SURGERY OF THE THYROID AND PARATHYROID GLANDS
| PRIMARY HYPERPARATHYROIDISM: A SURGICAL OVERVIEW —Elizabeth A. Blair, MD, Associate Professor of
Surgery, Department of Otolaryngology–Head and Neck Surgery, University of Chicago Pritzker School of Medicine, Chicago,
IL
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| General: classic clinical features—osteitis fibrosis cystica; renal calculi; peptic ulcers; pancreatitis; clinical
manifestations—depression and neuropsychiatric disorders; clinically, majority of patients have fatigue; anorexia, nausea
and vomiting, and constipation; changes in cardiac arrhythmias and QT interval; in patients with calcium level 11 to
12 mg/dL, systemic symptoms become common; at levels >13 mg/dL, calcification seen in kidneys and skin, with renal
insufficiency; levels 15 to 18 mg/dL medical emergency leading to coma and cardiac arrest
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| Primary hyperparathyroidism (HPT): 80% to 85% sporadic benign adenomas (solitary); double adenomas, 4% of
whole; primary parathyroid hyperplasia, 10%; <1% of familial syndromes parathyroid carcinoma; pathology—solitary
adenomas most common cause of primary HPT (smooth well-encapsulated lesions); hyperplasia—15% of patients; includes
hereditary syndromes, multiple endocrine neoplasia (MEN1, MEN2A, MEN2B); MEN2A—high penetration of
medullary thyroid cancer (multifocal), parathyroid hyperplasia, and pheochromocytoma; MEN2B—HPT seldom
present; medullary thyroid cancer, mucosal neuromas, and pheochromocytoma seen
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| Secondary hyperparathyroidism: result of partial resistance to parathyroid hormone (PTH); gland hyperplasia and
enlargement; chronic renal insufficiency or renal failure most common cause; also seen in vitamin D deficiency (deficient
response to PTH at receptor site)
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| Carcinoma: <1% of primary HPT; more severe clinical manifestations (eg, PTH levels 3-4 times normal, local invasion,
stony consistency of gland); propensity for recurrence
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| Classic operation: explore neck bilaterally; identify all glands; biopsy; remove all enlarged or abnormal tissue
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| Presentation: pattern changing from patients with renal and skeletal manifestations to asymptomatic patients; natural
history—primary HPT associated with increased risk for metabolic dysfunction and premature death; asymptomatic patients
have 23% to 62% risk for symptoms or complications in 10 yr; majority of patients present at >50 yr of age; paradigm
shift from increase in incidental hypercalcemia to steep increase in parathyroid surgery; National Institutes of Health Consensus
Conference (2002)—patients with primary HPT should have parathyroidectomy if age <50 yr, chance of consistent
follow-up poor, serum calcium ≥1 mg higher than upper limit of normal, urine calcium high, renal function decreasing, or
complications of HPT; American Association of Clinical Endocrinologists and Association of Endocrine Surgeons
(2005)—stated that parathyroidectomy only cure for primary HPT; procedure safe and cost effective; goal of operative
treatment is normalization of serum PTH and calcium, with minimum morbidity
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| Advances: intraoperative PTH assay; preoperative sestamibi scan; ultrasonography (US)
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| Minimally invasive parathyroidectomy: small incision (3 cm); unilateral exploration; outpatient surgery under local
anesthetic; 80% to 85% of patients have single enlarged gland; preoperative localization and reduction in length of
procedure and extent of dissection; intraoperative proof of cure
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| Localization studies and modalities: US—widely available; well tolerated; fine needle aspiration (FNA) of lesion
at same time; identification of coexistent thyroid abnormalities; not specific or useful for deep neck or mediastinal lesions;
sestamibi scan—most commonly utilized study; sensitivity 70% to 80%; false-negative scan if sestamibi taken up
by thyroid; multigland disease may not show up easily; inferior quality scan if picture taken too late and isotope washes
out early; not helpful in patients with hyperplasia; incidence of false negatives 20% to 30%; scan lights up based on mitochondrial
density, not absolute size of lesion (planar image); computed tomography (CT), magnetic resonance imaging
(MRI) and digital subtraction imaging—used separately or in conjunction with sestamibi scan; helpful in patients with
negative sestamibi scans
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| Surgery: need accurate diagnosis (calcium level and elevated PTH level); sestamibi scan or US localizes area of greatest
likelihood; intraoperative PTH assays (done in near real time; blood drawn on table and within 7-12 min know whether
change in PTH level); procedure—make incision in lower neck (more toward side to be explored first; PTH drawn in
preoperative holding area during intubation, and once lesion localized, level drawn at time zero and 10 min after resection;
10-min level should be 50% lower than baseline (failure to drop ≥50% suggestive of another adenoma); lack of decrease
in PTH—occurs 6% to 8% of time; reasons include PTH surge from manipulation (wait and repeat level in 10
min); multiple adenomas; ectopic adenoma; hyperplasia; further exploration needed; to confirm identification of gland—
perform transection, frozen sections, or needle aspiration; radiolocalization with gamma probe—sestamibi injected 2 hr
preoperatively; probe used to identify gland intraoperatively (most helpful in solitary adenomas and reoperations); adenomas
20% more radioactive than background tissue (background rule); pitfalls—Hürthle cell tumor or hyperplastic
