Differentials
Common
Stomach cancer
History
Helicobacter pylori infection, prior gastric ulcer or atrophic gastritis, epigastric/abdominal pain, nausea, hematemesis, melena, dysphagia
Exam
epigastric tenderness or mass, lymphadenopathy, hepatomegaly, signs of anemia, abrupt onset of multiple seborrheic keratoses (rare)
1st investigation
- upper GI endoscopy with biopsy:
tumor visualized
- stool heme test:
positive for occult blood
Other investigations
- CBC:
anemia
- serum iron:
decreased
- CT abdomen/pelvis:
metastatic lesions
More
Colorectal cancer
History
rectal bleeding, abdominal pain, change in stool caliber; more likely to be advanced if presenting with unintentional weight loss
Exam
abdominal distention or tenderness, abdominal or rectal mass
1st investigation
- colonoscopy:
tumor visualized
- stool heme or quantitative fecal immunochemical test:
positive for occult blood
More
Other investigations
- CBC:
anemia
- serum iron:
decreased
- CT abdomen/pelvis:
metastatic lesions
More
Esophageal cancer
History
smoking, alcohol use (squamous cell carcinoma), Barrett esophagus, progressive dysphagia, painful swallowing, fatigue, pain, nausea
Exam
may be normal
1st investigation
- esophagogastroduodenoscopy (EGD) with biopsy:
mucosal lesion, histology (squamous cell carcinoma or adenocarcinoma)
Other investigations
- CBC:
may show microcytic anemia
Pancreatic cancer
History
unintentional weight loss very common, nausea, anorexia, abdominal bloating, upper abdominal pain/discomfort
Exam
abdominal tenderness/mass, jaundice
1st investigation
- abdominal ultrasound:
pancreatic mass, biliary dilation
More - LFTs:
abnormal
Hepatoma
History
cirrhosis, hepatitis B or C infection, right upper quadrant pain
Exam
right upper quadrant mass, abdominal tenderness, jaundice, hepatomegaly, ascites
1st investigation
- abdominal ultrasound:
intrahepatic mass
- CT abdomen/pelvis:
intrahepatic mass
- LFTs:
abnormal
Other investigations
Small cell lung cancer
History
cough, hemoptysis, dyspnea, chest pain; bone pain, headache, seizures (metastases); altered mental status, abdominal pain, muscle weakness (paraneoplastic syndromes)
Exam
lung exam may be normal or show abnormalities (e.g., wheeze, rales, egophony, dullness to percussion); confusion, personality changes (metastases)
1st investigation
- CT chest:
pulmonary mass, mediastinal lymphadenopathy, pleural effusion, consolidation
More - chest x-ray:
pulmonary mass, mediastinal lymphadenopathy, pleural effusion, consolidation
Other investigations
- MRI/CT brain:
brain metastases
- serum electrolytes:
may show hypercalcemia, hyponatremia
Non-small cell lung cancer
History
cough, hemoptysis, dyspnea, chest pain; bone pain, headache, seizures (metastases)
Exam
lung exam may be normal or show abnormalities (e.g., wheeze, rales, egophony, dullness to percussion); confusion, personality changes (metastases)
1st investigation
- CT chest:
pulmonary mass, mediastinal lymphadenopathy, pleural effusion, consolidation
More - chest x-ray:
pulmonary mass, mediastinal lymphadenopathy, pleural effusion, consolidation
Other investigations
- MRI/CT brain:
brain metastases
- serum electrolytes:
may show hypercalcemia, hyponatremia
Non-Hodgkin lymphoma
History
night sweats, fatigue/malaise, enlarged lymph nodes
Exam
fever, lymphadenopathy, splenomegaly, hepatomegaly
1st investigation
- CBC:
leukocytosis, leukopenia, anemia, thrombocytopenia (variable)
- LDH:
elevated
Hodgkin lymphoma
History
usually young adults but has second peak in sixth decade, night sweats, chest pain (if mediastinal mass present), generalized pruritus
Exam
fever, lymphadenopathy (rubbery, firm, nontender), splenomegaly, hepatomegaly
1st investigation
- CBC:
leukocytosis, anemia, thrombocytopenia, eosinophilia (variable)
- LDH:
elevated
Chronic leukemia
History
unintentional weight loss more common compared with acute leukemia, night sweats
Exam
fever, lymphadenopathy
1st investigation
- CBC:
anemia, neutropenia, thrombocytopenia
More - peripheral blood smear:
increased lymphocytes
- flow cytometry:
clonal population of lymphocytes
Other investigations
- bone marrow biopsy:
may show marrow infiltration by leukemic cells (CLL); granulocytic hyperplasia (CML)
Multiple myeloma
History
fatigue, bone pain, infections
Exam
pallor, pathologic fractures
1st investigation
- CBC:
anemia
- serum electrolytes:
possible hypercalcemia
- serum creatinine:
elevated
- serum/urine electrophoresis:
monoclonal M protein band present
More
Other investigations
- bone marrow biopsy:
>10% myeloma plasma cells
- x-ray bone series:
may see lytic lesions
Oropharyngeal cancer
History
smoking/chewing tobacco, alcohol use, oral pain, sore throat, dysphagia
Exam
neck mass, cervical swelling or lymphadenopathy, tumor may be seen with laryngoscopy
Other investigations
Laryngeal cancer
History
smoking/chewing tobacco, alcohol use, dysphagia, painful swallowing, sore throat, hoarseness
Exam
neck mass, cervical swelling or lymphadenopathy, supraglottic/glottic mass may be seen with laryngoscopy
1st investigation
- CT head and neck:
tumor visualized
More
Other investigations
- rigid direct laryngoscopy:
ulcerative, friable, necrotic mass involving the larynx
More
Ovarian cancer
History
pelvic pain/pressure, abdominal bloating, increased abdominal girth (bulky disease or ascites), constipation, nausea, gastrointestinal or vaginal bleeding (less common); weight loss more common in advanced disease or metastases
Exam
adnexal mass, ascites
1st investigation
- pelvic ultrasound:
adnexal mass
More
Other investigations
- CA-125 level:
increased
More
Prostate cancer
History
obstructive urinary symptoms, bone pain, pelvic pain; weight loss more common in advanced disease or metastases
Exam
enlarged prostate with nodule or asymmetry, bone tenderness
1st investigation
- prostate specific antigen (PSA) level:
elevated
More
Other investigations
- MRI:
suspicious focus in prostate; dynamic contrast-enhanced imaging suspicious for malignancy
- prostate biopsy:
abnormal or cancer cells; cancer cells are graded and the two most common patterns added to give a Gleason score ranging from 6 to 10
More
Breast cancer
History
breast lump, bone pain; weight loss more common in advanced disease or metastases
Exam
palpable breast mass, lymphadenopathy, bone tenderness
1st investigation
- mammogram:
breast mass
More - breast ultrasound:
breast mass
Other investigations
- MRI:
heterogeneously enhancing area and significant architectural distortion
More
Celiac disease
History
diarrhea, bloating, abdominal pain/discomfort, fatigue
Exam
pallor, dermatitis herpetiformis
1st investigation
- total IgA:
may be normal or deficient
More - IgA-tTG (tissue transglutaminase):
elevated
More - esophagogastroduodenoscopy:
atrophy and scalloping of mucosal folds; nodularity and mosaic pattern of mucosa
- small bowel (duodenal) biopsy:
presence of intraepithelial lymphocytes, villous atrophy, and crypt hyperplasia
More
Exocrine pancreatic insufficiency
History
previous pancreatitis, cystic fibrosis, diarrhea, oily/floating/foul-smelling stools; unintentional weight loss usually only occurs in severe cases
Exam
abdominal tenderness (chronic pancreatitis)
1st investigation
- fecal fat:
high
Other investigations
- vitamin A, D, E, K levels:
may show low levels
More
Crohn disease
History
can occur in younger patients (ages 15-40 years) and peaks again in sixth decade, abdominal pain, diarrhea (may be bloody), bloating, fatigue
Exam
abdominal tenderness, perianal lesions, blood in stool
1st investigation
Other investigations
Ulcerative colitis
History
can occur in younger patients (ages 20-40 years) and peaks again in sixth decade, abdominal pain, diarrhea (usually bloody), rectal bleeding, fatigue, arthritis
Exam
abdominal tenderness, blood in stool
1st investigation
- CBC:
anemia
More - stool heme test:
positive for occult blood
- colonoscopy:
rectal involvement, continuous uniform involvement, loss of vascular marking, diffuse erythema, mucosal granularity, normal terminal ileum
- tissue biopsy:
continuous distal disease, mucin depletion, basal plasmacytosis, diffuse mucosal atrophy, absence of granulomata, anal sparing
Other investigations
Mesenteric ischemia
History
cardiovascular risk factors, postprandial pain (mild-to-severe), nausea/vomiting, diarrhea, hematochezia/melena; weight loss may be severe
Exam
abdominal tenderness, abdominal bruits may be present; exam may be normal
1st investigation
- CT scan with contrast/CT angiogram:
bowel wall thickening, bowel dilation, pneumatosis intestinalis, portal venous gas, occlusion of the mesenteric vasculature, bowel wall thickening with thumbprinting sign suggestive of submucosal edema or hemorrhage
More - doppler ultrasound (vascular/duplex):
flow abnormalities and stenoses in celiac/superior mesenteric arteries
More
Other investigations
