goldenberg - parathyroid - ahns · bony lesions in a patient with a parathyroid tumor • calcium...
TRANSCRIPT
10/4/2013
1
Parathyroid SurgeryParathyroid Surgery
David Goldenberg MD, FACS David Goldenberg MD, FACS Professor of Surgery and OncologyProfessor of Surgery and Oncology
1
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
10/4/2013
2
•• 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.
5
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
10/4/2013
3
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..
10
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..
11
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
12
10/4/2013
4
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
13
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
14
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
15
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
16
10/4/2013
5
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%%
17
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
19 20
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.
10/4/2013
6
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.
21
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.
22
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
23
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%%
24
10/4/2013
7
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
25
MIRPMIRP
26
Handheld gamma detection device employing a parathyroid probeHandheld gamma detection device employing a parathyroid probe
27
Surgery StepsSurgery Steps
28
10/4/2013
8
29 30
31 32
10/4/2013
9
•• 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
33
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
35
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
36
10/4/2013
10
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
37
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.
38
•• 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
10/4/2013
11
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)
41
• 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.
42
43
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.
44
10/4/2013
12
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
45
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%
48
10/4/2013
13
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
50
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
51
•• 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). ).
52
10/4/2013
14
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
53
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
54