ENDOCRINE SURGERY
From Advances in Breast, Endocrine, and Cancer Surgery, sponsored by University of Minnesota Medical School, Department
of Surgery and Continuing Medical Education
Educational Objectives
| The goal of this program is to improve the surgical management of endocrine tumors. After hearing and assimilating
this program, the clinician will be better able to:
|
 | 1. Recognize and choose the optimal treatment for patients with thyroid nodules.
|
| 2. Identify factors indicating likelihood of thyroid cancer in patients with thyroid nodules.
|
| 3. Choose between surgical excision and observation as treatment options for patients with adrenal incidentaloma.
|
| 4. Evaluate the risks and benefits of repeat surgery for patients with primary hyperparathyroidism.
|
| 5. Diagnose, locate, and treat endocrine tumors of the pancreas.
|
aFaculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty and members of the planning
committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts
of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health
care and not a proprietary business or commercial interest. For this program, Drs. Burmeister, van Heerden, and Farley, and
the planning committee reported nothing to disclose.
Acknowledgements
Lectures given by Drs. Burmeister, van Heerden, and Farley were recorded at Advances in Breast, Endocrine, and
Cancer Surgery, held June 14-16, 2007, in Minneapolis, MN, and sponsored by the University of Minnesota Medical
School, Department of Surgery and Continuing Medical Education. The Audio-Digest Foundation thanks the speakers
and the sponsors for their cooperation in the production of this program.
| CURRENT GUIDELINES FOR WORK-UP OF THE THYROID NODULE —Lynn A. Burmeister, MD, Associate Professor,
Division of Diabetes, Endocrinology, and Metabolism, Department of Medicine, University of Minnesota Medical School,
Minneapolis
|
| Background: guidelines published by United States Society of Radiologists in Ultrasound (SRU), American Association
of Clinical Endocrinologists (AACE), European Thyroid Association (ETA), and American Thyroid Association (ATA);
prevalence and diagnosis—50% of 50-yr-old patients have thyroid nodules; detection of nodules requires examination by
ultrasonography (US) or other imaging; thyroid cancer usually presents as nodule (but nodules rarely malignant); higher
risk populations— men, very young or older (>60 yr) patients, patients with family history of thyroid cancer (eg, recent
Swedish registry study showed 11-fold higher risk if patient’s sister has thyroid cancer) or familial adenomatous polyposis,
multiple hamartoma syndrome, or multiple endocrine neoplasia (MEN); papillary carcinoma; radiation exposure; vocal
cord paralysis might indicate thyroid malignancy; abnormal cervical adenopathy suggests papillary or medullary
carcinoma metastasized to regional lymph nodes
|
| Evaluation: laboratory testing—determine thyroid status by measuring thyrotropin (TSH); cancer most often associated
with euthyroid state, and malignancy not excluded by presence of hypothyroidism or thyrotoxicosis; imaging—magnetic
resonance imaging (MRI) and computed tomography (CT) not indicated for evaluation of nodular thyroid disease; US—
recommended for all patients who have palpable thyroid abnormalities, familial history of thyroid cancer, MEN type 2
(MEN-2), or cervical irradiation during childhood; also recommended for patients with adenopathy likely to have malignant
involvement in anterior or lateral neck; physical findings vs US—study of patients whose physical examination
showed solitary nodule; US confirmed 42% had solitary nodule, but 43% had multiple nodules, and 16% had no nodules;
clinically normal thyroid may still have nodules below surface; autopsy study—50% had solitary or multiple nodules
(some not palpable); ACE recommends US not be used—for patients with normal palpation; as substitute for physical examination;