- mesenteric angiography:
high-grade stenoses in celiac/superior mesenteric arteries
More
Depression
History
comorbid medical/psychiatric conditions (may coexist with other conditions in differential for unintentional weight loss), anhedonia, depressed mood, functional impairment, appetite changes, sleep disturbance, libido changes, low energy, poor concentration, excessive guilt, suicidal ideation; weight change (loss or gain) can be variable
Exam
psychomotor slowing
1st investigation
- clinical diagnosis:
diagnosis is made based on history and exam; should meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM-5-TR) criteria
More
Other investigations
Bipolar disorder
History
episodes of mania (elevated mood, increased energy, perceived decreased need for sleep, impulsivity) with periods of depression; weight loss may be significant
Exam
grandiosity, pressured speech, irritability, psychosis, depression (depending on whether manic or depressive episode)
1st investigation
- clinical diagnosis:
diagnosis is made based on history and exam; should meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM-5-TR) criteria
Other investigations
Generalized anxiety disorder
History
excessive worry for at least 6 months, anxiety, muscle tension, functional impairment, irritability, restlessness, poor concentration, fatigue, sleep disturbance; weight loss is not part of diagnostic criteria
Exam
usually normal
1st investigation
- clinical diagnosis:
diagnosis is made based on history and exam; should meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM-5-TR) criteria
More
Other investigations
Anorexia nervosa
History
comorbid psychiatric disorders, fear of gaining weight, food restriction, distorted body image, amenorrhea, suicidal ideation, bingeing/purging, history may be denied by patient
Exam
low BMI, bradycardia, hypothermia, hypotension, hair loss, muscle wasting, dental erosion (if coexisting bulimia), signs of cardiomyopathy; should meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM-5-TR) criteria
1st investigation
Other investigations
- bone densitometry:
helps illustrate effects of severe weight loss to patients who deny or minimize presence of eating disorder symptoms
More
Substance misuse
History
substance use/misuse (e.g., opioids, cocaine, amphetamine, cannabis, inhalant, hallucinogen, benzodiazepine, alcohol), comorbid psychiatric disorders, inadequate nutrition; weight loss when use/misuse is severe
Exam
depends on substance
1st investigation
- clinical diagnosis:
diagnosis is made based on history and exam and depends on substance
Other investigations
Parkinson disease
Dementia
Hyperthyroidism
History
palpitations, tremor, fatigue, weakness (may be subtle), heat intolerance, hair thinning/loss, anxiousness; older patients have fewer classic symptoms
Exam
tachycardia, fine tremor, hyperreflexia, bilateral lid retraction, proptosis
1st investigation
- serum TSH level:
suppressed (primary)
More
Other investigations
Tuberculosis
History
exposure to infection, endemic location, immunosuppression, fever, cough, night sweats, malaise, hemoptysis, dyspnea; weight loss is more common with reactivation
Exam
pulmonary: tachypnea, decreased breath sounds, crackles, dullness to percussion; extrapulmonary: findings dependent upon site, lymphadenopathy common
1st investigation
- chest x-ray:
may demonstrate atelectasis from airway compression, pleural effusion, consolidation, pulmonary infiltrates, mediastinal or hilar lymphadenopathy, upper zone fibrosis
More - sputum acid-fast bacilli smear and culture:
presence of acid-fast bacilli (Ziehl-Neelsen stain) in specimen
More - acid-fast bacilli smear and culture of extrapulmonary biopsy specimen:
positive
More - nucleic acid amplification tests (NAAT):
positive for M tuberculosis
More
Other investigations
- bronchoscopy and bronchoalveolar lavage:
positive for acid-fast bacilli
More - lateral flow urine lipoarabinomannan (LF-LAM) assay:
positive
More - contrast-enhanced chest computed tomography scan:
primary TB: mediastinal tuberculous lymphadenitis with central node attenuation and peripheral enhancement, delineated cavities; postprimary TB: centrilobular nodules and tree-in-bud pattern
More
Adverse medication effects
History
