MANAGING THYROID AND PARATHYROID DISEASE
| MEDICAL MANAGEMENT OF HYPERTHYROID AND HYPOTHYROID STATES —Ray Bauer Vaughters III, MD,
Clinical Endocrinologist, Aiken Regional Medical Center, Aiken, SC
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Hypothyroidism
| Options for thyroid hormone replacement: desiccated thyroid extract (Armour Thyroid)—contains desiccated
cow and pig thyroid; replaced by synthetic hormone; preferred by patients seeking “more natural” therapy; currently not
recommended for treating hypothyroidism; points about desiccated extract—thyroid function in humans differs from
thyroid function in cows and pigs; desiccated extract lacks precise standardization; some individuals developed thyrotoxicosis
after consumption of hamburger containing bovine thyroid tissue; levothyroxine (L-thyroxine; T4 ) [Levoxyl, Synthroid,
Unithroid]—gold standard for managing hypothyroidism; combination therapy with levothyroxine and
liothyronine (triiodothyronine [T3 ]; Cytomel)—patients with thyroid-stimulating hormone (TSH) ≤1 mIU/L who are
still “dragging and tired” while on 100 µg/day of levothyroxine can be switched to combination of 50 µg/day of levothyroxine
and 5 µg of liothyronine bid; if patient’s sense of well-being does not improve within 3 mo, withdraw liothyronine
and reinitiate 100 µg/day of levothyroxine; supplemental thyroid complexes, eg, Thyrin ATC—widely available; promoted
for optimal thyroid function and resultant weight loss; clinical data lacking to support routine use
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| Observations on thyroid hormone replacement: compliance problems mandate monitoring; elderly—achieve
maximum TSH levels of 10 to 15 mIU/L; should not receive 75 to 100 µg/day of levothyroxine immediately (aggressive
approach exacerbates preexisting problems, eg, heart failure); protocol for increasing levothyroxine dose—
12.5 µg/day for 2 wk; 25 µg/day for 2 wk; 50 µg/day for 2 wk
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 | Adrenal crisis: lack of adrenal reserve key concern when treating severe hypothyroidism; adrenal crisis avoided by obtaining
cortisol level before treating at-risk individuals (test results available in ≈3 days); recommended approach for managing
severe hypothyroidism—obtain cortisol level; initiate empiric therapy with hydrocortisone and levothyroxine; once cortisol
level determined, wean patient off hydrocortisone
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| Myxedema coma: misnomer because most patients can communicate verbally; potentially fatal if undetected prior to
surgery; can cause—neurologic symptoms; altered mental status; heart failure and other cardiac symptoms; evaluation
of patients with severe myxedema coma—TSH level relatively poor diagnostic tool because pituitary function
declines with prolonged disease; measurement of free T3 and free T4 recommended
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| Intravenous (IV) levothyroxine therapy: used because—most patients cannot swallow; IV T3 therapy prohibitively expensive;
patients usually demonstrate good response in ≤4 days; point—patient should have detectable thyroid hormone
levels before undergoing surgery; approach—administer 300- to 500-µg IV dose of levothyroxine initially (100
µg bid for patients who have cardiovascular disease); follow initial dose with 50 to 100 µg/day IV until oral replacement
can be initiated; IV hydrocortisone mandated by risk for adrenal failure and blunted adrenal response in severely
hypothyroid state
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Hyperthyroidism
| Low-uptake state: usually transient; sometimes intermittent anti-inflammatory or glucocorticoid therapy indicated for
patient with thyroiditis; surgery may be appropriate for patients with prolonged amiodarone-induced thyroiditis
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| High-uptake state: patients generally have Graves’ disease or toxic multinodular goiter
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| Nonsurgical options: propranolol—recommended β-blocker; decreases conversion of T4 to T3 ; if patient’s cardiovascular
status can tolerate approach, administer 40 mg qid initially (patients with low blood pressure can receive 20 mg
qid); speaker finds 6-hr dosing intervals for propranolol more effective than once-daily atenolol; compliance problem
among patients with hyperthyroidism (nature of disease; enlist family member to ensure patient follows protocol); methimazole
(Tapazole) and propylthiouracil (PTU) therapy—requires periodic assessment of transaminase levels; if
patient develops fever, monitor for low white blood cell count; supersaturated potassium iodide (SSKI; Lugol’s
solution)—causes Wolff-Chaikoff effect; inhibits iodide organification; effect transient; should not be administered
on outpatient basis (ie, situation may worsen if patient stops using solution without proper follow-up evaluation); unless
