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252 Laboratory Medicine in Psychiatry and Behavioral Science
Thyroid function testing: free thyroxine (continued)
Indications • Abnormal TSH result
• Signs/symptoms of thyroid disease (even if TSH is
normal)
• Monitoring effects of treatment for thyroid illness
Reference range Depends on the specific method used for assay; consult lab
reference values.
Critical value(s) <2 μg/dL or >20 μg/dL
Increased levels • Hyperthyroidism
• Treated hypothyroidism
Decreased levels • Primary hypothyroidism
• Secondary hypothyroidism (pituitary cause)
• Tertiary hypothyroidism (hypothalamic cause)
• Hypothyroidism treated with triiodothyronine (T3)
• Late pregnancy
Interfering factors FT4 levels fluctuate in pregnancy and in severe or chronic
illness. Different reference ranges apply in pregnancy.
Drugs that cause an increase in FT4 include amiodarone, as-
pirin, biotin, carbamazepine, furosemide, heparin, phenyt-
oin, propranolol, X-ray contrast agents, and valproate.
Drugs that cause a decrease in FT4 include lithium, carba-
mazepine, corticosteroids, estrogen, methadone, oral con-
traceptives, phenobarbital, and phenytoin.
Cross-references Hypothyroidism
Thyroid Function Testing: Thyroid-Stimulating Hormone
Thyrotoxicosis
Benvenga S: L-T4 therapy in the presence of pharmacological interferents.Front Endocrinol (Lausanne)
11:607446, 2020
Bowen R, Benavides R, Colón-Franco JM, et al: Best practices in mitigating the risk of biotin interference
with laboratory testing.Clin Biochem 74:1–11, 2019
Dworakowska D, Morley S, Mulholland N, Grossman AB: COVID-19-related thyroiditis: a novel disease
entity?Clin Endocrinol (Oxf) 95(3):369–377, 2021
Roberts CG, Ladenson PW: Hypothyroidism. Lancet 363:793–803, 2004
Soh SB, Aw TC: Laboratory testing in thyroid conditions: pitfalls and clinical utility.Ann Lab Med
39(1):3–14, 2019
Spaulding SW, Lippes H: Hyperthyroidism: causes, clinical features, and diagnosis. Med Clin North Am
69:937–951, 1985
Ylli D, Wartofsky L, Burman KD: Evaluation and treatment of amiodarone-induced thyroid
disorders.J Clin Endocrinol Metab 106(1):226–236, 2021
https://t.me/med1917
253 Laboratory Tests
Thyroid function testing: thyroid-stimulating hormone (TSH)
Type of test Blood
Background and explanation
of test
TSH secreted by the anterior pituitary stimulates the thyroid
gland to release stored triiodothyronine (T3) and thyroxine
(T4), hormones responsible for the regulation of metabolism.
TSH secretion is in turn regulated by thyrotropin-releasing
hormone (TRH) from the hypothalamus and by feedback
inhibition from T3 and T4. In the past, a combination of thy-
roid tests (thyroid panel) was used to screen for and diagnose
thyroid disease, but the thyroid panel has now largely been
replaced by the highly sensitive TSH assay for screening.
If the TSH is normal in suspected thyroid disease, no further
testing is indicated. If the TSH is not normal and the differen
-
tial diagnosis includes subclinical thyroid disease or dysfunc-
tion of the hypothalamic-pituitary axis, however, free T4
should be measured along with TSH.
TSH and free T4 (FT4) together suggest the following diag-
noses:
• TSH high, FT4 low: hypothyroidism
• TSH high, FT4 normal: subclinical hypothyroidism
• TSH low, FT4 high: hyperthyroidism
• TSH low, FT4 normal: subclinical hyperthyroidism
• TSH low, FT4 low: nonthyroidal illness
Relevance to psychiatry and
behavioral science
Patients with hyperthyroidism can present with delirium or
with psychiatric symptoms that suggest primary anxiety dis-
orders, mood disorders, or psychosis. The geriatric syndrome
of apathetic hyperthyroidism is described in the Thyrotoxico
-
sis entry in the Diseases and Conditions chapter.
