Organ function test and hormones
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I now have solid textbook material across liver, renal, thyroid, and adrenal systems. Let me compile a comprehensive answer.
Organ Function Tests & Hormones
A comprehensive overview covering the five major organs: liver, kidney, thyroid, adrenal gland, and pancreas.
1. LIVER FUNCTION TESTS (LFTs)
The liver operates as three functional systems, each tested differently:
System 1 - Hepatocyte Integrity (Chemical/Metabolic)
| Test | Marker | Clinical Significance |
|---|---|---|
| AST (Aspartate aminotransferase) | Enzyme | Rises in acute hepatitis, necrosis, trauma |
| ALT (Alanine aminotransferase) | Enzyme | More liver-specific than AST; same pattern |
| LD (Lactate dehydrogenase) | Enzyme | Rises with hepatocyte injury or mass lesions |
| Total protein / Albumin | Protein synthesis | Decreases only when >80% liver destroyed (cirrhosis, fulminant failure) |
| Ammonia | Urea cycle function | Rises when >80% liver tissue lost (only the liver detoxifies ammonia via the Krebs-Henseleit cycle) |
System 2 - Bilirubin Processing (RES / Kupffer Cells)
- Kupffer cells convert heme to biliverdin then bilirubin
- Indirect (unconjugated) bilirubin = pre-hepatic or hepatocyte failure
- Direct (conjugated) bilirubin = rises with cholestasis/obstruction
System 3 - Biliary Tract
| Test | Location | Significance |
|---|---|---|
| ALP (Alkaline phosphatase) | Canalicular surface | Cholestasis, biliary obstruction, space-occupying lesions |
| GGT (Gamma-glutamyltransferase) | Hepatic surface | Sensitive for biliary obstruction and alcohol use |
| 5'-Nucleotidase (5'-N) | Biliary tract | Confirms biliary origin of ALP elevation |
LFT Patterns in Disease
| Condition | AST/ALT | ALP/GGT | Bilirubin | Albumin | Ammonia |
|---|---|---|---|---|---|
| Acute hepatitis | Markedly ↑ | ↑ (mild) | Both ↑ | Normal | Normal |
| Cirrhosis | Normal/low | Normal | Both ↑ | ↓↓ | ↑↑ |
| Biliary obstruction | Normal | ↑↑ | Direct ↑ | Normal | Normal |
| Space-occupying lesion | Normal | ↑ (isolated) | Normal | Normal | Normal |
| Fulminant hepatic failure | >10,000 IU/L | ↑ | ↑↑ | ↓↓ | ↑↑ (encephalopathy) |
Key: In fulminant failure, AST rises disproportionately over ALT - a diagnostic hallmark. - Henry's Clinical Diagnosis and Management by Laboratory Methods
2. RENAL FUNCTION TESTS
Glomerular Filtration
- Serum creatinine (SCr): Single most common test; unreliable alone (same SCr = very different GFR in elderly vs young)
- Creatinine Clearance (CrCl) - Cockcroft-Gault Formula:
- Men: CrCl = [(140 - Age) × LBW] / [72 × SCr]
- Women: CrCl = 0.85 × (men's formula)
| CrCl | Interpretation |
|---|---|
| 74-160 mL/min | Normal |
| 40-60 mL/min | Mild impairment |
| 15-40 mL/min | Moderate impairment |
| <15 mL/min | Severe (consider dialysis) |
- BUN (Blood Urea Nitrogen): Rises in renal failure; also elevated in dehydration, GI bleed
- eGFR: Estimated GFR from CKD-EPI or MDRD equations; standard for staging CKD
Tubular Function - FENa (Fractional Excretion of Sodium)
FENa = (SCr × UNa) / (SNa × UCr) × 100
| FENa | Interpretation |
|---|---|
| <1% | Prerenal (kidneys retaining Na appropriately) |
| >2% | Intrinsic renal disease (damaged nephrons) |
| >4% | Postrenal (obstructive) |
Urine Analysis
- Proteinuria: Glomerular damage (e.g., nephrotic syndrome)
- Casts: RBC casts = glomerulonephritis; waxy casts = advanced CKD
- Urine osmolality: Concentrating ability (reflects tubular function)
From Roberts and Hedges' Clinical Procedures in Emergency Medicine
3. THYROID FUNCTION TESTS & HORMONES
The Hypothalamic-Pituitary-Thyroid (HPT) Axis
Hypothalamus → TRH (Thyrotropin-releasing hormone)
↓
Pituitary → TSH (Thyroid-stimulating hormone)
↓
Thyroid → T4 (Thyroxine) and T3 (Triiodothyronine)
↓
(T3/T4 feedback inhibit TRH and TSH)
Key Tests
| Test | Normal Role | Clinical Use |
|---|---|---|
| TSH | Pituitary hormone driving thyroid production | Best first-line test for thyroid dysfunction; small changes in T3/T4 cause large changes in TSH |
| Free T4 | Active prohormone | Ordered if TSH is abnormal |
| Free T3 | Most active thyroid hormone | Used in select situations (suspected T3 toxicosis) |
| TRH stimulation test | Hypothalamic hormone | Confirms pituitary hypothyroidism when TSH is equivocal |
| RAIU (Radioactive iodine uptake) | Nuclear medicine scan | ↑ in Graves disease / autonomous adenoma; ↓ in thyroiditis or exogenous hormone |
| Anti-TPO antibodies | Thyroid peroxidase antibody | Hashimoto's thyroiditis |
Interpretation
| TSH | Free T4 | Diagnosis |
|---|---|---|
| ↓ | ↑ | Primary hyperthyroidism |
| ↑ | ↓ | Primary hypothyroidism |
| ↓ | ↓ | Central (pituitary/hypothalamic) hypothyroidism |
| Normal | Normal | Euthyroid |
Important caveat: In critically ill patients ("euthyroid sick syndrome"), T4 and T3 fall while TSH is normal-to-low - do not interpret as hypothyroidism. Routine thyroid testing should be avoided in the ICU unless there is strong clinical suspicion. - Quick Compendium of Clinical Pathology, 5th Ed.