as screening test; for patients with nonspecific symptoms; biopsy—fine needle aspiration best for evaluating
thyroid nodules with high sensitivity and specificity if results positive or negative for malignancy; other findings include
insufficient for diagnosis (specimen inadequate) and indeterminate (gray zone); prevalence of cancer only 20% among
patients in indeterminate range
|
| Prevalence of thyroid cancer: study of patients with nodules >1 cm—US performed; biopsies done; found 14.8% incidence
of thyroid cancer in patients with single nodule >1 cm and 14.9% incidence in patients with multiple nodules;
conclusion—risk for cancer same whether patient has solitary or multiple nodules; patients with nodules <1 cm—in
studies, rate of occult cancer found at autopsy, <1% to 36%
|
| Criteria for recommendation of biopsy: size of nodule—ATA recommends biopsy for nodules >1 to 1.5 cm; ETA
recommends for nodules ≥1 cm; AACE does not use size cutoff; other criteria—characteristics seen via US, eg, degree
of solidness, echogenicity, halo, calcifications, comma-tailed shape, borders, blood flow; study found no significant difference
in malignancy rate for nodules varying from 1 to 3 cm; solid nodules more likely malignant than cystic nodules;
hypoechoic nodules more often malignant than hyperechoic or isoechoic; 23.3% malignancy rate for nodules with punctate
or psammomatous calcifications, but nodules without calcification still had risk; halos and margins not significantly
associated with malignancy in this study but significant in others; US characteristics—SRU recommends biopsy for nodules
≥1 cm if microcalcifications present, >1.5 cm if calcifications solid or coarse, ≥2 cm if mixed cystic or solid; also if
substantial growth observed; presence of abnormal lymph nodes; AACE recommends biopsy for all hypoechoic nodules
≥1 cm, chaotic intranodular vascular spots, when shape more tall than wide, or if microcalcifications present; also nodules
<10 mm if US features suspicious; nodules of any size in patients with neck irradiation or family history of medullary
thyroid cancer or MEN; ETA recommends biopsy for all nodules >1 cm; also for nodules <1 cm if solid,
hyperechoic, microcalcifications present, or patient has risk factors; multiple nodules—ETA recommends biopsy of dominant
nodule; ATA and AACE use US features as criteria; study of multiple nodules—86.3% chance of cancer (by biopsy)
in largest nodule if 2 nodules present in gland; 60% chance in largest if 3 nodules present; 40% chance in largest if 4 nodules;
overall, cancer found in largest nodule 72.5% of time; ATA recommends if TSH suppressed, thyroid may be
scanned with radioactive iodine but not necessary to biopsy hot nodule
|
| Other recommendations: preoperative neck US for contralateral lobe and cervical lymph nodes recommended for all
patients undergoing thyroidectomy for malignancy; routine preoperative use of other imaging not recommended
|
| ADRENAL INCIDENTALOMA —Jon A. van Heerden, MD, Professor, Department of Surgery, Mayo Clinic College of
Medicine, Rochester, MN
|
| Background: adrenal incidentaloma—found during 2% to 4% of all CTs performed for other indications; definition—
adrenal mass >1 cm, discovered accidentally during radiologic examination, no symptoms or clinical findings of adrenal
disease
|
| Treatment options: excision (risk for unnecessary surgery, morbidity, and mortality); observation (risk for failure to remove
adrenocortical cancer or clinically silent functioning tumor); National Institutes of Health (NIH) recommends all
patients have dexamethasone suppression test and measurements to rule out pheochromocytoma; hypertensive patients
should have serum potassium and plasma aldosterone tests; all functioning tumors and tumors >6 cm should be resected,
tumors <4 cm can be observed; use likelihood of malignancy to decide whether to use open or laparoscopic approach; radiologically
