Thyroid Dysfunction in Nonpregnant Adults

This Clinical Focus discusses the role that laboratory testing plays in the diagnosis and management of thyroid dysfunction in nonpregnant adults.

Clinical Focus

Thyroid Dysfunction in Nonpregnant Adults

Laboratory Testing for Diagnosis and Management in Nonpregnant Adults

Contents:

Clinical background

Individuals suitable for testing

Table 1. Signs and Symptoms of Hypo- and Hyperthyroidism

Test availability

Table 2. Laboratory Tests for Diagnosing and Managing Thyroid Dysfunction

Test selection

Figure. Testing Algorithm for Thyroid Dysfunction in Nonpregnant Adults

Test interpretation

Table 3. Interpretation of Thyroid Function Tests
Table 4. Drugs and Nutrients Affecting Thyroid Function Tests

References

Clinical background [return to contents]

Thyroid dysfunction affects 1 in every 20 Americans, occurring most frequently in women over 60 years of age.1 Symptoms vary according to the type of dysfunction (hypothyroidism or hyperthyroidism) and are easily overlooked or attributed to other causes. Hypothyroidism may be complicated by weight gain, constipation, hypercholesterolemia, and cardiovascular disease while hyperthyroidism may be complicated by osteoporosis and atrial fibrillation. Individuals with overt thyroid dysfunction2 (abnormal thyrotropin [thyroid stimulating hormone, TSH] and free thyroxine [T4] levels) usually respond well to treatment.

Certain clinical symptoms and signs (Table 1) or abnormal laboratory tests (other than thyroid function tests, see below) are compatible with hypo- or hyperthyroidism. In addition, a history of certain treatments or taking certain drugs (see below) can predispose patients to thyroid dysfunction; these patients should undergo routine screening for hypo- or hyperthyroidism.3

Laboratory tests enable detection of both subclinical and overt disease. In patients with subclinical disease, TSH is either elevated (hypothyroidism) or suppressed (hyperthyroidism) in the presence of normal free T4.2 In these patients, routine treatment may not be necessary.2 In patients with overt disease, the decision to treat or closely monitor hypo- or hyperthyroidism is made based on clinician experience and risk of complications.

Patients with overt thyroid disorders who are at lower risk of complications include young, asymptomatic individuals who have only mildly elevated or suppressed TSH and free T4 levels. Patients at higher risk include those who have a personal or family history of diseases of the hypothalamic-pituitary-thyroid (HPT) axis, are older, and have markedly suppressed (<0.10 mU/L) or increased (≥10.00 mU/L) TSH levels, or a high-titer thyroid autoantibody.2

This Clinical Focus discusses the important role that laboratory testing plays in the diagnosis and management of thyroid dysfunction. This information is not intended as medical advice. Test selection and interpretation, diagnosis, and patient management decisions should be based on the physician’s education, clinical expertise, and assessment of the patient.

Individuals suitable for testing [return to contents]

Individuals with a clinical presentation consistent with thyroid disorders (Table 1).
High-risk individuals including3,4

Individuals with a strong family or personal history of thyroid disorders.
Individuals with anemia, atrial fibrillation, cardiovascular disease, hypercalcemia, hyperprolactinemia, hyponatremia, osteoporosis, psychiatric disorders, pulmonary hypertension, or autoimmune disease (celiac, pediatric arthritis and rheumatic fever, pernicious anemia, polyglandular autoimmune syndrome, rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, type 1 diabetes, or vitiligo).
Individuals with a history of neck irradiation, iodine-131 treatment, thyroid surgery, and/or use of certain medications (amiodarone, lithium, interferon-α, interleukin-2, or tyrosine kinase inhibitors, and immune checkpoint inhibitors).

Screening is not recommended in the general population.2

Table 1. Signs and Symptoms of Hypo- and Hypothyroidism [return to contents]

Sign or symptom	Hypothyroidism	Hyperthyroidism
Facial appearance
Puffy face4	•
Eyebrow loss4	•
Periorbital edema5,a		•
Conjunctival edema6		•
Lid lag, prominent eyes, and eyelid retraction5		•
Proptosis7,a		•
Thyroid, throat
Goiter4	•
Hoarseness4	⚬
Enlargement of the tongue (macroglossia)8	•
Uniform thyroid enlargement5,a		⚬
Thyroid nodularity5,b		⚬
Tenderness7		•
Bruit on auscultation5,a		•
Neurological, psychological
Cognitive dysfunction4	•
Slow speech4	•
Depression4	•
Encephalopathy4	⚬
Prolonged ankle reflex relaxation9	•
Brisk peripheral reflexes5		•
Tremor5		•
Anxiety5		•
Emotional lability7		•
Insomnia5		•
Psychosis (if severe)5		•
Rapid pressured speech5		•
Cardiovascular, metabolic
Bradycardia4	•
Pericardial effusion4	•
Decreased left ventricular function4	•
Diastolic hypertension4	•
Weight gain4	•
Anemia4	⚬
Cold intolerance4	•
Weight loss5		•
Heat intolerance5		•
Tachycardia5		•
Diaphoresis5		•
Atrial fibrillation5		•
Systolic hypertension10		•
Heart failure5		•
Pulmonary
Dyspnea4,5	•	•
Pleural effusion4	•
Musculoskeletal
Muscle cramps4	•
Fatigue4	•
Paresthesia4	•
Carpal tunnel syndrome4	⚬
Myalgia4	⚬
Proximal muscular weakness5		•
Hyperreflexia		•
Bone loss11		•
Increased bone turnover11		•
Thyroid acropachy7		•
Endocrine, reproductive
Galactorrhea9	•
Subfertility4	•
Loss of libido4,10	•	•
Oligomenorrhea4,10	•	•
Amenorrhea4,10	•	•
Gynecomastia12		⚬
Dermatologic
Brittle nails4	•
Dry coarse skin4	⚬
Carotenemia13	•
Edema13	•
Decreased perspiration9	•
Hair thinning13	•	•
Onycholysis5		•
Increased perspiration7		•
Moist skin7		•
Vitiligo5,a		•
Pruritus13		⚬
Pretibial myxedema5,a		⚬
Gastrointestinal
Constipation4	•
Increased appetite5		•
Increased defecation (not diarrhea)5		•

•, common; ⚬, variable.
a	More typical of Graves disease.
b	More typical of multinodular goiter.

Test availability [return to contents]

Quest Diagnostics offers tests and panels for diagnosis of thyroid dysfunction and patient management after treatment (Table 2).

Table 2. Laboratory Tests for Diagnosing and Managing Thyroid Dysfunction [return to contents]

