THOUGHTS ON THYROID DISEASE
| UPDATE ON THYROID DISEASE IN WOMEN —Veronica Piziak, MD, PhD, Professor of Medicine and Endocrinology,
Texas A & M University System Health Science Center College of Medicine, College Station, and Chief of Endocrinology,
Scott and White Clinic, Temple, Texas
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| Screening: universal screening problematic; candidates for screening have—autoimmune disease; type 2 diabetes; family
history of thyroid disease; postpartum thyroiditis; iatrogenic causes of hypothyroidism—head and neck surgery; radiation
therapy for lymphoma or breast cancer; chemotherapy; iatrogenic thyroiditis; pharmacologic causes of thyroid
disease—amiodarone (most common medication causing hypothyroidism); lithium (50% incidence of goiter and clinically
significant hypothyroidism mandates screening people who take lithium); interleukin-2 (IL-2) increases risk for thyroiditis
among individuals with previous episode or family history of thyroid disease; high doses of iodine cause
thyroiditis; exclude thyroid disease as cause of other diseases—atrial fibrillation; obesity; unexplained weight loss;
dementia (hypo- and hyperthyroidism); unexplained neuropathy (hypothyroidism); muscle weakness (hyperthyroidism)
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| Approach to medication-related problem: stop or change medication; if medication cannot be changed, give short burst
of steroid for hyperthyroidism, or thyroid replacement therapy for hypothyroidism
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| Screening tools: thyroid-stimulating hormone (TSH) analysis—≈85% accurate; cannot assess patients with acute disease
or immediately after surgery; 85% accurate assays vary with laboratory; free T4 analysis—sorts out remaining 15% of patients;
current TSH values—0.4 to 4.0 µIU/mL considered normal; 4.0 to 10.0 µIU/mL indicates subclinical hypothyroidism
(free T4 and circulating hormone levels normal); >10 µIU/mL indicates primary hypothyroidism; T4 low); subclinical
hypothyroidism—treatment may not be necessary; free T4 and circulating hormones normal; patient may have thyroiditis
or other illness and may be progressing toward hypothyroidism; thyroid failure—in euthyroid situation, circulating T4
lowers TSH; as hypothyroidism develops, TSH increases, and first T4 , then T3 drops; caveat—definition of normal TSH
controversial
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| Thyroid function tests: TSH—inexpensive; assesses pituitary gland response to thyroid function; useless in patients with
severe illness, head injury, meningitis, or dysfunctional pituitary gland; total T4 —useless; includes binding protein abnormalities
found in all pregnant women; free thyroxine index (FTI)—expensive; does not involve binding protein abnormalities;
evaluates free circulating hormone levels; 123 I uptake—shows how well thyroid takes up iodine and
incorporates it into thyroid hormone (TH); differentiates hyperthyroidism with endogenous cause (eg, Graves’ disease)
from thyroiditis or hyperthyroidism caused by consumption of too much TH
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| Primary hypothyroidism: 26 yr old woman—presented with amenorrhea, gravida 1/para 1 (G1/P1), oral contraceptive use,
and maternal history of hypothyroidism; physical findings include narrow pulse pressure (blood pressure [BP] 140/96 mm Hg),
heart rate 60 bpm, height 5 ft 4 in, weight 120 lb, enlarged, firm, nonnodular thyroid, and no palpable lymph nodes in neck; laboratory
evaluation confirmed diagnosis of primary hypothyroidism with TSH 56 µIU/mL and prolactin 45 ng/mL; goals—
TSH between 0.5 and 3.0 µIU/mL or free T4 in upper third of reference range; achieved with thyroxine 1.5 to 1.7 µg/kg per day
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| Pregnancy and thyroid disease: women who are hypothyroid have difficulty becoming pregnant and may give birth to abnormally
developed babies; those who are hyperthyroid become pregnant relatively easily and may have placental insufficiency;
patients must be screened each trimester—free T4 levels valid throughout pregnancy; because placenta produces
TSH-like agent, TSH level may go up during first trimester or free T4 may drift down during second or third trimester;
treatment—replacement therapy averages ≈30 µg of thyroxine
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| Secondary hypothyroidism caused by prolactinoma: 46 yr old woman—presented with fatigue, swelling, tingling feet,
constipation, thickened skin, and amenorrhea; physical findings include narrow pulse pressure (BP 140/100 mm Hg),
heart rate 56 bpm, mild obesity, periorbital swelling, delayed reflex relaxation time (key finding; sensitive test for hypothyroidism),
and no goiter; laboratory analysis showed normal TSH (TSH level of no value), low FTI and free T4 levels,
prolactin 536 ng/mL, and low follicle-stimulating hormone [FSH] and cortisol levels; diagnosis—secondary
hypothyroidism; prolactinoma causing pituitary and thyroid problems; analysis of—prolactin level indicated in secondary
hypothyroidism (tumor marker for pituitary disease); cortisol level necessary when prolactin elevated (determines
risk for hypotensive event); management—treat tumor, hypothyroidism, and hyperprolactinemia; normalize free T4
(monitor FTI if free T4 unavailable); cabergoline (Dostinex) therapy avoids rage attacks and hallucinations associated