Hypothyroidism is associated with fatigue, depressed mood,
and memory impairment, symptoms that may improve with
thyroid replacement. Even among patients with TSH values
in the high-normal range, there is a higher frequency of de-
pressive episodes, symptoms are more severe, and antide-
pressant treatment response can be suboptimal. Thyroid
replacement with target TSH levels <2.5 mIU/L may be re
-
quired to achieve remission, and this is true for patients with
both bipolar and unipolar disease. Patients with treatment-
resistant depression may benefit from thyroid supplementa-
tion titrated to a target TSH level as low as <2.0 mIU/L.
Abnormal TSH with normal FT4 is consistent with subclini-
cal thyroid disease, which can manifest as a fully developed
or formes frustes picture of hyperthyroidism or hypothyroid
-
ism. Whether or how subclinical disease should be treated
has been controversial. Recent reviews suggest that subclin-
ical hypothyroidism in non-elderly patients should be
treated when the TSH level is >4.0 mIU/L. For elderly pa-
tients, a higher TSH cutoff may be appropriate, although
most healthy elderly persons have TSH levels <2.5 mIU/L.
https://t.me/med1917
254 Laboratory Medicine in Psychiatry and Behavioral Science
Thyroid function testing: thyroid-stimulating hormone (TSH) (continued)
Relevance to psychiatry and In a recent study, more than half of hospitalized patients with
behavioral science (continued) COVID-19 were found to have a TSH level below the normal
range. The level returned to normal with recovery from the
viral illness.
Preparation of patient Biotin supplements should be discontinued ≥ 2 days before
testing.
Indications • Diagnosing hypothyroidism or hyperthyroidism in a
symptomatic patient
• Screening for thyroid disease in patients at risk, such
as females older than 50 years or patients treated with
lithium
• Evaluating the effects of thyroid nodule or goiter
• Monitoring the efficacy of thyroid replacement therapy
in a patient with hypothyroidism
• Standard component of workup for patients with de-
pression, memory impairment, or dementia
Reference range 0.5–5.0 mIU/L is understood to be the general reference
range, but values differ slightly by lab, so the test report
should be consulted.
Note: With treatment for hypothyroid or hyperthyroid
states, TSH may remain abnormal for up to 6 weeks after
the euthyroid state has been attained.
Critical value(s) <0.1 mIU/L indicates primary hyperthyroidism or exoge-
nous thyrotoxicosis, with risk of atrial fibrillation (major risk
factor for stroke).
Increased levels • Primary hypothyroidism (≥ 100 times normal)
• TSH-producing tumor (e.g., breast or lung)
• Hashimoto’s thyroiditis
• Recovery phase of subacute thyroiditis or nonthyroidal
illness
• Insufficient thyroid replacement or thyroid hormone
resistance in treated hypothyroid patients
Decreased levels • Primary hyperthyroidism
• Secondary hypothyroidism (pituitary disease)
• Tertiary hypothyroidism (hypothalamic disease)
• Subclinical hyperthyroidism (e.g., toxic multinodular
goiter, treated Graves’ disease)
• Euthyroid sick syndrome
• Overreplacement of thyroid hormone
https://t.me/med1917
255 Laboratory Tests
Thyroid function testing: thyroid-stimulating hormone (TSH) (continued)
Interfering factors TSH levels have normal diurnal variation that must be con-
sidered in the test interpretation.
Numerous drugs—both psychotropic and non-psychotropic—
have the potential to interfere with thyroid function assays;
current and recently discontinued drugs should be listed on
the lab requisition form.
Two drugs that affect the thyroid itself are lithium and
amiodarone, an antiarrhythmic drug.
A recent meta-analysis found no impact of SSRI treatment on
TSH levels. Iodinated contrast medium does not affect TSH
level in patients with normal thyroid function. Carbamaze-
pine and other enzyme inducers can increase metabolism of
thyroid hormones and thereby cause an increase in TSH.
TSH levels are known to increase with age, although this
may indicate increasing thyroid dysfunction. Even though
most elderly persons have TSH levels <2.5 mIU/L, some ref
-
erences suggest an upper limit of normal for TSH as high as
10 mIU/L for patients >80 years of age.
