ABDI STUDY GUIDE

things from king abdi stidy guide

Primary Hyperthyroidism

• High fT4 & Low TSH

• Most common cause: Grave’s Disease! (anti-TSHR positive [thyroid stimulating hormone receptor])

• excess fT4 NOT dependent on hypothalamus-pituitary-thyroid axis

Pituitary Hyperthyroidism (RARE)

• TSH normal/high

• due to pituitary TSH-secreting tumor (benign)

Primary Hypothyroidism

• High TSH, Low fT4

• Low ft4 NOT dependent on hypothalamus-pituitary-thyroid axis

• Most common cause: Hashimoto Dz!

Secondary Hypothyroidism

• Low/Normal TSH, low fT4

• Hypopituitarism (pituitary gland not making enough hormones b/c of adenoma/radiation/destruction of pituitary

Cushing Syndrome

• persistent hypercortisolism (prolonged exposure to cortisol)

• Dx:

  • (+) 24hr UFC (urine free cortisol): 3x abv normal

  • overnight low dose DST: ≥10μg/dL highly suggestive (<1.8 strongly rules out Cushing syndrome)

• Primary caused by adrenal adenoma/carcinoma or bilateral adrenal hyperplasia

• “moon face”

• iatrogenic: most common cause of glucocorticoild admin

• Cushing Dz: pituitary adenomas

• Ectopic ACTH: lung cancer, pancreatic cancer

Investigation of high cortisol secretion mechanisms

• ACTH-dependent: 8am cortisol >15ug/dL = almost always pituitary gland

• Overnight High dose DST to differentiate from ectopic: 8am cortisol <5ug/dL, or suppression is 50% or more vs baseline, source is pituitary)

• ACTH-independent: high dose glucocorticoids administration should be excluded first. issue is with adrenal gland itself

Addison Disease

• Low 8am aldosterone/very small increase in cortisol lvl after cosyntropin (synthetic form of ACTH) stimulation

  • >18 ug/dL is indicative of normal adrenal function

• Primary Addison disease caused mainly by an autoimmune mechanism

Conn Syndrome

• Screening: Ratio of plasma aldosterone conc. to plasma renin (enzy from kidneys) activity, must be confirmed by 24h urinary aldosterone level

• Primary hyperaldosteronism, caused by adrenal adenoma or bilateral adrenal hyperplasia; adrenal glands produce too much aldosterone.

Diabetes insipidus neurogenic (BRAIN)

• Central DI: insufficient secretion of ADH by posterior pituitary gland (base of brain)

• Polyuria, low urine osmolality

• Overnight water deprivation test: patient not able to concentrate urine during deprivation but can after ADH injection!

Diabetes insipidus nephrogenic (KIDNEY)

• ADH receptor on collecting ducts or distal convoluted tubules not functional

• Polyuria, low urine osmolality

• Overnight water deprivation test: patient not able to concentrate urine in either case
  

Syndrome of inappropriate ADH (SIADH)

• Low plasma Na, High urine Na (>20mEq/L), urine osmolality >100mOsm

• Normal blood volume

• Caused by tumors such as small cell carcinoma of the lung, or drug chlorpropamide 

  • Body produces too much ADH (antidiuretic hormone) → body retains too much water → diluting blood & having critically low sodium lvls
    

GH (Growth Hormone) excess

Is always seen with high IGF-1 (insulin-like growth factor) (normal IGF-1 excludes GH excess)

Indicated by:

• Very high GH in a random blood specimen

• No response to glucose suppression test of a relatively normal GH patient

Immature menopause

• Persistently high FSH (best test) - follicle-stimulating hormone

Ovarian Failure

• Persistently high FSH

• due to elimination of follicles by pathologic process

Hyperprolactinemia

• high plasma prolactin (prolactin is a hormone related to lactation & breast tissue development

• Most common cause: prolactinoma (prolactin-secreting tumor)

• Causes amenorrhea in women & gynecomastia in men

Gonadal Fxn tests

• Females: No progesterone production following hCG stimulation indicates Primary Gonadal Hypofunction

• Males: testosterone lvl <150n/dL following hCG stimulation indicates Primary Hypogonadism

  • FSH ≤10 mU/mL: Hypogonadotropic

  • FSH: ≥20 mU/mL: Hypergonadotropic

PKU

• ↑↑in PA (phenylalanine) & its metabolites in serum and urine (mousy odor)

• Screened by Guthrie test on blood spots from newborns (bacterial growth is positive result), confirmed by HPLC or MS/MS.

• In urine: Phenistix reaction (blue-gray to green); rapid paper-strip urine test to detect elevated lvls of phenylpyruvic acid (by-pdt of phenylalanine)

• Mutation in PAH gene encodes phenylalanine hydroxylase

• Hyperphenylalaninemia may also happen in BH4 deficiency
  

Tyrosinosis

• High tyrosine and succinylacetone in blood and urine (cabbage-like odor), also tyrosine crystals in urine

• In urine: nitrosonaphtol test is positive 

• MS/MS for confirmation

• There are 3 types:

  • Type I more common and the most severe (cancer risk later in life)

• Mutation in FAH gene

Alkaptonuria

• Increase in homogentisic acid level in blood & urine

• Mutation in HGD gene which encodes homogentisic acid oxidase

• Darkening of urine upon standing

• Screening test: ferric chloride on urine (turns blue)