stable (for 6 mo) or hormonally inactive (for 4 yr) tumors require no further management
|
| Key questions about incidentaloma: whether tumor functioning or potentially malignant—aldosterone-producing
tumor unlikely if serum potassium level normal; serum and plasma metanephrine levels (and degradation products) indicate
pheochromocytoma; dexamethasone suppression test rules out hypercortisolism; study—based on CT in 61,000 patients,
rate of adrenal “abnormalities” 3.4%; 33% had metastatic disease, 18% had previous or concurrent malignancy,
and 16.5% had incidentaloma; all tumors <1 cm excluded; mean tumor diameter 2.5 cm; 55 patients underwent surgery, 5
had pheochromocytoma (3 undiagnosed preoperatively), 4 had primary adrenocortical carcinoma (AC), 2 had hypercortisolism,
1 had metastasis; 251 patients followed for >1 yr, with no changes observed; malignant tumors larger (5.5 to >11
cm diameter); mean diameter of AC, 14.5 cm; speaker recommends testing all tumors >1 cm for function, considering resecting
all tumors >4 cm, and retesting all tumors not removed; study of incidentalomas—mean follow-up > 7 yr (87 patients
had >4 yr of follow-up); all had repeat CT; 4 patients underwent surgery for growths >1 cm (all tumors benign
adenomas, and 2 patients had minor episodes of hemorrhage); no cancers or functional tumors detected during study;
concluded majority of incidentalomas harmless; resect tumor if functional or >4 cm; no further follow-up indicated when
tumor <4 cm and no change observed on 2 CTs over 6 mo; laparoscopic approach favored; consider removing 3- to 4-cm
tumors in young adults to avoid lifelong follow-up; fine needle aspiration of adrenal tumor usually not useful
|
| REOPERATIVE PARATHYROID SURGERY —David R. Farley, MD, Professor, Department of Surgery, Mayo Clinic
College of Medicine, Rochester
|
| Background: Patients with primary hyperparathyroidism (1°HPT) usually have adenoma (incidence 85%), hyperplasia
(12%-15%), or 2 to 3 adenomas (2%); parathyroid cancer very rare; 3 situations require repeat operations (ie, patient developed
1°HPT after previous neck surgery, recurrent 1°HPT, or persistent 1°HPT); among previous neck surgeries (eg,
thyroidectomy, carotid endarterectomy, thyroglossal duct cyst), repeat surgery after thyroidectomy most dangerous but
rare
|
| Recurrent 1°HPT: defined as reappearance of 1°HPT after patient remains eucalcemic for 6 mo; test for calcium and
parathyroid hormone (PTH), rule out benign familial hypocalciuric hypercalcemia (BFHH), and image again; determine
whether first surgery removed only largest hyperplastic gland or adenoma removed and now recurring
|
| Persistent 1°HPT: more common; patient hypercalcemic in ≤6 mo; test PTH and urinary calcium, also screen for thiazides
and lithium; review surgical notes and pathology report; repeat imaging
|
| Locating tumor: use US, possibly gamma probe; imaging sensitivity—sestamibi scintigraphy with or without US best;
CT, MRI, and vein sampling useful; study of 228 patients undergoing second surgery at Mayo Clinic found 89% cured,
3% developed hypoparathyroidism, and <1% developed vocal cord palsy; best chance to cure (98%) at first surgery (cure
rate at second surgery, 92%, and at third surgery 77%); researchers at University of California, San Francisco, studied before
and after intraoperative PTH monitoring (IOPTHM) in 102 patients undergoing second surgery; concluded IOPTH
not helpful in locating gland; study from Yale University of 130 patients found 94% cure rate, 1 case of vocal cord paralysis,
and 2 patients with hypoparathyroidism
|
| Locating gland: 75% of repeat surgeries find abnormality next to thyroid or recurrent laryngeal nerve, in tracheoesophageal
[TE] groove, or in thymus; rarely found in thyroid gland, carotid sheath, embedded in esophagus, in mediastinum,
or undescended; look in TE groove for low-lying superior gland
|
| Case reports: patient 1—during 4-hr first surgery, 3 glands biopsied; patient still had 1°HPT postoperatively; surgeon reported