Cross-references Hypothyroidism
Thyroid Function Testing: Free Thyroxine
Thyrotoxicosis
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed September 2021.
Barbesino G: Thyroid function changes in the elderly and their relationship to cardiovascular health: a
mini-review.Gerontology 65(1):1–8, 2019
Benvenga S: L-T4 therapy in the presence of pharmacological interferents.Front Endocrinol (Lausanne)
11:607446, 2020
Bowen R, Benavides R, Colón-Franco JM, et al: Best practices in mitigating the risk of biotin interference
with laboratory testing.Clin Biochem 74:1–11, 2019
Caye A, Pilz LK, Maia AL, et al: The impact of selective serotonin reuptake inhibitors on the thyroid func-
tion among patients with major depressive disorder: a systematic review and meta-analysis.Eur Neu-
ropsychopharmacol 33:139–145, 2020
Chen M, Zhou W, Xu W: Thyroid function analysis in 50 patients with COVID-19: a retrospective
study. Thyroid 31(1):8–11, 2021
Chrysant SG: The current debate over treatment of subclinical hypothyroidism to prevent cardiovascular
complications. Int J Clin Pract 74(7):e13499, 2020
Cohen BM, Sommer BR, Vuckovic A: Antidepressant-resistant depression in patients with comorbid sub-
clinical hypothyroidism or high-normal TSH levels.Am J Psychiatry 175(7):598–604, 2018
Favresse J, Burlacu MC, Maiter D, Gruson D: Interferences with thyroid function immunoassays: clinical
implications and detection algorithm.Endocr Rev 39(5):830–850, 2018
Soh SB, Aw TC: Laboratory testing in thyroid conditions: pitfalls and clinical utility.Ann Lab Med
39(1):3–14, 2019
https://t.me/med1917
256 Laboratory Medicine in Psychiatry and Behavioral Science
Total iron-binding capacity (TIBC)
Type of test Blood
Background and explanation
of test
The TIBC is the maximum amount of iron that can be bound
to transferrin, the protein in blood responsible for transport
-
ing iron to tissues. Iron is needed to produce hemoglobin and
to transport oxygen, among other functions. In the TIBC test,
iron is added to the patient’s serum until the transferrin
-
binding sites are saturated, then the excess iron is removed,
and the amount of bound iron remaining is measured. This
value—TIBC—can be used with serum iron and transferrin
levels in the evaluation of iron deficiency and iron overload
states. However, transferrin saturation is actually a better
measure of iron status, and this is calculated by dividing the
serum iron by the TIBCand then multiplying by 100. The
TIBC can be used to distinguish anemia (increased TIBC)
from inflammatory conditions (normal TIBC).
Relevance to psychiatry and
behavioral science
Patients with either hemochromatosis or iron deficiency
anemia may present with fatigue, lethargy, and weakness,
which could be mistaken for primary depression. In hemo
-
chromatosis, iron is deposited in the brain, increasing the
risk of confusional states, cognitive dysfunction, mood dis
-
orders, dizziness, and tinnitus. There is some evidence that
iron deposition may contribute to neurodegenerative dis-
eases such as Alzheimer’s disease. MRI studies have shown
that iron levels in subcortical gray structures including the
caudate, putamen, and globus pallidus are positively cor
-
related with liver iron levels in elderly males.
Preparation of patient Patients should fast for 12 hours before the test, with water
permitted. Blood should be drawn in the morning, if possible.
Indications •
Anemia (microcytic, hypochromic)
• Aiding in the diagnosis of iron deficiency anemia (see
Transferrin; Transferrin Saturation)
• Suspected hemochromatosis
Reference range Adults: 250–450 μg/dL
Critical value(s) None
Increased levels • Iron deficiency anemia (microcytic)
• Late pregnancy
• Blood loss (acute and chronic)
• Acute hepatitis
• Use of oral contraceptives
Decreased levels • Hemochromatosis
• Non–iron deficiency anemia (chronic disease, infection)
• Low protein levels (malnutrition, burns)
• Cirrhosis
• Renal disease
https://t.me/med1917
257 Laboratory Tests
Total iron-binding capacity (TIBC) (continued)
Decreased levels (continued) • Thalassemia
• Hyperthyroidism
• Use of ACTH, steroids, dextran, testosterone, asparagi-
nase, or chloramphenicol
Interfering factors TIBC and serum iron level may be normal in iron deficiency
anemia if hemoglobin is >9 g/dL.