Test code	Test name (component test codes for panels)	Clinical use
36574	T3 (Triiodothyronine) Antibodya	Evaluate discordant serum T3 (and TSH) levels
90963	T3 Reverse, LC/MS/MSa	Establish nonthyroidal illness as the cause for abnormal thyroid function tests, helps interpreting TFTs when the patient is taking amiodarone
861	T3 Uptake	Diagnose thyroid dysfunction by measuring percentage of T3 available to thyroid-binding globulin, indirectly estimates the amount of TBG in the blood (rarely used)
34429	T3, Free	Diagnose and monitor treatment of hyperthyroidism
36598	T3, Free, Tracer Dialysisa	Diagnose hyperthyroidism and detect possible protein-binding anomalies
859	T3, Total	Diagnose and monitor treatment of hyperthyroidism
36576	T4 (Thyroxine) Antibodya	Evaluate discordant serum T4 and TSH levels
867	T4 (Thyroxine), Total	Diagnose hypo- and hyperthyroidism; monitor LT4 treatment response
866	T4, Free (FT4)
35167	T4, Free, Direct Dialysisa
36725	T4 Free, Direct Dialysis and T4 Totala
870	TBG (Thyroxine Binding Globulin)	Distinguish quantitative TBG derangements from thyroid dysfunction
267	Thyroglobulin Antibodies	Establish autoimmune thyroid disease as the cause for thyroid dysfunction, establish presence of residual thyroid adenocarcinoma (follicular or papillary) after surgery; HAMA treatment, if necessary, allows analysis in the presence of human antimouse antibodies
30278	Thyroglobulin Panela Includes thyroglobulin antibodies and quantitative thyroglobulin.
19584	Thyroglobulin Panel With HAMA Treatmentb Includes thyroglobulin, pre and post HAMA precipitation, and thyroglobulin antibody.
15102	Thyroid Cascading Reflexb,c Includes TSH and reflexes. If TSH is abnormal, reflexes to free T4. If TSH is elevated and free T4 is normal or low, reflexes to TPO antibody. If TSH is low and free T4 is normal or low, reflexes to free T3.	Diagnose hypo- and hyperthyroidism, offered as a cascading reflex to expedite diagnosis
7020	Thyroid Panelb Includes T3 uptake, total T4 (thyroxine), and free T4 index (T7).	Diagnose thyroid dysfunction using T3 uptake along with the total T4 to provide an estimate (free T4 index) of the free T4 level (rarely used), provides indirect evidence of TBG changes
7260	Thyroid Peroxidase and Thyroglobulin Antibodiesb	Establish autoimmune hyperthyroidism, such as Graves disease or Hashitoxycosis
5081	Thyroid Peroxidase Antibodies
38683	TRAb (TSH Receptor Binding Antibody)
899	TSH	Diagnose hypo- and hyperthyroidism
36577	TSH Antibodya	Evaluate discordant serum TSH, free T4, and T3 levels
19537	TSH With HAMA Treatment	Diagnose hypo- and hyperthyroidism in the presence of HAMA
36127	TSH With Reflex to Free T4c	Diagnose hypo- and hyperthyroidism
30551	TSI (Thyroid Stimulating Immunoglobulin)	Establish autoimmune thyroid disease (eg, Graves disease)
Other useful tests for assessing or managing thyroid dysfunction
8658	Alpha Subunita	Identify patients with TSH-secreting pituitary adenomas
38149	Cortisol Response to ACTH Stimulation, Seruma	Assess adrenal insufficiency before starting LT4 therapy in patients with central hypothyroidism

ACTH, adrenocorticotropic hormone; HAMA, human antimouse antibody; LT4, levothyroxine; TBG, thyroxine binding globulin; TFT, thyroid function tests; TSH, thyroid-stimulating hormone.
a	This test was developed, and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
b	Panel components (test code) may be ordered separately.
c	Reflex testing performed at an additional charge with an additional CPT code.

Test selection [return to contents]

TSH measurement (test code 899) is the preferred initial test to confirm suspected thyroid dysfunction and has a clinical sensitivity of about 98% and specificity of about 92%.2 If thyroid dysfunction is suspected, ordering TSH with Reflex to Free T4 (TC 36127) or Thyroid Cascading Reflex (TC15102) may facilitate a quicker differential diagnosis. Abnormal findings should be followed up with repeat testing over a 3- to 6-month interval and include free T4 (test code 866), which helps distinguish overt from subclinical disease.2

Free T4 is measured using an automated competitive binding immunoassay involving a T4 analog; results can be affected when albumin or thyroid binding globulin (TBG) levels are abnormal. In these circumstances, equilibrium dialysis can provide accurate free T4 measurements that are unaffected by variations in binding protein levels (test code 35167). As the equilibrium dialysis proceeds over 16 to 18 hours, assessment of free T4 by this method should be reserved for when initial free T4 results are inconsistent with the clinical presentation.

A T3 test can distinguish between subclinical hyperthyroidism and T3 toxicosis (suppressed TSH with an in-range free T4).6 Options include free T3 (test code 34429) and total T3 (test code 859); total T3 is considered a more robust and better validated test than free T3, even though it is more affected by protein binding.6 Measuring free T3 after tracer dialysis (T3, Free, Tracer Dialysis; test code 36598) is another option less affected by protein binding anomalies. T3 should not be used to diagnose hypothyroidism.1

Thyroid antibody immunoassays (eg, thyroglobulin antibodies [test code 267], thyroid peroxidase [TPO, test code 5081] antibodies, and TSH receptor binding antibody [TRAb, test code 38683] assays) are used to diagnose autoimmune thyroid disorders such as Hashimoto thyroiditis, the most common cause of acquired hypothyroidism, and Graves disease, the most common cause of hyperthyroidism. Although elevated thyroglobulin autoantibodies can be useful for diagnosing an autoimmune thyroid etiology,1 this test is usually performed together with measuring thyroglobulin levels, in the context of evaluating the presence of residual disease in differentiated thyroid cancer.14 TPO antibody testing is recommended when evaluating subclinical hypothyroidism or nodular thyroid disease caused by autoimmune thyroid disease.1 TRAb levels predict remission and can guide when to stop antithyroid drug therapy (ADT) for hyperthyroidism.6

TRAb can also be measured in a functional bioassay, the thyroid stimulating immunoglobulin (TSI) test (test code 30551).6 In contrast to the TRAb immunoassay, which measures levels of both stimulating and inhibiting antibodies, the TSI test measures only stimulating activity (ie, the capacity of TSI to stimulate cyclic AMP production in engineered cells expressing chimeric human TSH receptors in culture as a percent increase over baseline). The assay has high clinical sensitivity (92%) and specificity (99%) for detection of Graves disease (vs other autoimmune disease and healthy control subjects).15

See Figure for a diagnostic testing strategy. Importantly, TSH, free T4, T3, and free T3 immunoassays are affected by biotin intake; biotin supplements should be avoided for at least 24 hours or, preferably, several days before these tests.16

Figure. Testing Algorithm for Thyroid Dysfunction in Nonpregnant Adults [return to contents]

Discordant results can be investigated using the following available tests:

T3 and T4 antibody assays (test codes 36574 and 36576): used when a patient has an elevated free T4 concentration that is discordant with normal or elevated serum TSH and/or clinical symptoms and signs. The antibodies compete with antibodies used in the immunoassays; assay interference results in an overestimation of free T4.17
TBG assay (test code 870): used when a patient has normal TSH and free T4/T3 (ie, euthyroid status) but elevated total T4/T3. Elevations in TBG, which binds most of the T4/T3 circulating in plasma, account for the discordance. This direct measurement of TBG is mostly used when congenital abnormalities in TBG result in extremely abnormal values. However, when TBG is needed, the T3 Uptake test (test code 861) combined with serum total T4 (test code 867) can be used to give an indirect estimation (Thyroid Panel, test code 7020).18
TSH antibody assay (test code 36577): used when a patient has a markedly elevated TSH concentration that is discordant with in-range free T3/T4 levels. TSH antibodies accumulate TSH in circulation in a “macro-TSH” complex that is not easily filtered by the kidneys, resulting in overestimation of TSH.19 This radioimmunoassay determines whether TSH antibodies are present.
TSH assay with human antimouse antibody (HAMA) treatment (test code 19537): used when elevated TSH concentrations are discordant with free T4. The presence of HAMA in a patient’s serum interferes with monoclonal mouse IgGs used immunoassays.17
Reverse T3 (rT3) assay (test code 90963): used when a patient has discordant T3 levels resulting from nonthyroidal illness or use of the antiarrhythmic drug, amiodarone.20 Normally T4 is converted into the active metabolite T3 (3,5,3’-triiodothyronine) by removal of an iodine from the molecule (deiodination) by type 1 or 2 deiodinases (also known as D1 and D2). The rT3 mass spectrometry-based assay measures levels of rT3 (3,3’,5’-triiodothyronine, rT3), which is a structural isomer of T3 formed by type 3 deiodinase (D3, a physiological inactivator). Amiodarone or nonthyroidal illness, including fasting, malnutrition, poorly controlled diabetes, trauma, surgery, and systemic illness can modify D3 vs D2 activity leading to increased rT3 and decreased T3.

