invasive Minimally Invasive

ParathyroidectomyParathyroidectomy

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Bilateral Neck ExplorationBilateral Neck Exploration

•• The The classic approach to the surgical management of primary HPT traditionally classic approach to the surgical management of primary HPT traditionally

has been bilateral neck exploration under general anesthesia, with has been bilateral neck exploration under general anesthesia, with

intraoperative, intraoperative, histopathologichistopathologic frozen section examination of excised frozen section examination of excised

parathyroid parathyroid tissuetissue

•• IdeallyIdeally, all the parathyroid glands are identified, and the surgeon removes the , all the parathyroid glands are identified, and the surgeon removes the

pathologically enlarged gland or pathologically enlarged gland or glandsglands

•• HistoricallyHistorically, patients were admitted to the hospital for 1 or 2 days and failure , patients were admitted to the hospital for 1 or 2 days and failure

rates in the best series were consistently less than 3% to 5rates in the best series were consistently less than 3% to 5%%

•• Standard Standard bilateral neck exploration is still considered an excellent operation, bilateral neck exploration is still considered an excellent operation,

with a complication rate in the 1% to 2% range and a cure rate (defined as with a complication rate in the 1% to 2% range and a cure rate (defined as

normocalcemianormocalcemia 6 6 months postoperatively) higher than 95months postoperatively) higher than 95%%

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Minimally Invasive Minimally Invasive ParathyroidectomyParathyroidectomy

(a.k.a. MIP, guided, focused, directed) (a.k.a. MIP, guided, focused, directed)

•• Because Because 8585--95% 95% of primary of primary

HPT results from a single HPT results from a single

adenoma and is cured by adenoma and is cured by

excision of the excision of the offending glandoffending gland--

directed surgery after accurate directed surgery after accurate

preoperative localization has preoperative localization has

been used with increased been used with increased

frequencyfrequency

•• MIP MIP involves the use of involves the use of

unilateral neck unilateral neck surgery under surgery under

regional or local anesthesia in regional or local anesthesia in

the ambulatory the ambulatory settingsetting

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MIRPMIRP

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Handheld gamma detection device employing a parathyroid probeHandheld gamma detection device employing a parathyroid probe

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Surgery StepsSurgery Steps

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29 30

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•• 305 patients who underwent MIRP in our institution 305 patients who underwent MIRP in our institution

between 1997 and 2007between 1997 and 2007

•• Data including symptoms, pre and postData including symptoms, pre and post--operative calcium operative calcium

levels, and PTH levels were collectedlevels, and PTH levels were collected

•• Evaluate the efficacy of Minimally Invasive Evaluate the efficacy of Minimally Invasive RadioguidedRadioguided

ParathyroidectomyParathyroidectomy (MIRP) based on:(MIRP) based on:

–– PathologyPathology

–– Calcium levelsCalcium levels

–– Parathyroid hormone levelsParathyroid hormone levels

–– Symptoms & signsSymptoms & signs

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ResultsResults

•• 100%100%-- IntraoperativeIntraoperative frozen pathology specimens were frozen pathology specimens were hypercellularhypercellular parathyroidsparathyroids

•• 100%100%-- Permanent pathology specimens were parathyroid Permanent pathology specimens were parathyroid adenomasadenomas

Pre-Op Post-Op

Serum Ca 10.9 9.8

Ionized Ca 1.45 1.23

Serum PTH 138 50

Rapid PTH 270 50

Surgery OtherSurgery Other

•• Video assistedVideo assisted

•• EndocopicEndocopic

•• RoboticRobotic

•• ReoperativeReoperative

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Secondary hyperparathyroidism Secondary hyperparathyroidism

•• Typically Typically managed initially managed initially medically, (medically, (vitamin D analogues vitamin D analogues & & calcimimeticcalcimimetic agents (e.g., agents (e.g.,

cinacalcetcinacalcet) )

Indications Indications for for SurgerySurgery-- severe refractory complicationssevere refractory complications