Cross-references Anemia
Hemochromatosis
Iron Level
Transferrin; Transferrin Saturation
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed September 2021.
Auerbach M, Adamson JW: How we diagnose and treat iron deficiency anemia.Am J Hematol 91(1):31–
38, 2016
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Killip S, Bennett JM, Chambers MD: Iron deficiency anemia.Am Fam Physician 75(5):671–678, 2007 [pub-
lished correction appears in Am Fam Physician 78(8):914, 2008]
Pietrangelo A: Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology
139:393–408, 2010
Zhu A, Kaneshiro M, Kaunitz JD: Evaluation and treatment of iron deficiency anemia: a gastroenterolog-
ical perspective. Dig Dis Sci 55:548–559, 2010
https://t.me/med1917
258 Laboratory Medicine in Psychiatry and Behavioral Science
Transferrin; transferrin saturation
Type of test Blood
Background and explanation
of test
Transferrin is a β-globulin and glycoprotein produced in the
liver that transports dietary iron to storage depots and sites
of hemoglobin synthesis. The transferrin test measures the
level of blood transferrin, which depends on liver function
and nutritional status. Transferrin saturation is calculated
by dividing the serum iron level by the total iron-binding
capacity (TIBC) and multiplying by 100. Normally, the satu
-
ration is between 20% and 50%. In iron deficiency, the iron
level is low and the TIBC is increased, so the saturation can
drop to a very low level. In hemochromatosis, the iron level
is high and the TIBC is low or normal, so the saturation is
high.
Relevance to psychiatry and
behavioral science
Patients with either hemochromatosis or iron deficiency
anemia may present with fatigue, lethargy, and weakness,
which could be mistaken for primary depression. In hemo
-
chromatosis, iron is deposited in the brain, increasing the
risk of confusional states, cognitive problems, mood disor
-
ders, dizziness, and tinnitus.
Preparation of patient Patients should fast for 12 hours before testing, with water
permitted.
Indications • Aiding in the diagnosis of iron deficiency as the cause of
anemia
• Diagnosing hemochromatosis
• Evaluating nutritional status
• Evaluating liver function
Reference ranges Transferrin
• 200–400 mg/dL
Transferrin saturation
• Males: 10%–50%
• Females: 15%–50%
Critical value(s) None
Increased levels Transferrin
• Iron deficiency anemia
•Pregnancy
•Estrogen therapy
Transferrin saturation
• Hemochromatosis
Decreased levels Transferrin
• Anemia of chronic disease (microcytic)
• Protein deficiency or loss
• Chronic infection
• Acute liver disease
https://t.me/med1917
259 Laboratory Tests
Transferrin; transferrin saturation (continued)
Decreased levels (continued) • Renal disease
• Genetic disease
• Hemochromatosis
Transferrin saturation
• Iron deficiency anemia
Interfering factors Increased transferrin
levels may be found with estrogen and
oral contraceptive use.
Decreased transferrin levels may be found with corticoste-
roid and testosterone use.
Lipemic or hemolyzed specimens may invalidate testing.
Cross-references Anemia
Hemochromatosis
Iron Level
Total Iron-Binding Capacity
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed September 2021.
ARUP Laboratories: Transferrin, serum, in Lab Test Directory. Salt Lake City, UT, ARUP Laboratories,