Test interpretation [return to contents]

Table 3 details test results associated with thyroid function tests (TFTs). Repeat TSH testing is recommended under certain circumstances. Examples include new symptoms of hypo- or hyperthyroidism, pregnancy or menopause, new medications that may affect levothyroxine (LT4) absorption or metabolism (see Table 4), or medical conditions affecting LT4 absorption (chronic gastritis, autoimmune gastric atrophy, chronic gastritis from Helicobacter pylori, celiac disease, lactose intolerance, pancreatic insufficiency).21

Note that, in contrast to primary hypothyroidism, central hypothyroidism is of hypothalamic or pituitary origin. Consequently, test results for central hypothyroidism should be interpreted based on free T4 and not TSH, which can be low or normal or high and biologically inactive.9

Table 3. Interpretation of Thyroid Function Tests [return to contents]

Thyroid status	TSH, mU/L	Free T4, ng/dL	Treatment recommendation	Monitoring
Euthyroid	0.40-4.50	NA	No treatment	NA
Primary hypothyroidism
Overt	≥10.00	<0.8	LT4	TSH: 4-8 weeks after starting/ changing treatment and until euthyroid, then yearly when euthyroid1
	4.51-9.99b	<0.8	LT4, if symptomatic for hypothyroidism, TPO Ab-positive, or at risk for ASCVD or HF1
Subclinicala	≥10.00	0.8-1.8	LT422	TSH:
				If the initial TSH value >15 mU/L, testing should be repeated in 1-2 weeks22
				Otherwise, 4-12 weeks after the initial test and prior to initiating treatment
				6 weeks after starting/changing treatment and until euthyroid, then yearly when euthyroid22
	7.00-9.99	0.8-1.8	LT4, consider treatment if age ≥65 years22
	4.51-6.99b	0.8-1.8	Consider LT4; if age ≥65 years no treatment recommended22
Central hypothyroidism
	0.40-4.50 (<10.00 if symptomatic)	<0.8	LT4b	fT4c: 6-8 weeks after starting treatment, then yearly when euthyroid23
Primary hyperthyroidism
Overt	<0.10	>1.8	ATDsd	fT4 and total T3e: 2-6 weeks after starting treatment, repeat in 4-6 weeks, then intervals of 2-3 months when euthyroid (can increase to 6 months for patients taking methimazole for >18 months)6; TRAb levels predict remission prior to stopping ATDs6
	0.10-0.39	>1.8
Subclinicala	<0.10	0.8-1.8	If TSH persistently <0.10 mU/mL, treat underlying cause (see Figure for etiology); all individuals ≥65 years, symptomatic,f or with risk factors should be treated and younger asymptomatic individuals considered for treatment6	TSH: intervals of 3-6 months6
	0.10-0.39	0.8-1.8	No treatment unless ≥65 years, symptomatic,f cardiac disease, or osteoporosis6
TSH-dependent hyperthyroidismg	>4.50	>1.8	Treat underlying causeh	fT4, total T3, and TSH6,i: after initiating therapy with somatostatin analogue, then every 2-3 months.24,j

ACTH, adrenocorticotropic hormone; ASCVD, atherosclerotic cardiovascular disease; ATD; antithyroid drug; fT4, free thyroxine; HF, heart failure; LT4, levothyroxine; TPO Ab, thyroid peroxidase antibody; TRAb, TSH receptor binding antibody; TSH, thyroid-stimulating hormone; TSHoma, thyrotropinoma.
a	Subclinical hypo- or hyperthyroidism is frequently transient.6,25
b	LT4 with steroid therapy if adrenal insufficiency is not ruled out.23 Perform Cortisol Response to ACTH Stimulation, Serum (test code 38149) before starting LT4.
c	TSH cannot be used to monitor therapy (suppressed to <0.1 mU/mL when LT4 restores normal fT4); however, if TSH can be measured 6 to 8 weeks after surgery that improves anterior pituitary function, consider monitoring TSH and fT4 and tapering LT4.23
d	For example, ATDs may include a thioamide and betablockers. The American Thyroid Association6 provides guidance if radioactive iodine therapy or thyroidectomy are indicated.
e	TSH is not typically measured as it may stay suppressed for months after starting treatment for overt hyperthyroidism.
f	In contrast to USPSTF,2 which defines subclinical disease as asymptomatic, guidelines in reference6 allow for subclinical hyperthyroidism as symptomatic entity.
g	Approximately 50% to 85% of patients with TSH-secreting pituitary adenomas have a high serum concentration of the alpha subunit of glycoprotein hormones (test code 8658).26
h	Somatostatin analogs are used to restore euthyroidism prior to transsphenoidal surgery on TSHomas.
i	Postoperatively monitor at frequent intervals.
j	Somatostatin receptor analogs can induce TSH deficiency, necessitating a reduction in the frequency of injections.

Results for TFTs are variable in patients consuming certain foods and nutrients. In addition, nonthyroidal illness, and medications used to treat the illness, can affect TFTs. Effects can be absorptive, metabolic, and/or toxic (Table 4). Some effects are transient (eg acute glucocorticoid dosing on TSH27) whereas others effects may be sustained and lead to thyroid dysfunction (eg, amiodarone20 or interferon28) or damage (eg, immune checkpoint29,30 or tyrosine kinase inhibitors31). Table 4 details common drugs and nutrients affecting TFTs as well as their predicted effects on patient test results.

Table 4 Drugs and Nutrients Affecting Thyroid Function Tests [return to contents]

Effect	Drug or nutrient	Test result
Absorption of T41	Calcium salts (carbonate, citrate, acetate)	↑TSH, ↓fT4, ↓Total T4
	Ferrous sulfate	↑TSH
	Protein pump inhibitors21	↑TSH
	Sucralfate	↑TSH, ↓Total T4
	Raloxifene	↑TSH, ↓Total T4
	Bile acid sequestrantsa	Possible ↑TSH, ↓Total T4
	Orlistatb	Possible ↑TSH
	Phosphate binders	↑TSH
	Milk21	↓Total T4
	Coffee	↑TSH, ↓Total T4
	Soy	↑TSH
	Papaya21	↑TSH, ↓fT4, ↓fT3
Increased thyroid binding globulin level1	Estrogens	↑Total T4, ↑TBG
	SERMs	↑Total T4, ↑TBG
	5-Flurouracil and capecitabine	↑Total T4, ↑TBG32
	Mitotane	↓fT4, normal fT3 and TSH33
Decreased thyroid binding globulin levels1	Androgens	↓Total T4, normal fT4 and TSH
	Glucocorticoids	↓TSH
	Nicotinic Acid	↓TSH
Increased metabolism of T41	Phenytoin	↑TSH, ↓T4, ↓T3c
	Phenobarbital
	Carbamazepine
	Rifampin
Inhibits conversion from T4 to T320	Amiodaroned	↑TSH,e ↑fT4, ↓T3, ↑rT3
	Propranolol34	↑fT4, ↓T3, ↑rT3
	Glucocorticoids27	↓TSH,e ↑fT4, ↓T3, ↑rT3
	Glucocorticoids27	↓TSH,e ↑fT4, ↓T3, ↑rT3
Associated with autoimmune thyroid dysfunction: ie, thyroiditis, Graves, hypothyroidism	Interferonf	↓TSH, ↑fT4, ↑T3
Associated with hypophysitis or hypothyroidism from destructive thyroiditis, or hyperthyroidism from a Graves disease-type mechanism	Immune checkpoint (CTLA-4 or PD-L1) inhibitors (eg, nivolumab, pembrolizumab, ipilimumab)29,30	Abnormal TFT results in line with the pathologic process
Degeneration of thyrocytes	Tyrosine kinase inhibitors (sunitinib, sorafenib, imatinib, motesanib)g	↑TSH, ↓T4
Associated with central hypothyroidism	Bexarotene	↓TSH, ↓fT435
Associated with TSH suppression	Dobutamine, dopamine, octreotide	↓TSH34

