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  Thyroid 12.6  Parathyroid 5.6  Adrenal 0.98  Pancreas 0.15

Mode 7-10 2 0 0

%w/o 0 1 38 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
 Find

the 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  Morbidity

1

0.3 %

Cord paralysis
 

Temporary Permanenet Temporary Permanent

6 2 11 1

2.4% 0.8% 3.0% 0.3%

Hypocalcemia
 

 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

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”

certainty- “exploration is not for

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
Serum calcium (above
upper limit of normal) 24 hr urinary calcium change Creatinine clearance Serum creatinine abnormal Bone mineral density Age >400 mg Reduced by 30% Not recommended Z-score <2.0 (forearm) <50 No No change If T-score <2.5 at any site <50

Guidelines, 1990
1-1.6 mg/dl

Guidelines, 2002 (Bilezikian)
1.0 mg/dl

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- Specitivity ficity 39 70 16 22 70 55 16 65 14 15 32 50 14 18 50 49 47 19 33 23 20 13 23 11 784 86 97.8 85 88 80 93 75 95 87 87 100 82 92.6 90 93 97.5 91 89.5 94 90 NA 93 92 100 90.74 97.5 100 100 100 100 93 100 98 100 100 100 98 100 100 100 100 NA 100 97 95 100 100 100 100 98.74

Bergenfelz et al (69) S Caixas et al (70) D Carter et al (71) D Casas et al (72) S Chapuis et al (20) D Chen et al (73) D Fjeld et al (74) S Hindie et al (75) S Khan et al (76) S Light et al (15) D Malhotra et al (77) D Martin et al (52) D Norman et al (22) D Norman & Chheda (28)D Norman D O’Doherty (13) S Perez-Monte et al (78) D Shaha et al (79) D Sofferman et al (23) D Taillefer et al (80) D Thompson et al (81) S Thule et al (82) S Wei et al (83) S Wei et al (84) S TOTAL

Cost of Parathyroid Localization Studies
Test Ultrasonography
201

(1993, non-Medicare)

Cost (non-Medicare) ($) 331.60 648.10 1154.80 1263.10 689.30
Mayo Clinic

T/99mTc

Computed tomography Magnetic resonance imaging Tc-99m sestamibi

Locations of Missing Parathyroid Tumors at Reoperation
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 Combined series from 1980 to present nerve, etc.)

Site

Frequency (%)

Anatomic Site of Disease at Reoperation
Site
Cervical Inferior pole (normal position) Superior pole (normal position) Thymic tongue Retrotracheal or retroesophageal Intrathyroidal Tracheoesophageal groove Carotid sheath Medial to upper pole Upper thyroid capsule Undescended

TOTAL (%)
79 (21.0) 77 (20.0) 38 (10.0) 23 (6.0) 21 (5.0) 15 (4.0) 10 (2.6) 6 (1.6) 4 (1.0) 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
Single gland disease Multiglandular disease
(incl. double adenomas, four-gland hyperplasias & asymmetrical hyperplasia)

Initial (%)
85 14

Redo (%)
70 27

Carcinoma

1

3

Frequency of Complications Following Reoperations for Hyperparathyroidism
Complication Frequency (%)
5-18 1-10 1-21 6-50 7-17 <1

Failure to cure HPT Recurrent laryngeal nerve injury Permanent hypoparathyroidism Autograft failure Autograft recurrence of HPT Mortality

Complications of Reoperative Parathyroid Surgery
Complication
Failure to cure hypercalcemia Recurrent laryngeal nerve injury Permanent hypoparathyroidism Autograft failure Autograft recurrence Mortality

Incidence %
7-19 4-8 13-25 6-50 7 <1

Parathyroid Carcinoma
Pre-op
• Ca > 14 mg

Intra-op

• Hard mass • Marked evaluation of PTH • Invasion of surrounding structures • Recurrent hypercalcemia • Lymphadenopathy • Bony changes • Recurrent urolithiasis

Confirmation

Pathology
• • • •

• Positive lymph nodes

• Vascular invasion Invasion into surrounding • Distant metastases structures 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 judgment

PTH Re-exploration

Technical 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 state of the art

Biochemistry

Thank You

 Acknowledgements:

MSKCC Head and Neck Service
 

Dr. Jatin P. Shah Dr. Ashok R. Shaha

Mamadi-Soudavar Memorial Fellowship

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