2013-10-07

The prevalence of hyperthyroidism in the general population is about 1-2%, and is ten times more likely in women than men. The spectrum of hyperthyroidism ranges from asymptomatic or subclinical disease to thyroid storm. So how do we diagnose various presentations of hyperthyroidism in the Emergency Department? Below are answers to 7 common questions that commonly arise.

What’s the difference between hyperthyroidism, thyrotoxicosis, and thyroid storm?

Hyperthyroidism refers to conditions in which the production of thyroid hormone is increased. Thyrotoxicosis is any state where the concentration of thyroid hormone is increased in the circulation, which includes overproduction, release from an injured gland, or exogenous hormone. Thyroid storm is a life-threatening decompensation of thyrotoxicosis, with extremes in clinical symptoms including fever, marked tachycardia, CNS and GI dysfunction, with decompensation of one organ system, such as shock or heart failure. [1]

When should I think about hyperthyroidism in my patients?

Have a low suspicion to screen for hyperthyroidism in patients who have symptoms that cannot be explained by other causes. Fatigue and generalized weakness is very common, along with weight loss and decreased appetite. Neuropsychiatric complaints include anxiety, tremor, insomnia, and emotional lability. Cardiopulmonary symptoms are very common and include palpitations, tachycardia, atrial fibrillation, and dyspnea on exertion. In these patients, examining their thyroid for enlargement or nodules is helpful, and a screening TSH should be part of their workup. [1]

When should I think about thyroid storm?

Thyroid storm is a clinical diagnosis. Pay attention to certain features in the history, vitals, and exam: 

Underlying hyperthyroidism – Most common in patients with a history of Graves’ disease, and occasionally in toxic multinodular goiter and toxic adenoma

Fever – Thyroid storm patients have lost the ability to vasodilate and thermoregulate. Temperature can exceed 104-106 F.

Altered mental status – A key to diagnosis. This ranges from restlessness to delirium, seizures, or coma.

Suspected precipitating event – Common causes include infection, trauma, surgery, and excessive diuresis.

Other signs and symptoms can include marked tachycardia (can be >140 bpm), congestive heart failure, and GI symptoms like nausea, vomiting, and abdominal pain.

Hyperthyroidism is especially difficult to diagnose in the elderly, who will often not show overt physical signs. Clues to diagnosis include supraventricular arrhythmias, heart failure, inappropriately youthful skin.

Thyroid storm has a high mortality rate.  Bottom line: if you suspect it, treat it. [2] 

What labs are useful in diagnosing hyperthyroidism? Is TSH enough or should I send free T4 and T3?

Serum TSH measurement has the highest sensitivity and specificity of any single blood test used in the evaluation of suspected hyperthyroidism and should be used as an initial screening test. A normal TSH essentially excludes hyperthyroidism (except in the rare circumstance of a TSH-producing pituitary adenoma or thyroid hormone resistance). Measurement of thyroid hormone levels (free T4 and free T3) is subsequently required for definitive diagnosis. 

Other lab abnormalities seen in hyperthyroidism include anemia, thrombocytopenia, low creatinine (cannot convert creatine to creatinine), hyperglycemia, and hypercalcemia. [3,4]

What is the differential diagnosis when TSH is low?

TSH

Free T4

Free T3

Condition

Normal

Normal

Normal

None

Low

High

High

Hyperthyroidism

Low

Normal

Normal

Subclinical hyperthyroidism

Low

Normal

High

T3 toxicosis

Low

High

Normal

Thyroiditis, T4 ingestion, hyperthyroidism in chronic illness

Low

Low

Low

Euthyroid sick syndrome, central hypothyroidism [1]

How do I diagnose hyperthyroidism in pregnancy? 

TSH levels in the first half of pregnancy may normally be lower than the non-pregnant population, due to stimulation of the thyroid by serum bHCG. In the second half of pregnancy, TSH levels will return back to normal. Due to variations in thyroxine-binding globulin (TBG), free T3 and free T4 levels are also trimester-specific and each laboratory has their own reference values.

According to 2011 Guidelines from American Thyroid Association, normal TSH levels in pregnancy are:

First trimester: 0.1-2.5 mIU/L

Second trimester: 0.2-3.0 mIU/L

Third trimester: 0.3-3.0 mIU/L [5]

Is measuring TSH useful in undifferentiated Emergency Department patients with palpitations or atrial fibrillation?

