Lawrence Kim, 2016 NCANA Annual Meeting

1. Anesthetic Aspects of Endocrine
Surgery
Lawrence T. Kim, M.D.
Professor of Surgery
University of North Carolina

2. Anesthetic Aspects of Endocrine
Surgery
• Thyroid cancer
• Airway management in goiter
• Intraoperative nerve monitoring
• Pheochromocytoma and Paraganglioma
• Changing approaches for hyperparathyroidism

3. Differentiated Thyroid Cancers (DTC)
• Fastest rising incidence of all cancers
• Estimated 64,300 U.S. cases 2016
• 63,000 U.S. cases 2014
• 37,200 U.S. cases 2009
• Almost the entire increase is papillary
• Disproportionate increase in small tumors

4. Thyroid Cancer Incidence
Davies and Welch, JAMA Otolaryngology–Head & Neck Surgery Published online February 20, 2014

5. Copyright restrictions may apply.
Davies, L. et al. JAMA 2006;295:2164-2167.
Trends in Incidence of Thyroid Cancer (1973-2002) and Papillary
Tumors by Size (1988-2002) in the United States

9. Clinically Silent Thyroid Cancer
• Very Common
• In autopsy series papillary ca found in up to
1/3 of specimens
– Harach HR et al., Cancer 1985;56(3):531–538.
• Recent meta-analysis 7.6%
– 12% if including only studies that examined the
entire gland
– Valle and Kloos, J Clin Endocrinol Metab 96: E109–
E113, 2011

11. Vaccarella S et al. N Engl J Med 2016;375:614-617.
Observed versus Expected Changes in Age-Specific Incidence of
Thyroid Cancer per 100,000 Women, 1988–2007.
Reported in NY Times, Aug.
23, 2016

12. • Cancer patients 2.5 times more likely to
declare bankruptcy
• Thyroid cancer patients second highest (3X
risk)
• Health Aff (Millwood). 2013 June; 32(6): 1143-1152

13. • Age of patient
• Sex
• Presence of metastases
• Tumor size
• Local invasion
Determinants of Prognosis

14. TNM staging
Papillary or follicular (differentiated) thyroid cancer in patients younger than 45
Stage I (any T, any N, M0)
Stage II (any T, any N, M1)
Papillary or follicular (differentiated) thyroid cancer in patients 45 years and
older
Stage I (T1, N0, M0)
Stage II (T2, N0, M0)
Stage III:
T3, N0, M0
T1 to T3, N1a, M0
Stage IVA:
T4a, any N, M0
T1 to T3, N1b, M0
Stage IVB (T4b, any N, M0)
Stage IVC (any T, any N, M1)

15. Surgical Treatment
• Mainstay of thyroid cancer treatment
• Became more aggressive over last 20 years
• Pendulum now swinging towards less
aggressive surgery
• Selected patients may be followed without
surgery

16. Surgical options
• Lobectomy
• Total thyroidectomy
• Total thyroidectomy plus lymph node
dissection
– Ipsilateral or bilateral central compartments
– Lateral compartments

17. Surgical Risks
• Recurrent laryngeal nerve injury
– Unilateral, hoarseness, globus sensation.
– Seldom causes airway issue
• Hypoparathyroidism
– Permanent approx. 1%
– Temporary very common

18. Hypoparathyroidism
• High dose calcium
• Calcitriol. 1,25 OH Vitamin D
• Often given to prevent temporary
hypocalcemia after thyroidectomy
• Low PTH post-operatively can predict
hypocalcemia

19. Anesthetic Aspects of Endocrine
Surgery
• Thyroid cancer
• Airway management in goiter
• Intraoperative nerve monitoring
• Pheochromocytoma and Paraganglioma
• Changing approaches for hyperparathyroidism

20. Airway Management in Goiter
• Thyroid nodules can cause airway symptoms
• Nodule size not well correlated with
symptoms
• Tracheal deviation
• Tracheal compression

21. Pt. presentation
• 72 y.o. F
• 5 yr. history of goiter, observation
recommended
• Hx of CAD
• Presented to outside ER because of dyspnea
• Transferred by air to UNC
• On arrival, stridorous but in no acute distress

