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242 Laboratory Medicine in Psychiatry and Behavioral Science
Syphilis testing
Type of test Blood, skin scraping from a visible lesion, CSF
Background and explanation
of test
Antibody tests are used for the screening and diagnosis of
syphilis. These are of two types: nontreponemal and trepo
-
nemal. Nontreponemal tests do not detect antibodies to the
bacteria that cause syphilis but instead detect other antibod
-
ies produced in the presence of syphilis infection. These
tests are sensitive but not specific; false-positive results can
occur with autoimmune disease, pregnancy, tuberculosis,
and other conditions noted in the Interfering Factors section
below. Nontreponemal tests include the RPR and VDRL
tests. A positive result from either of these tests is confirmed
with a more specific t
reponemal test.
Treponemal tests detect antibodies directed to the Tre p o-
nema pallidum organism. These tests include the FTA-ABS,
the T. pallidum particle agglutination assay (TP-PA), the
microhemagglutination assay for T. pallidum antibodies
(MHA-TP), and various immunoassays. These tests are
very specific for syphilis. Once treponemal antibodies
form, however, they stay in the circulation indefinitely, so
these tests cannot be used to distinguish a recent from a
past infection. Nontreponemal antibodies, in contrast,
disappear from the body with adequate treatment after
~3 years. FTA-ABS testing is useful 3–4 weeks after expo-
sure. TP-PA testing is less often used but is more
specific
than FTA-ABS. If the treponemal test confirms infection,
the disease should be staged and treated.
Two methods of direct detection of
T. pallidum include dark-
field microscopy and molecular testing by PCR. Microscopy
can be used in the early stages of syphilis with scrapings
from a chancre. PCR can be used on scrapings, blood, or
CSF.
For suspected neurosyphilis, VDRL is performed on CSF.
FTA-ABS, which is less specific than VDRL but highly sensi
-
tive, can be used to exclude neurosyphilis. PCR can be used
to detect bacterial DNA in CSF or other samples.
Relevance to psychiatry and
behavioral science
Among psychiatric patients, the risk of sexually transmitted
infection (STI) is higher in those with alcohol or drug abuse
or dependence, bipolar disorder, and certain personality dis-
orders and in those who are HIV positive. With these risks in
mind, appropriate vigilance regarding STI testing can be
maintained. Neurosyphilis is associated with dementia,
mood disorders, and behavioral changes.
Preparation of patient None needed
Indications •
Chancre, skin rash, or other signs of syphilis as noted in
the Diseases and Conditions chapter.
• Screening a patient with another STI, such as gonorrhea
• Screening a patient with newly diagnosed HIV infection
• Screening for syphilis in pregnancy
https://t.me/med1917
243 Laboratory Tests
Syphilis testing (continued)
Reference range Negative or nonreactive
Positive test Reactive RPR or VDRL and positive treponemal testing
Negative test Nonreactive RPR or VDRL and negative treponemal testing
Interfering factors False-positive RPR or VDRL results can be found in the
presence of pneumonia, HIV disease, herpes simplex virus,
malaria, primary antiphospholipid syndrome, IV drug use,
SLE, Lyme disease, tuberculosis, rheumatoid arthritis, preg
-
nancy, Hansen’s disease, or other treponemal diseases.
False-positive FTA-ABS results may occur in the presence of
autoimmune disease, Hansen’s disease, febrile illness, ad
-
vanced age, Lyme disease, or other treponemal diseases.
Cross-references Syphilis
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed September 2021.
Clyne B, Jerrard DA: Syphilis testing. J Emerg Med 18:361–367, 2000
Young H: Guidelines for serological testing for syphilis. Sex Transm Infect 76:403–405, 2000
https://t.me/med1917
244 Laboratory Medicine in Psychiatry and Behavioral Science
Temazepam level
Type of test Blood
Background and explanation
of test
Benzodiazepines are Schedule IV sedative-hypnotic drugs
used to treat anxiety and insomnia. Temazepam is a drug
with a slow onset of action and a half-life of up to 2 days. It is
not extensively metabolized in the liver. In general, levels are
checked when either overdose or noncompliance is sus
-
pected or to detect use without a prescription. In the latter
case, a urine drug screen is more likely to be ordered than a
blood level.