started new medication; common drugs include anticonvulsants (e.g., topiramate, zonisamide), antidepressants (e.g., selective serotonin-reuptake inhibitors, bupropion), stimulants (e.g., dextroamphetamine), diabetes medications (e.g., metformin; exenatide, glucagon-like peptide-1 receptor agonists, sodium-glucose co-transporter 2 inhibitors), antibiotics and other medications that cause diarrhea, cholinesterase inhibitors (e.g., donepezil), diuretics, laxatives, thyroid hormone (from misuse); withdrawal of drugs that support/maintain weight loss (e.g., pancreatic enzymes, mirtazapine); no other significant history
Exam
usually normal
1st investigation
- medication withdrawal trial:
reversal of weight loss
More
Other investigations
Sarcopenia
History
difficulty rising from chair and climbing stairs, difficulty performing activities of daily living, presence of comorbidities affecting muscle mass and/or function
Exam
low hand grip strength, slow gait, emaciation
1st investigation
Other investigations
- bioimpedance analysis (BIA):
reduced
More
Uncommon
Cholangiocarcinoma
History
primary sclerosing cholangitis, fever, right upper quadrant pain, pruritus; usually presents late
Exam
right upper quadrant mass, abdominal tenderness, jaundice, hepatomegaly
1st investigation
- LFTs:
abnormal; typically greater elevation in bilirubin and alkaline phosphatase than aminotransferases
- abdominal ultrasound:
biliary duct dilation, bile duct tumor
More
Acute leukemia
History
unintentional weight loss less common compared with chronic leukemia/lymphoma, fatigue, infections, bone pain, bleeding
Exam
fever, pallor, hypotension, petechiae, bone tenderness, ecchymosis
1st investigation
- CBC:
anemia, leukopenia, thrombocytopenia
- peripheral blood smear:
presence of blasts; Auer rods (acute myeloid leukemia)
Other investigations
- LDH:
elevated
- bone marrow biopsy:
presence of >20% blasts; Auer rods (acute myeloid leukemia)
Zollinger-Ellison syndrome
History
GERD, peptic ulcer disease, diarrhea, abdominal pain, fatigue, weight loss uncommon; may be part of multiple endocrine neoplasia syndrome (type 1) or associated with hyperparathyroidism or pituitary tumors
Exam
abdominal tenderness, pallor
1st investigation
- fasting serum gastrin level:
elevated
More
Other investigations
VIPoma
Carcinoid syndrome
History
diarrhea, wheezing, GI bleeding, weight loss due to diarrhea is uncommon
Exam
flushing, tumor is not usually palpable
1st investigation
- 24-hour urinary 5-hydroxyindoleacetic acid:
elevated
Other investigations
Peptic ulcer disease
History
nonsteroidal anti-inflammatory drug (NSAID) use, Helicobacter pylori infection, epigastric pain (especially after meals, classically with a delay of a few hours), dark stools (if bleeding)
Exam
epigastric tenderness
1st investigation
- H pylori breath test or stool antigen test:
positive if H pylori present
- stool heme test:
positive for occult blood
- upper GI endoscopy:
peptic ulcer visualized
Other investigations
- fasting serum gastrin level:
elevated levels in pernicious anemia and other hypochlorhydric states results in low specificity
Chronic hepatitis
History
risk of exposure (hepatitis B or C), fatigue, malaise, right upper quadrant pain, pruritus
Exam
fever; jaundice, edema, ascites (cirrhosis); exam may be normal
1st investigation
- LFTs:
abnormal
- serology:
hepatitis B antigen: positive; hepatitis C antibody: positive
Other investigations
- HBV or HCV PCR:
positive
- serum bilirubin level:
may be elevated in advanced disease
Esophageal webs, rings, and diverticula
History
usually asymptomatic; dysphagia, decreased oral intake (severe cases)
Exam
usually normal
1st investigation
- endoscopy:
esophageal pathology visualized
Other investigations
- esophagram:
esophageal pathology visualized
More
Small intestinal bacterial overgrowth (SIBO)
History
prior gastrointestinal surgery/short bowel syndrome, systemic sclerosis (scleroderma), diarrhea, abdominal pain, bloating; unintentional weight loss in severe cases
Exam
usually normal
1st investigation
- hydrogen breath test:
increased hydrogen after administration of sugar/carbohydrate
More
Other investigations
- CBC:
may have anemia, variable
Gastroparesis
History
diabetes mellitus, postprandial epigastric pain or nausea/vomiting; unintentional weight loss in severe cases
Exam
usually normal
1st investigation
- gastric emptying scintigraphy:
delayed transit time through stomach
Other investigations
- upper gastrointestinal endoscopy:
Retained food in the stomach
More
Postsurgical complications
History
prior gastrointestinal surgery/short bowel syndrome, diarrhea, abdominal pain, nausea