•• Renal Renal osteodystrophyosteodystrophy ((osteitisosteitis fibrosafibrosa cysticacystica, , osteomalaciaosteomalacia, and , and adynamicadynamic bone bone

disease) disease)

•• Uremic Uremic pruritus, or severe itching with endpruritus, or severe itching with end--stage renal failure, stage renal failure,

•• General General weakness is common in uremic patients, weakness is common in uremic patients,

•• anemia anemia is common in uremic is common in uremic patientspatients

•• CalciphylaxisCalciphylaxis is a rare, severe, and lifeis a rare, severe, and life--threatening complication of secondary HPT threatening complication of secondary HPT

characterized by calcification of the media of small to mediumcharacterized by calcification of the media of small to medium--sized arteries; it results sized arteries; it results

in ischemic damage in dermal and epidermal structures. Calcification can lead to in ischemic damage in dermal and epidermal structures. Calcification can lead to

nonhealingnonhealing ulcers, gangrene, sepsis, and ulcers, gangrene, sepsis, and deathdeath

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Surgical StrategiesSurgical Strategies

•• GenerallyGenerally, preoperative imaging before initial , preoperative imaging before initial parathyroidectomyparathyroidectomy for for

secondary HPT is not indicated because bilateral neck exploration is secondary HPT is not indicated because bilateral neck exploration is

required for identification of all glands, given that the underlying required for identification of all glands, given that the underlying

pathology is parathyroid pathology is parathyroid hyperplasiahyperplasia

•• Subtotal Subtotal parathyroidectomyparathyroidectomy

•• Total Total parathyroidectomyparathyroidectomy with heterotopic with heterotopic autotransplantationautotransplantation

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Subtotal Subtotal parathyroidectomyparathyroidectomy

AdvantagesAdvantages

•• A wellA well--vascularized vascularized eutopiceutopic gland will maintain gland will maintain

function, in contrast to an function, in contrast to an autotransplantedautotransplanted gland, gland,

which would need to undergo neovascularization. which would need to undergo neovascularization.

•• Good for noncompliant Good for noncompliant patient who is less likely to patient who is less likely to

take calcium and vitamin D supplementation take calcium and vitamin D supplementation

faithfully faithfully postoperatively postoperatively

•• Choosing Choosing an accessible gland and marking it with a an accessible gland and marking it with a

clip for potential identification make clip for potential identification make reexplorationreexploration

easier. easier.

•• Avoiding Avoiding an arm incision allows easier hemodialysis an arm incision allows easier hemodialysis

access. access.

Disadvantages Disadvantages

•• are are that a second neck surgery is necessary if HPT that a second neck surgery is necessary if HPT

recurs, and recurs, and hypoparathyroidismhypoparathyroidism with significant with significant

hypocalcemiahypocalcemia may develop if the remnant is not well may develop if the remnant is not well

vascularized. vascularized.

•• HoweverHowever, because it is advantageous to avoid , because it is advantageous to avoid

remedial cervical exploration, heterotopic remedial cervical exploration, heterotopic

parathyroid transplantation is attractive.parathyroid transplantation is attractive.

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•• Total Total parathyroidectomyparathyroidectomy with with autotransplantationautotransplantation removes removes

all identified glands and uses an easily accessible area, most all identified glands and uses an easily accessible area, most

commonly the forearm or the sternocleidomastoid muscle, as commonly the forearm or the sternocleidomastoid muscle, as

the site for the site for implantationimplantation

•• The The gland to be transplanted is minced into 1gland to be transplanted is minced into 1--mm pieces and mm pieces and

12 to 18 pieces are embedded in well12 to 18 pieces are embedded in well--vascularized muscle and vascularized muscle and

marked with a stitch or marked with a stitch or clipclip

•• Some Some groups use a technique of injection into subcutaneous groups use a technique of injection into subcutaneous

tissue. tissue.

•• Neovascularization Neovascularization occurs over a period of several weeks. occurs over a period of several weeks.