adequate supervision exists to support outpatient therapy, administer solution in hospital for 1 to 2 days before surgery;
131 I may—take ≤6 mo to work (thyroid hormone levels may increase within first 2 to 4 wk after treatment);
exacerbate exophthalmos in patients with Graves’ eye disease
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| Surgery: new technology has produced smaller scars and improved outcomes; patients respond quickly and are pleased
with results; candidates for surgery—have large goiters or high thyroid hormone levels that have not decreased significantly
on oral therapy; are not considered capable of maintaining appropriate follow-up; immediate surgery—
performed to maximize therapeutic benefit; letting patient remain thyrotoxic for 3 to 6 mo can adversely affect cardiac
function; preoperatively—start methimazole (40 mg/day initially) and β-blocker therapy; administer SSKI 5 to 7
days before surgery; glucocorticoids can be given when concerned about inflammation or when thyroid hormone levels
markedly elevated
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| Postoperatively: usually wait 5 to 7 days before initiating thyroid hormone therapy (in some cases therapy may be started
3 days after surgery); some patients can be given prescription to initiate low-dose therapy on outpatient basis (look for
residual thyroid function at 2 wk); TSH—good screening tool but poor follow-up test until patient stabilizes on appropriate
replacement dose of levothyroxine (may take 3-6 mo for TSH level to decrease; data obtained during time lag
may prompt physician to administer overdose of levothyroxine); pointers—use free T3 and T4 to monitor patient until
TSH drops into normal range
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| Bottom line: potential risks of surgery outweighed by low complication rates, risks associated with postponing definitive
therapy, rapid improvement that occurs after surgery, and ability to avoid problems associated with noncompliance and
poor follow-up
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| Points on compliance: call pharmacy to make sure patient has filled prescription within last 6 mo; if problem occurs,
address issue with patient
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| CONTROVERSIES IN THYROID AND PARATHYROID SURGERY —David J. Terris, MD, Porubsky Professor and
Chair, Department of Otolaryngology–Head and Neck Surgery, Medical College of Georgia, Augusta
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| Outpatient thyroid and parathyroid surgery: requires patients stay in recovery 90 to 120 min before going home;
made possible by modern technology; proven safe and desirable in selected patients; traditional requirement for 1- to
3-day hospital admission based on—perceived need to elevate subplatysmal flaps; 4-gland exploration during parathyroidectomy;
common use of drains; need to monitor calcium levels for 1 to 3 days after surgery
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| Factors contributing to new interest in outpatient surgery: smaller incisions; reduced dissection achieved by abandoning
subplatysmal flap; harmonic technology; reassessment of need for drains—most surgeons place drains routinely after
endocrine surgery of neck to prevent seromas and expanding hematomas; data show lack of drain placement does
not alter treatment outcome; routine oral calcium supplementation after total thyroidectomy—eliminates need for
prolonged hospitalization mandated by postoperative calcium monitoring; avoids transient hypocalcemia that often develops
after thyroid surgery; requires patient undergo 3-wk taper of oral calcium, starting on evening of surgery (administer
1.8 g/day in 3 divided doses during first week, 1.2 g/day during second week, and 600 mg/day during third
week); patients and family members must be counseled to identify signs and symptoms of hypocalcemia (if problems
develop, admit patient to emergency department); data show no patients who received oral calcium supplementation
after total or completion thyroidectomy developed hematomas or permanent vocal cord paralysis
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| Additional aspects: outpatient surgery—reduces costs; allows patient to convalesce at home; decreases exposure to
nosocomial organisms (general anesthesia renders patient immunocompromised); protects patients from iatrogenic
problems inherent in hospital environment; patients who require hospitalization—are medically infirm; have large
dead space that requires drainage after surgery; have known bleeding dyscrasia and anticipated postoperative oozing that
requires drain placement; prefer being hospitalized overnight
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| Nerve monitoring: laryngeal electromyographic (EMG) endotracheal tube major advancement in monitoring technology;
surface electrodes bridge vocal cords, and muscle twitch provides audible feedback that informs surgeon if nerve being