• MS/MS

MSUD

• Accumulation and excretion of α-ketoacids in urine (maple syrup odor)

• Modified Guthrie test (inhibitor 4-azaleucine)

• Microfluorometric assay 

• MS/MS

• Complete absence or severe deficiency of BCKD enzyme complex

  • Branched amino acids: valine, leucine, isoleucine 

    
    

Homocystinuria

• Increase in homocysteine and methionine levels

• Mutation in CBS gene which encodes cystathionine β-synthase required for methionine metabolism

• Modified Guthrie test (inhibitor L-methionine sulfoximine)

Acute inflammation

Negative Acute Phase Reactants:

1. Albumin

2. Transferrin

Positive Acute Phase Reactants:

1. CRP

2. Haptoglobin

3. Complement

4. β2M

5. Ceruloplasmin

**Increased α1 and α2 on SPE

Cirrhosis

• SPE pattern: Polyclonal increase in gamma with beta-gamma bridging

Blood-brain barrier damage (meningitis)

CSF electrophoresis: increase on protein

Multiple Sclerosis (MS)

• CSF electrophoresis: oligoclonal bands, Myelin basic protein (MBP), sign of myelin damage in general (not specific)

Jaundice: pre-hepatic

• increase in unconjugated bilirubin

• Amount of bilirubin delivered to liver increased 

• Most common cause hemolytic anemia

Jaundice: hepatic (d/os of bilirubin transport or metabolism)

• Crigler-Najjar syndrome, Gilbert's disease, and neonatal physiologic jaundice of the newborn: Increase in unconjugated bilirubin 

• Dubin-Johnson syndrome, Rotor syndrome: Increase in conjugated bili

Crigler-Najjar syndrome

rare but serious, risk of kernicterus.

D-J syndrome

excretion into bile defective, dark granules on liver biopsy 

Rotor syndrome

clinically similar to D-J syndrome, excellent prognosis, no dark granules on liver biopsy  

Alcoholic fatty liver

• slight increase in ALT, AST, GGT (Gamma-Glutamyl Transferase)

• fatty infiltrates in vacuoles of liver cells on biopsies

• mildest form of liver Dz

Alcoholic Hepatitis

• mod. increase in ALT, AST, GGT, ALP, total bili >5mg/dL

• AST/ALT ratio (De Ritis ratio) >2.0

• Albumin reduced; INR increased

• Threatening sign: increased creatinine (may precede hepatorenal syndrome and death) 

• Moderate severity

Alcoholic Cirrhosis

• increase in LFTs (ALT, AST, GGT, ALP, total bili), decrease in albumin,

• definitive Dz: liver biopsy

• last & most severe form :O

Hepatitis B

HBSAg: first to be detected during acute phase, not infectious by itself 

HBeAg: second to be detected, with HBSAg only during acute phase, highly infectious. 

HBcAb: first Ab to be detected, core window: IgM HBcAb the only marker to be detected, blood could be infective.

HBeAb: second Ab to be detected (may indicate HBeAg loss) 

HBSAb: detected late during infection (around 3-6 months after infection), can also be detected years after, indicating clearance of the virus and natural active immunity.

IgG HBcAb: it may be detected with HBSAb which indicates recent infection

Hepatitis C

• Positive anti-HCV Ab using ELISA

• Real time PCR for virus load

• Some patients may clear the virus (Ab+, HCV RNA -)

Myocardial Infarction (MI)

CK-MB: rapidly post-MI (4 to 6 hours) returns to baseline after 2 to 4 days (short window of time after a suspected MI)

LD: levels remain elevated for up to 1 week but are not detectable until 24 to 48 hours post-MI.

Cardiac troponins: detectable in the plasma at 3 to 12 hours after myocardial injury, peaking at 12 to 24 hours and remaining elevated for more than 1 week: 8 to 21 days for TnT and 7 to 14 days for TnI.

Predominant hyperlipidemia

• Plasma cholesterol level >200 mg/dL

• Related to high LDL (bad cholesterol)

• Most common primary cause is Familial hypercholesterolemia (AD deficiency of LDL-R)

• Secondary causes: DM, hypothyroidism

Predominant hypertriglyceridemia

Usually, elevated VLDL (bad triglycerides) or chylos (milky, lipid rich)

• Primary cause: familial LPL deficiency, familial apo-CII deficiency

Tangier Disease

• Low cholesterol, high TG, absent HDL, absent apo-A1

• cholesteryl esters deposit in tonsils, lymph nodes, spleen

Correlations with CHD or CAD

Hypercholesterolemia (curvilinear, >200, related to high LDL), low HDL (<40), HDL<35 an independent risk factor, Lp(a)>30

Labeled Immunoassay

1. Radioactive (RIA, IRMA)

2. Fluorescent (FIA)

3. Chemiluminescent (CLA)

4. Enzyme (EIA)

Competitive Immunoassay

• Ag* and Ag compete for binding with the Ab

• Ag* concentration is constant and limited

• As the Ag concentration increases, more bind with Ab and less Ag* binds, bound Ag* is always measured.

**The highest concentration of the Ag generates lowest signal and vice versa

Non-Competitive Immunoassay

Ab reagent is labeled and is always added in excess (to avoid limiting the reaction)

Concentration of the Ag is directly proportional to the bound labeled Ab up to a limit, but above that it will be prone to “hook effect”