2021. Available at: https://ltd.aruplab.com/Tests/Pub/0050570. Accessed September 2021.
Auerbach M, Adamson JW: How we diagnose and treat iron deficiency anemia. Am J Hematol 91(1):31–
38, 2016
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Killip S, Bennett JM, Chambers MD: Iron deficiency anemia.Am Fam Physician 75(5):671–678, 2007 [pub-
lished correction appears in Am Fam Physician 78(8):914, 2008]
Pietrangelo A: Hereditary hemochromatosis: pathogenesis, diagnosis, and treatment. Gastroenterology
139:393–408, 2010
Zhu A, Kaneshiro M, Kaunitz JD: Evaluation and treatment of iron deficiency anemia: a gastroenterolog-
ical perspective. Dig Dis Sci 55:548–559, 2010
https://t.me/med1917
260 Laboratory Medicine in Psychiatry and Behavioral Science
Triglycerides
Type of test Blood
Background and explanation
of test
Most dietary fat intake is in the form of triglycerides (TGs),
which are an important energy source for the body. At any
given time, most TGs are stored in adipose tissue as glycerol,
fatty acids, and monoglycerides. Lesser amounts are present
in the circulation, and this is what the assay measures. After
a meal, TG levels can increase dramatically as the body con-
verts dietary energy into adipose tissue. Between meals, adi-
pose tissue stores are reconverted to TGs to meet energy
demands.
High TG levels are associated with a heightened risk of heart
disease and stroke. Certain medical and lifestyle factors are in
turn associated with elevated TGs, including diabetes, kidney
disease, sedentary lifestyle, smoking, excessive alcohol con
-
sumption, and being overweight.
TGs and other lipids can be assayed with a fasting or non-
fasting blood sample. A fasting sample is recommended for
those with type 2 diabetes, excessive alcohol intake, or obe
-
sity. When TGs are measured, cholesterol is also measured
because both represent risk factors for atherosclerotic disease,
and the two can vary independently.
Relevance to psychiatry and
behavioral science
TG levels may be elevated in alcohol use disorder, anorexia
nervosa, and other conditions. In addition, psychotropic
drugs such as mirtazapine, risperidone, and β-blockers are
associated with TG elevations. Before such drugs are initi
-
ated, a fasting lipid profile should be obtained. High TG
levels increase the patient’s risk of pancreatitis and predict a
more severe course of COVID-19 infection.
Preparation of patient Routine non-fasting test requires no preparation.
For fasting test, patients should abstain from food for
12 hours, with water permitted.
Indications • Component of lipid panel, obtained every 4–6 years in
healthy adults
• Screening for patients with family history of lipid dis-
order
• Assessing cardiovascular disease risk
• Evaluating patients being considered for lipid-lowering
treatments
• Monitoring effects of lipid-lowering treatments
• Assessing a patient with pancreatitis
Reference range Normal: <150 mg/dL
Mild elevation: 150–499 mg/dL
Moderate elevation: 500–886 mg/dL
Very high/Severe elevation: >886 mg/dL
Note: These cutoffs apply to fasting samples.
https://t.me/med1917
261 Laboratory Tests
Triglycerides (continued)
Critical value(s) A level >500 mg/dL represents increased risk of pancreatitis.
A level >5,000 mg/dL is associated with eruptive xan-
thoma, arcus cornealis, enlarged liver and spleen, and
lipemia retinalis.
Increased levels • Hyperlipoproteinemia
• Alcohol use disorder
• Liver disease, including fatty liver (non-alcoholic)
• Kidney disease, nephrotic syndrome
• Hypothyroidism
• Type 2 diabetes
• Pancreatitis
• Glycogen storage disease
• MI
• Gout
• Werner’s syndrome
• Down syndrome
• Anorexia nervosa
Decreased levels •
Low-fat diet
• Malnutrition
• Malabsorption
• Hyperthyroidism
• Hyperparathyroidism
• Severe stroke
Interfering factors Food intake increases TG levels within hours of a meal. Alco-
hol use increases TG levels. Fasting TG levels may vary from
day to day.
Transient decrease occurs after strenuous exercise.
Levels increase in pregnancy.
Poorly controlled blood sugar in patients with diabetes can
drive TG levels up.
Levels increase with
acute illnesses such as colds or
influenza.
Certain drugs increase TG levels, including β-blockers, cor-
ticosteroids, estrogens, furosemide, hydrochlorothiazide,
interferon-α-2a, isotretinoin, mirtazapine, oral contracep-
tives, protease inhibito
rs, risperidone, and warfarin.
Other drugs decrease triglyceride levels, including ACE
inhibitors, hydroxychloroquine, indomethacin, insulin,
levodopa, niacin, psyllium, and statins and other drugs used
to treat high triglyceride levels.
https://t.me/med1917
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