Initial Tests, Definitive Diagnosis, and other gold standard things

Adrenal Insufficiency...

8am plasma cortisol levels and ACTH levels --> dx A synthetic ACTH stim test (cosyntropin) is the test of choice if morning cortisol levels are nondiagnostic. A 8am cortisol <3 in the absence of exogenous glucocorticoid administration is dx of AI Failure of cortisol to rise >20 with ACTH admin confirms the diagnosis

Testing for Mesenteric Ischemia

AXR and CT: may reveal bowel wall edema (thumbprinting) and air within the bowel wall (pneumatosis intestinalis) Mesenteric/CT angiography: definitive test but conventional angiography allows for intervention of thrombosis/embolism

Testing for Gallstone ileus...

AXR with characteristics of SBO and pneumobilia (gas in the biliary tree) confirms the diagnosis. Upper GI barium contrast will show no contrast in the colon.

Initial test of SBO...

Abdominal films - show stepladder pattern of dilated small bowel loops, air fluid levels and paucity of gas in colon

Initial test of Ileus...

Abdominal films: distended loops of small and large bowel, air seen throughout colon and rectum (VS SBO)

Porphyria

Accumulation of porphyrins. Porphyria cutanea tarda is most common. Lead poisoning can cause a porphyria like disorder Combination of photodermatitis, neuropsych complaints, visceral like colicky ab pain and seizures. Physical shows tachycardia, skin erythema, blisters, areflexia and nonspecific abdominal pain. Acute attacks can be caused by fasting, chemical exposures, alcohol, barbs, OCPs. Urine- pink or brown after attack. Best initial test: urine and plasma porphyrin levels. Most accurate test: specific mutation or enzyme analysis. High levels of glucose may help during attack (neg feedback to heme synthesis pathway)

Polycythemia Vera

Best initial test is CBC --> elevated RBC, WBC and platelets with an ABG and EPO level. EPO is decreased, normal O2, and HCT >60% Most accurate test is JAK2 mutation

Iron Deficiency Anemia

Best initial test is a CBC with iron studies. Will see low ferritin (iron stores), high RBC distribution width (RDW-size variation), high TIBC (lots of empty receptors, could bind a lot), and low serum iron Most accurate test is a bone marrow biopsy, rarely done. Peripheral smear - hypochromic and microcytic RBCs with low reticulocyte count.

Neutropenia

Best initial test is a CBC with smear. In the hx, look for drug or toxin exposure, infection, autoimmunity, or neoplasia. Follow neutropenia with CBC and ANC. If thrombocytopenia or anemia present, get a BM biopsy and aspirate. Serum immunologic eval, ANA levels, and a workup for collagen vascular disorders.

Acute Leukemia

Best initial test: CBC with smear --> blast cells Most accurate test: Bone marrow biopsy with flow cytometry to classify leukemia type AML: leukemic cells are myeloblasts. ALL: they are lymphoblasts. If WBC in AML is very high >100,000 --> risk of leukostasis (blasts occluding the microcirc leading to pulm edema, CNS symptoms, ischemic injury and DIC

PNH

CD55/59 proteins found on surface of RBCs protect from complement mediated hemolysis. PNH is a deficiency in GPI anchor molecules that keep CD55/59 attached --> hemolysis via complement. Can manifest as anemia, dark urine, venous thrombosis, and abdominal pain Most accurate dx: CD55/59 absence via flow cytometry.

Multiple Myeloma

CRAB symptoms: hyperCalcemia, Renal involvement, Anemia, Bone lytic lesions/back pain. Best initial test: Serum protein electrophoresis showing IgG or IgA monoclonal spikes. Most accurate test: Bone marrow biopsy showing >10% monoclonal CD138+ plasma cells. CBC with smear may show rouleaux formation, whereas a urinalysis may show Bence Jones protein (paraprotein). Total protein:albumin gap is often elevated. M protein alone is insufficient for dx of MM (as MGUS, CLL, lymphoma, Waldenstrom macroglobulinemia, and amyloidosis can also show increased M protein. Patient should also have a skeletal survey.