•• The The principal advantage of this technique is that residual principal advantage of this technique is that residual

parathyroid function is easily monitored and recurrences can parathyroid function is easily monitored and recurrences can

be treated by partial resection under local anesthesia without be treated by partial resection under local anesthesia without

the need for cervical the need for cervical reexplorationreexploration. .

•• There There are several disadvantages. More aggressive medical are several disadvantages. More aggressive medical

treatment is necessary postoperatively to maintain adequate treatment is necessary postoperatively to maintain adequate

serum calcium levels and avoid serious serum calcium levels and avoid serious hypocalcemichypocalcemic

complications. complications.

•• AutograftAutograft failure can lead to failure can lead to hypoparathyroidismhypoparathyroidism, which can be , which can be

profound. Retrieval of all small grafts may be difficult at profound. Retrieval of all small grafts may be difficult at

reoperation. Implantation into muscle may interfere with reoperation. Implantation into muscle may interfere with

hemodialysis access in the future; invasive growth of hemodialysis access in the future; invasive growth of autograftsautografts

into muscle and adjacent tissue requiring radical resection has into muscle and adjacent tissue requiring radical resection has

been described. Finally, supernumerary glands may still be been described. Finally, supernumerary glands may still be

present in the neck, thereby resulting in two potential sites of present in the neck, thereby resulting in two potential sites of

recurrence.recurrence.

Secondary HyperparathyroidismSecondary Hyperparathyroidism

•• Surgical treatment is indicated and recommended Surgical treatment is indicated and recommended for patients with for patients with –– bone pain,bone pain,

–– pruritus, and a calciumpruritus, and a calcium--phosphate product >=70, phosphate product >=70,

–– Ca greater than 11 mg/dL with markedly elevated PTHCa greater than 11 mg/dL with markedly elevated PTH

–– CalciphylaxisCalciphylaxis

–– progressive renal osteodystrophy,progressive renal osteodystrophy,

–– softsoft--tissue calcificationtissue calcification

Tertiary HyperparathyroidismTertiary Hyperparathyroidism

•• Long standing renal failure s/p renal transplantLong standing renal failure s/p renal transplant

•• autonomous parathyroid gland function and tertiary HPT. autonomous parathyroid gland function and tertiary HPT.

•• Can cause problems similar to primary Can cause problems similar to primary hyperparathyroidismhyperparathyroidism

•• Operative intervention Operative intervention

–– symptomatic disease symptomatic disease

–– autonomous PTH secretion persists for more than 1 autonomous PTH secretion persists for more than 1 year after a successful transplantyear after a successful transplant

–– subtotal or total parathyroidectomy with subtotal or total parathyroidectomy with autotransplantationautotransplantation

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Multiple Endocrine Multiple Endocrine NeoplasiaNeoplasia

• MEN1 syndrome: Primary HPT resulting from parathyroid hyperplasia

associated with lesions of the pancreas and pituitary

• The parathyroid glands are asymmetrically enlarged and there is a high

incidence of supernumerary glands (up to 20%)

• Parathyroid surgery in patients with MEN1 is thought of as a debulking or

palliative procedure because recurrence is inevitable if survival is unlimited; it

is indicated to treat and prevent the complications of HPT

• The initial surgical procedure of choice in a patient with MEN1 and HPT is

subtotal parathyroidectomy or total parathyroidectomy with heterotopic

autotransplantation of resected parathyroid tissue; transcervical thymectomy

is also performed at the initial operation.

• (cryopreservation of parathyroid tissue is performed at the time of total

parathyroidectomy whenever possible)

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• MEN2A syndrome: is marked by the findings of medullary thyroid cancer,

pheochromocytoma, and primary HPT

• HPT in MEN2A is the least common manifestation and occurs in 20% to 30%

of patients

• HPT in MEN2A differs from MEN1 in several important features, and the

indications for parathyroidectomy and diagnostic criteria are more similar to

those of sporadic primary HPT

• When compared with HPT in MEN1, HPT in MEN2A tends to be milder and

more often asymptomatic because of a single adenoma, although

multiglandular hyperplasia does occur. Therefore, curative resection can be

less aggressive.