34. • Awake fiberoptic oral intubation attempted.
Failed because couldn’t “turn corner” into
trachea
• Attempted awake direct laryngoscopy without
success
• Fiberoptic nasotracheal intubation
successfully completed
• No operative complications
• Pt. discharged POD 1

35. • 4572 pts in database, 919 with retrosternal
goiter
• 133 pts further analyzed
• 32 identified as likely difficult airway

36. Retrosternal Goiter
• 17 pts had awake fiberoptic intubation. In two
pts attempt abandoned and had IV induction
• 11 pts had inhalational induction. Two converted
to IV induction
• “We found no good evidence that thyroid surgery
patients with retrosternal goitre, with or without
symptoms and signs of tracheal compression,
present the experienced anaesthetist with an
airway that cannot be managed using
conventional techniques.”

37. Personal Observations
• Fiberoptic laryngoscopy must be mastered
under “easy” conditions before being used in
the most difficult cases
• Coughing, gagging, aspiration, airway irritation
and trauma are common with awake
intubations
• Orotracheal awake intubations are particularly
difficult

38. Anesthetic Aspects of Endocrine
Surgery
• Thyroid cancer
• Airway management in goiter
• Intraoperative nerve monitoring
• Pheochromocytoma and Paraganglioma
• Changing approaches for hyperparathyroidism

39. Intraoperative Nerve Monitoring
• Recurrent Laryngeal Nerve
• Innervates all but one of the muscles of the
larynx
• Injury to the nerve results in paralysis of the
vocal cord on that side.

45. Goals of Intraoperative Nerve
Monitoring
• Prevent Nerve Injury
• Warn when nerve is stressed
• Anatomical identification of nerve

46. Outcomes of Nerve Monitoring
• Does not prevent injury to recurrent nerve
• May help confirm that a nerve is functionally
intact prior to proceeding to the other side
• May help the surgeon improve nerve handling
• Can have both false-positive and false-
negative signals

47. Anesthetic Aspects of Endocrine
Surgery
• Thyroid cancer
• Airway management in goiter
• Intraoperative nerve monitoring
• Pheochromocytoma and Paraganglioma
• Changing approaches for hyperparathyroidism

48. Pheochromocytoma and
Paraganglioma
• Pheochromocytoma: Catecholamine secreting
adrenal tumor arising from chromaffin cells of
adrenal medulla
– Chromaffin cells derive from the neural crest.They
contain granules which stain with oxidizing agents.
• Paraganglioma: Extra-adrenal pheo

49. Prevalence
• Affects approximately 0.2% of hypertensives
• Peak incidence 4th/5th decades
• 3-9% of Incidentalomas (Incidental finding on
CT Scan)

51. Adrenal Medulla
• Stored catecholamines
• 80% stored as epinephrine,
• 20% as norepinephrines
• All are derived from tyrosine

53. Activity of catecholamines:
• Increase glycogenolysis
• Increase gluconeogenesis
• Increase glucagon secretion
• Decrease glucose uptake
• Clearance: by urine, peripheral enzymatic
degradation, uptake at nerve endings

54. b1 Chronotrope, inotrope,
lipolysis, sweat release
Tachycardia, diaphoresis
b2 Smooth muscle relaxation,
vasodilation, glycogenolysis,
gluconeogenesis, insulin
secretion
Hypotension,
hyperglycemia
a1 Smooth muscle contraction,
glycogenolysis,
gluconeogenesis, sodium
reabsorption, sweat release
Hypertension,
hyperglycemia,
diaphoresis
a2 Inhibits release of
norepinephrine,
vasoconstriction, stimulates
cognition
Pallor

55. Pheochromocytoma:
the 10 % Tumor
• Bilateral
• Malignant
• Multifocal
• Extra adrenal
• Children
• Familial

56. Presentation of Pheochromocytoma
Signs:
• Hypertension
• Tachycardia
Symptoms:
• Headaches
• Diaphoresis
• Nausea/vomiting
• Anxiety

57. Diagnosis of Pheochromocytoma
• Signs and symptoms
– Frequently asymptomatic or subclinically symptomatic
• Incidental finding on CT Scan
• Sporadic versus Familial
• Confirmation by biochemical testing and localization
studies