Pheochromocytoma...

CT and MRI are both sensitive for pheo A nuclear MIBG scan localize extra-adrenal lesions and metastatic disease Look for elevated plasma free metanephrines (metanephrine and normetanephrine) or 24 urine levels of metanephrines and catecholamines

Definitive test of ileus...

CT of abdomen

Definitive test of SBO...

CT of the abdomen- further characterize obstruction and evaluate for etiology

Imaging for Diverticulitis...

CT scan is used to dx. May reveal inflammation or abscess. Avoid sigmoidoscopy in initial stages of disease (perforation risk).

Imaging for Ischemic Colitis...

CT scan with contrast initial test. Thickened bowel wall, atherosclerosis Colonoscopy: pale mucosa with petechial bleeding.

Pulmonary hypertension/cor pulmonale

CXR shows enlargement of central pulmonary arteries ECG shows RVH Echo (initial) and right heart cath (definitive) may show signs of right ventricle overload and may aid in dx of underlying cause

Sarcoidosis...

CXR/CT (initial): Radiographic findings of lymphadenopathy and nodules are used to stage the disease Biopsy (definitive): Lymph node biopsy or transbronchial/video lung biopsy --> non caseating granulomas PFTs: Restrictive or obstructive pattern and decreased DLCO Other findings: Increased ACE levels, hypercalcemia, hypercalciuria, increased alk phos (with liver involved), lymphopenia, CN defects, arrhythmias

Testing for Gonorrhea and chlamydia...

Chlamydia: culture is gold standard, Urine NAAT are a rapid means of detection, and DNA probes/immunofluorescence (for G/C) takes 48-72 hours. Gonorrhea: Gram stain and culture is gold standard. NAAT can be sent on penile/vaginal tissue or urine.

vWF disease

Initial bleeding workup will show an increased bleeding time in all vWD types. Increased PTT will be seen due to low VIII factor. PT and platelet count will be normal Most accurate test: Ristocetin cofactor assay of patient plasma (measures capacity of vWF to agglutinate platelets, decreased agglutination=dx ) and vWF antigen level.

Test for influenza...

Initial: Rapid influenza nasopharyngeal swab more definitive diagnosis: DFA tests, viral culture or PCR. Usually a clinical diagnosis. Leukopenia is a common finding.

Hypocalcemia

Ionized Ca and PTH are the most useful tests.

Hyperaldosteronism...

Labs show hypokalemia, metabolic alkalosis, hypomag, hyperaldosteronism, and increased aldosterone to plasma renin activity ratio (>30) CT or MRI may reveal an adrenal mass. Adrenal venous sampling may be needed to localize the adenoma or to confirm bilateral adrenal hyperplasia.

GH disease

Labs: Measure IGF-1 levels (increased with acromegaly). Confirm dx with an oral glucose suppression test (GH levels remain elevated despite glucose). Baseline GH is NOT reliable for a test Imaging: MRI shows a sellar lesion.

Dx for hyperparathyroid disease...

Labs: hypercalcemia, hypophosphatemia, and hypercalciuria. Intact PTH is inappropriately elevated relative to total and ionized calcium. DEXA: may show low BMD, or frank osteoporosis A 99m tc sestamibi scan and a thyroid US --> solitary adenoma (most likely).

Polycystic Kidney Disease

Diagnose based on US (most common) or CT scan. Multiple bilateral cysts will be present throughout the parenchyma and renal enlargement will be visualized. Genetic testing also available.

Aplastic Anemia

Diagnosed by clinical presentation and CBC. Most accurate test is a bone marrow biopsy --> hypocellularity and space occupied by fat.

Thalassemia

Diagnosed by hemoglobin electrophoresis and DNA studies. Alpha Thal--> mutation of one+ of four genes that encode it, BThal--> mutation of one or both genes that encode B Labs: Microcytic anemia with normal iron studies, African, Middle eastern or Asian descent.

Diagnosis for Mono...