Relevance to psychiatry and
behavioral science
Toxicity with chronic benzodiazepine ingestion may mani-
fest as confusion, disorientation, memory impairment,
ataxia, decreased reflexes, and dysarthria. With acute over
-
dose, patients may exhibit somnolence, confusion, ataxia, de-
creased reflexes, vertigo, dysarthria, respiratory depression,
and coma. Treatment of overdose is supportive. More serious
consequences usually involve co-ingestion of alcohol or other
sedatives, and in these cases, airway management is re
-
quired. The choice to use flumazenil, an antagonist at the
benzodiazepine receptor, is made on a case-by-case basis.
Flumazenil does not affect the drug level. Activated charcoal
is no longer recommended, and neither dialysis nor bowel
irrigation has a role in treatment of overdose.
Preparation of patient None needed
Indications • Screening for drug use
• Suspicion of overdose
• Signs of toxicity in a treated patient
• Suspected noncompliance with prescribed therapy
Reference range 0.4–0.9 μg/mL
Critical value(s) Levels significantly above reference
Increased levels • Overdose
• Overuse
Decreased levels Noncompliance
Interfering factors None
Cross-references Benzodiazepines
Urine Drug Screen
Kang M, Galuska MA, Ghassemzadeh S: Benzodiazepine toxicity, in StatPearls. Treasure Island, FL, Stat-
Pearls Publishing, 2021. Available
at:
https://www.statpearls.com/ArticleLibrary/viewarticle/
30312. Accessed September 2021.
https://t.me/med1917
245 Laboratory Tests
Testosterone level
Type of test Blood
Background and explanation
of test
In response to stimulation by LH from the anterior pituitary,
the testes secrete testosterone, a steroid hormone that in pu
-
berty stimulates the development of male sexual characteris-
tics, including enlargement of the penis, growth of body hair,
muscle development, and a deepening voice. In adult males,
testosterone regulates sex drive and helps to maintain muscle
mass. In females, testosterone is produced in small amounts
by the ovaries and is converted to estradiol. In both sexes, tes
-
tosterone is also secreted by the adrenal glands.
Testosterone levels peak in the early morning hours (between
4:00
A.M. and 8:00 A.M.) and are lowest in the evening (be-
tween 4:00
P.M. and 8:00 P.M.). Most testosterone in the circu-
lation is bound to protein; only about 1%–4% circulates as free
testosterone.
New guidelines for the diagnosis and management of testos-
terone deficiency were published by the American Urological
Association in 2018 to guide replacement therapy for males
with documented deficiency. This requires two separate
morning tests showing a total testosterone level <300 ng/dL
in conjunction with typical clinical signs/symptoms. If total
testosterone is low, serum LH is measured. If LH is also low,
serum prolactin is measured. These values determine the
need for further testing or endocrinology referral.
Relevance to psychiatry and Testosterone deficiency
behavioral science
In addition to classic symptoms of testosterone deficiency
such as reduced sex drive, erectile dysfunction, and infertility,
common symptoms of deficiency in males include fatigue, re
-
duced energy, reduced endurance, diminished physical per-
formance, reduced motivation, poor concentration, impaired
memory, and irritability. Symptoms could be erroneously
construed as a depressive episode.
Obesity and the metabolic syndrome are associated with low
total and free testosterone levels. The relationship is bidirec-
tional. Waist circumference is a modifiable risk factor for low
testosterone. Stress, which is implicated in both the metabolic
syndrome and hypogonadism, is also associated with low-
ered testosterone levels.
Alcoholism with cirrhosis is associated with low testosterone
levels. Hypothalamic and pituitary disease can be associated
with low testosterone levels and with tertiary or secondary
hypogonadism, respectively.
Psychotropic drugs associated with reduced testosterone lev-
els include carbamazepine, conjugated estrogens, danazol,
prednisone, dexamethasone, and medroxyprogesterone.
https://t.me/med1917
246 Laboratory Medicine in Psychiatry and Behavioral Science
Testosterone level (continued)
Relevance to psychiatry and Testosterone excess
behavioral science (continued)
Testosterone excess in males is associated with aggressive
behavior, mood swings, irritability, impaired judgment, and
euphoria. This is uncommon except in those taking steroids
or testosterone to enhance athletic performance or to build
muscle mass. Excess testosterone has numerous adverse
physical effects, including heart muscle damage, liver dis-
ease, prostate enlargement, hypertension, edema, weight
gain, headaches, high cholesterol, insomnia, and increased
risk of blood clotting.
