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Annals of Internal Medicine In the Clinic® Hyperthyroidism
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Annals of Internal Medicine䊛In the Clinic®
Hyperthyroidism Screening
Diagnosis
T
hyrotoxicosis is a general term for excess
circulating and tissue thyroid hormone
levels, whereas hyperthyroidism specifi-
cally denotes disorders involving a hyperactive Treatment
thyroid gland (Graves disease, toxic multinodu-
lar goiter, toxic adenoma). Diagnosis and deter-
mination of the cause rely on clinical evaluation, Practice Improvement
laboratory tests, and imaging studies. Hyperthy-
roidism is treated with antithyroid drugs, radio-
active iodine ablation, or thyroidectomy. Other
types of thyrotoxicosis are monitored and
treated with -blockers to control symptoms
given that most of these conditions resolve
spontaneously.
CME/MOC activity available at Annals.org.
Physician Writer doi:10.7326/AITC202004070
Michael T. McDermott, MD
From University of Colorado CME Objective: To review current evidence for screening, diagnosis, treatment, and practice
School of Medicine, Denver, improvement of hyperthyroidism.
Colorado (M.T.M.) Funding Source: American College of Physicians.
Disclosures: Dr. McDermott, ACP Contributing Author, has nothing to disclose. The form can
be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M19
-3638.
With the assistance of additional physician writers, the editors of Annals of Internal Medi-
cine develop In the Clinic using MKSAP and other resources of the American College of
Physicians. The patient information page was written by Monica Lizarraga from the Patient
and Interprofessional Partnership Initiative at the American College of Physicians.
In the Clinic does not necessarily represent official ACP clinical policy. For ACP clinical
guidelines, please go to https://www.acponline.org/clinical_information/guidelines/.
© 2020 American College of Physicians
, Thyrotoxicosis is a clinical state range, and it is considered “sub-
1. Ross DS, Burch HB, Coo-
per DS, et al. 2016 Ameri- characterized by excess serum clinical” when the TSH level is low
can Thyroid Association and tissue concentrations of thy- or undetectable but levels of
guidelines for diagnosis
and management of hy- roxine (T4), triiodothyronine (T3), both T4 (free or total T4) and total
perthyroidism and other
causes of thyrotoxicosis. or both. The term hyperthyroid- T3 are within the reference range.
Thyroid. 2016;26:1343- ism refers specifically to thyrotox- Therefore, overt and subclinical
421. [PMID: 27521067]
2. Burch HB. Drug effects on icosis resulting from hyperactivity thyrotoxicosis are defined bio-
the thyroid. N Engl J Med. of the thyroid gland. Thyrotoxico- chemically without regard for
2019;381:749-61. [PMID:
31433922] sis is considered “overt” when clinical features. The prevalence
3. Barroso-Sousa R, Barry WT,
Garrido-Castro AC, et al. the serum thyroid-stimulating of thyrotoxicosis in the United
Incidence of endocrine hormone (TSH) level is low or States is estimated at 1.2%,
dysfunction following the
use of different immune undetectable and serum T4 (free with approximately 40% of cases
checkpoint inhibitor regi- or total T4) level, total T3 level, or being overt and 60% being
mens: a systematic review
and meta-analysis. JAMA both are above the reference subclinical (1).
Oncol. 2018;4:173-82.
[PMID: 28973656]
4. Brahmer JR, Lacchetti C,
Schneider BJ, et al; Na-
tional Comprehensive
Cancer Network. Manage-
Screening
ment of immune-related Who has elevated risk for should also be considered in pa-
adverse events in patients
treated with immune
thyrotoxicosis? tients with medical conditions
checkpoint inhibitor ther- Persons at increased risk for thy- that may be caused or aggra-
apy: American Society of
Clinical Oncology clinical rotoxicosis include those with vated by thyrotoxicosis (osteopo-
practice guideline. J Clin rosis, atrial fibrillation, supraven-
Oncol. 2018;36:1714-68.
goiters, type 1 diabetes, other
[PMID: 29442540] autoimmune diseases, and a fam- tricular tachycardia, or heart
5. Pariani N, Willis M, Muller
I, et al. Alemtuzumab- ily history of thyroid disease. failure). Screening is also recom-
induced thyroid dysfunc- Medications that increase risk mended in women older than
tion exhibits distinctive
clinical and immunologi- include amiodarone, 50 years (6) because of the
cal features. J Clin Endo-
crinol Metab. 2018;103:
interferon-␣, interleukin-2, lith- higher prevalence of thyroid dis-
3010-8. [PMID: ium, iodide, iodinated contrast ease in this group.
