NLE Endocrine & Metabolic Nursing — Adrenal DisordersDetailed Explanation

Adrenal Physiology and the HPA Axis

Before understanding adrenal disease, you must understand what the healthy adrenal gland does. The adrenal CORTEX has three zones: the zona glomerulosa (makes aldosterone), the zona fasciculata (makes cortisol), and the zona reticularis (makes androgens). The adrenal MEDULLA makes catecholamines — epinephrine (adrenaline) and norepinephrine. CORTISOL is regulated by the Hypothalamic-Pituitary-Adrenal (HPA) axis in a negative feedback loop. When you are stressed, the hypothalamus releases CRH (corticotropin-releasing hormone) → the pituitary releases ACTH (adrenocorticotropic hormone) → the adrenal cortex makes cortisol. When cortisol is high enough, it feeds back and tells the hypothalamus and pituitary to stop. This is called NEGATIVE FEEDBACK. Cortisol: raises blood glucose (gluconeogenesis), suppresses inflammation/immunity, helps the body handle stress, breaks down protein and fat. ALDOSTERONE (mineralocorticoid): retains sodium and water (raises BP), excretes potassium. Think of the mnemonic: 'Aldosterone = Saves Na, Loses K.' This is the Renin-Angiotensin-Aldosterone System (RAAS) at work. CATECHOLAMINES (epinephrine and norepinephrine): released in the 'fight-or-flight' response — raises heart rate, BP, and blood glucose. Why does ACTH cause hyperpigmentation? Because ACTH shares its precursor molecule (POMC) with MSH (melanocyte-stimulating hormone). When ACTH is very high (as in primary Addison's disease), MSH is also elevated, causing excess melanin — the bronze/tan discoloration that is a classic sign of Addison's. This does NOT occur in secondary adrenal insufficiency because ACTH is low there.

Cushing's Syndrome — Excess Cortisol

Cushing's syndrome is the clinical condition caused by CHRONIC EXCESS of glucocorticoids (cortisol). The most common cause in the Philippines and worldwide is EXOGENOUS — patients taking corticosteroids (like prednisone or dexamethasone) long-term for asthma, lupus, rheumatoid arthritis, kidney disease, or transplant immunosuppression. Among endogenous causes, the most common is a pituitary ACTH-secreting adenoma — called Cushing's DISEASE (note: 'Cushing's disease' specifically refers to the pituitary cause; 'Cushing's syndrome' is the broader clinical picture from any cause). Other endogenous causes include adrenal tumors and ectopic ACTH production (e.g., from small-cell lung cancer). PATHOPHYSIOLOGY IN SIMPLE TERMS: Excess cortisol → raises blood glucose (steroid diabetes), causes fat redistribution to the trunk and face (while extremities stay thin), breaks down muscle protein (muscle wasting and weakness), suppresses the immune system (infection risk with masked signs), causes fluid and sodium retention (high BP), and causes potassium loss (hypokalemia). Excess cortisol also weakens bone by inhibiting osteoblasts (osteoporosis) and thins the skin (fragile capillaries → easy bruising and purple stretch marks called STRIAE). CLASSIC PHYSICAL SIGNS: - MOON FACE: round, full face from fat redistribution - BUFFALO HUMP: fat deposit at the back of the neck/upper back - TRUNCAL OBESITY with THIN EXTREMITIES (spindle limbs) - PURPLE STRIAE: stretch marks on abdomen, thighs — purple/violet in color (versus the white/silver striae of normal weight gain) - EASY BRUISING and thin, fragile skin - Poor wound healing - Muscle weakness (especially proximal — trouble climbing stairs, rising from a chair) LABORATORY FINDINGS: - Hyperglycemia (high blood glucose) - Hypertension (high BP) with fluid retention - Hypokalemia (low K+) — cortisol has mild mineralocorticoid activity - Elevated serum cortisol with LOSS OF DIURNAL VARIATION (normally cortisol peaks in the morning; in Cushing's it stays elevated all day) - Elevated 24-hour urinary free cortisol - Dexamethasone suppression test: in normal people, giving dexamethasone (synthetic steroid) suppresses ACTH and cortisol. In Cushing's, cortisol does NOT suppress appropriately. NURSING MANAGEMENT — organized by nursing process: ASSESSMENT: vital signs (especially BP), blood glucose, weight, I&O, skin integrity, signs of infection (remember: immune suppression masks fever and other signs — a patient with Cushing's can have a serious infection with a low-grade temperature only). NURSING DIAGNOSES (NANDA): - Risk for Infection r/t immunosuppression - Disturbed Body Image r/t physical changes (moon face, obesity, striae) - Risk for Injury (falls, fractures) r/t osteoporosis and muscle weakness - Excess Fluid Volume r/t sodium and water retention - Imbalanced Nutrition: More Than Body Requirements r/t altered metabolism INTERVENTIONS: - Protect from infection: private room if possible, strict hand hygiene, avoid contact with sick individuals, monitor for SUBTLE signs of infection (may not have fever/redness clearly) - Protect from injury: fall precautions, gentle handling (fragile skin and bones), no rough linen changes, use soft toothbrush - Monitor: blood glucose QID (hyperglycemia management), BP, electrolytes (especially K+), weight, I&O - DIET: LOW SODIUM (reduce fluid retention and hypertension), HIGH PROTEIN (counter muscle wasting), HIGH POTASSIUM foods (bananas, orange juice, potatoes — to replace K+ losses), CALCIUM and VITAMIN D (bone protection) - For exogenous Cushing's: never stop steroids abruptly — taper gradually - Surgical treatment (adrenalectomy or pituitary surgery): see post-op care below - Emotional support for body image disturbances — emphasize that many changes are reversible when the cause is treated