injured or stimulated; helps confirm presence and integrity of nerve and provides feedback about nerve traction; skill
improves with experience; reasons for not monitoring nerve—added cost; false-positive findings (frustrating); possibility
of false-negative finding requires that surgeon not rely totally on nerve monitor during surgery; data show—
identifying and dissecting nerve safer than trying to avoid nerve; statistically significant improvement in safety achieved
when nerve monitor used while operating on patients with Graves’ disease or during thyroid surgery performed in “medium-volume”
hospitals (in United States, most thyroid surgery performed in medium-volume hospitals); key points—
relatively low incidence of nerve injuries prevents definitive evaluation of true efficacy of nerve monitoring; surgeons
who operate on <45 at-risk nerves each year derive greatest benefit from using nerve monitor
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| Endoscopic and minimally invasive parathyroid surgery: lends itself to focused approach; performed using
general or local anesthesia; improves cosmesis because approach requires minimal incision (0.5-0.75 in); reduced dissection
decreases trauma to patient; performed on outpatient basis
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| Disease localization: sestamibi scans for evaluating tertiary hyperparathyroidism—useful; modest investment that
can save time in surgery and avoid frustration from not locating ectopic parathyroid gland; detected higher rate of ectopic
glands in patients with tertiary hyperparathyroidism; sensitivity good; to improve efficacy, physicians should
read scans themselves
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| Intraoperative identification of adenoma: image-guided surgery rarely performed with radioprobe; evaluation using IV
methylene blue—rarely performed; uses large (7.5 mg/kg) dose of methylene blue; not approved by Food and Drug
Administration (FDA); not without risk; helpful in selected cases; must include anesthesiologist because O2 saturation
monitor does not work while methylene blue being infused and therefore cannot detect spurious downward shift in O2
saturation
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| Localization: facilitates directed surgery for primary hyperparathyroidism; identifies ectopic gland before initiating surgery
for tertiary hyperparathyroidism
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| PAPILLARY MICROCARCINOMA —Douglas S. Ross, MD, Associate Professor of Medicine, Harvard Medical School;
Co-Director, Thyroid Associates, Massachusetts General Hospital, Boston
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| Papillary microcarcinoma: major factor contributing to perceived increase in incidence of thyroid cancer; defined as
papillary carcinoma ≤10 mm in maximal diameter; occult papillary carcinoma—term formerly used to describe disease;
defined as <10- to 15-mm nonpalpable, intrathyroidal lesions; concept rendered obsolete by introduction of high-
resolution ultrasonography, ie, <2-mm lesions no longer occult; data show—≈6% mean prevalence in United States;
variability in prevalence rates can be traced to how carefully researchers look for microcarcinoma; prevalence often independent
of age; prevalence ranges from 2% to 24% for microcarcinomas detected incidentally during thyroidectomy for
benign thyroid disease; assessing “epidemic”—data show rate of diagnosed thyroid cancer has doubled over last several
decades, but mortality rate has not changed; ascertainment bias exists because of role played by aggressive use of ultrasonography
in creating epidemic of papillary microcarcinoma
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| Natural history of papillary microcarcinoma: <2% of lesions attract clinical attention; observations from Japanese
data—aggressive approach not necessary for nodules <10 mm (little happens to these nodules over time); when
nodules grow to >10 mm or patients develop lateral nodes, intervention may be necessary; factors increasing risk for
recurrence—age >45 yr; extrathyroidal extension; nodal metastases; bilateral disease
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| Most series reviewed show: rates of incidentally discovered disease vary widely; multifocal disease approximately one
third of cases, and bilateral disease 10% to 16% of cases; incidence of—extrathyroidal disease ranges from 2% to 5%;
nodal metastases ≈20%; distant metastases range from 0.2% to 0.4% overall; nodal recurrence rates 2.5% to 5.0%; local
recurrence rates <4%; mortality rate <1%
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| Selection of treatment approach: data suggest extensive near-total thyroidectomy should be performed when disease
detected in advance
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| Nonrandomized trial evaluating extent of node dissection: patients—with palpable nodes underwent therapeutic node