• Enlarged parathyroids encountered during thyroidectomy for medullary

thyroid cancer in a normocalcemic patient are resected.

• Most but not all endocrine surgeons leave normal-appearing parathyroids in

situ, although total parathyroidectomy with autotransplantation to the

forearm has been advocated by some.

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Parathyroid CarcinomaParathyroid Carcinoma

•• Parathyroid Parathyroid carcinoma carcinoma is the leastis the least--common endocrine malignancy, accounting for 0.005% of all common endocrine malignancy, accounting for 0.005% of all

cancer cases in the UScancer cases in the US

•• Most Most patients with carcinomas have marked patients with carcinomas have marked hypercalcemiahypercalcemia (>14(>14 mg/mg/dLdL) and are more likely to ) and are more likely to

have associated bone and renal disease than those with adenomas. have associated bone and renal disease than those with adenomas.

•• Extremely Extremely high high iPTHiPTH level, a palpable neck mass on physical examination, significant uptake on level, a palpable neck mass on physical examination, significant uptake on

sestamibisestamibi scan, or ultrasound evidence of invasion with loss of planes between the parathyroid and scan, or ultrasound evidence of invasion with loss of planes between the parathyroid and

thyroid, occasionally with lymphadenopathy.thyroid, occasionally with lymphadenopathy.

•• Initial Initial aggressive surgical approach involving en bloc tumor resection, aggressive surgical approach involving en bloc tumor resection, ipsilateralipsilateral thyroid lobectomy, thyroid lobectomy,

and resection of adjacent soft tissues is performed because this is the only potentially curative and resection of adjacent soft tissues is performed because this is the only potentially curative

treatment. treatment.

•• En En bloc resection is associated with a 40% local recurrence rate and an overall survival rate of 89% bloc resection is associated with a 40% local recurrence rate and an overall survival rate of 89%

(mean follow(mean follow--up, 119 monthsup, 119 months))

•• Distant Distant metastases generally develop in the lungs, liver, and bone; they can occasionally be treated metastases generally develop in the lungs, liver, and bone; they can occasionally be treated

by resection of individual tumor deposits. Generally, control of by resection of individual tumor deposits. Generally, control of hypercalcemiahypercalcemia by surgical resection by surgical resection

of metastases or local recurrence is more effective than medical treatment. of metastases or local recurrence is more effective than medical treatment.

•• Most patients with metastatic or locally Most patients with metastatic or locally unresectableunresectable disease die of the metabolic effects of disease die of the metabolic effects of

uncontrolled uncontrolled hypercalcemiahypercalcemia. .

•• There There are still no generally accepted staging systems for parathyroid carcinoma.are still no generally accepted staging systems for parathyroid carcinoma.

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Secondary (revision) parathyroid survey:Secondary (revision) parathyroid survey:

•• Examination for abnormal Examination for abnormal

parathyroidsparathyroids in locations beyond in locations beyond

the primary survey when it fails to the primary survey when it fails to

reveal all pathologic glandsreveal all pathologic glands

(A) Examination of thymus (A) Examination of thymus

(B) Palpation of (B) Palpation of retroesophagealretroesophageal space space

and anterior cervical spineand anterior cervical spine

(C) Mobilization of superior thyroid (C) Mobilization of superior thyroid

polepole

(D) Exploration of carotid sheath. (D) Exploration of carotid sheath.

(E) Abnormal parathyroid glands (E) Abnormal parathyroid glands

located located intrathyroidallyintrathyroidally

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Complications of Parathyroid Complications of Parathyroid

SurgerySurgery

•• Persistent Persistent HPT HPT -- 11--20% (experience dependent)20% (experience dependent)

•• temporary temporary --20%20%

•• Permanent Permanent hypocalcemiahypocalcemia –– 1%1%

•• Nerve Nerve injury injury -- recurrent or superior laryngeal recurrent or superior laryngeal --

11--1010%%

•• BBleeding leeding -- <5%<5%

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How do we know that surgery is How do we know that surgery is

successful?successful?