with bromocriptine
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| Subclinical hypothyroidism: 72 yr old woman—presented with angina and tachycardia treated with amiodarone; findings
on initial laboratory analysis included TSH of 10 µIU/mL (indicative of subclinical hypothyroidism), free thyroxine level 1.2
ng/dL (no problem with circulating thyroid hormone [TH]), and ejection fraction of 58%; patient failed to return in 1 mo;
overt hypothyroidism diagnosed at 3 mo (TSH 76 µIU/mL; weight gain, goiter, pericardial effusion); treatment—to improve
symptoms; probably will not reduce TSH to 2.5 µIU/mL; increase initial 12.5 to 25 µg/day thyroxine dose by 25 µg every 2
wk
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| Replacement therapy: L -thyroxine—use brand name drugs; alternatives not bioequivalent and may lack bioavailability;
avoid desiccated thyroid (fixed T3 dose can cause problems in elderly or patients with arrhythmias); replacement requirements
affected by—medications that speed up metabolism, eg, phenobarbital and phenytoin (Dilantin); medications
that interfere with absorption (eg, cholestyramine, multivitamins with iron, sucralfate, and calcium complex); herbal
agents; point—absorption problems avoided by not taking thyroxine at same time as charged agents; 5% of patients develop
problems when switched to another brand of thyroxine—monitor patient; if problem develops, check TSH
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| Hypothyroidism: subclinical—management controversial; 20% of patients progress to overt hypothyroidism; risk for progression
high among patients with thyroid peroxidase antibodies; 30% of patients have thyroiditis and experience resolution
of problem; treatment—decreases cholesterol and weight; increases cardiac contractility, cardiac O2 demand, bone loss,
and risk for arrhythmia; when treating subclinical disease—monitor patient; maintain normal TSH levels; wait 6 to 8 wk
between dosage changes; unhappy hypothyroid patient—has normal TH values; usually has mixed symptoms, eg, lacks
energy, skin dry; achieve TSH of 2.0 to 2.5 µIU/mL or maximum free T4 value (do not allow TSH to drop below 0.4 µIU/
mL); point—combination of T3 and T4 does not enhance clinical efficacy
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| Ophthalmologic emergency: in hyperthyroidism, orbital erythema can lead to congestive ophthalmopathy and blindness;
treat with radioactive iodine and thyroxine
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| Antithyroid medications: less effective than definitive therapy; indicated in pregnant women; monitoring—free T4 in
most patients; TSH levels in nonpregnant women; options—propylthiouracil indicated in pregnant women; methimazole
(has fewer side effects and longer half-life) used most often in nonpregnant patients; point—long-term use of antithyroid
medications contraindicated
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| Subclinical hyperthyroidism: 22 yr old woman—asymptomatic; total T3 , free T3 , and free T4 levels normal; treatment unnecessary;
monitor free T4 on annual basis, sooner if symptoms develop; increased incidence of atrial fibrillation and
embolic disorders—risk associated with monitoring; should problems develop, eg, palpitations, patient can take aspirin
and call physician; 17 yr old girl—presented with weight loss, nausea, vomiting, diarrhea, muscle weakness, TSH of 0.31
µIU/mL, and normal thyroid on palpation; if disease suspected and other tests normal, perform 123 I uptake test; if thyroiditis
present, treat symptoms—buffered aspirin for pain; low-dose β-blockers for tachycardia; hydration; methylprednisolone
for marked problem
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| Multinodular goiter: TSH evaluation—necessary when biopsy not performed; if TSH normal, biopsy necessary; if TSH elevated,
patient has hypothyroidism and requires 3 mo of suppression (if situation does not improve at 3 mo, obtain biopsy); if
TSH suppressed, obtain free T4 ; if free T4 elevated, obtain 123I scan
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| ADJUVANT 131I THERAPY FOR THYROID CANCER —Hadyn T. Williams, MD, Associate Professor of Radiology,
and Section Chief of Nuclear Medicine, Medical College of Georgia School of Medicine, Augusta
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| Thyroid cancer management: total thyroidectomy cannot eliminate all diseased tissue; 131 I ablation—ablates multifocal
and occult cancer; facilitates detection and treatment of metastases; improves sensitivity of follow-up thyroglobulin assays
or 131 I whole-body scans; patients at increased risk of dying from cancer—≥40 yr of age; had near-total thyroidectomy;
have less well differentiated or ≥5-cm tumor; have papillary cancer extending through thyroid capsule or
follicular cancer extending through tumor capsule; have multifocal or metastatic disease; require 131 I therapy after surgery;
patients at decreased risk—young; underwent total thyroidectomy; have well-differentiated, ≤1.5-cm lesion confined
to thyroid or tumor capsule; have unifocal disease; no metastases; point—patients presenting with all features of
decreased risk may not need 131 I therapy; patients with borderline risk—have 1- to 5-cm tumors; have disease that does
not extend through capsule; have unifocal disease, no metastases and require 131 I ablation