Diagnosed by heterophile antibody (monospot) test, may be negative in the first few weeks of symptoms. EBV specific antibodies can be ordered if clinical suspicion but negative Monospot. Infectious mono syndromes that are negative for both --> most often CMV. CBC- thrombocytopenia, lymphocytosis, and >10% atypical t lymphocytes Comprehensive metabolic panel usually reveals elevated AST/ALT, Alk phos and total bilirubin.

Diagnosis for genital lesions... Haemophilus ducreyi

Difficult to culture, dx made clinically, culture on specialized media

Idiopathic thrombocytopenic purpura

Dx of exclusion. Other causes of Thrombocytopenia have been ruled out. Bone marrow biopsy would show increased megakaryocytes but is done only in atypical cases or patients >60.

Test for HIV...

ELIZA test (Screening, high sens, mod spec): Detects anti-HIV antibodies in the bloodstream (can take up to 6 months after exposure to appear) Western Blot (Confirmatory, low sens, high spec) HIV rapid tests now available. Baseline eval: HIV RNA PCR (viral load), CD4 count, CXR, PPD or quantiferon gold, pap smear, mental status exam, VDRL/RPR, serologies for CMV, viral hepatitis, toxoplasmosis, and VZV Eval for acute retroviral syndrome (acute HIV): HIV RNA PCR (viral load), ELIZA might still be negative.

Testing for choledocholithiasis

MRCP and ERCP can diagnose, ERCP is also therapeutic.

Test of choice for osteomyelitis...

MRI --> shows increased signal in bone marrow and associated soft tissue infection Definitive diagnosis --> made by bone aspiration with gram stain and culture. Clinical diagnosis made by probing through the soft tissue to bone is usually sufficient, as aspiration of the bone could spread the infection.

Hyperprolactinemia...

Prolactin level >200. If a mass.. MRI --> sellar lesion.

Paget Disease (BONE)

Radiographic diagnosis- lytic and sclerotic lesions, diagnose via plain films, but baseline radionuclide bone scan necessary to see extent of disease Labs: INCREASED alk phos with normal Ca and P. Must be distinguished from met bone disease.

G6PD

Seen with Mediterranean or African descent, sulfa (TMP-SMX), antimalarials, infections, fava beans, metabolic acidosis, dapsone, nitrofurantoin. Best initial test is a CBC with smear showing hemolytic anemia with bite cells and Heinz bodies. Most accurate test is a G6PD level a month after an episode.

Diagnosis for genital lesions... Treponema pallidum

Spirochetes seen on dark field microscopy T. pallidum identified by serum antibody test.

CLL

malignant clonal proliferation of functionally incompetent lymphocytes that accumulate in BM, peripheral blood, lymph nodes, spleen and liver. Almost all cases are with well differentiated B lymphocytes. Best initial: CBC with differential and smear --> lymphocytosis and characteristic smudge cells Most accurate: flow cytometry showing the CD5 marker on B cells (normally seen on T cells). Will have granulocytopenia, anemia, thrombocytopenia. Abnormal function of leukemic cells --> hypogammaglobulinemia Bone marrow biopsy rarely required but may help with prognostic info

Hodgkin Lymphoma

primarily a B-cell malignancy, associated with EBV infection, bimodal 30 and 60. Contiguous spread Pel-Ebstein fevers (1-2 wks of high fever alternating with 1-2 weeks of afebrile) and alcohol induced pain at nodal sites are rare specific signs for HL. Best initial: Excisional lymph node biopsy showing Reed-sternberg cells Staging based on: number of nodes, presence of B symptoms, and whether it spread to both sides of diaphragm.

Thyroid function testing...

-TSH: single best test for screening of thyroid, unless history of brain injury -RAI and scan: shows the level and distribution of iodine uptake. Determines if nodule is functioning or nonfunctioning and requires a biopsy. -Total T4: Not an adequate screening test. 99% of circulating T4 is bound to TBG. -Free T4: preferred screening test for thyroid hormone levels.