58. Biochemical Testing for
Pheochromocytoma
• Plasma Metanephrines
• 24 hr urine catecholamines (norepi, epinephrine,
dopamine) and metabolites (metanephrine,
normetanephrine, vanillylmandelic acid)
• Elevations will be dramatic in
pheochromocytoma
• Elevated serum epinephrine suggests
pheochromocytoma at adrenal medulla or at the
organ of Zuckerkandl because –
phenylethanolamine N methylating enzyme is
found at these sites

59. Perioperative Management
Goals:
• Treat hypertension:
adequate alpha blockade
• Volume expansion:
vasoconstricted and intravascularly depeleted
• Control cardiac arrhythmia:
addition of beta blockade

60. Alpha blockade
• Phenoxybenzamine: Alpha adrenergic antagonist
– Initiate 1-3 weeks before resection
– Titrate dose to mild orthostasis
– Expensive and difficult to find
• Doxazosin: Alpha 1 antagonist
– May be as effective as Phenoxybenzamine
– May reduce intra and post-op hypotension

61. Once adequately alpha blocked:
• Adequate alpha blockade: fluid retention leading to
weight gain; orthostatic hypotension
• May initiate beta blockade for arrhythmias
• Never initiate blockade with beta antagonists
– Unopposed alpha effect of catecholamine will worsen
vasoconstriction and precipitate hypertensive crisis or
pulmonary edema

62. Intraoperative monitoring
• Avoid anesthetics which precipitate
catecholamine secretion
• Least cardiac depressant: isoflurane,
enflurane,nitroprusside, phentolamine
• A line: blood pressure
• Nitroprusside
• Labetolol

63. Treatment during Pregnancy
• 1st trimester: initiate medical therapy and
resect in 2nd trimester
• If noted late in pregnancy: elective c section at
term, avoid vaginal delivery- may percipitate
hypertensive crisis

64. Anesthetic Aspects of Endocrine
Surgery
• Thyroid cancer
• Airway management in goiter
• Intraoperative nerve monitoring
• Pheochromocytoma and Paraganglioma
• Changing approaches for hyperparathyroidism

66. Parathyroid Gland
• Composed primarily of Chief cells
– Secrete PTH
– Prominent Golgi
– Contain secretory granules
• Oxyphil cells
– Begin to appear at puberty
– Do not secrete PTH
– Function not known
• Fat
– Increases to about 30% by age 25, remains
constant

67. Parathyroid Hormone
• 84 amino acid polypeptide
• Secreted from parathyroid cells in response to
low calcium
– Lithium increases PTH secretion and decreases cell
sensitivity to Ca++
– 1,25 (OH)2 D decreases PTH secretion

68. Effects of PTH
• Increases activity of osteoclasts causing
release of calcium from bone
• Increases calcium reabsorption from urine in
the kidney
• Increases urinary phosphate excretion
• Increases renal production of 1,25 (OH)2 D
• Which causes increased GI absorption of
calcium

69. Primary Hyperparathyroidism
• Incidence approximately 21 per 100,000 per
year
• Incidence slowly declining
• Peak age early 50’s
• Female: male 3:1
• Most common cause of hypercalcemia in
outpatients

70. Primary Hyperparathyroidism
• Approximately 85% caused by single adenoma
• Approximately 10% diffuse hyperplasia
• Approximately 5% multiple adenomas

72. Signs/Symptoms
• Stones, Bones, Groans, Moans
– Renal
– Skeletal
– Abdominal
– Cardiovascular
– Psychiatric and neuromuscular

73. Signs/Symptoms
• Neuropsychiatric Manifestations
– Easy fatiguability
– Depression
– Inability to concentrate
– Memory problems
– Proximal myopathy

74. Management
• Surgery the only cure
• Bisphosphonates can lower calcium but do
not lower and may increase PTH
• Cinacalcet lowers calcium but only modestly
lowers PTH. Does not decrease calcium
excretion.
• Does everyone need surgery?