Addison's Disease — Adrenal Insufficiency

Addison's disease (primary adrenal insufficiency) is the condition where the adrenal CORTEX is destroyed or severely damaged, resulting in deficiency of BOTH cortisol AND aldosterone. The most common cause worldwide and in the Philippines is AUTOIMMUNE destruction (the body's immune system attacks the adrenal cortex). Other causes include tuberculosis (TB — important in the Philippine context where TB is endemic), fungal infections, metastatic cancer, and adrenal hemorrhage. SECONDARY adrenal insufficiency occurs when there is not enough ACTH to stimulate the adrenal cortex. The most common cause is ABRUPT WITHDRAWAL of long-term steroid therapy (the pituitary has been suppressed and cannot suddenly produce ACTH). Other causes include pituitary tumors or damage. In secondary insufficiency: cortisol is low, but aldosterone is usually near-normal (because aldosterone is primarily regulated by RAAS, not ACTH), and there is NO hyperpigmentation (ACTH is low). PATHOPHYSIOLOGY — think in terms of what is MISSING: 1. LOW CORTISOL → hypoglycemia (cortisol raises glucose; without it, glucose falls), weakness, fatigue, inability to respond to stress 2. LOW ALDOSTERONE → cannot retain Na and water → hyponatremia, hypovolemia, hypotension; cannot excrete K+ → hyperkalemia 3. LOW ANDROGENS → decreased libido, body hair loss (especially in women) CLINICAL MANIFESTATIONS (remember: the MIRROR IMAGE of Cushing's): - HYPOTENSION (sometimes orthostatic) — low aldosterone → fluid loss - HYPONATREMIA — sodium not retained - HYPERKALEMIA — potassium not excreted - HYPOGLYCEMIA — cortisol not raising glucose - Weight LOSS, anorexia, nausea, vomiting, diarrhea (GI symptoms common) - Profound fatigue, muscle weakness - HYPERPIGMENTATION (bronze/tan skin) — in PRIMARY Addison's only; due to very high ACTH stimulating MSH and melanin. Look for it in sun-exposed areas AND areas not normally exposed: inside the mouth (buccal mucosa), creases of the hands, scars, areolae - SALT CRAVING — the body's attempt to compensate for sodium loss DIAGNOSTICS: - Morning serum cortisol: LOW (drawn at 8 AM when cortisol should be highest) - ACTH stimulation test (Cosyntropin test): synthetic ACTH is given; in healthy people cortisol RISES; in primary Addison's, cortisol FAILS TO RISE (adrenal cortex is destroyed and cannot respond) - Serum ACTH level: HIGH in primary (pituitary works, keeps trying), LOW in secondary (pituitary also suppressed) - Electrolytes: Low Na+, High K+, Low glucose NURSING DIAGNOSES (NANDA): - Deficient Fluid Volume r/t aldosterone deficiency - Risk for Electrolyte Imbalance (hyperkalemia, hyponatremia) - Fatigue r/t cortisol and aldosterone deficiency - Deficient Knowledge r/t lifelong steroid replacement needs and sick-day rules - Risk for Injury r/t hypotension and hypoglycemia PHARMACOLOGY AND TREATMENT: - GLUCOCORTICOID REPLACEMENT: Hydrocortisone (first choice; has some mineralocorticoid activity) OR Prednisone. Usually given in the morning (mimics natural diurnal pattern) WITH FOOD (reduces GI irritation and peptic ulcer risk) - MINERALOCORTICOID REPLACEMENT: Fludrocortisone (Florinef) — replaces aldosterone; helps retain Na and excrete K+ - SICK-DAY RULES — critical patient teaching: During ANY physical stress (fever, infection, injury, surgery, vomiting, extreme exercise), the normal adrenal gland would triple its cortisol output. A patient with Addison's must MANUALLY INCREASE the steroid dose (usually 2-3× the daily dose). Failure to do this can precipitate adrenal crisis. CRITICAL PATIENT TEACHING (life-saving — NLE favorite): 1. NEVER stop steroid medications abruptly 2. INCREASE steroid dose during stress, illness, fever, surgery (follow physician's sick-day instructions) 3. Wear a MEDICAL ALERT BRACELET at all times (so emergency responders can identify and treat accordingly) 4. Carry an EMERGENCY INJECTABLE HYDROCORTISONE KIT (self-injection kit for crisis situations when oral medication cannot be taken) 5. Report to the emergency room or call a physician if experiencing vomiting, diarrhea, high fever, or if unable to take oral medications 6. ADEQUATE SODIUM INTAKE — do not restrict salt; increase during hot weather, heavy exercise, or GI fluid losses 7. Regular follow-up for cortisol and electrolyte monitoring