4. ADRENAL FUNCTION TESTS & HORMONES
The adrenal gland has two zones with distinct hormones:
Adrenal Cortex
| Layer | Hormone | Stimulus | Function |
|---|---|---|---|
| Zona glomerulosa | Aldosterone (mineralocorticoid) | Angiotensin II, hyperkalemia | Na+ retention, K+ excretion, BP regulation |
| Zona fasciculata | Cortisol (glucocorticoid) | ACTH | Stress response, gluconeogenesis, immune suppression |
| Zona reticularis | DHEA / androgens | ACTH | Sex hormone precursors |
Adrenal Medulla
| Hormone | Effect |
|---|---|
| Epinephrine (adrenaline) | Tachycardia, bronchodilation, glycogenolysis |
| Norepinephrine | Vasoconstriction, ↑ BP |
Key Diagnostic Tests
For Cushing Syndrome (excess cortisol):
- 24-hour urinary free cortisol - screening test
- Late-night salivary cortisol - screening (cortisol should be lowest at midnight)
- 1 mg overnight dexamethasone suppression test - if cortisol is NOT suppressed to <1.8 mcg/dL, Cushing syndrome is likely
- ACTH level: High ACTH = pituitary (Cushing disease) or ectopic source; Low ACTH = adrenal adenoma/carcinoma
For Adrenal Insufficiency (Addison's disease):
- Morning serum cortisol <3 mcg/dL is diagnostic of insufficiency
- ACTH stimulation test (Synacthen test): Cortisol should rise to >18 mcg/dL; failure = adrenal insufficiency
- Primary (Addison's): high ACTH, low cortisol, low aldosterone
- Secondary (pituitary failure): low ACTH, low cortisol, aldosterone relatively preserved
For Hyperaldosteronism (Conn syndrome):
- Aldosterone-to-Renin Ratio (ARR): Elevated ratio (>30) suggests primary hyperaldosteronism
- Confirmed with saline infusion test
From Tietz Textbook of Laboratory Medicine, 7th Ed. and Goldman-Cecil Medicine
5. PANCREATIC FUNCTION TESTS & HORMONES
Exocrine Tests
| Test | Significance |
|---|---|
| Serum amylase | Rises within hours of acute pancreatitis; returns to normal in 3-5 days |
| Serum lipase | More specific than amylase; stays elevated longer (7-14 days) |
| Fecal elastase-1 | Tests exocrine sufficiency (steatorrhea, malabsorption) |
Endocrine Hormones (Islets of Langerhans)
| Cell | Hormone | Function |
|---|---|---|
| Beta (β) | Insulin | ↓ blood glucose; promotes glycogen synthesis, lipogenesis |
| Alpha (α) | Glucagon | ↑ blood glucose; promotes glycogenolysis, gluconeogenesis |
| Delta (δ) | Somatostatin | Inhibits both insulin and glucagon; inhibits GI motility |
| PP cells | Pancreatic polypeptide | Inhibits pancreatic secretion |
Diabetes Investigations
| Test | Reference Range | Use |
|---|---|---|
| Fasting plasma glucose | <100 mg/dL normal; ≥126 mg/dL = DM | Diagnosis |
| HbA1c | <5.7% normal; ≥6.5% = DM | Diagnosis + 3-month glycaemic control monitoring |
| Oral Glucose Tolerance Test (OGTT) | 2-hr <140 normal; ≥200 = DM | Pregnancy screening (GDM), prediabetes |
| C-peptide | Equimolar with endogenous insulin | Distinguishes Type 1 (low) from Type 2 (normal/high); also detects insulinoma |
| Fasting insulin | Hyperinsulinism, insulin resistance | HOMA-IR calculation |
Quick Summary Table: Organ - Hormone/Marker - Disease Link
| Organ | Key Hormone/Marker | High | Low |
|---|---|---|---|
| Liver | ALT/AST | Hepatitis, necrosis | - |
| Liver | Albumin | - | Cirrhosis, liver failure |
| Kidney | Creatinine | AKI, CKD | Malnutrition, low muscle mass |
| Thyroid | TSH | Hypothyroidism | Hyperthyroidism |
| Thyroid | T3/T4 | Hyperthyroidism | Hypothyroidism |
| Adrenal | Cortisol | Cushing syndrome | Addison disease |
| Adrenal | Aldosterone | Conn syndrome | Adrenal insufficiency |
| Pancreas | Glucose/HbA1c | Diabetes mellitus | Insulinoma |
| Pancreas | Amylase/Lipase | Acute pancreatitis | Exocrine insufficiency |
Sources: Henry's Clinical Diagnosis and Management by Laboratory Methods | Quick Compendium of Clinical Pathology, 5th Ed. | Tietz Textbook of Laboratory Medicine, 7th Ed. | Goldman-Cecil Medicine | Roberts and Hedges' Clinical Procedures in Emergency Medicine
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