fT4, free thyroxine; SERMs, selective estrogen receptor modulators; TBG, thyroxine binding globulin; TFT, thyroid function tests; TSH, thyroid-stimulating hormone.
a	Inhibit enterohepatic circulation of T4; usually coadministered with antithyroid drugs in cases of refractory hyperthyroidism, thyroid storm, and iodine-induced hyperthyroidism.36,37
b	May interfere with LT4 absorption in patients with hypothyroidism on LT4 supplementation.38
c	T4 and TSH concentrations are in the normal range for patients with unaffected HPT axis; increased hormone metabolism is counteracted by increased thyroid hormone production. However, in the setting of subclinical or overt hypothyroidism, thyroid hormone production and secretion cannot be increased, and the latent hypothyroidism of these patients may become overt.32
d	May cause hypo- or hyperthyroidism (amiodarone can induce amiodarone-induced thyrotoxicosis type 1 [AIT1], and amiodarone-induced thyrotoxicosis type 2 [AIT2]).20
e	Over time, TSH normalizes, but the other abnormalities persist.27
f	May cause hypo- or hyperthyroidism. Hypothyroidism is a frequent complication observed in patients with positive thyroid antibodies at the beginning of the treatment or who have developed thyroid antibodies after a previous treatment.28 Hyperthyroidism due to autoimmune thyroiditis is the most frequent occurrence, followed by hyperthyroidism that develops by a Graves-related mechanism.
g	May cause degeneration of thyrocytes, which is followed by progressive hypothyroidism with below range fT4 and above range TSH. In patients with pre-existing hypothyroidism, TFTs should be checked periodically as thyroid hormone requirements may increase. The mechanism has to do with the pleiotropic effect of these drugs, which affects several TKIs, including VEGF receptor kinase inhibitors that cause regression of the vascular supply.31

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Persani L, Brabant G, Dattani M, et al. 2018 European Thyroid Association (ETA) guidelines on the diagnosis and management of central hypothyroidism. Eur Thyroid J. 2018;7(5):225-237. doi:10.1159/000491388
Illouz F, Chanson P, Sonnet E, et al. Somatostatin receptor ligands induce TSH deficiency in thyrotropin-secreting pituitary adenoma. Eur J Endocrinol. 2021;184(1):1-8. doi:10.1530/EJE-20-0484
Meyerovitch J, Rotman-Pikielny P, Sherf M, et al. Serum thyrotropin measurements in the community: five-year follow-up in a large network of primary care physicians. Arch Intern Med. 2007;167(14):1533-1538. doi:10.1001/archinte.167.14.1533
Socin HV, Chanson P, Delemer B, et al. The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients. Eur J Endocrinol. 2003;148(4):433-442. doi:10.1530/eje.0.1480433
Salvatore D, Davies TF, Schlumberger M-J, et al. Thyroid physiology and diagnostic evaluation of patients with thyroid disorders. In: Melmed S, Polonsky KS, Larsen PR, et al, eds. Williams Textbook of Endocrinology. 13th ed. Elsevier; 2017:333-368.
Nair Kesavachandran C, Haamann F, Nienhaus A. Frequency of thyroid dysfunctions during interferon alpha treatment of single and combination therapy in hepatitis C virus-infected patients: a systematic review based analysis. PLoS One. 2013;8(2):e55364. doi:10.1371/journal.pone.0055364
Barroso-Sousa R, Barry WT, Garrido-Castro AC, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis. JAMA Oncol. 2018;4(2):173-182. doi:10.1001/jamaoncol.2017.3064
Husebye ES, Castinetti F, Criseno S, et al. Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline. Eur J Endocrinol. 2022;187(6):G1-G21. doi:10.1530/EJE-22-0689
Kotwal A, McLeod DSA. Thyroid dysfunction from treatments for solid organ cancers. Endocrinol Metab Clin North Am. 2022;51(2):265-286. doi:10.1016/j.ecl.2021.12.006
Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014;24(12):1670-1751. doi:10.1089/thy.2014.0028
Russo M, Scollo C, Pellegriti G, et al. Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism. Clin Endocrinol (Oxf). 2016;84(4):614-619. doi:10.1111/cen.12868
Haugen BR. Drugs that suppress TSH or cause central hypothyroidism. Best Pract Res Clin Endocrinol Metab. 2009;23(6):793-800. doi:10.1016/j.beem.2009.08.003
Sherman SI, Gopal J, Haugen BR, et al. Central hypothyroidism associated with retinoid X receptor-selective ligands. N Engl J Med. 1999;340(14):1075-1079. doi:10.1056/NEJM199904083401404
Skelin M, Lucijanic T, Amidzic Klaric D, et al. Factors affecting gastrointestinal absorption of levothyroxine: A review. Clin Ther. 2017;39(2):378-403. doi:10.1016/j.clinthera.2017.01.005
Satoh T, Isozaki O, Suzuki A, et al. 2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition). Endocr J. 2016;63(12):1025-1064. doi:10.1507/endocrj.EJ16-0336
XENICAL (orlistat) Capsules. Package insert. Genentech Inc. Updated November, 2022. Accessed February 17, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020766s038lbl.pdf

Content reviewed 03/2023

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This Clinical Focus discusses the role that laboratory testing plays in the diagnosis and management of thyroid dysfunction in nonpregnant adults.

Test Guide List

Thyroid Dysfunction in Nonpregnant Adults

Clinical Focus

Thyroid Dysfunction in Nonpregnant Adults

Laboratory Testing for Diagnosis and Management in Nonpregnant Adults

Contents:

Clinical background

Individuals suitable for testing

Table 1. Signs and Symptoms of Hypo- and Hyperthyroidism

Test availability

Table 2. Laboratory Tests for Diagnosing and Managing Thyroid Dysfunction

Test selection

Figure. Testing Algorithm for Thyroid Dysfunction in Nonpregnant Adults

Test interpretation

Table 3. Interpretation of Thyroid Function Tests
Table 4. Drugs and Nutrients Affecting Thyroid Function Tests

References

Clinical background [return to contents]

Individuals suitable for testing [return to contents]

Individuals with a clinical presentation consistent with thyroid disorders (Table 1).
High-risk individuals including3,4

Individuals with a strong family or personal history of thyroid disorders.
Individuals with anemia, atrial fibrillation, cardiovascular disease, hypercalcemia, hyperprolactinemia, hyponatremia, osteoporosis, psychiatric disorders, pulmonary hypertension, or autoimmune disease (celiac, pediatric arthritis and rheumatic fever, pernicious anemia, polyglandular autoimmune syndrome, rheumatoid arthritis, Sjögren syndrome, systemic lupus erythematosus, type 1 diabetes, or vitiligo).
Individuals with a history of neck irradiation, iodine-131 treatment, thyroid surgery, and/or use of certain medications (amiodarone, lithium, interferon-α, interleukin-2, or tyrosine kinase inhibitors, and immune checkpoint inhibitors).

Screening is not recommended in the general population.2

Table 1. Signs and Symptoms of Hypo- and Hypothyroidism [return to contents]