Hereditary spherocytosis

AD defect or deficiency in spectrin or ankyrin, an RBC membrane protein resulting in decreased RBC surface area. --> Extravascular hemolytic anemia in spleen. Best initial test is CBC with smear --> spherocytes. Most accurate test is osmotic fragility test. Manage with splenectomy.

Hypercoagulable diseases

APS: Lupus anticoagulant and anticardiolipin antibody and middle aged female with recurrent miscarriages or thrombosis. HIT (PF4 antibody and serotonin release assay) and thrombocytopenia and on heparin anticoagulation.

autoimmune hemolytic anemia

Autoantibodies against RBC membrane destroy blood cells. Warm- IgG, associated with SLE, CLL, drugs Cold- IgM, associated with Mycoplasma pneumonia and mono Dx: with direct coombs test.

Sickle cell

B-chain - Glu replaced by val --> Decreased RBC survival and sickling/aggregation of RBCs. May first present with dacylitis in childhood, lifelong hemolysis --> anemia, jaundice, pigmented cholelithiasis, increased CO --> murmur, eventual CHF, and delayed growth. Triggers- cold temps, dehydration, infection, high altitude. Fastest initial test: smear showing sickle cells and howell jolly bodies (functional hypoplenia/asplenia). Most accurate test --> hemoglobin electrophoresis

Megaloblastic anemia...

Best initial test: CBC with smear showing RBCs with an elevated MVC >100, hypersegmented (6+) neutrophils. Serum vitamin levels-poorly diagnostic and are used with adjunctive tests --> methylmalonic acid and homocysteine levels. B12 deficiency- Increased MMA and homocysteine. Folate- Normal MMA and increased homocysteine. Bone marrow sample --> giant neutros and hypersegmented mature neutros. Schilling test: absorption of cobalamin via ingestion of radiolabeled cobalamin with and without IF. The pt is gien an unlabeled B12 IM shot to saturate B12 in the liver and an oral challenge of radiolabeled B12. The radiolabeled B12 will pass in the urine if properly absorbed as the liver's B12 receptors will already be saturated by the IM dose. If radiolabeled B12 in urine --> dietary B12 deficiency. If no radiolabeled B12 in urine- consider pernicious anemia, bacterial overgrowth, or pancreatic enzyme deficiency.

hairy cell leukemia

Best initial test: CBC with smear showing pathognomonic hairy cells (mononuclear cells cytoplasmic projections), that stain with TRAP. Leukopenia can also be seen. Most accurate: Flow cytometry identifying hairy cells

Non-Hodgkin Lymphoma (NHL)

Best initial test: Excisional LN biopsy- disease staged by Ann Arbor. Stage I-single site, II-two sites on same side of diaphragm, III-multiple on both sides of diaphragm, IV-Diffuse disease. A-no systemic, B-systemic symptoms A CSF should be done in patients with HIV, neuro symptoms, or primary CNS lymphoma

Hemophilia

Best initial test: Mixing study. Mix patient's plasma with normal plasma --> will correct PTT. Labs: Increased PTT. PT and bleeding time normal. Most accurate test: obtain specific factor assays for factors VII, VIII, IX, XI, and XII.

Thrombotic Thrombocytopenic Purpura

Clinical - presence of shistocytes (broken RBCs/helmet cells) on peripheral smear and low platelets and increasing creatinine. HUS can present similarly to TTP - Renal failure, hemolytic anemia, and low platelets without neuro symptoms. Severe increases in Cr seen more in HUS than TTP. Schistocytes seen in both.

Hemolytic Anemia

Clinical dx. Increased LDH, increased Indirect bilirubin, increased reticulocyte count, and DECREASED haptoglobin

Diagnosis for genital lesions...Klebsiella granulomatis (granuloma inguinale)

Clinical exam, biopsy (See donovan bodies)

Diagnosis for genital lesions... HPV

Clinical exam, biopsy for confirmation

DIC

Clinical features and lab findings (depletion of clotting factors and platelets) -May be confused with liver disease, but unlike liver disease --> factor VIII is depressed.

