Role of Surgery in

Endocrine Disorders

Ida Marie Tabangay Lim, MD,

 PARATHYROID
GLAND DISORDERS

ROLE OF SURGERY
 Parathyroid Literature
1982 - 2002

Total number of papers 14,945

Hyperparathyroidism 8,763
Localization studies 788
Localization studies (5 yrs) 347

Google search – parathyroid – 126,000

Parathyroid Gland Location
Parathyroid glands- location
Parathyroid glands- vascular supply
Endocrine Procedures by US Residents
1993-1994

Mean Mode %w/o

 Thyroid 12.6 7-10 0
 Parathyroid 5.6 2 1
 Adrenal 0.98 0 38
 Pancreas 0.15 0 85
History
 In 1849 Sir Richard Owen
performed an autopsy on
a rhinoceros and gave the
first description of the
parathyroid gland.

 “a small compact yellow

glandular body was
attached to the thyroid at
the point where the veins
emerged”
 The first description of the
parathyroid glands in human
beings was by Ivar Sandström,
a medical student in Uppsala,
Sweden in 1880.

 He suggested that these

glands be named the
glandulae parathyroideae.

 The function of these

structures was unknown at
that time.
 In 1926, at the Massachusetts
General Hospital, Edward
Churchill, assisted by an intern
named Oliver Cope, operated
for the seventh time on the
famous sea captain Charles
Martell, for severe primary
HPT.
 An ectopic adenoma was
found in the substernal
position.
 Captain Martell died 6 weeks
after the successful seventh
operation, most likely from
laryngeal spasm, during a
procedure to relieve ureteral
obstruction secondary to
stones.
 “The problem of surgery of
hyperparathyroidism resolves itself into
training of the eye, understanding the
abnormal physiology of the parathyroid
glands and recognition of their
widespread distribution.”

Oliver Cope
1941
 Incidence

• 100,000 new cases of HPT in

USA
• 5 – 10% failure
• 8,500 failed operations
Excess PTH
 hypercalcemia
 hypercalciuria

 hyperoxaluria
Cervical Exploration : Goals
 Findthe disease
 Remove the disease

 Minimal complications

 Maximum success
How to Design an Ideal
Operation
 Surgeons--- There should be no surprises
 Anesthesiologists---There should be no train
rails
 Patient--- Low operative morbidity/mortality

---Excellent short and long term outcome

---Better than other treatment modalities
Mayo Clinic Experience on Primary
Hyperparathyroidism (1983-1984)
379 patients undergoing conventional parathyroid
surgery (von Herdeen)

 F=280
 M= 99

 Mean age= 58 y/o

 88% single adenoma

 3% multiple adenoma

 9% hyperplasia
Complications:
 Mortality 1 0.3 %

 Morbidity
 Cord paralysis
 Temporary 6 2.4%
 Permanenet 2 0.8%
 Hypocalcemia
 Temporary 11 3.0%
 Permanent 1 0.3%
 Percent cured ( in 6 months PTH is normal) =
99.5%

 Conclusion;Still, conventional
parathyroidectomy is widely used
Surgical options:

 Conventional

 Minimally
Invasive
 Endoscopic
Operation for Primary
Hyperparathroidism---Menu

 Conventional exploration
 Pre-op localization- focused exploration + ioPTH
 Pre-op localization – focused exploration + gamma
probe
 Pre-op localization – focused endoscopic
exploration + iopTH
 Pre-op localization – focused exploration alone
Successful cervical exploration entails:
 Diagnostic certainty- “exploration is not for
diagnosis”
 Meticulous/gentle techniques-“touch of a
lady-allergy to blood”
 Ability to recognize the normal/abnormal
“experience”
 Being “in tune” with embryology “hiding
places”
 Patience “better for the patient”
Causes of Failed Initial Exploration

• Incorrect diagnosis
• Inexperienced surgeon
• Missing gland – “hiding places”
• Multiple gland disease
• Failure to locate ectopic gland
• Supernumerary glands
• PTH carcinoma
• Parathyromatosis – initial spillage
 Parathyroid Surgery

“The ‘ultimate’ success in the management

of patients with continuing parathyroid
disease depends on the surgeon. He alone
must reconsider where the mistake lies
and how to correct it.”