Sign or symptom	Hypothyroidism	Hyperthyroidism
Facial appearance
Puffy face4	•
Eyebrow loss4	•
Periorbital edema5,a		•
Conjunctival edema6		•
Lid lag, prominent eyes, and eyelid retraction5		•
Proptosis7,a		•
Thyroid, throat
Goiter4	•
Hoarseness4	⚬
Enlargement of the tongue (macroglossia)8	•
Uniform thyroid enlargement5,a		⚬
Thyroid nodularity5,b		⚬
Tenderness7		•
Bruit on auscultation5,a		•
Neurological, psychological
Cognitive dysfunction4	•
Slow speech4	•
Depression4	•
Encephalopathy4	⚬
Prolonged ankle reflex relaxation9	•
Brisk peripheral reflexes5		•
Tremor5		•
Anxiety5		•
Emotional lability7		•
Insomnia5		•
Psychosis (if severe)5		•
Rapid pressured speech5		•
Cardiovascular, metabolic
Bradycardia4	•
Pericardial effusion4	•
Decreased left ventricular function4	•
Diastolic hypertension4	•
Weight gain4	•
Anemia4	⚬
Cold intolerance4	•
Weight loss5		•
Heat intolerance5		•
Tachycardia5		•
Diaphoresis5		•
Atrial fibrillation5		•
Systolic hypertension10		•
Heart failure5		•
Pulmonary
Dyspnea4,5	•	•
Pleural effusion4	•
Musculoskeletal
Muscle cramps4	•
Fatigue4	•
Paresthesia4	•
Carpal tunnel syndrome4	⚬
Myalgia4	⚬
Proximal muscular weakness5		•
Hyperreflexia		•
Bone loss11		•
Increased bone turnover11		•
Thyroid acropachy7		•
Endocrine, reproductive
Galactorrhea9	•
Subfertility4	•
Loss of libido4,10	•	•
Oligomenorrhea4,10	•	•
Amenorrhea4,10	•	•
Gynecomastia12		⚬
Dermatologic
Brittle nails4	•
Dry coarse skin4	⚬
Carotenemia13	•
Edema13	•
Decreased perspiration9	•
Hair thinning13	•	•
Onycholysis5		•
Increased perspiration7		•
Moist skin7		•
Vitiligo5,a		•
Pruritus13		⚬
Pretibial myxedema5,a		⚬
Gastrointestinal
Constipation4	•
Increased appetite5		•
Increased defecation (not diarrhea)5		•

•, common; ⚬, variable.
a	More typical of Graves disease.
b	More typical of multinodular goiter.

Test availability [return to contents]

Quest Diagnostics offers tests and panels for diagnosis of thyroid dysfunction and patient management after treatment (Table 2).

Table 2. Laboratory Tests for Diagnosing and Managing Thyroid Dysfunction [return to contents]

Test code	Test name (component test codes for panels)	Clinical use
36574	T3 (Triiodothyronine) Antibodya	Evaluate discordant serum T3 (and TSH) levels
90963	T3 Reverse, LC/MS/MSa	Establish nonthyroidal illness as the cause for abnormal thyroid function tests, helps interpreting TFTs when the patient is taking amiodarone
861	T3 Uptake	Diagnose thyroid dysfunction by measuring percentage of T3 available to thyroid-binding globulin, indirectly estimates the amount of TBG in the blood (rarely used)
34429	T3, Free	Diagnose and monitor treatment of hyperthyroidism
36598	T3, Free, Tracer Dialysisa	Diagnose hyperthyroidism and detect possible protein-binding anomalies
859	T3, Total	Diagnose and monitor treatment of hyperthyroidism
36576	T4 (Thyroxine) Antibodya	Evaluate discordant serum T4 and TSH levels
867	T4 (Thyroxine), Total	Diagnose hypo- and hyperthyroidism; monitor LT4 treatment response
866	T4, Free (FT4)
35167	T4, Free, Direct Dialysisa
36725	T4 Free, Direct Dialysis and T4 Totala
870	TBG (Thyroxine Binding Globulin)	Distinguish quantitative TBG derangements from thyroid dysfunction
267	Thyroglobulin Antibodies	Establish autoimmune thyroid disease as the cause for thyroid dysfunction, establish presence of residual thyroid adenocarcinoma (follicular or papillary) after surgery; HAMA treatment, if necessary, allows analysis in the presence of human antimouse antibodies
30278	Thyroglobulin Panela Includes thyroglobulin antibodies and quantitative thyroglobulin.
19584	Thyroglobulin Panel With HAMA Treatmentb Includes thyroglobulin, pre and post HAMA precipitation, and thyroglobulin antibody.
15102	Thyroid Cascading Reflexb,c Includes TSH and reflexes. If TSH is abnormal, reflexes to free T4. If TSH is elevated and free T4 is normal or low, reflexes to TPO antibody. If TSH is low and free T4 is normal or low, reflexes to free T3.	Diagnose hypo- and hyperthyroidism, offered as a cascading reflex to expedite diagnosis
7020	Thyroid Panelb Includes T3 uptake, total T4 (thyroxine), and free T4 index (T7).	Diagnose thyroid dysfunction using T3 uptake along with the total T4 to provide an estimate (free T4 index) of the free T4 level (rarely used), provides indirect evidence of TBG changes
7260	Thyroid Peroxidase and Thyroglobulin Antibodiesb	Establish autoimmune hyperthyroidism, such as Graves disease or Hashitoxycosis
5081	Thyroid Peroxidase Antibodies
38683	TRAb (TSH Receptor Binding Antibody)
899	TSH	Diagnose hypo- and hyperthyroidism
36577	TSH Antibodya	Evaluate discordant serum TSH, free T4, and T3 levels
19537	TSH With HAMA Treatment	Diagnose hypo- and hyperthyroidism in the presence of HAMA
36127	TSH With Reflex to Free T4c	Diagnose hypo- and hyperthyroidism
30551	TSI (Thyroid Stimulating Immunoglobulin)	Establish autoimmune thyroid disease (eg, Graves disease)
Other useful tests for assessing or managing thyroid dysfunction
8658	Alpha Subunita	Identify patients with TSH-secreting pituitary adenomas
38149	Cortisol Response to ACTH Stimulation, Seruma	Assess adrenal insufficiency before starting LT4 therapy in patients with central hypothyroidism

ACTH, adrenocorticotropic hormone; HAMA, human antimouse antibody; LT4, levothyroxine; TBG, thyroxine binding globulin; TFT, thyroid function tests; TSH, thyroid-stimulating hormone.
a	This test was developed, and its analytical performance characteristics have been determined by Quest Diagnostics. It has not been cleared or approved by the US Food and Drug Administration. This assay has been validated pursuant to the CLIA regulations and is used for clinical purposes.
b	Panel components (test code) may be ordered separately.
c	Reflex testing performed at an additional charge with an additional CPT code.

Test selection [return to contents]

Figure. Testing Algorithm for Thyroid Dysfunction in Nonpregnant Adults [return to contents]

Discordant results can be investigated using the following available tests:

T3 and T4 antibody assays (test codes 36574 and 36576): used when a patient has an elevated free T4 concentration that is discordant with normal or elevated serum TSH and/or clinical symptoms and signs. The antibodies compete with antibodies used in the immunoassays; assay interference results in an overestimation of free T4.17
TBG assay (test code 870): used when a patient has normal TSH and free T4/T3 (ie, euthyroid status) but elevated total T4/T3. Elevations in TBG, which binds most of the T4/T3 circulating in plasma, account for the discordance. This direct measurement of TBG is mostly used when congenital abnormalities in TBG result in extremely abnormal values. However, when TBG is needed, the T3 Uptake test (test code 861) combined with serum total T4 (test code 867) can be used to give an indirect estimation (Thyroid Panel, test code 7020).18
TSH antibody assay (test code 36577): used when a patient has a markedly elevated TSH concentration that is discordant with in-range free T3/T4 levels. TSH antibodies accumulate TSH in circulation in a “macro-TSH” complex that is not easily filtered by the kidneys, resulting in overestimation of TSH.19 This radioimmunoassay determines whether TSH antibodies are present.
TSH assay with human antimouse antibody (HAMA) treatment (test code 19537): used when elevated TSH concentrations are discordant with free T4. The presence of HAMA in a patient’s serum interferes with monoclonal mouse IgGs used immunoassays.17
Reverse T3 (rT3) assay (test code 90963): used when a patient has discordant T3 levels resulting from nonthyroidal illness or use of the antiarrhythmic drug, amiodarone.20 Normally T4 is converted into the active metabolite T3 (3,5,3’-triiodothyronine) by removal of an iodine from the molecule (deiodination) by type 1 or 2 deiodinases (also known as D1 and D2). The rT3 mass spectrometry-based assay measures levels of rT3 (3,3’,5’-triiodothyronine, rT3), which is a structural isomer of T3 formed by type 3 deiodinase (D3, a physiological inactivator). Amiodarone or nonthyroidal illness, including fasting, malnutrition, poorly controlled diabetes, trauma, surgery, and systemic illness can modify D3 vs D2 activity leading to increased rT3 and decreased T3.