So far there have been no studies performed on the prevalence of hyperthyroidism in undifferentiated patients with palpitations. In a large study of patients with new-onset atrial fibrillation, less than 1% were caused by overt hyperthyroidism. Therefore, although serum TSH is typically measured in the inpatient and primary care settings in patients with new-onset atrial fibrillation or palpitations, this association is uncommon in the absence of additional symptoms and signs of hyperthyroidism. Thus it is not a specific recommendation in the emergency department setting without other signs or symptoms of hyperthyroidism. [6]

References 

Marx JA, Hockberger RS, Walls RM, et al., eds. Rosen’s Emergency Medicine: Concepts and Clinical Practice. Philadelphia, PA: Mosby/Elsevier; 2010.

Lopresti, Jonathan, Stuart Swadron, and Mel Herbert, perf. “Hyperthyroidism.” EMRAP. N.p., 06 2010. web. 19 Sep 2013.

Bahn Chair RS, Burch HB, Cooper DS, Garber JR, Greenlee MC, Klein I, Laurberg P, McDougall IR, Montori VM, Rivkees SA, Ross DS, Sosa JA, Stan MN; American Thyroid Association; American Association of Clinical Endocrinologists. Hyperthyroidism and other causes of thyrotoxicosis: management guidelines of the  American Thyroid Association and American Association of Clinical Endocrinologists. Thyroid. 2011 Jun;21(6):593-646. [PMID: 21510801]

Ross DS. Serum thyroid-stimulating hormone measurement for assessment of thyroid function and disease. Endocrinol Metab Clin North Am. 2001 Jun;30(2):245-64, vii. Review. PubMed [PMID: 11444162]

Stagnaro-Green A, Abalovich M, Alexander E, et al. Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and postpartum. Thyroid. 2011;21:1081-1125. [PMID: 21787128]

Krahn AD, Klein GJ, Kerr CR, Boone J, Sheldon R, Green M, Talajic M, Wang X, Connolly S. How useful is thyroid function testing in patients with recent-onset atrial fibrillation? The Canadian Registry of Atrial Fibrillation Investigators. Arch Intern Med. 1996 Oct 28;156(19):2221-4. [PMID: 8885821] 

Expert Peer Review 

Unrecognized and untreated hyperthyroidism can have profound systemic effects on an individual. As summarized in this excellent review, the acute consequences of thyroid hormone excess can include congestive heart failure, atrial fibrillation, and the ultimate in thyroid storm. Chronic, untreated hyperthyroidism has been associated with premature cardiovascular-related mortality that increases with advancing age and osteoporosis with fracture. Finally, unrecognized and untreated hyperthyroidism in pregnancy has risks for both the mother and fetus. These include higher incidence of preeclampsia, small for gestational age babies, increase in both premature delivery and miscarriage. This makes it mandatory that hyperthyroidism be diagnosed early in its course and aggressively treated to minimize the above mentioned complications.

In these times when much of primary care is completed in the emergency room, emergency physicians need to be aware of the possibility of hyperthyroidism in their patients. This requires a careful history focusing on the symptoms accurately summarized in the review. A thorough physical examination focusing on the eyes (Graves’ eye disease), thyroid gland (enlargement), cardiovascular system (supraventricular tachycardia, atrial fibrillation, CHF), neurologic (tremors), and skin (warm and moist, pretibial myxedema) to corroborate clinical suspicion is warranted. Finally, confirmation of one’s suspicion for hyperthyroidism is made by the measurement of serum thyroid hormone indices where one would expect an undetectable serum TSH level and an elevated circulating T4 concentration.

The turn around time to receive the results is rapid and if the tests come back consistent with hyperthyroidism, specific therapy with methimazole should be initiated (20 mg daily as a maximum dose). Patients should be warned about the dreaded complication of agranulocytosis (unexpected fever and sore throat as the clinical symptoms) and stop the drug if suspected by these symptoms. The role of beta blockade in the management of hyperthyroidism is dependent on the severity of the concurrent adrenergic symptoms. Follow-up with an endocrinologist should be within one month of starting medical management.”

Jonathan LoPresti, MD PhD, Associate Professor of Clinical Medicine and Director of the Thyroid Clinic at University of Southern California

 

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