29878256]
6. U.S. Preventive Services agents, immune checkpoint in-
Task Force. Screening for hibitors, and alemtuzumab (2–5). What screening tests should be
thyroid disease: recom- used?
mendation statement.
Ann Intern Med. 2004; Should clinicians screen for Serum TSH measurement is the
140:125-7. [PMID: thyrotoxicosis?
14734336] best test for thyrotoxicosis. TSH is
7. Burch HB. Overview of the Screening in the general popula- undetectable or low in both overt
clinical manifestations of
thyrotoxicosis. In: Braver- tion is not cost-effective because and subclinical thyrotoxicosis be-
man LE, Cooper DS, eds.
Werner & Ingbar's The
of the low prevalence of thyrotox- cause of negative feedback by
Thyroid: A Fundamental icosis (6). However, case finding elevated or high normal T4
and Clinical Text, 11th
Edition. Wolters Kluwer;
is recommended in persons who and/or T3 levels on the pituitary
2020. are at high risk because of co- gland. TSH assays are standard-
8. Boelaert K, Torlinska B,
Holder RL, et al. Older morbid conditions, family history, ized, accurate, and widely
subjects with hyperthy-
roidism present with a
or medication use. Testing available.
paucity of symptoms and
signs: a large cross-
sectional study. J Clin
Endocrinol Metab. 2010;
95:2715-26. [PMID:
20392869] Screening... Screening for thyrotoxicosis in the general population is
9. Nordyke RA, Gilbert FI Jr,
Harada AS. Graves' dis-
not cost-effective. Experts recommend measuring serum TSH levels in
ease. Influence of age on persons with goiters, type 1 diabetes, other autoimmune diseases, os-
clinical findings. Arch teoporosis, atrial fibrillation, supraventricular tachycardia, heart failure,
Intern Med. 1988;148:
626-31. [PMID: 3341864] or a family history of thyroid disease; those taking amiodarone, immune
10. Trivalle C, Doucet J, checkpoint inhibitors, or alemtuzumab; and women older than 50
Chassagne P, et al. Dif-
ferences in the signs and
years.
symptoms of hyperthy-
roidism in older and
younger patients. J Am
Geriatr Soc. 1996;44: CLINICAL BOTTOM LINE
50-3. [PMID: 8537590]
11. Smith TJ, Hegedüs L.
Graves' disease. N Engl J
Med. 2016;375:1552-
65. [PMID: 27797318]
姝 2020 American College of Physicians ITC50 In the Clinic Annals of Internal Medicine 7 April 2020
, Diagnosis
What symptoms should include tachycardia and/or an
prompt clinicians to consider irregularly irregular heart rate; 12. Fatourechi V, Aniszewski
thyrotoxicosis or goiter; warm, moist skin; hand JP, Fatourechi GZ, et al.
Clinical features and
hyperthyroidism? tremor; and adrenergic eye signs outcome of subacute
(stare and lid lag) (Appendix thyroiditis in an inci-
Symptoms that suggest thyrotoxi- dence cohort: Olmsted
cosis include nervousness, in- Table 1) (7–9). Other features County, Minnesota,
study. J Clin Endocrinol
creased sweating, heat intoler- may indicate the specific cause. Metab. 2003;88:2100-5.
ance, palpitations, fatigue, Graves disease is characterized [PMID: 12727961]
13. Ide A, Amino N, Kang S,
weight loss, tachycardia, dys- by diffuse goiter, thyroid bruit, et al. Differentiation of
postpartum Graves'
pnea, weakness, leg edema, eye inflammatory/congestive eye thyrotoxicosis from post-
symptoms, emotional lability, signs (proptosis, periorbital partum destructive thyro-
toxicosis using antithyro-
and frequent defecation (7–9). edema, chemosis, extraocular tropin receptor
muscle dysfunction), pretibial antibodies and thyroid
Elderly patients tend to have blood flow. Thyroid.
milder, more subtle, and less typ- myxedema (usually on the shins), 2014;24:1027-31.