Chiu-An-Wang
1977
Endocrine Armamentarium
 Competent team of endocrinologists assuring
high degree of accuracy
 Surgeons who are knowledgeable in
embryology and who did a fair volume of
endocrine surgery
 Surgical pathologists well versed in the
inexactitude of endocrine pathology
 Expert radiologists
Asymptomatic Primary Hyperparathyroidism

Measurement Guidelines, 1990 Guidelines, 2002

(Bilezikian)
Serum calcium (above 1-1.6 mg/dl 1.0 mg/dl
upper limit of normal)

24 hr urinary calcium >400 mg No

change

Creatinine clearance Reduced by 30% No change

Serum creatinine Not recommended If

abnormal

Bone mineral density Z-score <2.0 (forearm) T-score <2.5

at any site

Age <50 <50

 Initial Failure

• Is the diagnosis correct?

• R/O benign familial hypocalciuric
hypercalcemia
• Repeat diagnostic work up
• CA, P, PTH
• 24 hour urinary calcium
• Asymptomatic/symptomatic patient
 Possible Locations :
“Missing Gland”
Generally in the Neck
• Medial to the upper pole of the thyroid
• Superior mediastinum (in thymic capsule)
• Retroesophageal
• In the carotid sheath
• Undescended parathyroid up to the hyoid
bone (parapharyngeus)
• Intrathyroid – thyroid lobectomy
In the Mediastinum
• Anterior - superior
• Post mediastinum
• Aortopulmonary window
Parathyroid Localization

“The only localization

study indicated in a patient
with untreated primary
hyperparathyroidism is to
localize an experienced
parathyroid surgeon.”

John Doppman
 Metaanalysis of the Sensitivity and
Specificity of Sestamibi Scans
Author (reference) Scan n Sensi- Speci-
tivity ficity

Bergenfelz et al (69) S 39 86 97.5

Caixas et al (70) D 70 97.8 100
Carter et al (71) D 16 85 100
Casas et al (72) S 22 88 100
Chapuis et al (20) D 70 80 100
Chen et al (73) D 55 93 93
Fjeld et al (74) S 16 75 100
Hindie et al (75) S 65 95 98
Khan et al (76) S 14 87 100
Light et al (15) D 15 87 100
Malhotra et al (77) D 32 100 100
Martin et al (52) D 50 82 98
Norman et al (22) D 14 92.6 100
Norman & Chheda (28)D 18 90 100
Norman D 50 93 100
O’Doherty (13) S 49 97.5 100
Perez-Monte et al (78) D 47 91 NA
Shaha et al (79) D 19 89.5 100
Sofferman et al (23) D 33 94 97
Taillefer et al (80) D 23 90 95
Thompson et al (81) S 20 NA 100
Thule et al (82) S 13 93 100
Wei et al (83) S 23 92 100
Wei et al (84) S 11 100 100
TOTAL 784 90.74 98.74
Cost of Parathyroid
Localization Studies (1993, non-Medicare)

Test Cost (non-Medicare) ($)

Ultrasonography 331.60
201
T/99mTc 648.10

Computed tomography 1154.80

Magnetic resonance imaging 1263.10

Tc-99m sestamibi 689.30

Mayo Clinic
 Locations of Missing Parathyroid
Tumors at Reoperation

Site Frequency (%)

Normal (also thyroid subcapsular, 40
thyrothymic ligament)
Posterior superior mediastinum (thoracic 30
inlet)
Mediastinal (intrathymic) 15
Posterior midline (retroesophageal/tracheal 5
/pharyngeal)
Mediastinal (non-thymic associated) 5
Intrathyroidal (intraparenchymal) 2
Undescended (parathymus & 2
parapharyngeus)
Other rare (within carotid sheath, vagus 1
nerve, etc.) Combined series from 1980 to present
 Anatomic Site of Disease at
Reoperation
Site
Cervical TOTAL (%)
Inferior pole (normal position) 79 (21.0)
Superior pole (normal position) 77 (20.0)
Thymic tongue 38 (10.0)
Retrotracheal or retroesophageal 23 (6.0)
Intrathyroidal 21 (5.0)
Tracheoesophageal groove 15 (4.0)
Carotid sheath 10 (2.6)
Medial to upper pole 6 (1.6)
Upper thyroid capsule 4 (1.0)
Undescended 4 (1.0)
Collected from Wong et al 1977, Grant et al
1986, Levin & Clark 1989, Akerstrom et al
1992
Reoperative Parathyroid
Surgery

Missing superior gland

Missing inferior gland

 Pathological Findings at
Operations
for Hyperparathyroidism

Pathology Initial (%) Redo (%)

Single gland disease 85 70
Multiglandular disease 14 27
(incl. double adenomas,
four-gland hyperplasias &
asymmetrical hyperplasia)
Carcinoma 1 3
 Frequency of Complications
Following Reoperations for
Hyperparathyroidism