nodules (occasionally >20% higher than background); scheduling injection and performing procedure within 2 hr; postoperative
considerations—tingling; hypocalcemia (25%-47% of time; associated with secondary HPT); hungry bone
syndrome (patients with severe osteoporosis or high levels of PTH); normocalcemia with persistent elevation of PTH (related
in many cases to vitamin D deficiency); insomnia, tremulousness, and anxiety (due to hyperthyroidism resulting
from operative trauma)
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| Laboratory evaluation: baseline—serum creatinine and calcium; 24-hr urine calcium (familial hyperparathyroid hypocalciuria
not surgical disease); bone density scan; follow-up—biannual serum calcium; annual creatinine; annual bone
density scan; results should approach 97% cure rate at 6 mo postoperatively
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| Serious complications: 2%; greater in reoperations; recurrent laryngeal nerve (RLN) palsy; persistent or recurrent HPT
(most common); hypocalcemia; permanent hypoparathyroidism; bleeding; hematoma; seroma
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| Reasons for failure: initially—persistent elevated calcium (due to persistent disease in 75% of patients); disease in
multiple glands, supernumerary, or ectopic glands; hyperplasia; parathyroid carcinoma; over 6 mo—hyperplasia with regrowth;
parathyromatosis; parathyroid cancer; locally recurrent adenoma
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| Distribution of parathyroids: upper more consistently seen in pericricoidal region; occasionally retroesophageal and
retropharyngeal and behind upper pole; lower gland has greater variability; number of glands varies, with majority having
4 glands, but up to 8 glands reported in literature
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| Reoperation: problems with scarring; dealing with unusual gland locations; chance of increased complications
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| Issues: cost; operative time; hospital stay; patient outcome; standard in community—should patient have subtotal parathyroidectomy
for hyperplasia or total parathyroidectomy with autotransplantation into forearm?
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| Parathyroid carcinoma: calcium level >14 mg/dL; PTH >5 times higher than normal; symptomatic neck mass or invasion
of surrounding tissue; en bloc resection indicated
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| Evaluation: in patient with elevated calcium, order PTH, 24-hr urine (calcium, phosphorous, and creatinine clearance);
rule out MEN syndromes; order bone density scan; sestamibi and US complementary; go to nuclear medicine; counsel
patients about options and complications; schedule surgery and arrange to have PTH done
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| MINIMALLY INVASIVE SURGERY —Richard Hodin, MD, Professor of Surgery, Harvard Medical School, and Chief,
Endocrine Surgical Service, Massachusetts General Hospital, Boston, MA
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| Minimally invasive parathyroidectomy: potential benefits—smaller scar; less pain; quicker recovery; improved
cosmesis; decreased operating time; local anesthesia; shorter hospital stay; decreased complications; reason for rise in
procedure—minimal access surgery in other fields; push by patients and referring physicians; better preoperative localization
studies; availability of rapid intraoperative PTH assays; advent of sestamibi scans; what constitutes minimally
invasive—different answers from different people; size of scar; type of anesthesia; number of sides explored; number of
glands explored; open incision vs endoscopy; hospital stay; patients not candidates—negative preoperative localization
studies; preoperative localization studies or other clinical clues suggesting multigland disease; need for concomitant thyroid
resection
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| Minimally invasive radio-guided parathyroidectomy (MIRP): sestamibi scans—literature biased; sestamibi
scans not 100% accurate; MIRP—based on sestamibi scan (many patients also get US); if positive in one spot, give sestamibi
injection on day of surgery; in operating room (OR), make small incision (under local anesthesia) and use gamma
probe to help guide to radioactive gland; targeted operation; problem with MIRP—background signal from thyroid; sestamibi
potentially helpful when thyroid tissue absent
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| Complications: bleeding and RLN injury (rare); postoperative hypocalcemia; failure to cure (success rates similar
whether minimally invasive or standard operation); study—unilateral (minimally invasive) vs bilateral neck exploration;
prospective randomized trial; cure rates similar; unilateral surgery quicker; decreased postoperative hypocalcemia in unilateral
group
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| Intraoperative PTH monitoring: standard in most centers; important to help identify rare cases of multigland disease
(especially double adenomas); studies—3 studies showed that in ≤50% of cases of double adenomas, intraoperative
PTH failed (PTH levels did not drop appropriately despite cure [problem with assay or blood draw] or levels drop
but patient not cured); problems—takes extra time; potentially not reliable; study—suggests can use various preoperative
studies and intraoperative clues to predict cure, making intraoperative PTH unnecessary
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| Redo parathyroid surgery: important to confirm diagnosis and review previous notes and pathology; repeat studies
often necessary and useful; more extensive localization studies potentially needed if US and sestamibi do not show location
of missing gland; needle aspiration to confirm localization of parathyroid; targeted approach
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| Approaches to parathyroid surgery: techniques with scopes; question whether all large glands functional at time of