Testosterone excess
in females can be recognized
clinically by
the development of excess facial and body hair, male pattern
baldness, acne, menstrual irregularities,
deepening of the
voice, and weight gain. Depression and anxiety are also seen.
Psychotropic drugs associated with elevated testosterone
levels include anabolic steroids, barbiturates, bromocrip
-
tine, danazol, estrogen/progestin, mifepristone, naloxone,
phenytoin, and valproate.
Preparation of patient None needed
Indications Males
• Erectile dysfunction
• Reduced sex drive
• Infertility
• Hypogonadism
• Cryptorchidism
• Testicular tumor
Females
• Virilization, hirsutism
• Reduced sex drive
• Infertility
• Workup for polycystic ovary syndrome
Transgender individuals (female-to-male)
• Monitoring testosterone levels to determine whether tar-
get male ranges have been achieved
Reference range Total testosterone
• Adult males: 270–1,070 ng/dL
• Adult females: 15–70 ng/dL
• Pregnant females: 3–4 times normal value
• Postmenopausal females: 8–35 ng/dL
Free testosterone
• Adult males: 50–210 pg/mL
• Adult females: 1.0–8.5 pg/mL
https://t.me/med1917
247 Laboratory Tests
Testosterone level (continued)
Critical value(s) Total testosterone <300 ng/dL in males on two separate
morning tests supports the diagnosis of testosterone defi
-
ciency.
Total testosterone >200 ng/dL in females suggests the
presence of androgenic tumor, particularly in the presence
of hirsutism.
Increased levels Increased total testosterone in males
• Hyperthyroidism
• Adrenal tumors
• Testicular tumors
• Use of anabolic steroids
• Androgen resistance syndromes
• Congenital adrenal hyperplasia (infants and children)
• Precocious puberty
Increased total testosterone in females
• Congenital adrenal hyperplasia
• Ovarian tumor
• Adrenal gland tumor
• Idiopathic hirsutism
• Hilar cell tumor
• Trophoblastic disease of pregnancy
• Testosterone exposure from testosterone topical prod-
ucts in a close contact
Increased free testosterone in females
• Polycystic ovary syndrome
• Virilization
Decreased levels Decreased total testosterone in males
• Hypothalamic or pituitary disease
• Genetic conditions such as Klinefelter’s, Kallmann,
Prader-Willi, and Down syndromes
• Myotonic dystrophy with testicular failure
• Chronic disease (e.g., diabetes, HIV, autoimmune disease)
• Acquired testicular injury (mumps or physical injury, in-
cluding chemotherapy or radiation)
• Alcohol use disorder with cirrhosis
• Chronic use of antidepressants or narcotics
Decreased free testosterone in males
• Hypogonadism
• Normal age-related decline
https://t.me/med1917
248 Laboratory Medicine in Psychiatry and Behavioral Science
Testosterone level (continued)
Interfering factors Testosterone levels fluctuate in a diurnal pattern, so the time
of sampling affects results. In addition, levels decrease with
age and increase after exercise.
Thyroid disease can increase or reduce the level of sex hor-
mone–binding globulin and thereby influence the test results.
Many laboratories use immunoassays that are not suffi-
ciently sensitive to measure testosterone in patients with low
values such as females and children, so samples from these
patients should be sent to r eference laboratories using mass
spectroscopy techniques.
Medications that affect results include all drugs that raise
prolactin levels, anticonvulsants, estrogens, androgens, corti-
costeroids, digoxin, spironolactone, barbiturates, and other
drugs listed above.
Cross-references Alcohol Use Disorder
Cirrhosis
Hypogonadism
Klinefelter’s Syndrome
Metabolic Syndrome
Prader-Willi Syndrome
Thyrotoxicosis
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed September 2021
Hall SA, Esche GR, Araujo AB, et al: Correlates of low testosterone and symptomatic androgen deficiency
in a population-based sample. J Clin Endocrinol Metab 93:3870–3877, 2008
Harvard Medical School: Testosterone: what it does and doesn’t do. Harvard Health Publishing, August
29, 2019. Available at: https://www.health.harvard.edu/medications/testosterone--what-it-does-
and-doesnt-do. Accessed September 2021.