Addisonian (Adrenal) Crisis — Emergency Management

Adrenal crisis (Addisonian crisis) is an ACUTE, LIFE-THREATENING emergency that occurs when the body suddenly cannot produce enough cortisol to meet the demands of physiological stress. It is the most dangerous complication of adrenal insufficiency and requires IMMEDIATE medical intervention. PRECIPITATING CAUSES (triggers): - Infection or sepsis (the most common trigger) - Physical trauma or surgery - Sudden withdrawal of corticosteroid therapy (patient stopped prednisone cold turkey) - A patient with Addison's who cannot take oral medications (vomiting, diarrhea) - Adrenal hemorrhage (bilateral — e.g., Waterhouse-Friderichsen syndrome in meningococcal sepsis) - Post-adrenalectomy (especially bilateral) without adequate IV steroid coverage PATHOPHYSIOLOGY: Without cortisol, the body cannot maintain blood pressure (cortisol supports vasomotor tone), cannot maintain blood glucose, and cannot modulate the immune/inflammatory response. Without aldosterone, sodium and water are lost (further drops BP) and potassium accumulates. The result: vascular collapse/shock. CLINICAL MANIFESTATIONS — THINK: Profound HYPOTENSION + HYPONATREMIA + HYPERKALEMIA + HYPOGLYCEMIA: - SEVERE HYPOTENSION → cardiovascular shock (the most dangerous sign) - High fever, severe weakness, extreme fatigue - Severe nausea, vomiting, abdominal pain (can mimic acute abdomen) - Severe dehydration - Confusion, altered mental status - HYPERKALEMIA → cardiac arrhythmias (can be fatal) - HYPOGLYCEMIA → confusion, seizures - HYPONATREMIA PRIORITY MANAGEMENT — ORDERED SEQUENCE (NLE CRITICAL): 1. IMMEDIATE IV HYDROCORTISONE (Solu-Cortef) — 100 mg IV bolus, then continuous infusion or q6-8h. This is THE priority medication. Restores cortisol and has mineralocorticoid effect at high doses. 2. IV FLUIDS — Normal Saline (0.9% NaCl) with Dextrose (D5NSS). This corrects: hypovolemia/hypotension (NSS), hyponatremia (saline), and hypoglycemia (dextrose). Large volumes rapidly administered. 3. MONITOR AND TREAT HYPERKALEMIA — cardiac monitoring (ECG), potassium-lowering measures if severe (hydrocortisone itself helps by increasing K+ excretion) 4. IDENTIFY AND TREAT THE TRIGGER — blood cultures, antibiotics for infection; identify and address the precipitating cause 5. CONTINUOUS MONITORING — vital signs Q15 minutes initially, blood glucose, electrolytes, cardiac rhythm 6. MINIMIZE STRESS — keep patient calm, cluster care, reduce stimuli 7. Position: Trendelenburg or supine with legs elevated (for hypotension/shock) FOLLOW-UP: Once stabilized, gradually taper IV hydrocortisone and transition to oral replacement. Educate patient on crisis prevention (sick-day rules, never stopping steroids, emergency kit). MEMORY DEVICE FOR CRISIS LABS: In Addisonian crisis — think the OPPOSITE of Cushing's: - Cushing's: HIGH glucose, HIGH BP, LOW K+ - Addisonian crisis: LOW glucose, LOW BP, HIGH K+

