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192 Laboratory Medicine in Psychiatry and Behavioral Science
Mammography (continued)
Indications (continued) • Mammography exams should continue as long as the
patient is in good health and expected to live another
10 years.
• Patients at high risk of breast cancer* should undergo
mammography and breast MRI annually starting at age
30 years.
Normal findings Normal breast tissue is imaged. Any calcifications are
evenly distributed. Normal duct contrast and architecture.
Abnormal findings • Mass in breast tissue or nipple
• Signs of breast cancer: asymmetric density; poorly de-
fined, spiculated mass; fine, stippled, clustered calcifica-
tions; thickening of overlying skin
• Signs of malignant breast cancer: irregular, poorly de-
fined, unilateral mass
Interfering factors False-positive findings may result from fibrocystic breast
disease, postoperative changes, post–radiation therapy
changes, tattoos on overlying skin, sebaceous gland secre-
tions, or talcum powder.
Dense breast tissue or breast implants may yield false-
negative findings.
Cross-references Brain Tumor
*See the American Cancer Society guidelines referenced below for definitions of average and high risk.
American Cancer Society: Recommendations for the Early Detection of Breast Cancer. Atlanta, GA,
American Cancer Society, 2021. Available at:
https://www.cancer.org/cancer/breast-cancer/
screening-tests-and-early-detection/american-cancer-society-recommendations-for-the-early-
detection-of-breast-cancer.html. Accessed November 2021.
Brosnan EM, Anders CK: Understanding patterns of brain metastasis in breast cancer and designing ra-
tional therapeutic strategies. Ann Transl Med 6(9):163, 2018
Løberg M, Lousdal ML, Bretthauer M, Kalager M: Benefits and harms of mammography screening. Breast
Cancer Res 17(1):63, 2015
Narayan AK, Lee CI, Lehman CD: Screening for breast cancer.Med Clin North Am 104(6):1007–1021, 2020
Polat DS, Evans WP, Dogan BE: Contrast-enhanced digital mammography: technique, clinical applica-
tions, and pitfalls. Am J Roentgenol 215(5):1267–1278, 2020
Schattner E: Correcting a decade of negative news about mammography.Clin Imaging 60(2):265–270, 2020
https://t.me/med1917
193 Laboratory Tests
Mean corpuscular volume (MCV)
Type of test Blood
Background and explanation
of test
The MCV is the average volume (size) of RBCs in circulation,
either measured directly or calculated from the hematocrit
and RBC count. Included as a component of the CBC, the
MCV is primarily used in the differential diagnosis of anemia.
A mildly abnormal MCV can be an incidental finding on the
CBC in the absence of anemia or other pathology. Very ele
-
vated MCV values may be found in association with vitamin
B
12
or folate deficiency and in disease states involving re-
lease of cold agglutinins (e.g., viral infections).
Recent studies have shown increased mortality in patients
with elevated MCV in the context of medical conditions such
as esophageal cancer and chronic kidney disease, but the
pathophysiology of this association is not yet understood. At
the other end of the spectrum, benign elevation of MCV that
is relatively mild (<115 fL) in the absence of anemia and other
abnormalities on history, physical exam, and other laboratory
tests does not require treatment.
Relevance to psychiatry and
behavioral science
Several conditions relevant to clinical psychiatry are asso-
ciated with an elevated MCV. These include alcohol use dis-
order, liver disease/cirrhosis, vitamin B
12
or folate
deficiency, smoking, and hypothyroidism. The greater the
MCV elevation, the more likely it is due to vitamin B
12
or
folate deficiency.