•• IntraoperativeIntraoperative appearanceappearance

•• Frozen sectionFrozen section

•• Drop in Drop in intraoperativeintraoperative PTH = 50%PTH = 50%

•• Ex Vivo radioactivity > 20% of basinEx Vivo radioactivity > 20% of basin

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ParathyromatosisParathyromatosis

•• ParathyromatosisParathyromatosis, a condition in which , a condition in which

hyperfunctioninghyperfunctioning parathyroid tissue is distributed parathyroid tissue is distributed

throughout the neck throughout the neck

•• Multiple nodules of Multiple nodules of hyperfunctioninghyperfunctioning parathyroid parathyroid

tissue scattered through the neck and tissue scattered through the neck and

mediastinummediastinum) due to spillage of otherwise benign ) due to spillage of otherwise benign

parathyroid tissue during surgeryparathyroid tissue during surgery

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•• ParathyromatosisParathyromatosis. (. (AA) Early ) Early sestamibisestamibi image image

shows physiologic uptake in the thyroid shows physiologic uptake in the thyroid

gland (gland (arrowarrow) and salivary glands ) and salivary glands

((arrowheadsarrowheads), and several other foci ), and several other foci

scattered through the neck. (scattered through the neck. (BB) Late ) Late

sestamibisestamibi image confirms that many of these image confirms that many of these

additional foci (additional foci (arrowsarrows) are rests of ) are rests of

hyperfunctioninghyperfunctioning parathyroid tissue. (parathyroid tissue. (CC) Axial ) Axial

contrastcontrast--enhanced CT image shows multiple enhanced CT image shows multiple

nonspecific briskly enhancing nodules nonspecific briskly enhancing nodules

((arrowsarrows), which correspond to the increased ), which correspond to the increased

sestamibisestamibi uptake on fused SPECTuptake on fused SPECT--CT (CT (DD and and

EE). ).

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CryopreservationCryopreservation

•• Cryopreservation of parathyroid tissue is an alternate technique developed to treat Cryopreservation of parathyroid tissue is an alternate technique developed to treat

patients with permanent patients with permanent hypoparathyroidismhypoparathyroidism

•• This method allows for parathyroid tissue to be stored and then This method allows for parathyroid tissue to be stored and then autotransplantedautotransplanted in a in a

delayed fashion once permanent delayed fashion once permanent hypoparathyroidismhypoparathyroidism is confirmedis confirmed

•• Permanent Permanent hypoparathyroidismhypoparathyroidism is defined as persistent is defined as persistent hypocalcemiahypocalcemia requiring calcium requiring calcium

and vitamin D supplementation 6 months after surgeryand vitamin D supplementation 6 months after surgery

•• The The parathyroid tissue removed during surgery is dissected into 30 to 40 pieces of 1 parathyroid tissue removed during surgery is dissected into 30 to 40 pieces of 1 ××1 1 ×× 1 mm. The pieces are then placed into a sterile vial containing ice1 mm. The pieces are then placed into a sterile vial containing ice--chilled saline. chilled saline.

The vial is then transported. The supernatant is decanted; about 10 tissue fragments The vial is then transported. The supernatant is decanted; about 10 tissue fragments

are transferred into each sterile freezing vial to be are transferred into each sterile freezing vial to be resuspendedresuspended in the freezing media.in the freezing media.

•• FreezingFreezing

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Questions you will be askedQuestions you will be asked

•• Embryology of PTH glandsEmbryology of PTH glands

•• Localization techniques for primary Localization techniques for primary hyperPTHhyperPTH

•• Survey order and location for parathyroid Survey order and location for parathyroid

explorationexploration-- Where to look when you can’t find a Where to look when you can’t find a

PTH gland (PTH gland (first time and redo)first time and redo)

•• Question about redo Question about redo parathyroidectomyparathyroidectomy

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