Pheochromocytoma — Catecholamine-Secreting Tumor

Pheochromocytoma is a tumor — usually BENIGN — of the adrenal MEDULLA that secretes EXCESS CATECHOLAMINES (epinephrine and norepinephrine). Unlike the cortical disorders, this one is about too much fight-or-flight hormones. Imagine the 'fight-or-flight' response stuck in overdrive. The tumor can secrete catecholamines constantly or in sudden episodic bursts (paroxysms), triggered by physical pressure, certain foods (aged cheese, red wine), or medications. PHEOCHROMOCYTOMA CLASSIC TRIAD (memorize this — extremely NLE-tested): 1. Severe HEADACHE (pounding, sudden) 2. PALPITATIONS / Tachycardia 3. Profuse DIAPHORESIS (sweating) Additional manifestations: - SEVERE HYPERTENSION — may be persistent OR paroxysmal (episodic, sudden spikes that can be dangerously high). This is the most dangerous feature — can cause stroke, myocardial infarction, or hypertensive encephalopathy - Tremor, anxiety, sense of 'impending doom' - Pallor (vasoconstriction from norepinephrine) or flushing - HYPERGLYCEMIA — catecholamines stimulate glycogenolysis and inhibit insulin - Weight loss DIAGNOSTICS: - 24-HOUR URINE for METANEPHRINES and VANILLYLMANDELIC ACID (VMA) — the catecholamine metabolites. This is the MOST IMPORTANT diagnostic test — NLE favorite. - Plasma free metanephrines (very sensitive) - CT or MRI to localize the tumor - SPECIAL INSTRUCTIONS for 24-hour VMA urine collection: Avoid caffeine (coffee, tea, cola), avoid certain foods (bananas, vanilla, chocolate, aged cheese), and avoid certain medications as ordered (some antihypertensives can affect results). Collect ALL urine for 24 hours in a special container with preservative, stored in the refrigerator. NURSING MANAGEMENT: PRE-OPERATIVE (most critical nursing phase): - CONTROL BLOOD PRESSURE — this is the priority before surgery - ALPHA-BLOCKERS FIRST (phenoxybenzamine, prazosin): block alpha-adrenergic receptors (vasoconstriction) → reduces BP. Must be given BEFORE beta-blockers. - BETA-BLOCKERS SECOND (if needed, for tachycardia): only AFTER adequate alpha blockade is established - CRITICAL SAFETY RULE: NEVER give BETA-BLOCKERS ALONE or FIRST in pheochromocytoma. Reason: Catecholamines act on both alpha (vasoconstriction) and beta (vasodilation in some vessels) receptors. Blocking beta receptors ALONE leaves alpha receptors unopposed → MASSIVE VASOCONSTRICTION → HYPERTENSIVE CRISIS. This is a potentially fatal medication error. - DO NOT PALPATE THE ABDOMEN: Physical pressure on the tumor triggers a massive catecholamine release → hypertensive crisis. Tell patients, doctors, and all staff — NO abdominal palpation. - Provide a CALM, LOW-STRESS ENVIRONMENT: Emotional stress, noise, and anxiety can trigger catecholamine release. - Monitor blood pressure very frequently (Q1-4h or continuous arterial line in ICU) - HIGH-CALORIE DIET: due to hypermetabolic state and weight loss - Identify and avoid TRIGGERS: no heavy lifting, no straining, no pressure on abdomen INTRAOPERATIVE: - Blood pressure can swing wildly: extreme hypertension when the tumor is manipulated, extreme