Preparation of patient None needed
Indications Component of CBC
Reference range Adults 18–44 years
• Males: 80–99 fL
• Females: 81–100 fL
Adults 45–64 years
• Males: 81–101 fL
• Females: 81–101 fL
Adults 65–74 years
• Males: 81–103 fL
• Females: 81–102 fL
Increased levels • Excessive alcohol intake
• Vitamin B
12
deficiency
• Folate deficiency
• Increased RBC production (acute blood loss, hemolysis,
liver disease, or disseminated malignancy)
• Myelodysplastic syndrome
• Multiple myeloma
• Hypothyroidism
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194 Laboratory Medicine in Psychiatry and Behavioral Science
Mean corpuscular volume (MCV) (continued)
Increased levels (continued) • Smoking
• Advanced age
• Pregnancy
• Drugs: antihistamines, proton pump inhibitors, anticon-
vulsants, aspirin, acyclovir, isoniazid, metformin, chemo-
therapeutic agents, neomycin, colchicine, allopurinol,
triamterene, nitrofurantoin, oral contraceptives, trimeth
-
oprim, valproic acid, and reverse transcriptase inhibitors,
among others
Decreased levels • Iron deficiency anemia
• Anemia of chronic disease
• Thalassemia
• Certain hemoglobinopathies
• Hypothyroidism (uncommon presentation)
Interfering factors The MCV value is not reliable in the presence of large num-
bers of reticulocytes, abnormal erythrocytes (e.g., sickle cells),
or a dimorphic population of erythrocytes.
A common cause of falsely elevated MCV is RBC clumping in
the test tube, which occurs in the presence of inflammatory or
neoplastic disorders, cold agglutinins, or anticoagulant mal
-
function in the blood drawing tube.
Severe hyperglycemia or leukocytosis may also falsely ele-
vate MCV.
Cross-references Alcohol Use Disorder
Anemia
Cirrhosis
Complete Blood Count
Folate Deficiency
Vitamin B
12
Deficiency
Fischbach FT, Fischbach MA: A Manual of Laboratory and Diagnostic Tests, 10th Edition. Philadelphia,
PA, Wolters Kluwer Health/Lippincott Williams and Wilkins, 2018
Hsieh YP, Chang CC, Kor CT, et al: Mean corpuscular volume and mortality in patients with CKD.Clin J
Am Soc Nephrol 12(2):237–244, 2017
Veda P: Evaluation of macrocytosis in routine hemograms.Indian J Hematol Blood Transfus 29(1):26–30,
2013
Wu AHB: Tietz Clinical Guide to Laboratory Tests, 4th Edition. St. Louis, MO, WB Saunders, 2006
https://t.me/med1917
195 Laboratory Tests
Metanephrines
Type of test Blood, urine
Background and explanation
of test
Metanephrines are breakdown products of epinephrine
found in blood and urine that aid in the diagnosis of the
chromaffin cell tumors pheochromocytoma and paraganglioma.
Patients with these tumors have variable clinical presenta
-
tions, the classic triad being episodic headache, sweating,
and tachycardia. The predominant symptom for many pa
-
tients is severe, variable hypertension that is associated with
end-organ damage. Anxiety and panic attacks often bring
patients to the attention of psychiatrists. Other symptoms
are discussed in the Pheochromocytoma entry in the Dis-
eases and Conditions chapter. Pheochromocytoma and
paraganglioma are diagnosed by plasma free metaneph
-
rines or urine metanephrines, with plasma metanephrine
testing preferred because of convenience and factors inter
-
fering with urine testing. Because metanephrines are se-
creted continuously by the tumor, blood can be drawn at
any time; it is not necessary to draw samples during a panic
attack or hypertensive episode.
Relevance to psychiatry and
behavioral science
Pheochromocytoma and paraganglioma can cause episodic
panic attacks that closely resemble primary panic disorder.
Attacks are associated with somatic signs and symptoms
noted in the Pheochromocytoma entry referenced above.
Attacks may be spontaneous or induced by a range of stim
-
uli, including abdominal compression, urination, trauma,
anesthesia, surgery, biopsy or other invasive procedures,
medications, or foods with high tyramine content.
Preparation of patient Strict preparation requires a 3-day diet without caffeine,
black tea, nicotine, alcohol, bananas, cheese, almonds, nuts,
chocolate, eggs, or vanilla. Drugs listed below that may
cause spurious results should be avoided if possible.
Indications Clinical suspicion of pheochromocytoma or paraganglioma
Reference range Free normetanephrine: 0.0–0.89 nmol/L
Free metanephrine: 0.0–0.49 nmol/L
Critical value(s) Plasma levels > 2 times the upper limit of normal for the lab-
oratory reference range are consistent with pheochromocy-
toma. Most patients with one of these tumors have a plasma
free normetanephrine level >2.2 nmol/L and/or a meta-
nephrine level >1.1 nmol/L.