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| Hospitalization: recommended by Medical College of Georgia for all patients who receive ≥100 mCi of 131 I (because of
Georgia state regulations governing responsibility for radiation exposure); provides opportunity to treat side effects, eg,
nausea; prevents radiation exposure to other people; point—with biologic half life of 131 I <1 day, most patients released
from hospital after overnight stay
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| High-dose 131 I therapy: complications rare with initial dose ≤200 mCi; initial administration of high-dose 131 I provides
best opportunity for cure; fixed dosing schedule equals efficacy of individualized dosing and administers—100 to
150 mCi to disease localized to thyroid bed; 150 to 200 mCi for cervical metastases; 200 to 300 mCi for distant metastases;
caveat—metastatic lesions highly avid for fluorodeoxyglucose on positron-emission tomography (FDG-PET)
more resistant to 131 I therapy
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| 131 I therapy: β-particles—majority of radiation dose; penetrate ≈2 mm into tissue, ie, short pathway limits damage to
surrounding tissues and explains spotty distribution of 131 I in neoplastic foci; ionizing radiation from β-particles causes
cell death; γ-radiation—10% of radiation dose; irradiates patient and environment; metabolism of 131I—altered in cancer
tissue; uptake via sodium/iodide symporter (NIS) system decreases (inability to detect activity produces false-negative
scans); organification and effective half-life decrease; response to TSH stimulation usually present, even when uptake of 131 I
not clinically evident on scan; heterogeneous uptake of 131 I in tumors explains why treatment ineffective in some patients
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| Diagnostic 131 I scan: used to follow patients who have had thyroidectomy and 131 I ablation and return for yearly evaluation
after withdrawal of TH therapy or stimulation with recombinant TSH; scan—detects uptake of 131 I in cancers amenable to
retreatment with higher doses of 131 I; less sensitive than whole-body scans after therapy with higher doses of 131 I; additional
aspects—lack of rise in thyroglobulin in response to TSH elevation more reliable test; patients with elevated thyroglobulin
and negative 131 I scans can undergo FDG-PET evaluation or empiric retreatment with 131 I
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| Stunned thyroid: low-dose 131 I makes some tumor cells radioresistant and diminishes radioactive uptake in remaining
gland; to avoid problem, do not perform 4-wk post-thyroidectomy preablation whole-body scan if—total thyroidectomy
performed by experienced surgeon; serum TSH elevated to >30 µIU/mL; 131 I ablation dosing should be based on
whether patient has—tumor confined to gland; cervical metastases; distant metastases
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| Points: 131I therapy can be augmented with recombinant human TSH (not approved by Food and Drug Administration
[FDA]) in patients—whose TSH does not increase sufficiently post-thyroidectomy; undergoing retreatment who will
not stop taking TH; during treatment—thyroxine can maintain TSH suppression and prevent tumor growth; options for
augmenting radiation delivered by 131I when thyroglobulin levels increase and tumor recurrence suspected—strict
low-iodine diet (no evidence of benefit); lithium carbonate; redifferentiating therapy with retinoic acid (investigational)
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| Concerns about use of 131 I: side effects—minimal and transient; include nausea, gastritis, soreness in salivary glands,
and loss of taste; pregnancy—131 I therapy contraindicated in pregnant and lactating women; patient should have negative
pregnancy test before undergoing therapy; genetic effect—ovaries exposed to irradiation via bladder (urinary tract main
route of excretion for 131 I); although data suggest 131 I therapy does not exert long-term genetic effect, women should delay
conception for 1 yr after irradiation; carcinogenic effects—debatable; some, although risk rare; consent form must contain
information about potential risk for leukemia; radiation safety—depends on proximity to radiation source, duration of
exposure, and degree of shielding; radiation uptake in thyroid tissue low because bulk of tissue removed surgically, 131 I
has short biologic and effective half-life(12-15 hr), and hydration promotes urinary excretion
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| Additional points: postablation 131I scans—essential; increased dose of 131 I improves detection of distant metastases;
liver uptake on postablation 131I scan—indicates presence of residual thyroid tissue or functioning metastases; pediatric
thyroid carcinoma—rare; associated with higher incidence of pulmonary metastases; when compared to adults, children
respond better to 131 I therapy, have higher rate of recurrence, respond better to retreatment, and have better
prognosis, even when metastatic disease present initially
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Educational Objectives
| The goal of this program is to educate the listener about the diagnosis and management of thyroid disease. After hearing and
assimilating this program, the clinician will be better able to:
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 | 1. Identify patients who should be screened for thyroid disease.