HYPOTENSION when it is removed (sudden catecholamine drop) - Anesthesia team must be prepared with vasoactive medications POST-OPERATIVE: - HYPOTENSION is the major concern — once the tumor is removed, catecholamine levels drop sharply - If BILATERAL adrenalectomy: adrenal insufficiency and need for lifelong steroid replacement - Monitor blood pressure, blood glucose, and fluid status closely - Check that serum/urine catecholamines and metanephrines NORMALIZE post-operatively (confirms complete tumor removal) - Recurrence monitoring: some pheochromocytomas are bilateral or associated with familial syndromes (MEN2, von Hippel-Lindau)

Primary Hyperaldosteronism (Conn's Syndrome)

Primary hyperaldosteronism (Conn's syndrome) occurs when the adrenal cortex produces EXCESS ALDOSTERONE — usually from a benign aldosterone-secreting adenoma (Conn's adenoma), or from bilateral adrenal hyperplasia. The key pathophysiology: excess aldosterone acts on the kidneys to maximally retain sodium and water, and maximally excrete potassium. CLINICAL MANIFESTATIONS — all explained by excess aldosterone: - HYPERTENSION: Often SEVERE and RESISTANT to standard antihypertensives (because the cause is hormonal, not simply blood vessel dysfunction). This is actually a common presentation — think Conn's in any young-to-middle-aged patient with resistant hypertension. - HYPOKALEMIA (LOW K+): Potassium is continuously excreted. This causes: muscle weakness and cramps, fatigue, POLYURIA and polydipsia (low K+ interferes with kidney's ability to concentrate urine), cardiac arrhythmias (dangerous), and PARESTHESIAS (tingling, numbness) - METABOLIC ALKALOSIS: Potassium excretion is linked to hydrogen ion excretion — loss of H+ causes alkalosis - NOTABLY ABSENT: Despite sodium and water retention causing hypertension, significant EDEMA is usually ABSENT in Conn's syndrome — because sodium retention is balanced by an 'escape mechanism' in the kidneys. This is a classic NLE trick: hypertension WITHOUT edema in the setting of sodium retention. - Headache (from hypertension) DIAGNOSTICS: - Aldosterone-to-Renin Ratio (ARR): The screening test. In primary hyperaldosteronism, aldosterone is HIGH and renin is LOW (because the autonomous aldosterone production suppresses renin through feedback). A high ARR is suggestive. - Serum electrolytes: Hypokalemia, hypernatremia - 24-hour urine aldosterone - CT/MRI of adrenal glands to identify adenoma NURSING MANAGEMENT AND TREATMENT: - POTASSIUM-SPARING DIURETIC: SPIRONOLACTONE (Aldactone) — blocks the aldosterone receptor in the kidney. This reduces sodium retention and reduces potassium loss. It is the MEDICAL TREATMENT of choice especially for bilateral hyperplasia. - CORRECT HYPOKALEMIA: Oral or IV potassium replacement; high-potassium diet (bananas, potatoes, orange juice) - SURGICAL: ADRENALECTOMY if a single adenoma (Conn's adenoma) is identified — the surgical cure for the hormonal excess - MONITOR: Blood pressure (target normotension), serum potassium, renal function - Educate on sodium restriction and antihypertensive medication compliance