[PMID: 24400892]
ical symptoms that are often and thyroid acropachy (soft tis- 14. Bartalena L, Bogazzi F,
dominated by fatigue, depres- sue enlargement and clubbing of Chiovato L, et al. 2018
European Thyroid Associ-
sion, weight loss, and atrial fibril- the fingers) (1, 11). The diagnosis ation (ETA) guidelines for
the management of
lation (7–10); the term apathetic of toxic multinodular goiter or amiodarone-associated
thyrotoxicosis describes this toxic adenoma is supported by thyroid dysfunction. Eur
Thyroid J. 2018;7:55-66.
presentation. palpating multiple thyroid nod- [PMID: 29594056]
ules or a solitary nodule. Fever 15. Li D, Radulescu A, Shres-
tha RT, et al. Association
and thyroid tenderness suggest of biotin ingestion with
Some elements of the history performance of hormone
subacute thyroiditis (12). and nonhormone assays
may also suggest the specific in healthy adults. JAMA.
cause of thyrotoxicosis (Appen- What laboratory tests should 2017;318:1150-60.
[PMID: 28973622]
dix Table 1, available at Annals clinicians use to diagnose 16. Burch HB, Cooper DS.
.org). Eye pain or swelling, dou- Management of Graves
thyrotoxicosis or disease: a review. JAMA.
ble vision, or a skin disorder on hyperthyroidism? 2015;314:2544-54.
[PMID: 26670972]
the shins point to Graves dis- Serum TSH measurement is the 17. Cooper DS. Antithyroid
ease as the cause (1, 11). Recent best test for diagnosis of thyro- drugs. N Engl J Med.
2005;352:905-17.
pregnancy raises the possibility toxicosis. Levels are usually unde- [PMID: 15745981]
18. Burch HB, Cooper DS.
of postpartum thyroiditis. Ante- tectable in overt thyrotoxicosis Anniversary Review:
rior neck pain, malaise, fever, and low but often detectable in antithyroid drug therapy:
70 years later. Eur J
and sore throat are characteristic subclinical thyrotoxicosis. Either Endocrinol. 2018;179:
of subacute thyroiditis. Use of R261-R274. [PMID:
should prompt the clinician to 30320502]
amiodarone, lithium, interferon-␣, order a free T4 or total T4 (if free 19. Azizi F, Amouzegar A,
Tohidi M, et al. Increased
interleukin-2, potassium iodide, T4 is not available) test. If the free remission rates after
immune checkpoint inhibitors or total T4 level is normal, a total long-term methimazole
therapy in patients with
(especially ipilimumab and niv- T3 test should be ordered be- Graves' disease: results
of a randomized clinical
olumab) (3, 4), or alemtuzumab cause some patients have normal trial. Thyroid. 2019;29:
(5) or recent exposure to iodin- T4 levels but elevated T3 levels 1192-200. [PMID:
31310160]
ated radiocontrast agents in- (T3 toxicosis). Measurement of 20. Feldt-Rasmussen U,
crease the likelihood of drug- Schleusener H, Carayon
free T3 levels is not recom- P. Meta-analysis evalua-
induced or iodine-induced mended because of inaccuracy tion of the impact of
thyrotropin receptor
thyrotoxicosis (2). Surreptitious of the available assays. antibodies on long term
ingestion of thyroid hormone remission after medical
therapy of Graves' dis-
must also be considered. Once thyrotoxicosis is diag- ease. J Clin Endocrinol
nosed, the cause must be deter- Metab. 1994;78:98-102.
What physical examination mined. When the physical exami-
[PMID: 8288723]
21. Tun NN, Beckett G, Zam-
findings indicate possible nation strongly suggests Graves mitt NN, et al. Thyrotro-
pin receptor antibody
thyrotoxicosis or disease (diffuse goiter, thyroid levels at diagnosis and
after thionamide course
hyperthyroidism? bruit, thyroid orbitopathy [inflam- predict Graves' disease
Physical signs often identified matory/congestive eye signs], relapse. Thyroid. 2016;
26:1004-9. [PMID:
with thyrotoxicosis of any cause pretibial myxedema, thyroid 27266892]
7 April 2020 Annals of Internal Medicine In the Clinic ITC51 姝 2020 American College of Physicians
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