Exam
surgical scars, abdominal tenderness
1st investigation
- clinical diagnosis:
diagnosis is made based on history and exam
Other investigations
Stomatitis
History
malnutrition, dentures, prior radiation therapy or chemotherapy, oral trauma, oral pain, xerostomia
Exam
erythema or ulceration of oral mucosa
1st investigation
- clinical diagnosis:
diagnosis is made based on history and exam
Other investigations
- CBC:
variable; may show leukocytosis and/or neutropenia
Bulimia nervosa
History
recurrent episodes of binge eating and compensatory behavior (e.g., purging, fasting, exercise), depression, low self-esteem, concern about body image/weight, menstrual irregularities
Exam
dental erosion, Russell sign (scarring over dorsum of hands from inducing vomiting), arrhythmia, parotid hypertrophy; should meet Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM-5-TR) criteria
1st investigation
- CBC:
may have anemia
- basic metabolic panel:
may be deranged
- LFTs:
may be abnormal
Other investigations
- serum electrolytes:
may show hypokalemia or alkalosis
Multiple sclerosis
History
focal neurologic deficits lasting >24 hours in different regions, vision loss, numbness, pain, weakness, dizziness, fatigue, depression
Exam
internuclear ophthalmoplegia, limb weakness, sensory deficits
Other investigations
- CSF evaluation:
increased oligoclonal bands
More
Amyotrophic lateral sclerosis
History
progressive upper and lower motor neuron deficits, limb weakness, dementia (uncommon), dyspnea
Exam
muscle atrophy, fasciculations, weakness (lower motor neuron involvement); muscle atrophy, weakness, hyperreflexia (upper motor neuron involvement); facial or oropharyngeal weakness (bulbar involvement); decreased air movement, crackles from atelectasis (respiratory involvement)
1st investigation
- electromyography:
evidence of diffuse, ongoing, chronic denervation
Other investigations
- repetitive nerve stimulation:
modest decreases in compound motor action amplitude after repetitive stimuli
Prion disease
History
Creutzfeld-Jakob disease, prion exposure, rapidly progressive cognitive dysfunction, sleep disturbance, personality changes, dementia
Exam
myoclonus, altered mental status, ataxia
1st investigation
- MRI brain:
often demonstrates hyperintensity in the cerebral cortex (cortical ribboning), basal ganglia (caudate and putamen), and thalamus on diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences, and hypointensity (restricted diffusion) on attenuated diffusion coefficient map (ADC) sequences
More
Other investigations
- EEG:
generalized slowing, focal or diffuse, and periodic polyspike-wave complexes and sharp waves
More - brain biopsy:
vacuolation (spongiform changes), neuronal loss, astrogliosis, presence of pathogenic prion (PrPSc) by immunohistochemistry or western blot, may show amyloid
Cardiac cachexia syndrome
History
symptoms of advanced heart failure (e.g., dyspnea on exertion, fatigue, orthopnea and paroxysmal nocturnal dyspnea, peripheral edema)
Exam
muscle wasting/atrophy, signs of advanced heart failure (e.g., S3 gallop, rales, lower extremity edema, elevated jugular venous pressure, neck vein distention); distinguish intentional weight loss (i.e., diuretic therapy) from unintentional (i.e., cardiac cachexia)
1st investigation
- clinical diagnosis:
diagnosis is made based on history and exam; patient has a prior diagnosis of heart failure
More
Other investigations
Poststroke complications
History
prior stroke, depression, cognitive impairment, dysphagia, arm/hand weakness
Exam
decreased oropharyngeal function, speech and/or swallowing impairment
1st investigation
- swallow study:
inability to swallow properly
More
Other investigations
Pulmonary cachexia syndrome
History
symptoms of advanced COPD or interstitial lung disease (e.g., cough, dyspnea)
Exam
muscle wasting/atrophy, signs of advanced COPD or interstitial lung disease (e.g., decreased breath sounds and air movement, increased work of breathing, lung crackles, wheezing, hypoxia, tachypnea)
1st investigation
- clinical diagnosis:
diagnosis is made based on history and exam; patient has a prior diagnosis of COPD or lung disease
More
Other investigations
Cystic fibrosis
History
cough, dyspnea, diarrhea, oily/floating stool, failure to gain weight (children), chronic pulmonary/sinus infections
Exam
lung hyperinflation, rales (if infection), wheezing
1st investigation