Increased levels Pheochromocytoma, paraganglioma
Decreased levels Not applicable
Interfering factors Patient positioning affects the results; blood should be
drawn after 15 minutes of rest, with the patient in the supine
position.
Drugs and some foods (see Preparation of Patient section
above) affect the results.
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196 Laboratory Medicine in Psychiatry and Behavioral Science
Metanephrines (continued)
Interfering factors (continued) Spurious results can be obtained with the following: aceta-
minophen, alcohol (withdrawal), aminophylline, amphet-
amines, benzodiazepines (withdrawal), buspirone, caffeine,
chloral hydrate, chlorpromazine, clonidine, dexamethasone,
epinephrine, imipramine, lithium, MAOIs, opioids, salicy
-
lates, TCAs, and tobacco, among other drugs.
Vigorous exercise can affect results.
Cross-references Pheochromocytoma
ARUP Laboratories: Metanephrines, plasma (free), in Lab Test Directory. Salt Lake City, UT, ARUP Lab-
oratories, 2021. Available at: https://ltd.aruplab.com/Tests/Pub/0050184. Accessed August 2021.
Därr R, Kuhn M, Bode C, et al: Accuracy of recommended sampling and assay methods for the determi-
nation of plasma-free and urinary fractionated metanephrines in the diagnosis of pheochromocytoma
and paraganglioma: a systematic review. Endocrine 56(3):495–503, 2017
Farrugia FA, Martikos G, Tzanetis P, et al: Pheochromocytoma, diagnosis and treatment: review of the
literature. Endocr Regul 51(3):168–181, 2017
Garcia-Carbonero R, Matute Teresa F, Mercader-Cidoncha E, et al: Multidisciplinary practice guidelines
for the diagnosis, genetic counseling and treatment of pheochromocytomas and paragangliomas.
Clin Transl Oncol 23(10):1995–2019, 2021
Peaston RT, Graham KS, Chambers E, et al: Performance of plasma free metanephrines measured by liq-
uid chromatography–tandem mass spectrometry in the diagnosis of pheochromocytoma. Clin Chim
Acta 411:546–552, 2010
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197 Laboratory Tests
Methanol level
Type of test Blood
Background and explanation
of test
Methanol, also known as methyl alcohol or wood alcohol, is
a highly toxic substance found in windshield washer fluid,
gas line antifreeze, carburetor cleaner, copy machine fluid,
perfumes, food warming fuel, and other types of fuels. In the
past, exposure to methanol occurred accidentally, because of
contaminated home-distilled and fermented beverages, or in-
tentionally, with ingestion of products such as windshield
washer fluid as a means of suicide, use of food-warming fuel
as a substitute for ethanol when the latter was unavailable,
and abuse of carburetor cleaner via inhalation (“huffing”).
More recently, worldwide exposures occurred starting in 2020
with the COVID-19 pandemic, when false rumors appeared
on social media that the virus could be prevented or treated
by drinking or gargling hand sanitizer. A significant number
of those hand sanitizers, notably those from Mexico, con-
tained methanol rather than ethyl alcohol or isopropanol.
As little as 2 tbsp of methanol can be lethal for a child, and
2 fl oz for an adult. The prognosis with poisoning depends on
the amount ingested and how soon treatment is adminis
-
tered. Once ingested, methanol is rapidly absorbed and oxi-
dized by alcohol dehydrogenase to formaldehyde, and then
by aldehyde dehydrogenase to formic acid. As metabolism
proceeds, an initial high osmolal gap decreases and an anion
gap increases. Formic acid is the primary toxic metabolite,
causing retinal toxicity and later parkinsonism. Treatment
consists of supportive care, correction of acidosis, use of an
alcohol dehydrogenase inhibitor (fomepizole, or ethanol
orally or intravenously if fomepizole is not available), and he-
modialysis. Left untreated, methanol poisoning can be fatal.
Relevance to psychiatry and
behavioral science
Psychiatrists may encounter methanol poisoning in patients
who are suicidal, in those with alcohol use disorder who lack
access to ethanol, in patients using solvents for “huffing,” and
in misguided patients ingesting hand sanitizer. On presenta-
tion, patients might initially appear normal or inebriated. On-
set of clinical and laboratory features can be delayed for days
with co-ingestion of ethanol. Initial symptoms are GI related,
followed by CNS depression and hyperventilation. Visual
changes such as blurred vision, decreased acuity, photopho
-
bia, and “halo vision” are associated with an abnormal fun-
duscopic exam. Seizures can occur. Several weeks after
exposure, parkinsonian signs can be seen, with tremor, cog-
wheel rigidity, hypokinesia, stooped posture, and shuffling
gait. Necrosis of the putamen and globus pallidus are associ
-
ated with these findings.