Test interpretation [return to contents]

Table 3. Interpretation of Thyroid Function Tests [return to contents]

Thyroid status	TSH, mU/L	Free T4, ng/dL	Treatment recommendation	Monitoring
Euthyroid	0.40-4.50	NA	No treatment	NA
Primary hypothyroidism
Overt	≥10.00	<0.8	LT4	TSH: 4-8 weeks after starting/ changing treatment and until euthyroid, then yearly when euthyroid1
	4.51-9.99b	<0.8	LT4, if symptomatic for hypothyroidism, TPO Ab-positive, or at risk for ASCVD or HF1
Subclinicala	≥10.00	0.8-1.8	LT422	TSH:
				If the initial TSH value >15 mU/L, testing should be repeated in 1-2 weeks22
				Otherwise, 4-12 weeks after the initial test and prior to initiating treatment
				6 weeks after starting/changing treatment and until euthyroid, then yearly when euthyroid22
	7.00-9.99	0.8-1.8	LT4, consider treatment if age ≥65 years22
	4.51-6.99b	0.8-1.8	Consider LT4; if age ≥65 years no treatment recommended22
Central hypothyroidism
	0.40-4.50 (<10.00 if symptomatic)	<0.8	LT4b	fT4c: 6-8 weeks after starting treatment, then yearly when euthyroid23
Primary hyperthyroidism
Overt	<0.10	>1.8	ATDsd	fT4 and total T3e: 2-6 weeks after starting treatment, repeat in 4-6 weeks, then intervals of 2-3 months when euthyroid (can increase to 6 months for patients taking methimazole for >18 months)6; TRAb levels predict remission prior to stopping ATDs6
	0.10-0.39	>1.8
Subclinicala	<0.10	0.8-1.8	If TSH persistently <0.10 mU/mL, treat underlying cause (see Figure for etiology); all individuals ≥65 years, symptomatic,f or with risk factors should be treated and younger asymptomatic individuals considered for treatment6	TSH: intervals of 3-6 months6
	0.10-0.39	0.8-1.8	No treatment unless ≥65 years, symptomatic,f cardiac disease, or osteoporosis6
TSH-dependent hyperthyroidismg	>4.50	>1.8	Treat underlying causeh	fT4, total T3, and TSH6,i: after initiating therapy with somatostatin analogue, then every 2-3 months.24,j

ACTH, adrenocorticotropic hormone; ASCVD, atherosclerotic cardiovascular disease; ATD; antithyroid drug; fT4, free thyroxine; HF, heart failure; LT4, levothyroxine; TPO Ab, thyroid peroxidase antibody; TRAb, TSH receptor binding antibody; TSH, thyroid-stimulating hormone; TSHoma, thyrotropinoma.
a	Subclinical hypo- or hyperthyroidism is frequently transient.6,25
b	LT4 with steroid therapy if adrenal insufficiency is not ruled out.23 Perform Cortisol Response to ACTH Stimulation, Serum (test code 38149) before starting LT4.
c	TSH cannot be used to monitor therapy (suppressed to <0.1 mU/mL when LT4 restores normal fT4); however, if TSH can be measured 6 to 8 weeks after surgery that improves anterior pituitary function, consider monitoring TSH and fT4 and tapering LT4.23
d	For example, ATDs may include a thioamide and betablockers. The American Thyroid Association6 provides guidance if radioactive iodine therapy or thyroidectomy are indicated.
e	TSH is not typically measured as it may stay suppressed for months after starting treatment for overt hyperthyroidism.
f	In contrast to USPSTF,2 which defines subclinical disease as asymptomatic, guidelines in reference6 allow for subclinical hyperthyroidism as symptomatic entity.
g	Approximately 50% to 85% of patients with TSH-secreting pituitary adenomas have a high serum concentration of the alpha subunit of glycoprotein hormones (test code 8658).26
h	Somatostatin analogs are used to restore euthyroidism prior to transsphenoidal surgery on TSHomas.
i	Postoperatively monitor at frequent intervals.
j	Somatostatin receptor analogs can induce TSH deficiency, necessitating a reduction in the frequency of injections.

Table 4 Drugs and Nutrients Affecting Thyroid Function Tests [return to contents]

Effect	Drug or nutrient	Test result
Absorption of T41	Calcium salts (carbonate, citrate, acetate)	↑TSH, ↓fT4, ↓Total T4
	Ferrous sulfate	↑TSH
	Protein pump inhibitors21	↑TSH
	Sucralfate	↑TSH, ↓Total T4
	Raloxifene	↑TSH, ↓Total T4
	Bile acid sequestrantsa	Possible ↑TSH, ↓Total T4
	Orlistatb	Possible ↑TSH
	Phosphate binders	↑TSH
	Milk21	↓Total T4
	Coffee	↑TSH, ↓Total T4
	Soy	↑TSH
	Papaya21	↑TSH, ↓fT4, ↓fT3
Increased thyroid binding globulin level1	Estrogens	↑Total T4, ↑TBG
	SERMs	↑Total T4, ↑TBG
	5-Flurouracil and capecitabine	↑Total T4, ↑TBG32
	Mitotane	↓fT4, normal fT3 and TSH33
Decreased thyroid binding globulin levels1	Androgens	↓Total T4, normal fT4 and TSH
	Glucocorticoids	↓TSH
	Nicotinic Acid	↓TSH
Increased metabolism of T41	Phenytoin	↑TSH, ↓T4, ↓T3c
	Phenobarbital
	Carbamazepine
	Rifampin
Inhibits conversion from T4 to T320	Amiodaroned	↑TSH,e ↑fT4, ↓T3, ↑rT3
	Propranolol34	↑fT4, ↓T3, ↑rT3
	Glucocorticoids27	↓TSH,e ↑fT4, ↓T3, ↑rT3
	Glucocorticoids27	↓TSH,e ↑fT4, ↓T3, ↑rT3
Associated with autoimmune thyroid dysfunction: ie, thyroiditis, Graves, hypothyroidism	Interferonf	↓TSH, ↑fT4, ↑T3
Associated with hypophysitis or hypothyroidism from destructive thyroiditis, or hyperthyroidism from a Graves disease-type mechanism	Immune checkpoint (CTLA-4 or PD-L1) inhibitors (eg, nivolumab, pembrolizumab, ipilimumab)29,30	Abnormal TFT results in line with the pathologic process
Degeneration of thyrocytes	Tyrosine kinase inhibitors (sunitinib, sorafenib, imatinib, motesanib)g	↑TSH, ↓T4
Associated with central hypothyroidism	Bexarotene	↓TSH, ↓fT435
Associated with TSH suppression	Dobutamine, dopamine, octreotide	↓TSH34

fT4, free thyroxine; SERMs, selective estrogen receptor modulators; TBG, thyroxine binding globulin; TFT, thyroid function tests; TSH, thyroid-stimulating hormone.
a	Inhibit enterohepatic circulation of T4; usually coadministered with antithyroid drugs in cases of refractory hyperthyroidism, thyroid storm, and iodine-induced hyperthyroidism.36,37
b	May interfere with LT4 absorption in patients with hypothyroidism on LT4 supplementation.38
c	T4 and TSH concentrations are in the normal range for patients with unaffected HPT axis; increased hormone metabolism is counteracted by increased thyroid hormone production. However, in the setting of subclinical or overt hypothyroidism, thyroid hormone production and secretion cannot be increased, and the latent hypothyroidism of these patients may become overt.32
d	May cause hypo- or hyperthyroidism (amiodarone can induce amiodarone-induced thyrotoxicosis type 1 [AIT1], and amiodarone-induced thyrotoxicosis type 2 [AIT2]).20
e	Over time, TSH normalizes, but the other abnormalities persist.27
f	May cause hypo- or hyperthyroidism. Hypothyroidism is a frequent complication observed in patients with positive thyroid antibodies at the beginning of the treatment or who have developed thyroid antibodies after a previous treatment.28 Hyperthyroidism due to autoimmune thyroiditis is the most frequent occurrence, followed by hyperthyroidism that develops by a Graves-related mechanism.
g	May cause degeneration of thyrocytes, which is followed by progressive hypothyroidism with below range fT4 and above range TSH. In patients with pre-existing hypothyroidism, TFTs should be checked periodically as thyroid hormone requirements may increase. The mechanism has to do with the pleiotropic effect of these drugs, which affects several TKIs, including VEGF receptor kinase inhibitors that cause regression of the vascular supply.31