surgery or functional later; bilateral exploration—study of 350 patients with sporadic primary HPT with bilateral explorations
found additional 15% of patients had enlarged glands after removal of target gland and drop in PTH; imperative to
look for other glands (bilateral exploration in everyone); targeted operation—study showed success rate of 97%; 3% incidence
of multigland disease; some big glands not hyperfunctional at time of surgery (question of potential future hyperfunctioning);
standard 4-gland exploration—reasonable; takes more time; may have increased complication rates; not
needed in majority of patients; leads to identification of big glands potentially not hyperfunctioning
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| PAPILLARY CARCINOMA: PREOPERATIVE ULTRASONOGRAPHIC STAGING —Hernán E. Gonzalez, MD, Assistant
Professor, Head and Neck Surgery, Division of Surgery, University of Texas MD Anderson Cancer Center, Houston
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| Introduction: papillary thyroid carcinoma—high rate of lymph node metastases; in routine endocrine practice, patients
with thyroid nodule undergo US and FNA; if malignancy confirmed, patients referred to surgery with no further evaluation;
if staging of neck based only on physical examination, possible that small macroscopic metastases may escape diagnosis;
high-definition US has allowed localization of small pathologic nonpalpable lymph nodes and better planning of
surgery
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| Study: 60 patients with FNA-confirmed diagnosis of papillary thyroid carcinoma in whom thyroid US showed nonpalpable
neck disease admitted to study; lymph nodes considered highly suspicious for metastasis if minor axis >10 mm, minor
axis >50% of major axis, hyperechogenicity present (with or without microcalcifications); if US negative, careful
exploration of central compartment performed to search for undetected adenopathy; presence of macroscopic metastases
confirmed by US-guided FNA or intraoperative frozen sections; if metastases confirmed in central compartment, paratracheal
dissection done; if metastases confirmed in lateral neck, comprehensive dissection of all levels performed; removed
lymph nodes divided in OR and sent to pathologist so status of each node level found by US could be correlated with pathology
report; only macroscopic metastases considered; results—of 60 patients with clinically negative necks, US identified
12 patients with suspicious adenopathy (20%); of these patients, biopsy confirmed 11 positive for metastases;
summary of results—positive predictive value 92%; sensitivity 92%; specificity 98%; in lateral neck, all sites identified
by US as having pathologic lymph nodes confirmed by final pathology report; in central compartment of 9 patients reported
to have disease, 8 patients confirmed by pathology; one patient found to have disease by central compartment exploration
(missed on US); of patients undergoing comprehensive dissection, microscopic metastases found in 9 additional
neck levels; significant proportion of patients (18%) with papillary carcinoma and nonpalpable adenopathy have microscopic
neck disease; conclusion—in papillary thyroid carcinoma, preoperative neck US effective in identifying patients
with nonpalpable neck metastases
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| MINIMALLY INVASIVE VIDEO-ASSISTED THYROIDECTOMY —David Terris, MD, Porubsky Professor and Chairman,
Department of Otolaryngology, Medical College of Georgia, Augusta
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| Introduction: study to explore incidence of complications and safety of procedure; minimal incision (15-20 mm low
in neck); video assistance primarily critical for superior pole but helpful in identifying RLN inferiorly; harmonic
shears essential for managing inferior and superior pedicles through small incision; drains usually not required; Dermabond
used instead of sutures; outpatient procedure; patient selection critical (nonobese individuals; nodule size 25-30
mm; normal-sized thyroid gland; no preoperative thyroiditis); most lesions follicular neoplasms of unclear malignant
potential, low-risk papillary thyroid carcinoma, and small multinodular goiters
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| Surgery: vessels individually ligated with harmonic technology; can get to within 2 to 3 mm of nerve because of reduced
temperatures (80°C-100°C vs 400°C with electrocautery); 3-person surgery (surgeon, camera assistant, and retractor assistant);
find nerve low, using inferior thyroid artery branches as landmark; blunt dissection perpendicular to direction of
nerve
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| Study: 228 patients candidates for endoscopic surgery; mean age 44 yr; majority hemithyroidectomies; mean incision
length ≈1 in; ≈20% malignant; complication rate 7.4% (no hematomas; no permanent hypocalcemia; no permanent vocal
cord paralysis; results compare favorably with conventional open surgery); advantages of endoscopic approach—
superior visualization with endoscope; small incision confers better cosmetic outcome; reduced dissection (rapid wound
healing); disadvantages—additional equipment required (endoscopic tower); 2 assistants necessary; longer surgery
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Suggested Reading
Aarum S et al: Operation for primary hyperparathyroidism: the new versus the old order. A randomized controlled trial
of preoperative localization. Scan J Surg 96:26, 2007; Abraham D et al: Utility of ultrasound-guided fine-needle aspiration
of parathyroid adenomas for localization before minimally invasive parathyroidectomy. Endocr Pract 13:333, 2007;
Barczynski M et al: Intraoperative parathyroid hormone assay improves outcomes of minimally invasive parathyroidectomy
mainly in patients with a presumed solitary parathyroid adenoma and missing concordance of preoperative imaging.