75. Management
• Surgery vs. observation in asymptomatic pts.*
• Consensus conferences 1990, 2002, 2008, 2013
1990 2002 2008 2013
Age <50 <50 <50 <50
Bone density Z-score < 2.0
(forearm)
T-score < 2.5
(any site)
T-score < 2.5
(any site) or
fracture
T-score<2.5
(multiple sites)
Vertebral fx
Serum calcium
(above normal)
1-1.6 mg/dl 1 mg/dl 1 mg/dl 1 mg/dl
24 hr urine ca >400 >400 Not used except
to exclude FHH
>400 and stone
risk
Creatinine
clearance
30% below
normal
30% below
normal
eGFR < 60
ml/min
Cr Clearance
<60 ml/min

76. *Surgery is also indicated in patients for whom
medical surveillance is neither desired nor
possible and in patients opting for surgery, in
the absence of meeting any guidelines, as long
as there are no medical contraindications

77. Why everyone (almost) needs surgery
for hyperparathyroidism
• When end organ damage occurs it is
irreversible
• Neuropsychiatric symptoms are common and
often subtle
• The operation is very effective and has
minimal morbidity

78. Surgical Treatment
• Removal of all affected glands (one or more
adenomas)
• For diffuse hyperplasia, removal of all but
approximately 50-70 mg of parathyroid tissue

79. Surgical Technique
• Full neck exploration (gold standard)
– 99% success rate
– Requires visualization of all four glands
• Directed parathyroidectomy
– Beginning in 1990’s directed parathyroidectomy
largely replaced the full neck exploration
– Requires preoperative imaging
– Requires (?) intraoperative PTH monitoring
– Success approaches 100%

80. “Badges? We don’t need no badges.”

81. Parathyroid Imaging
• Sestamibi scan
• Ultrasound
• CT (4D CT)
• MRI
Overall sensitivity around 70-80%. All very poor at
multi-gland disease

82. Parathyroid adenoma

85. Intraoperative PTH assay
• Objective is to confirm that all abnormal
parathyroid tissue has been removed without
the need to physically examine all glands

86. Initial Report of Intraoperative PTH Assay
Intraoperative Measurement of Parathyroid Hormone in the
Surgical Mangement of Hyperparathyroidism
SR Nussbaum, AR Thompson, KA Hutcheson, RD Gaz, C-A Wang
Surgery 1988;104:1121-1127
A New, Practical Intraoperative Parathyroid Hormone Assay
George L. Irvin, III, MD, George T. Deriso, III, BS, Miami, Florida
Amer J Surg 1994;168:466-581

87. Rationale for ioPTH Testing
• PTH produced only in the parathyroids
• PTH t1/2 ~ 4 min
• PTH secretion suppressed in normal glands
after removal of abnormal tissue
• [PTH] declines rapidly after removal of
hyperfunctioning parathyroids
• Availability of a simple, rapid PTH assay

88. Irvin Protocol for ioPTH Testing
• Peripheral vein blood samples, collected in
EDTA tubes, obtained at specific time intervals
during the surgical procedure:
– after anesthesia induction but before neck incision
(“0-min” or baseline sample)
– during manipulation of a suspected
hyperfunctioning gland (pre-excision)
– 5-min after gland excision
– 10-min after gland excision
– 20-min (occasionally) after gland excision

89. Irvin Protocol for ioPTH Testing
 Criterion used to indicate that the offending
glands have been excised and the remaining
parathyroids are not hyperfunctioning:
>50% decline in the [PTH] of the postexcision sample
from baseline

90. Outcomes after surgery
• Approx. 99% success rate
• Increased bone density
• Resolution of hypercalciuria. Decreased (but
not eliminated) risk of stones.
• Improvement in neurocognitive symptoms
• Improvement in functional ability in the
elderly

92. • Bilateral explorations
• 848 pts operated under local anesthesia
• In last 5 years of series, >90% done under local

93. Anesthetic Aspects of Endocrine
Surgery
• Thyroid cancer
• Airway management in goiter
• Intraoperative nerve monitoring
• Pheochromocytoma and Paraganglioma
• Changing approaches for hyperparathyroidism

94. Things We Didn’t Talk About
• Cushing’s syndrome
• Adrenal suppression / Addisonian crisis
• Steroid replacement
• Carcinoid crisis

95. Larry Kim
Lawrence_Kim@med.unc.edu
Cell 919-537-2301