Mayo
Clinic Laboratories: Testosterone, Total and Free, Serum. Available at: https://
www.mayocliniclabs.com/test-catalog/Overview/8508
. Accessed September 2021.
Mulhall JP, Trost LW, Brannigan RE, et al: Evaluation and management of testosterone deficiency: AUA
guideline.J Urol 200(2):423–432, 2018
Qaseem A, Horwitch CA, Vijan S, et al: Testosterone treatment in adult men with age-related low testos-
terone: a clinical guideline from the American College of Physicians.Ann Intern Med 172(2):126–133,
2020
https://t.me/med1917
249 Laboratory Tests
Thiamine level
Type of test Blood
Background and explanation
of test
Thiamine (vitamin B
1
) is a nutrient essential to carbohydrate
metabolism for energy production and to protein and fat
metabolism. Thiamine is also required for cognitive func
-
tion, circulation, blood formation, normal growth, mainte-
nance of muscle tone, and other processes. It acts as an
antioxidant, protecting the body from the degenerative ef
-
fects of aging, smoking, and alcohol consumption. Body
stores of thiamine are limited, and deficiency can occur in as
little as 10 days with inadequate dietary intake. Thiamine
deficiency is commonly known as beriberi, with two types
recognized: wet beriberi, which affects the heart and circu-
latory system, and dry beriberi, which affects the nervous
system. Severe dry beriberi can be associated with Wer-
nicke’s encephalopathy, which can progress to Korsakoff’s
syndrome if untreated.
Thiamine requirements are directly related to caloric intake,
especially carbohydrates. Across the age spectrum, thiamine
deficiency is underdiagnosed and thus undertreated. Popula
-
tions at risk of deficiency are often seen by psychiatrists and
behavioral health specialists, as noted below. When a patient
with a potential deficiency presents to an emergency setting,
thiamine must be replaced before glucose is administered to
prevent precipitation of Wernicke’s encephalopathy in a mar-
ginally deficient patient. A mnemonic for the correct order of
therapy is Thank God
I gave thiamine before glucose!
It is the active form of thiamine—thiamine diphosphate (py-
rophosphate)—that is measured in a sample of whole blood.
It is not necessary to wait for the result before thiamine is ad
-
ministered, especially in the emergency setting. Overtreat-
ment is preferred to undertreatment because thiamine has an
excellent safety profile, whereas continuing deficiency can re
-
sult in persistent neurocognitive impairment and is some-
times fatal.
Relevance to psychiatry and
behavioral science
Individuals at risk of thiamine deficiency include those with
alcohol use disorder (AUD), HIV/AIDS, rapid weight loss,
anorexia nervosa, malnutrition due to other factors such as
delusions of food poisoning, refeeding syndrome after starva
-
tion, hyperemesis gravidarum, or COVID-19 with protracted
vomiting, as well as those who have undergone GI surgery,
and elderly patients treated with diuretic drugs. Recent pub-
lications have highlighted the prevalence of thiamine defi-
ciency in critically ill patients, particularly those with severe
burns, septic shock, end-stage renal disease, and heart failure
and those who have undergone major surgery.
The classic triad of the Wernicke-Korsakoff syndrome—men-
tal status changes, ocular signs, and ataxia—is not often seen,
although it may be more prevalent among patients with an-
orexia than those with AUD.
https://t.me/med1917
250 Laboratory Medicine in Psychiatry and Behavioral Science
Thiamine level (continued)
Relevance to psychiatry and
behavioral science (continued)
Among ICU patients, deficiency can present with delirium
only. Other neuropsychiatric signs include the sensorimotor
dysfunction, vertigo, confusion, and coma. The presence of
multiple signs and symptoms may suggest a late recognition
of deficiency.
Preparation of patient Patients should fast overnight and should abstain from alco-
hol for 24 hours before testing.
Indications • Suspected thiamine deficiency in a patient at risk
• Cardiac, neurological, or constitutional signs consistent
with thiamine deficiency
Reference range 70–180 nmol/L
Critical value(s) None
Increased levels Toxicity is seen only with extremes of parenteral dosing.
Decreased levels • AUD
• Anorexia nervosa
• Starvation, diets restricted to white rice or processed
carbohydrates
• Prolonged vomiting or diarrhea
• Chronic illness, such as diabetes
• Excessive consumption of raw fish or tea
• Elderly patients
• Long-term diuretic therapy
• Cancer
Interfering factors Barbiturates decrease thiamine levels.