Preparation of patient None needed
Indications Clinical suspicion of methanol ingestion
Reference range Not applicable. Methanol is not detectable at levels < 5 mg/dL.
Critical values Toxicity at levels >20 mg/dL
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198 Laboratory Medicine in Psychiatry and Behavioral Science
Methanol level (continued)
Increased levels • Ingestion of hand sanitizer containing methanol
• Accidental ingestion
• Intentional overdose
• Abuse in place of ethanol
Decreased levels Not applicable
Interfering factors Plasma level may be below the assay’s limit of detection
even though the patient shows signs of toxicity.
Laboratory findings may be delayed up to 3–4 days when
ethanol is co-ingested.
Cross-references Methanol Poisoning
Osmolality
ARUP Laboratories Test Directory: Methanol, in Lab Test Directory. Salt Lake City, UT, ARUP Laborato-
ries, 2021. Available at: https://ltd.aruplab.com/Tests/Pub/0090165. Accessed August 2021.
Liu YS, Lin KY, Masur J, et al: Outcomes after recurrent intentional methanol exposures not treated with
alcohol dehydrogenase inhibitors or hemodialysis. J Emerg Med 58(6):910–916, 2020
Mehrpour O, Sadeghi M: Toll of acute methanol poisoning for preventing COVID-19.Arch Toxicol
94(6):2259–2260, 2020
Sefidbakht S, Lotfi M, Jalli R, et al: Methanol toxicity outbreak: when fear of COVID-19 goes viral.Emerg
Med J 37(7):416, 2020
Yip L, Bixler D, Brooks DE, et al: Serious adverse health events, including death, associated with ingesting
alcohol-based hand sanitizers containing methanol: Arizona and New Mexico, May–June 2020.
MMWR Morb Mortal Wkly Rep 69(32):1070–1073, 2020
Zakharov S, Pelclova D, Navratil T, et al: Fomepizole versus ethanol in the treatment of acute methanol
poisoning: comparison of clinical effectiveness in a mass poisoning outbreak.Clin Toxicol (Phila)
53(8):797–806, 2015
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199 Laboratory Tests
Methylmalonic acid (MMA) level
Type of test Blood
Background and explanation
of test
In past practice, the serum MMA level was often used (along
with serum total homocysteine) to determine the signifi
-
cance of a low-normal vitamin B
12
level. In normal metabo-
lism, vitamin B
12
is a necessary cofactor for the conversion of
methylmalonyl coenzyme A (CoA) to succinyl CoA; when
B
12
is deficient, methylmalonyl CoA is converted to MMA
instead, and levels rise in the blood and urine. Research has
demonstrated that a substantial proportion of individuals
with low B
12
levels have normal MMA levels, and clinical
opinion now differs as to the utility of MMA in determining
B
12
status. Serum holotranscobalamin is a more sensitive
indicator of B
12
deficiency, although that test is not available
in all laboratories. Serum MMA is still used in some centers
for the workup of suspected B
12
deficiency.
Relevance to psychiatry and
behavioral science
Vitamin B
12
deficiency is associated with numerous psychi-
atric signs and symptoms, as noted in the Diseases and Con-
ditions chapter.
Preparation of patient Ideally, patients should fast overnight before the test.
Indications •
Detecting early or mild vitamin B
12
deficiency
• Follow-up to B
12
levels at lower end of the normal range
• Diagnosing methylmalonic acidemia (plasma and
urine)
• Detecting cobalamin genetic defects (plasma and urine)
Reference range Adults: <0.2 μmol/L
Note: Degree of elevation above this cutoff correlates poorly
with severity of deficiency as well as prognosis.
Critical value(s) ≥ 0.3 μmol/L associated with poor functional status
Increased levels • Vitamin B
12
deficiency
• Impaired kidney function
• Cobalamin genetic defects
• Methylmalonic acidemia (in infants)
Decreased levels Not known to have clinical significance
Interfering factors Results invalidated by renal failure and volume depletion
(dehydration).