Clin Endorinol 66:878, 2007; Di Stasio E et al: Parathyroidectomy monitored by intra-operative PTH: the
relevance of the 20 min end-point. Clin Biochem 40:595, 2007; Johnson NA et al: Parathyroid imaging: technique and
role in the preoperative evaluation of primary hyperparathyroidism. AJR Am J Roentgenol 188:1706, 2007; Lombardi
CP et al: Minimally invasive video-assisted functional lateral neck dissection for metastatic papillary thyroid carcinoma.
Am J Surg 193:114, 2007; Ogawa T et al: Preoperative evaluation of thyroid pathology in patients with primary hyperparathyroidism.
Thyroid 17:59, 2007; Prasannan S et al: Minimally invasive parathyroidectomy using surgeon-performed
ultrasound and sestamibi. ANZ J Surg 77:774, 2007; Richards ML, Grant CS: Current applications of the
intraoperative parathyroid hormone assay in parathyroid surgery. Am Surg 73:311, 2007; Riss P et al: A “defined baseline”
in PTH monitoring increases surgical success in patients with multiple gland disease. Surgery 142:398, 2007; Rubello
D et al: Minimally invasive radio-guided parathyroidectomy on a group of 452 primary hyperparathyroid patients:
refinement of preoperative imaging and intraoperative procedure. Nuklearmedizin 46:5, 2007; Somashekhar SP et al:
Minimally invasive radioguided surgery for parathyroid adenomas (MIRP). Natl Med J India 20:13, 2007; Terris DJ,
Chin E: Clinical implementation of endoscopic thyroidectomy in selected patients. Laryngoscope 116:1745, 2006; Venkatramen
L et al: Primary hyperparathyroidism and metastatic carcinoma within parathyroid gland. J Clin Pathol
60:1058, 2007; Yew MK, Thompson IJ: Minimally invasive parathyroidectomy: an audit of a change in clinical practice.
ANZ J Surg 77:24, 2007.
 | Educational Objectives
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| The goal of this program is to improve the surgical management of parathyroid and thyroid diseases. After hearing
and assimilating this program, the clinician will be better able to:
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| 1. Review the evaluation and treatment of primary hyperparathyroidism.
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| 2. Discuss minimally invasive approaches to parathyroid surgery.
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| 3. Explain the use of intraoperative monitoring of parathyroid hormone.
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| 4. Explain the use of ultrasonography in the staging of papillary thyroid carcinoma.
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| 5. List advantages and disadvantages of the endoscopic approach to thyroidectomy.
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Faculty Disclosure
In adherence to ACCME Standards for Commercial Support, Audio-Digest requires all faculty members 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, the following has been disclosed: Dr. Terris was course director of Thyroid Symposium
for Ethicon Endo-Surgery and consultant for instrument development for Medtronic Xomed.
Acknowledgements
Dr. Blair was recorded at the Chicago Laryngological and Otological Society (CLOS) program held February 5, 2007
in Chicago, IL. Drs. Gonzalez and Terris were recorded at 2007 Annual Meeting, The American Head & Neck Society
during the Combined Otolaryngology Society Meetings (COSM) held April 28-29, 2007, in San Diego, CA. Dr. Hodin
was recorded at Surgery of the Thyroid and Parathyroid Glands, held November 17-18, 2006, in Boston, MA, and
sponsored by Harvard Medical School, Massachusetts Eye Infirmary, and Massachusetts General Hospital. The Audio-Digest
Foundation thanks the speakers and the sponsors for their cooperation in the production of this program.
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