Cross-references Thiamine Deficiency
Wernicke’s Encephalopathy and Wernicke-Korsakoff
Syndrome
ARUP Laboratories: Vitamin B
1
(thiamine), whole blood, in Lab Test Directory. Salt Lake City, UT, ARUP Lab-
oratories, 2021. Available at: https://ltd.aruplab.com/Tests/Pub/0080388. Accessed September 2021.
Ghishan FK, Kiela PR: Vitamins and minerals in inflammatory bowel disease. Gastroenterol Clin North
Am 46(4):797–808, 2017
Kho J, Mandal AKJ, Geraldes R, et al: COVID-19 encephalitis and Wernicke’s encephalopathy.J Med Virol
93(9):5248–5251, 2021
Lange S, Medrzycka-Dabrowska W, Friganovic A, et al: Delirium in critical illness patients and the poten-
tial role of thiamine therapy in prevention and treatment: findings from a scoping review with impli-
cations for evidence-based practice.Int J Environ Res Public Health 18(16):8809, 2021
Lo Gullo A, Rifici C, Caliri S, et al: Refeeding syndrome in a woman with pancreatitis: a case report.J Int
Med Res 49(2):300060520986675, 2021
Oudman E, Wijnia JW, Oey MJ, et al: Preventing Wernicke’s encephalopathy in anorexia nervosa: a sys-
tematic review. Psychiatry Clin Neurosci 72(10):774–779, 2018
Polegato BF, Pereira AG, Azevedo PS, et al: Role of thiamine in health and disease.Nutr Clin Pract
34(4):558–564, 2019
Sinha S, Kataria A, Kolla BP, et al: Wernicke encephalopathy: clinical pearls. Mayo Clin Proc 94(6):1065–
1072, 2019
Truong T, Hetzel F, Stiff KM, Husnain MG: Case of hypoactive delirium precipitated by thiamine defi-
ciency. BMJ Case Rep 14(3):e239886, 2021
https://t.me/med1917
251 Laboratory Tests
Thyroid function testing: free thyroxine
Type of test Blood
Background and explanation
of test
Thyroxine (T4) is a hormone produced in the thyroid gland
and secreted in response to stimulation by TSH from the an
-
terior pituitary. The small fraction of T4 that circulates in the
unbound (free) form is metabolically active and has critical
roles in determining the basal metabolic rate, release of cal
-
cium from bone, synthesis of proteins, and metabolism of
lipids, carbohydrates, and vitamins. Through a feedback
mechanism, the circulating T4 level influences the release of
TSH and thyrotropin-releasing hormone (TRH) from the hy
-
pothalamus.
The free T4 (FT4) level is measured in preference to total T4
because its measurement is not affected by blood protein
levels. FT4 is usually ordered after an abnormal TSH test has
been returned or when clinical suspicion of thyroid disease
remains even when the TSH level is normal. TSH and FT4
together suggest the following diagnoses:
• 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
If TSH is high and FT4 is normal, thyroid antibodies are
checked.
If TSH is low and FT4 is high, thyroid antibodies are
checked.
Relevance to psychiatry and
behavioral science
Hyperthyroidism can cause delirium or psychiatric symp-
toms suggestive of primary mood disorders or psychosis.
So-called apathetic hyperthyroidism is a syndrome affecting
elderly patients that can be mistaken for other conditions.
This is discussed further in the Thyrotoxicosis entry in the
Diseases and Conditions chapter.
Hypothyroidism is associated with fatigue, depressed
mood, and memory impairment, symptoms not uncom-
monly attributed to primary depression.
Normal FT4 with high or low TSH is consistent with subclin-
ical thyroid disease, which can manifest as a fully developed
or formes frustes picture of hyperthyroidism or hypothyroid
-
ism.
Euthyroid sick syndrome, characterized by low FT4 and low
TSH, commonly accompanies nonthyroidal illness in
acutely ill patients, including those with COVID-19 infec-
tion. Of the psychotropic drugs noted in the Interfering Fac-
tors section below, lithium has the most significant effect on
thyroid function and FT4 level.
Preparation of patient Biotin supplements should be discontinued ≥ 2 days before
testing.
https://t.me/med1917
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