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| 2. Interpret the results of thyroid screening tests.
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| 3. Diagnose and administer appropriate replacement therapy to women presenting with hypo- and hyperthyroidism.
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| 4. Describe the role of 131 I therapy in the management of thyroid cancer.
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| 5. Discuss current concepts about the proper dosimetry and safety of 131 I therapy.
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Discussed on This Program
Aldesleukin (interleukin-2; IL-2) [Proleukin]
Amiodarone HCl [Cordarone, Pacerone]
Aspirin (several trade names and preparations)
Bromocriptine mesylate [Parlodel, Parlodel Snap Tabs]
Cabergoline [Dostinex]
Cholestyramine (several trade names and preparations)
Iodine [Iodopen]
Levothyroxine sodium (T4 ; L -thyroxine) [Levothroid, Levoxyl, Synthroid, Unithroid]
Lithium [Eskalith, Eskalith CR, Lithobid, Lithonate, Lithotabs]
Methimazole [Tapazole]
Methylprednisolone [Medrol]
Phenobarbital [Bellatal, Luminal Sodium, Solfoton]
Phenytoin sodium [Dilantin]
Prednisone (several trade names)
Promethazine HCl [Phenergan]
Propylthiouracil (PTU)
Retinoic acid (several trade names and preparations)
Sucralfate [Carafate]
Suggested Reading
Barrington SF et al: Radiation dose rates from patients receiving 131 I therapy for carcinoma of the thyroid. Eur J Nucl
Med 23:123, 1996; Pacilio M et al: Management of 131 I therapy for thyroid cancer: cumulative dose from in-patients, discharge
planning, and personnel requirements. Nucl Med Commun 26:623, 2005; Rosario PW et al: Efficacy of low and
high 131 I doses for thyroid remnant ablation in patients with differentiated thyroid carcinoma based on post-operative cervical
uptake. Nucl Med Commun 25:1077, 2004; Venencia CD et al: Hospital discharge of patients with thyroid carcinoma
treated with 131 I. J Nucl Med 43: 61, 2002; Wang KL et al: Chronic myeloid leukemia after treatment with 131 I for thyroid
carcinoma. J Chin Med Assoc 68:230, 2005.
Faculty Disclosure
In adherence to ACCME guidelines, the Audio-Digest Foundation requests all lecturers to disclose any significant financial
relationship with the manufacturer or provider of any commercial product or service discussed. The following has been disclosed:
Dr. Piziak is affiliated with AstraZeneca, Aventis, GlaxoSmithKline, Lilly, Novartis, P & G Pharmaceuticals, Pfizer
Inc., and Roche; Dr. Williams is affiliated with Philips Medical Systems.
Dr. Piziak gave her scientific presentation at The Adult Patient: Male and Female Issues presented June 20 to 24,
2005 in South Padre Island, Texas, by Scott and White Clinic of Temple, Texas, and the Texas A&M University System
Health Science Center College of Medicine; Dr. Williams gave his scientific presentation at Contemporary Management
of Thyroid and Parathyroid Disorders, presented April 28-30, 2005, in Augusta, Georgia, by the Medical
College of Georgia School of Medicine. The Audio-Digest Foundation thanks the speakers and the sponsors for their
cooperation in the production of this program.
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