removing left inferior gland, sestamibi showed abnormality in lower left of neck, but surgeon found left superior
gland stuck in TE groove; to locate, find inferior thyroid artery, and open space cephalad to it (often see small blood vessel
in groove near abnormality); patient 2 with persistent 1°HPT—calcium levels 12.5 mg/dL, PTH 120 pg/mL (normal 10-65
pg/mL), urinary calcium high; first surgery removed left inferior gland; second removed left superior gland and right inferior
gland biopsied, right superior gland not found; adenoma actually located in right superior gland, but appeared to be in
inferior gland because of its position in TE groove; patient 3—underwent 2 thoracotomies and 4 neck operations; MEN diagnosed;
patient had high levels of calcium, PTH, and kidney stones; parathyroid tissue located between carina and bifurcation
of trachea; used IOPTHM and patient had PTH level of 200 preoperatively, near undetectable at 10 min;
postoperative difficulties included hypocalcemia, but after 4 yr, calcium level reached 8.4 to 8.7 mg/dL; patient 4—had
undergone 5-hr left-sided thyroidectomy; many dissections and bleeding; pathology report stated left superior gland removed,
biopsy of right inferior and superior glands showed normal tissue; left inferior gland not found; sestamibi scan suggested
parathyroid adenoma; US confirmed no remaining left lobe of thyroid, suggested Hashimoto’s thyroiditis on right,
and detected no enlarged parathyroid glands; another surgery with IOPTHM performed to remove scarred right thyroid
gland (no parathyroid apparent); patient currently has normal calcium levels but PTH of 110.0 pg/mL, and calcium expected
to rise
|
| ENDOCRINE TUMORS OF THE PANCREAS — Dr. van Heerden
|
| Islet cell tumors: among neural crest tumors (formerly, apudomas), which can make any of the polypeptide hormones;
most common include insulinomas, gastrinomas, and carcinoid syndrome; among 322 patients at Mayo Clinic, insulinomas
most common, followed by nonfunctioning tumors (mostly carcinomas), and gastrinomas; at diagnosis, islet cell carcinomas
often large and not curable; must differentiate from more common ductal carcinoma; islet cell cancer less
frequent but more often resectable, with better survival and greater response to chemotherapy than ductal cancer
|
| Key questions: whether tumor functional; whether benign or malignant; whether sporadic or MEN-1—MEN syndrome
often multicentric and bilateral; >99% of patients who have sporadic insulinomas have solitary islet cell adenoma; patients
who have MEN-1 have 15 to 20 insulinomas and need different treatment; age of patient—nesidioblastosis occurs
in neonatal patients but rarely in adults
|
| Glucagonoma: relatively rare; presents as type 2 diabetes, or with rash known as necrolytic migratory erythema (NME);
glucagonoma occurs in alpha cells; large, often in tail; treat by combination of resection plus streptozocin/somatostatin
|
| Gastrinomas: signs of possible Zollinger-Ellison syndrome—peptic ulcer at young age; ulcer that is virulent, perforated,
or bleeding massively; ulcer located in unusual site, eg, jejunum, third or fourth portions of duodenum; presence of large
volume of nasogastric juice in unobstructed stomach; large rugal fold in stomach may indicate Menetrier’s disease, gastric
lymphoma, or Zollinger-Ellison syndrome; recurrent ulcer that develops after proximal gastric vagotomy (PGV) or
truncal vagotomy and enterectomy; unexplained (especially steatorrheic) diarrhea or presence of other endocrinopathies
in patient or family; location—most in duodenum; 11% primary extranodal carcinoid tumors, most in “gastrinoma triangle”;
almost three-fourths of pancreatic tumors found in body and tail; treatment—duodenotomy; study of 151 patients
found only 34% cure rate at 10 yr in patients who had sporadic form because of 65% to 70% rate of malignancy with