- sweat test:
positive
Other investigations
- genetic testing:
positive
Microscopic polyangiitis
History
overlap with granulomatosis with polyangiitis and lung disease, hematuria
Exam
fever, joint tenderness or synovitis
1st investigation
- urinalysis:
presence or red blood cells, casts
- antineutrophil cytoplasmic antibody (ANCA):
positive
More - antimyeloperoxidase antibody:
positive
Other investigations
- conventional angiography or magnetic resonance angiography:
beading, aneurysm, or smooth, tapering vessel stenosis
Renal cachexia syndrome
History
symptoms of advanced renal failure (e.g., fatigue, edema)
Exam
muscle wasting/atrophy, symptoms of uremia (e.g., confusion, bleeding, pericardial rub)
1st investigation
- clinical diagnosis:
diagnosis is made based on history and exam; patient has a prior diagnosis of renal failure
More
Other investigations
- kidney biopsy:
variable depending on etiology
Diabetes mellitus
History
polyuria, polydipsia, infections, history of poor glycemic control may be chronic symptoms of type 1; nausea, vomiting, anorexia (diabetic ketoacidosis); type 1 more frequently presents with or is complicated by weight loss than type 2, and ketosis compounds weight loss
Exam
acetone breath, Kussmaul respiration, abdominal tenderness (diabetic ketoacidosis); dry mucous membranes, hypotension, tachycardia, tachypnea, decreased level of consciousness (diabetic ketoacidosis or hyperosmolar hyperglycemic state)
1st investigation
- HbA1c:
6.5% or greater
- plasma glucose:
elevated
Other investigations
- serum creatinine level:
elevated (diabetic ketoacidosis)
- serum sodium level:
hyponatremia (diabetic ketoacidosis)
- serum potassium level:
hyperkalemia (diabetic ketoacidosis)
- ABG:
acidosis (diabetic ketoacidosis)
Adrenal insufficiency
History
metastases, tuberculosis, autoimmune endocrinopathies (primary adrenal insufficiency); glucocorticoid exposure (tertiary adrenal insufficiency); fatigue, decreased appetite, weakness, diarrhea, abdominal pain
Exam
orthostasis, hyperpigmentation (primary adrenal insufficiency), shock (adrenal crisis)
1st investigation
Other investigations
- serum sodium level:
hyponatremia
- serum potassium level:
possible hyperkalemia
Hypopituitarism
History
infiltrative disease (e.g., sarcoidosis, hemochromatosis), hypotension, fatigue; headache, vision loss (pituitary adenoma)
Exam
coarse voice, thickened skin, bradycardia, delayed deep tendon reflexes (hypothyroidism); decreased muscle mass, testicular atrophy (hypogonadism); increased fat mass, decreased muscle mass (growth hormone deficiency); no hyperpigmentation; loss of body hair, growth retardation
1st investigation
- TFTs:
low TSH and T4
- insulin-like growth factor (IGF-1) level:
low
- 8 a.m. cortisol and ACTH:
low
- testosterone, FSH, LH (men):
low
- estradiol, FSH, LH (women):
low
Other investigations
Pheochromocytoma
History
may be part of multiple endocrine neoplasia syndrome (type 2); symptoms can be episodic; headache, sweats, palpitations, tremor, weakness
Exam
tachycardia, diaphoresis, hypertension, orthostasis
1st investigation
- serum catecholamines:
elevated
More
Other investigations
- 24-hour urine collection for catecholamines and metanephrines:
elevated
More
Rheumatoid arthritis
History
symmetric polyarthritis, joint pain/swelling
Exam
joint subluxation/destruction (advanced disease)
1st investigation
Other investigations
- CBC:
mild anemia
- ESR and CRP:
elevated
More
Systemic lupus erythematosus
History
rash, fatigue, arthralgia/arthritis, Raynaud phenomenon, chest pain, dyspnea
Exam
fever, malar rash, joint tenderness, hematuria, pleural effusion, pericardial rub, confusion (lupus cerebritis), thrombosis
1st investigation
- antinuclear antibody (ANA), anti-dsDNA:
positive
More - CBC:
anemia, leukopenia, thrombocytopenia
- serum creatinine level:
elevated
- urinalysis:
hematuria, proteinuria
- ESR and CRP:
may be elevated
Other investigations
- antiphospholipid antibody:
may be positive
Granulomatosis with polyangiitis
History
cough, dyspnea, hemoptysis, sinusitis, earache, fatigue, arthralgia/arthritis, myalgia, numbness, muscle weakness, abdominal pain, diarrhea, nausea/vomiting; presentation variable depending on systems affected
Exam
fever, hematuria, skin lesions (e.g., purpura), joint tenderness/swelling, may have signs of consolidation (single lung nodules may have otherwise normal lung exam)
1st investigation
- chest x-ray:
lung mass, infiltrates, pleural effusion, lymphadenopathy
- CT chest:
lung mass, infiltrates, pleural effusion, lymphadenopathy
- antineutrophil cytoplasmic antibody (ANCA):
positive
Other investigations
- tissue biopsy:
granulomatous inflammation, necrosis, and vasculitis
More
Polyarteritis nodosa
History
history of hepatitis B or C, myalgia/arthralgia, paresthesia, abdominal pain, purpura, livedo reticularis, skin ulcers, muscle tenderness
Exam
fever, weight loss, neurologic manifestations (e.g., mononeuritis multiplex and peripheral neuropathy), cutaneous manifestations (e.g., nodules and livedo reticularis), renal manifestations (e.g., hypertension), gastrointestinal manifestations (e.g., abdominal pain), high diastolic BP, mononeuritis multiplex
1st investigation
- CBC:
anemia, elevated platelets, and WBC count
- ESR and CRP:
elevated
- complement:
reduced
- antineutrophil cytoplasmic antibody (ANCA):
negative
- antinuclear antibody (ANA), anti-dsDNA:
negative
- rheumatoid factor:
negative
- anticyclic citrullinated peptide antibody:
negative
Other investigations
- angiography:
saccular or fusiform aneurysms and stenotic lesions in the mesenteric, hepatic, and renal arteries and their subsequent branches
Systemic sclerosis (scleroderma)
History
positive family history, hand swelling, Raynaud phenomenon, skin thickening/tightness, loss of hand function, dysphagia, heartburn, abdominal bloating, melena, myalgia/arthralgia, fatigue
Exam
digital pits/ulcers, sclerodactyly, joint tenderness, telangiectasias, crackles
1st investigation
- antinuclear antibody (ANA):
positive
- CBC:
may be normal or show anemia
- ESR and CRP:
may be elevated
Other investigations
Sarcoidosis
History
cough, dyspnea, fatigue, arthralgia, photophobia, vision changes; symptoms are highly variable and depend on organ involved
Exam
wheezing, rhonchi, lymphadenopathy
1st investigation
- chest x-ray:
hilar and/or paratracheal adenopathy with upper lobe predominant, bilateral infiltrates; pleural effusion (rare)
- CBC:
may show anemia or leukopenia
- LFTs:
abnormal
- serum creatinine:
may be elevated
- serum calcium:
hypercalcemia
- PFTs:
restrictive or obstructive pattern (or mixed)
Other investigations
Mixed connective tissue disease (overlap syndromes)
History
digital pallor/pain, Raynaud phenomenon, arthralgia/arthritis, myalgia, swollen hands, dyspnea, cough, heartburn
Exam
sclerodactyly, nail fold vascular changes, lymphadenopathy, hematuria
1st investigation
- CBC:
may show anemia or leukopenia
- ESR and CRP:
elevated
- rheumatoid factor:
may be positive
- antinuclear antibody (ANA):
positive
- anticyclic citrullinated peptide antibody:
may be positive
- antiribonucleoprotein antibodies:
positive
Other investigations
- urinalysis:
variable; may show proteinuria, hematuria, occasional RBC casts
Adult-onset Still disease
History
daily-spiking fevers, rash, abdominal pain, nausea, arthralgia/arthritis
Exam
salmon-colored rash (especially during febrile periods), lymphadenopathy, joint tenderness/swelling
1st investigation
- serum ferritin level:
may be very high
More - CBC:
anemia, leukocytosis
- ESR and CRP:
elevated
Other investigations
HIV infection
History
injection drug use, unprotected sex, needle stick injury, transfusions of blood or blood products prior to 1986 or in regions without adequate testing, night sweats, diarrhea, oral ulcers, altered mental status, opportunistic infections; weight loss more common with advanced disease
Exam
fever, skin rashes, oral thrush, muscle wasting (advanced disease), Kaposi sarcoma
1st investigation
Other investigations
Mycobacterium avium complex (MAC)
History
underlying lung disease, cough, dyspnea, fatigue
Exam
fever, lymphadenopathy, rales, or consolidation
1st investigation
- blood culture:
positive for MAC
- sputum culture:
positive for MAC
- lymph node biopsy:
positive for MAC
More
Other investigations
Histoplasmosis
History
exposure to spores, endemic region, immunosuppression, cough, dyspnea, headache, abdominal pain, chest pain; weight loss more common with disseminated disease
Exam
fever, scattered crackles, bronchial breathing, distant breath sounds
1st investigation
- chest x-ray/CT:
may be normal or show focal infiltrates, hilar and mediastinal lymphadenopathy, calcified granulomas, pulmonary nodules, diffuse interstitial or reticulonodular infiltrates, cavitary lesions, or pleural effusion
- sputum culture:
positive for Histoplasma capsulatum
- antigen testing:
positive for H capsulatum antigen
Other investigations
- immunodiffusion precipitin test:
positive for H capsulatum antibody
Amebiasis
History
exposure history (e.g., visit to endemic area), immunosuppression, diarrhea, dysentery, abdominal pain
Exam
fever, abdominal tenderness
1st investigation
- stool antigen detection:
positive for parasite antigen
- PCR of stool:
amplification of amebic DNA
- serum antibody test:
positive for antiamebic antibodies
Other investigations
- stool microscopy:
identification of Entamoeba in stool
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Giardiasis
History
exposure history (contaminated water), nonbloody diarrhea (severity varies), malaise, bloating; weight loss in severe and/or chronic disease
Exam
may have abdominal tenderness
1st investigation
- stool antigen detection:
positive for cyst wall
More
Other investigations
Cryptosporidiosis
History
exposure history (contaminated water), diarrhea, abdominal pain, loss of appetite; may be mild and self-limiting unless patient is immunosuppressed
Exam
may have abdominal tenderness
1st investigation
- stool microscopy:
positive for Cryptosporidium cysts
More
Other investigations
Cystoisosporiasis
History
exposure history to Cystoisospora belli (contaminated food or water), nonbloody diarrhea; may be mild and self-limiting unless patient is immunosuppressed
Exam
may have abdominal tenderness
1st investigation
- stool microscopy:
positive for Cystoisospora belli oocysts
More
Other investigations
Cyclosporiasis
History
exposure history to Cyclospora (contaminated food or water), nonbloody diarrhea; may be mild and self-limiting unless patient is immunosuppressed
Exam
may have abdominal tenderness
1st investigation
- stool microscopy:
positive for Cyclospora cysts
More
Other investigations
Strongyloidiasis
History
history of exposure (e.g., contaminated soil), abdominal pain, change in bowel habit; pulmonary syndrome (e.g., cough, wheezing) may develop; weight loss can occur in immunosuppressed patients
Exam
may be normal
1st investigation
- stool microscopy:
positive for strongyloides larvae
- CBC:
eosinophilia
- serology:
positive
More
Other investigations
Infective endocarditis
History
prior dental work, injection drug use, prosthetic heart valves, cough, hemoptysis, dyspnea, night sweats, fatigue, myalgia/arthralgia, weakness
Exam
fever, cardiac murmur, Osler nodes, Janeway lesions
1st investigation
- blood culture:
bacteremia, fungemia
More - echocardiogram:
valvular vegetation
Other investigations
Whipple disease
History
male gender, diarrhea, abdominal pain, joint pain
Exam
fever, may be normal
1st investigation
- endoscopy with biopsy:
villous blunting with periodic acid-Schiff (PAS) staining in macrophages
More
Other investigations
Bartonella infection
History
Bartonella henselae often follows bite or scratch from a cat (other types are associated with travel or indigent/homeless people), abdominal pain, nausea/vomiting
Exam
fever, papular/pustular lesion
1st investigation
- serology (Bartonella henselae):
positive
- culture:
positive for B henselae
- lymph node biopsy:
granuloma formation, microabscesses, follicular hyperplasia
Other investigations
Inadequate nutrition
History
older age, poverty, inadequate resources, taste changes, dental problems, fewer social interactions, reduced or no access to food and different types of food
Exam
signs of starvation
1st investigation
- clinical diagnosis:
diagnosis is made based on history and exam
Other investigations
Elder abuse/neglect
History
recurrent injuries, unstable home environment, inconsistent/changing history, unexplained/inconsistent injuries
Exam
signs of starvation, ecchymosis, burn marks, bone fractures, head injuries
1st investigation
- x-ray/CT area of injury:
may show bone fracture or intracranial bleeding
Other investigations
- clinical photograph:
record of bruises or wounds
Child abuse/neglect
History
recurrent injuries, unstable home environment, inconsistent/changing history, unexplained/inconsistent injuries
Exam
signs of starvation, ecchymosis, burn marks, bone fractures, head injuries
1st investigation
- x-ray/CT area of injury:
may show bone fracture or intracranial bleeding
Other investigations
- clotting profile/coagulation studies:
normal, mild abnormalities may be present in head trauma
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