Complication Frequency (%)

Failure to cure HPT 5-18

Recurrent laryngeal nerve injury 1-10
Permanent hypoparathyroidism 1-21
Autograft failure 6-50
Autograft recurrence of HPT 7-17
Mortality <1
 Complications of Reoperative
Parathyroid Surgery
Complication Incidence %

Failure to cure hypercalcemia 7-19

Recurrent laryngeal nerve injury 4-8
Permanent hypoparathyroidism 13-25
Autograft failure 6-50
Autograft recurrence 7
Mortality <1
 Parathyroid Carcinoma
Pre-op Intra-op
• Ca > 14 mg • Hard mass
• Marked evaluation of PTH • Invasion of surrounding
structures
• Recurrent hypercalcemia
• Lymphadenopathy
• Bony changes
Confirmation
• Recurrent urolithiasis
• Positive lymph nodes
Pathology
• Vascular invasion
• Invasion into surrounding
structures • Distant metastases
• Pseudorosette formation•
Recurrent disease
• Desmoplastic reaction
• Mitosis
 New Approach to Parathyroid
Surgery
Irwin, et al.
• ‘Quick’ parathormone assay
• Chemi-immuno-luminescent PTH assay – 15 min
• Sestamibi scan and scan directed
explorations
•Do ‘quick’ PTH after removal of enlarged
parathyroid gland
• If 50% drop in PTH – SUCCESSFUL OUTCOME
Result of the intraoperative quick iPTH assay of a patient who
Underwent endoscopic parathyroidectomy. iPTH level rapidly
Decreased after the removal of the parathyroid adenoma.
Minimally Invasive Parathyroidectomy
 Sestamibi guided unilateral exploration
 Scan guided surgery with ‘quick’ PTH
 Outpatient parathyroidectomy
 Parathyroidectomy under local anesthesia
 Scan directed parathyroidectomy with intraoperative
gamma probe (physiologic approach)
 Endoscopic parathyroidectomy
 Cervical

 Mediastinal

 Thoracic

 Video assisted parathyroidectomy

Radio-Guided Parathyroidectomy

 Credit however goes to

James Norman for
perfecting this
technique.

 The philosophy for use

of the gamma probe is
to look at parathyroid
surgery
physiologically rather
than anatomically.
 MSKCC
Experience with radio-guided parathyroidectomy
 Studied 10 patients from Sept 1998 – Mar 2000

 20% rule used in all cases

 8 pts had accurate MIBI pre-op localization of 1 enlarged gland

 Gamma probe identified the parathyroid tissue and it was in

the same region as seen by the positive MIBI scan
 In the 2 pts where MIBI scans were not confirmatory, the
gamma probe was not helpful and both pts had bilat. expl.
 We feel that if the pre-op MIBI scan is strongly positive, then
the gamma probe is unlikely to assist much during the surgery.
 Larger studies with long term follow-up are necessary to
confirm the usefulness, as well as to understand and
appreciate the pitfalls of this new technology.
 Recurrent/Persistent
Hyperparathyroidism

• U/S guided ethanol injection

• Angiographic ablation
• Cryopreservation of parathyroid
tissue
• Management of recurrent
carcinoma
 Reoperative Strategy
• Cervical exploration – informed consent –
risks
• Preop laryngoscopy
• May not be successful
• Mediastinal exploration
• Intraoperative localization
• Intraop U/S
• Quick PTH – selective venous
sampling
• Methylene blue
• Intraop – gamma probe
• Confocal micrography
 Reoperative Strategy

• Best way “prevention”

• Do the best first time
• Correct diagnosis
• Use all help – localization, quick PTH,
etc
• Use of loupes
• Bipolar cautery
• Do no harm – primum non nocere!
The proof of successful parathyroid
surgery is normocalcemia
 Parathyroid Surgery

Anatomical knowledge

Sound PTH Re-exploration Technical

judgment experience

Surgical challenge
The eyes and hands of an experienced
surgeon are the best tools available
for intraoperative parathyroid
localizaton

Orlo Clark
1987
 Parathyroid Surgery

Experienced parathyroid surgeon

Endocrinologist Endocrine Armamentarium Pathologist

Diagnostic radiologist Biochemistry

state of the art
Thank You
 Acknowledgements:
 MSKCC Head and Neck Service
 Dr. Jatin P. Shah
 Dr. Ashok R. Shaha

 Mamadi-Soudavar Memorial Fellowship