Broad-spectrum antibiotic therapy at time of testing may
lead to false-negative results.
Cross-references Folate Deficiency
Folate Level
Homocysteine Level
Vitamin B
12
Deficiency
Vitamin B
12
Level
https://t.me/med1917
200 Laboratory Medicine in Psychiatry and Behavioral Science
Methylmalonic acid (MMA) level (continued)
American Association for Clinical Chemistry: Testing.com. Available at: https://www.testing.com. Ac-
cessed August 2021.
ARUP Laboratories: Methylmalonic acid, serum or plasma (vitamin B
12
st atu s), in L ab Test D irecto ry. Salt
Lake City, UT, ARUP Laboratories, 2021. Available at:
https://ltd.aruplab.com/Tests/Pub/0099431.
Accessed August 2021.
Hill MH, Flatley JE, Barker ME, et al: A vitamin B-12 supplement of 500 μg/d for eight weeks does not
normalize urinary methylmalonic acid or other biomarkers of vitamin B-12 status in elderly people
with moderately poor vitamin B-12 status. J Nutr 143(2):142–147, 2013
Remacha AF, Sardà MP, Canals C, et al: Role of serum holotranscobalamin (holoTC) in the diagnosis of
patients with low serum cobalamin: comparison with methylmalonic acid and homocysteine. Ann
Hematol 93(4):565–569, 2014
Wolffenbuttel BHR, Wouters HJCM, de Jong WHA, et al: Association of vitamin B
12
, methylmalonic acid,
and functional parameters.Neth J Med 78(1):10–24, 2020
https://t.me/med1917
201 Laboratory Tests
Multiple sleep latency test (MSLT) and
maintenance of wakefulness test (MWT)
Type of test Neurophysiology
Background and explanation
of test
The MSLT provides an objective index of an individual’s de-
gree of daytime sleepiness and detects the inappropriate
early appearance of REM sleep after sleep onset. The MSLT
is an all-day test consisting of four or five scheduled naps
separated by 2-hour breaks. It is performed the day after a
PSG study in which sleep quality and duration are ob
-
served. The MSLT monitors EEG, eye and muscle move-
ment, and ECG and identifies times of sleep onset and sleep
stages, including REM sleep. The results are used to diag
-
nose narcolepsy and idiopathic hypersomnia.
The MWT provides an objective index of an individual’s
daytime alertness. In this test, patients are instructed to re-
sist the urge to fall asleep during the test period of ≤40 min-
utes; otherwise, the protocol is much like that used for the
MSLT. Results can be used to assess an individual’s ability
to stay awake when there is a question of individual or pub
-
lic safety and to evaluate response to treatment for excessive
daytime sleepiness.
Relevance to psychiatry and
behavioral science
Daytime somnolence is often reported by patients with Par-
kinson’s disease, Alzheimer’s disease, chronic fatigue syn-
drome, depression, and fibromyalgia and other chronic pain
syndromes. It also plagues those treated with highly sedat
-
ing medications such as anticonvulsants, antipsychotics,
and certain antidepressants.
Positive urine drug screens in a substantial minority of pa-
tients presenting for MSLT/MWT prompted the current rec-
ommendation that urine drug screening be performed on
the morning of testing. Drugs detected included amphet-
amines, cannabinoids, opiates, and benzodiazepines, and
use of these drugs was not self-reported. Drug and medica
-
tion use must be known in order to correctly interpret
MSLT/MWT results.
Preparation of patient A sleep medicine consult should be performed before the test
is scheduled. All wake-promoting and REM-suppressing
drugs should be stopped ≥15 days before testing (≥5half-
lives of drug and metabolites). Cannabis (THC and canna-
bidiol [CBD]) cause REM rebound and sleep-onset REM
when discontinued; 4 weeks of abstinence is recommended.
Smoking should be stopped 30 minutes before each nap. As
noted in the Relevance section above, urine drug screen
should be performed on the morning of testing.
Indications •
Confirming clinical diagnoses of narcolepsy and idio-
pathic hypersomnia
• Evaluating daytime hypersomnia
• Determining effectiveness of treatment for hypersomnia
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