dissection; with disease diagnosed in advance, underwent prophylactic node dissection; did not undergo node dissection
if tumor discovered incidentally; comparison of data shows—recurrence rates similar with or without prophylactic
node dissection; patients who underwent therapeutic node dissection had worse disease and experienced higher
recurrence rates; conclusion—findings suggest prophylactic node dissection unnecessary
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| Role of 131 I therapy: data suggest 131 I for papillary cancer—of no value for patients with stage 1 disease, tumors <1
cm, or low-risk disease in general; helpful for multifocal disease, bilateral disease, or disease with lymph node involvement
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| In patients who do not have stage 1 papillary microcarcinoma: according to TNM staging, among patients—<45 yr of
age (131 I therapy unnecessary; development of distant metastases only way disease can advance to stage 2); >45 yr of
age (central nodal involvement classifies patient as having stage 3 disease; one third of patients with papillary microcarcinomas
have central nodes)
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| Treatment recommendations: near-total thyroidectomy when appropriate; if nodes palpable, perform therapeutic
node dissections (avoid prophylactic node dissections); treat patients with stage 2 to 4 disease with completion thyroidectomy
or 131 I therapy; stage 1 disease—controversial; American Thyroid Association guidelines recommend using 131 I
ablation to manage selected patients with stage 1 disease, ie, individuals with multifocal disease, nodal metastases, extrathyroidal
or vascular invasion, and/or more aggressive histologies
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Suggested Reading
Abraham P et al: Antithyroid drug regimen or treating Grave’s hyperthyroidism. Cochrane Database Syst Rev
(2):CDOO3420, 2005; Hass SN: Management of papillary microcarcinoma of the thyroid. SD Med 59:425, 2006; Ito Y,
Miyauchi A: A therapeutic strategy for incidentally detected papillary microcarcinoma of the thyroid. Nat Clin Pract
Endocrinol Metab 3:240, 2007; Ross DS: The medical management of Graves’ disease. Endocr Pract 1:193, 1995;
Terris DJ et al: Outpatient thyroid surgery is safe and desirable. Otolaryngol Head Neck Surg 136:556, 2007; Terris
DJ et al: Ultrasonic technology facilitates minimal access thyroid surgery. Laryngoscope 116:851, 2006; Terris DJ,
Chin E: Clinical implementation of endoscopic thyroidectomy in selected patients. Laryngoscope 116:1745, 2006;
Varughese GI et al: Caveats in treating thyroid disease: practical implications. JR Soc Med 99:582, 2006; Wartofsky
L: Myxedema coma. Endocrinol Metab Clin North Am 35:687, 2006.
Educational Objectives
| The goal of this program is to improve the management of common thyroid and parathyroid diseases. After hearing and assimilating
this program, the clinician will be better able to:
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| 1. Implement appropriate therapy for hypothyroidism and myxedema coma.
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| 2. Discuss appropriate management options for treating low-uptake and high-uptake hyperthyroidism.
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| 3. Review current developments that have increased the therapeutic viability of outpatient surgery for thyroid and parathyroid
disease.
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| 4. Assess the current role of nerve monitoring, endoscopy, and imaging in the management of parathyroid disease.
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| 5. Make use of current data on the natural history and management of papillary microcarcinoma.
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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 is affiliated with Ethicon Endosurgery
and Medtronic-Xomed.
Acknowledgements
Dr. Ross gave his scientific lecture at Surgery of the Thyroid and Parathyroid Glands, held November 17-18, 2006, in
Boston, MA, and sponsored by Harvard Medical School, Massachusetts Eye and Ear Infirmary, and Massachusetts General
Hospital; Dr. Terris addressed the Annual Clinical Conference of the Kansas City Society of Ophthalmology and Otolaryngology,
held January 5-6, 2007, in Kansas City, MO; Dr. Vaughters gave his scientific lecture at Minimally Invasive Surgical
Management of Thyroid and Parathyroid Disorders, held November 10-11, 2007, in Augusta, GA, and sponsored by
the Medical College of Georgia, Augusta. The Audio-Digest Foundation thanks the speakers, Harvard Medical School, the
Kansas City Society of Ophthalmology and Otolaryngology, Massachusetts Eye and Ear Infirmary, Massachusetts General
Hospital, and the Medical College of Georgia for their cooperation in the production of this program.
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