References [return to contents]

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Ylli D, Soldin SJ, Stolze B, et al. Biotin interference in assays for thyroid hormones, thyrotropin and thyroglobulin. Thyroid. 2021;31(8):1160-1170. doi:10.1089/thy.2020.0866
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Favresse J, Burlacu MC, Maiter D, et al. Interferences with thyroid function immunoassays: clinical implications and detection algorithm. Endocr Rev. 2018;39(5):830-850. doi:10.1210/er.2018-00119
Bartalena L, Bogazzi F, Chiovato L, et al. 2018 European Thyroid Association (ETA) guidelines for the management of amiodarone-associated thyroid dysfunction. Eur Thyroid J. 2018;7(2):55-66. doi:10.1159/000486957
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Persani L, Brabant G, Dattani M, et al. 2018 European Thyroid Association (ETA) guidelines on the diagnosis and management of central hypothyroidism. Eur Thyroid J. 2018;7(5):225-237. doi:10.1159/000491388
Illouz F, Chanson P, Sonnet E, et al. Somatostatin receptor ligands induce TSH deficiency in thyrotropin-secreting pituitary adenoma. Eur J Endocrinol. 2021;184(1):1-8. doi:10.1530/EJE-20-0484
Meyerovitch J, Rotman-Pikielny P, Sherf M, et al. Serum thyrotropin measurements in the community: five-year follow-up in a large network of primary care physicians. Arch Intern Med. 2007;167(14):1533-1538. doi:10.1001/archinte.167.14.1533
Socin HV, Chanson P, Delemer B, et al. The changing spectrum of TSH-secreting pituitary adenomas: diagnosis and management in 43 patients. Eur J Endocrinol. 2003;148(4):433-442. doi:10.1530/eje.0.1480433
Salvatore D, Davies TF, Schlumberger M-J, et al. Thyroid physiology and diagnostic evaluation of patients with thyroid disorders. In: Melmed S, Polonsky KS, Larsen PR, et al, eds. Williams Textbook of Endocrinology. 13th ed. Elsevier; 2017:333-368.
Nair Kesavachandran C, Haamann F, Nienhaus A. Frequency of thyroid dysfunctions during interferon alpha treatment of single and combination therapy in hepatitis C virus-infected patients: a systematic review based analysis. PLoS One. 2013;8(2):e55364. doi:10.1371/journal.pone.0055364
Barroso-Sousa R, Barry WT, Garrido-Castro AC, et al. Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis. JAMA Oncol. 2018;4(2):173-182. doi:10.1001/jamaoncol.2017.3064
Husebye ES, Castinetti F, Criseno S, et al. Endocrine-related adverse conditions in patients receiving immune checkpoint inhibition: an ESE clinical practice guideline. Eur J Endocrinol. 2022;187(6):G1-G21. doi:10.1530/EJE-22-0689
Kotwal A, McLeod DSA. Thyroid dysfunction from treatments for solid organ cancers. Endocrinol Metab Clin North Am. 2022;51(2):265-286. doi:10.1016/j.ecl.2021.12.006
Jonklaas J, Bianco AC, Bauer AJ, et al. Guidelines for the treatment of hypothyroidism: prepared by the American Thyroid Association Task Force on Thyroid Hormone Replacement. Thyroid. 2014;24(12):1670-1751. doi:10.1089/thy.2014.0028
Russo M, Scollo C, Pellegriti G, et al. Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism. Clin Endocrinol (Oxf). 2016;84(4):614-619. doi:10.1111/cen.12868
Haugen BR. Drugs that suppress TSH or cause central hypothyroidism. Best Pract Res Clin Endocrinol Metab. 2009;23(6):793-800. doi:10.1016/j.beem.2009.08.003
Sherman SI, Gopal J, Haugen BR, et al. Central hypothyroidism associated with retinoid X receptor-selective ligands. N Engl J Med. 1999;340(14):1075-1079. doi:10.1056/NEJM199904083401404
Skelin M, Lucijanic T, Amidzic Klaric D, et al. Factors affecting gastrointestinal absorption of levothyroxine: A review. Clin Ther. 2017;39(2):378-403. doi:10.1016/j.clinthera.2017.01.005
Satoh T, Isozaki O, Suzuki A, et al. 2016 Guidelines for the management of thyroid storm from The Japan Thyroid Association and Japan Endocrine Society (First edition). Endocr J. 2016;63(12):1025-1064. doi:10.1507/endocrj.EJ16-0336
XENICAL (orlistat) Capsules. Package insert. Genentech Inc. Updated November, 2022. Accessed February 17, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020766s038lbl.pdf

Content reviewed 03/2023

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Test Code 30278

Thyroglobulin Panel

Thyroglobulin (TG) is a secretory product only of the thyroid gland. The major clinical use of serum TG measurement is to monitor, but not to diagnose, patients with well-differentiated thyroid cancers. The measurement of thyroglobulin, after thyroidectomy and ablation of the thyroid gland, is useful to determine metastasis.
Deficient TG synthesis is observed in infants with goitrous hypo-thyroidism. Most patients with thyroid autoimmune disease have thyroglobulin antibody. With immunomet

Test Code 36127

TSH with Reflex to Free T₄

This test may be useful in assessing thyroid dysfunction when pituitary disease is not suspected. In patients with clinical suspicion of hyperthyroidism or hypothyroidism, testing thyroid stimulating hormone (TSH) is the initial step [1]. An abnormal TSH result will reflex to a free thyroxine (T4) test to aid in diagnosis and guide further testing if needed.

TSH stimulates the thyroid gland to synthesize and secrete triiodothyronine (T3) and T4. TSH production is reduced in response to hi

Test Code 36725

T₄ Free, Direct Dialysis and T₄ Total

For the differential diagnosis of euthyroid hyperthyroxinemia from hyperthyroidism or for the differential diagnosis of euthyroid hypothyroxinemia from hypothyroidism.

Test Code 90963

T₃ Reverse, LC/MS/MS

3,3',5'-Triiodothyronine (reverse T3, rT3) is, along with 3,3,5'-Triiodothyronine (T3) a deiodinated metabolite of thyroxine (T4), the major secretory product of the thyroid gland and is secreted into the bloodstream. Unlike T3, however, rT3 is thought to be metabolically inert.
The process of 5'-monodeiodination that converts T4 to T3, and rT3 to diiodothyronine (DTT) is inhibited in a wide variety of conditions, collectively referred to as nonthyroidal illnesses (NTI) or the 'euthyroid

Test Code 30551

TSI (Thyroid Stimulating Immunoglobulin)

Graves' disease is a classic form of hyperthyroid disease, affecting approximately 0.4% of the population of the United States. It is caused by IgG immunoglobulins, collectively known as thyroid stimulating immunoglobulins (TSI). Patients who are candidates for antithyroid drug therapy may not respond to this treatment when TSI levels are markedly elevated. The determination of TSI can also assist in predicting hyperthyroidism in neonates, due to placental transmission of the immunoglobulins fro

Test Code 267

Thyroglobulin Antibodies

Measurement of thyroglobulin antibodies is useful in the diagnosis and management of a variety of thyroid disorders including Hashimoto's thyroiditis, Graves' disease and certain types of goiter.

Test Code 35167

T₄ Free, Direct Dialysis

For the differential diagnosis of euthyroid hyperthyroxinemia from hyperthyroidism or for the differential diagnosis of euthyroid hypothyroxinemia from hypothyroidism.