nodal metastases; no cures found among patients with MEN-1; detection—somatostatin receptor scintigraphy (octreotide
scan) best method aided by endoscopic US (EUS); endoscopic instruments allow cryo- or thermoablation
|
| Insulinomas: diagnosis—retrospective study showed hyperinsulinism correctly diagnosed in only 50% of patients; incorrect
diagnoses included psychologic and/or behavioral disorders; to confirm, document hypoglycemia and simultaneous
inappropriate hyperinsulinemia, elevated levels of C-peptide (proinsulin), negative test results for certain
medications (eg, sulfonylurea); localization—selective angiography with subtraction techniques, CT used, MRI not favored,
US highly sensitive and shows adjacent anatomy; percutaneous transhepatic selective venous sampling invasive,
poor at localizing, and expensive; EUS useful; intraoperative and preoperative US helpful; speaker recommends monitoring
glucose intraoperatively; treatment—cavitron ultrasonic surgical aspiration (CUSA); do not do blind pancreatectomy
if insulinomas not found
|
Suggested Reading
Bilimoria KY et al: Prognostic score predicting survival after resection of pancreatic neuroendocrine tumors: analysis
of 3851 patients. Ann Surg 247:490, 2008; Coltrera MD et al: Evaluation and imagaing of a thyroid nodule. Surg Oncol
Clin N Am 17:37, 2008; Duenschede F et al: Malignant and unclear histological findings in incidentalomas. Eur Surg
Res 40:235, 2008; Gharib H, Papini E: Thyroid nodules; clinical importance, assessment, and treatment. Endocrinol
Metab Clin North Am 36:707, 2007; Hessman O et al: High Success Rate of Parathyroid Reoperation may be Achieved
with Improved Localization Diagnosis. World J Surg 32:774, 2008; Ito F et al: The utility of intraoperative bilateral internal
jugular venous sampling with rapid parathyroid hormone testing. Ann Surg 245:959, 2007; Lefevre JH et al: Reoperative
surgery for thyroid disease. Langenbecks Arch Surg 392:685, 2007; Libe R et al: Adrenocortical cancer:
pathophysiology and clinical management. Endocr Relat Cancer 14:13, 2007; Modlin IM et al: Gastroenteropancreatic
neuroendocrine tumours. Lancet Oncol 9:61, 2008; Nissan A et al: Prospective trial evaluating electrical impedance
scanning of thyroid nodules before thyroidectomy: final results. Ann Surg 247:843, 2008; Pinchera A: Thyroid incidentalomas.
Horm Res 68 Suppl 5:199, 2007; Quayle FJ et al: Needle biopsy of incidentally discovered adrenal masses is
rarely informative and potentially hazardous. Surgery 142:497, 2007; Salmashoglu A et al: Predictive Value of Sonographic
Features in Preoperative Evaluation of Malignant Thyroid Nodules in a Multinodular Goiter. World J Surg April
[Epub ahead of print], 2008; Samra JS et al: Surgical management of carcinoma of the head of pancreas: extended lymphadenectomy
or modified en bloc resection? ANZ J Surg 78:228, 2008; Schaberg FJ Jr et al: Incidental findings at
surgery. Part 1. Curr Probl Surg 45:325, 2008; Schlosser K et al: Surgical treatment of tertiary hyperparathyroidism: the
choice of procedure matters! World J Surg 31:1947, 2007; Schnelldorfer T et al: Long-term survival after pancreatoduodenectomy
for pancreatic adenocarcinoma: is cure possible? Ann Surg 247:456, 2008; Showalter SL et al: Extra-
gastrointestinal stromal tumor of the pancreas: case report and a review of the literature. Arch Surg 143:305, 2008; Solorzano
CC et al: Intra-operative parathyroid hormone monitoring in patients with parathyroid cancer. Ann Surg Oncol
14:3216, 2007; Tee YY et al: Fine-needle aspiration may miss a third of all malignancy in palpable thyroid nodules: a
comprehensive literature review. Ann Surg 246:714, 2007; Volante M, Papotti M: A Practical Diagnostic Approach to
Solid/Trabecular Nodules in the Thyroid. Endocr Pathol April [Epub ahead of print], 2008; Wiseman JE et al: Cystic
pancreatic neoplasm in pregnancy: a case report and review of the literature. Arch Surg 143:84, 2008;
|