CML

Clonal expansion of myeloid precursor cells, leukocytosis with excess granulocytes and basophils and sometimes RBC and platelets. Need to have BCR-ABL translocation (9,22). Affects middle age patients. Most accurate: Philadelphia chromosome via PCR or FISH shows 9,22 translocation. WBC --> very high count (>100,000- 500,000). Shows granulocytes at all stages of matuirty. Could even cause hyperviscous syndrome. LDH, uric acid and B12 also elevated

Osteoporosis...

DEXA: Recommended as screening for women >65, men>70 and those with risk factors. DX when BMD is -2.5 less than young normal person (t-score). BMD between 1 and 2.5 is osteopenia. Lab: Normal calcium, phosphate, and PTH levels. X-ray: Global demineralization only apparent after 30% of bone density is lost.

Testing for UC....

Definitive diagnosis is Colonoscopy with biopsy, Will see diffuse and continuous rectal involvement, friability, edema, and pseudopolyps.

Testing for Crohn's Disease...

Definitive dx is colonoscopy with biopsy. Will see aphthoid, linear, or stellate ulcers, strictures, cobblestoning, skip lesions, creeping fat on laparatomy. Also do GI series imaging for small bowel.

Hypopituitarism

Measure 8am cortisol, free T4, Test/Estrogen levels, IGF-1

Waldenstrom Macroglobulinemia

Most accurate test: Bone marrow biopsy and aspirate. Marrow shows abnormal plasma cells, classically with Dutcher bodies (PAS+ IgM deposits around nucleus). Serum and urine protein electrophoresis and immunofixation also used. Nonspecific labs: Increased ESR, uric acid, LDH and alk phos

Eosinophilia

NAACP- Neoplasm, allergy, asthma, Collagen vascular disease, Parasites CBC with differential should be obtained. CSF analysis showing eosinophilia is suggestive of a drug reaction or infection with coccidioidomycosis or a helminth. Hematuria with eosinophilia --> schistosomiasis.

Amyloidosis

Tissue biopsy with congo red staining --> apple green birefringence under polarized light. immunohistochem can identify the protein type.

Diagnosis for genital lesions... HSV-1 or 2

Tzank smear shows multinucleated giant cells (Best INITIAL test) Viral cultures (most ACCURATE test) could also do DFA (direct fluorescent antibody) or serology.

Testing for cholelithiasis

US is initial and definitive test

Testing for Acute cholangitis...

US is initial study, diagnostic for CBD dilation. ERCP is definitive- both Dx and Tx

Testing for Acute Cholecystitis...

US is the initial test, may show stones, bile sludge, pericholcystic fluid, thickened gallbladder, gas in wall of gb, or US murphy sign. If US is equivocal, obtain a HIDA scan. Uses a radiotracer excreted through the biliary system, nonvisualization of the GB suggests acute cholecystitis.

Diagnosis for UTI...

Urinalysis: best initial test. Many will have +Leuk esterase and nitrites, increase pH (proteus infections), and hematuria sometimes seen. Pyuria (>5 WBC/hpf) and bacteriuria (1 organism/hpf =10^6 organisms/ML) Urine Culture: most accurate test. Gold standard is >10^5 CFU/mL.

SIADH dx

Urine osmolality is >50-100 mOSM/kg in the setting of serum hypo-osmolarity without a physiologic reason for increased ADH Urinary sodium level is often >40 mEq/L

Diabetes Inspidus...

Water deprivation test: in psychogenic polydipsia and normal renal physiology --> water restriction will lead to more concentrated urine. In central and nephro DI --> patients excrete a high volume of inappropriately dilute urine. Desmopressin acetate (DDAVP-synthetic analogue of ADH) replacement test: in central, decrease urine output and increase urine osmolarity (by 50-100%). If nephro, no effect seen. MRI--> may show pit mass in central DI.

Differentiating between a Leukemoid reaction and hematologic malignancy...

When WBC is very high (>50,000) Order a leukocyte alk phos (LAP) to distinguish. An increased LAP --> Leukemoid reaction Decreased LAP --> Malignancy