Test Code 36574

T₃ (Triiodothyronine) Antibody

This test helps identify triiodothyronine (T3) thyroid hormone autoantibodies (THAAbs), which may interfere with T3 immunoassays in individuals with discordant serum T3 levels [1].

THAAbs may present in healthy individuals but are more common in patients with autoimmune thyroid diseases. THAAbs may affect both 1-step and 2-step immunoassays; the interference may be transient or persist for years. T3 THAAbs interfere with T3 measurements by competing with T3 antibodies used in the T3 immun

Test Code 36576

T₄ (Thyroxine) Antibody

This test helps identify thyroxine (T4) thyroid hormone autoantibodies (THAAbs), which may interfere with T4 immunoassays in individuals with discordant serum T4 levels [1].

THAAbs may present in healthy individuals but are more common in patients with autoimmune thyroid diseases. THAAbs may affect both 1-step and 2-step immunoassays; the interference may be transient or persist for years. T4 THAAbs interfere with T4 measurements by competing with T4 antibodies used in the T4 immunoassays

Test Code 36577

TSH Antibody

This test may help identify thyroid stimulating hormone (TSH) autoantibodies. When the serum TSH level is discordant with clinical manifestations or other test results (eg, markedly elevated TSH with normal free triiodothyronine and free thyroxine levels), this test may be used to determine if TSH autoantibodies are the cause of discordance.

TSH autoantibodies can bind TSH to form a macromolecule (macro-TSH) that has low biological activity but interferes with TSH immunoassays [1]. Interf

Test Code 38149

Cortisol Response to ACTH Stimulation, Serum

The cortisol response to infusion of synthetic ACTH is useful in diagnosing patients with adrenal insufficiency (Addison's disease).

Test Code 7260

Thyroid Peroxidase and Thyroglobulin Antibodies

Measurement of thyroglobulin antibodies and thyroid peroxidase antibodies is useful in the diagnosis and management of a variety of thyroid disorders including autoimmune thyroiditis, Hashimoto's Disease, Graves Disease and certain types of goiter.

Test Code 867

T₄(Thyroxine), Total

For diagnosis of hypothyroidism and hyperthyroidism.

Test Code 870

TBG (Thyroxine Binding Globulin)

Thyroxine-binding globulin (TBG), a glycoprotein produced in the liver, binds both thyroxine (T4) and triiodothyronine (T3) with high affinity. Because TBG accounts for 76% of plasma protein thyroxine-binding activity, an increase or decrease in its circulating level alters total concentrations of T4 and T3 in blood, leading to potential confusion with true thyroid gland dysfunction. A number of diseases and medications, as well as inherited alterations in TBG gene expression, can change th

Test Code 861

T₃ Uptake

Decreased: Pregnancy, estrogens, hyperproteinemia, acute intermittent porphyria.
Increased: Androgens, hyperproteinemia, stress, acute liver disease.
This assay is a measure of available thyroid hormone binding sites and should be interpreted with thyroxine levels.

Test Code 859

T₃ Total

Total T₃ measurements are used to diagnose and monitor treatment of hyperthyroidism and are essential for recognizing T₃ toxicosis.

Test Code 15102

Thyroid Cascading Reflex

The Thyroid Cascading Reflex order code that will act as an aid to physicians in the diagnosis of common adult thyroid disorders. The initial results of a TSH will determine further reflex orders of T₄, Free, TPO Antibodies and T₃, Free orders and provided an interpretation based upon the results of the reflexed tests.

Test Code 19584

Thyroglobulin Panel with HAMA Treatment

Thyroglobulin (TG) is a secretory product only of the thyroid gland. The major clinical use of serum TG measurement is to monitor, but not to diagnose, patients with well-differentiated thyroid cancers. The measurement of thyroglobulin, after thyroidectomy and ablation of the thyroid gland, is useful to determine metastasis. Deficient TG synthesis is observed in infants with goitrous hypothyroidism.

Test Code 34429

T₃, Free

The T3, Free (FT3) test measures serum triiodothyronine (T3) not bound to thyroid hormone-binding proteins (thyroid hormone-binding globulin [TBG], transthyretin, albumin). It is used, primarily in concert with measurement of thyroid-stimulating hormone (TSH, test code 899) and free T4 (FT4, test code 866), in the diagnosis and management of hyperthyroidism and to clarify thyroid hormone status in the presence of a possible thyroid hormone-binding protein abnormality.

The FT3 (or

Test Code 38683

TRAb (TSH Receptor Binding Antibody)

Measurement of TRAb is used to diagnose and manage Graves' disease, neonatal hypothyroidism, and postpartum thyroid dysfunction. TRAb, which measures the ability of antibodies to inhibit TSH binding to its receptor, reflects the presence of either or both the stimulatory and inhibitory immunoglobulin classes.

Test Code 8658

Alpha Subunit

This assay is useful in the diagnosis and management of various pituitary, placental, pancreatic and hCG-producing tumors. The assay can also be useful for investigations where alpha subunit is increased under various physiological stimuli, e.g., GnRH stimulation and TRH stimulation tests.

Test Code 866

T₄Free (FT₄)

The T4 Free (FT4) test measures serum thyroxine (T4) that is not bound to thyroid hormone-binding proteins (thyroid hormone-binding globulin [TBG], transthyretin, albumin) and is thus readily available to target cells. This test is used with thyroid-stimulating hormone measurement (TSH, test code 899) in the diagnosis of hyperthyroidism (usually displaying elevated FT4) and hypothyroidism (low FT4), including congenital and acquired hypothyroidism.

The FT4 test is used to assess thyroid f

Test Code 19537

TSH with HAMA Treatment

Precision in the estimation of TSH is crucial to the follow-up of subjects with thyroid disorders. The preincubation of samples to remove HAMA immunoglobulins provides a way to ensure that an otherwise unsuspected rise or drop in TSH concentration will not be interpreted as either a false positive or false negative.

Test Code 36598

T₃ Free, Tracer Dialysis

T₃ measurements are used to diagnose hyperthyroidism. This test can also be used to clarify thyroid status in the presence of possible protein-binding abnormalities.

Test Code 7020

Thyroid Panel

For diagnosis of hypothyroidism and hyperthyroidism.

Test Code 899

TSH

For differential diagnosis of primary, secondary, and tertiary hypothyroidism. Also useful in screening for hyperthyroidism. This assay allows adjustment of exogenous thyroxine dosage in hypothyroid patients and in patients on suppressive thyroxine therapy for thyroid neoplasia.

Test Code 5081

Thyroid Peroxidase Antibodies (TPO)

Assists in the diagnosis of thyroid diseases such as endemic goiter, Graves Disease, autoimmune thyroiditis, Addison's Disease, insulin-dependent diabetes mellitus, Hashimoto's Disease and polyendocrine auto-immunopathies.

IG/Reference Manual

Test Guide List

This page is a complete list of Test Guides created by Quest Diagnostics.

Test Summary

Cardiometabolic Disease Assessment (CMDA) Panel

This panel is used to assess cardiometabolic dysfunction in the context of (1) early-stage measures of dyslipidemia and glycemic control, (2) common endocrine disorders, and (3) downstream adverse effects on end-organ dysfunction, including liver and kidney.

Clinical Focus

Hypogonadism and Low Testosterone in Men: Laboratory Support of Diagnosis and Management

This Clinical Focus describes approaches to testing for the diagnosis of low testosterone and monitoring during testosterone therapy in men with hypogonadism. Details of available tests are provided, as well as information about interpreting test results.

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Reference ranges are provided as general guidance only. To interpret test results use the reference range in the laboratory report.

The tests listed by specialty and category are a select group of tests offered. For a complete list of Quest Diagnostics tests, please adjust the filter options chosen, or refer to our Directory of Services.

Thyroid Dysfunction in Nonpregnant Adults

Thyroid Dysfunction in Nonpregnant Adults

Clinical Focus

Clinical Focus

(27) Related Tests

(3) Related Guides