Corticosteroid Therapy — Cross-Cutting Safety Points

Corticosteroid therapy is one of the most commonly used and most frequently mismanaged drug classes in Philippine clinical practice. Because it is used for so many conditions — autoimmune disease, organ transplant, severe asthma, nephrotic syndrome, inflammatory conditions — nurses encounter it in almost every clinical area. The NLE tests corticosteroid safety repeatedly because it bridges pharmacology, pathophysiology, and patient teaching. COMMON CORTICOSTEROIDS: - Prednisone (oral) — most common long-term - Hydrocortisone (IV — Solu-Cortef) — used for acute situations and adrenal crisis - Dexamethasone — used for brain edema, croup, and the dexamethasone suppression test - Methylprednisolone (Solu-Medrol) — IV for severe inflammatory conditions - Fludrocortisone (Florinef) — mineralocorticoid replacement in Addison's KEY SAFETY TEACHING POINTS: 1. NEVER STOP ABRUPTLY — ALWAYS TAPER Reason: Long-term steroid use suppresses the HPA axis. Abrupt withdrawal → no cortisol → adrenal crisis. A taper schedule (gradually decreasing dose over weeks to months) gives the axis time to recover. 2. TAKE WITH FOOD Reason: Corticosteroids irritate the gastric mucosa and can cause peptic ulcer disease. Taking with food or milk reduces GI irritation. A proton pump inhibitor (omeprazole) or H2 blocker (ranitidine) may also be prescribed. 3. TAKE IN THE MORNING Reason: Mimics the natural cortisol diurnal peak (highest in the morning). Taking it at night disrupts sleep (corticosteroids are stimulating) and does not follow the natural pattern. For twice-daily dosing: larger dose in morning, smaller dose at noon/early afternoon. 4. STRESS DOSING (SICK-DAY RULES) During physical stress (illness, fever, injury, surgery, dental procedures), the dose must be INCREASED (usually 2-3×) because the adrenal glands cannot make extra cortisol. Failure to increase the dose can cause relative adrenal insufficiency. 5. MONITOR FOR CUSHING'S-LIKE EFFECTS (SIDE EFFECTS OF LONG-TERM USE): - HYPERGLYCEMIA — monitor blood glucose; may need insulin - HYPERTENSION and fluid retention — monitor BP and weight daily - HYPOKALEMIA — potassium-rich diet; monitor K+ levels - OSTEOPOROSIS — calcium and Vitamin D supplementation; weight-bearing exercises - DELAYED WOUND HEALING — careful wound care, monitor for infection - IMMUNOSUPPRESSION — INFECTION RISK with MASKED SIGNS (low-grade fever may indicate serious infection); avoid crowds and sick contacts; monitor WBC - MOOD CHANGES/PSYCHOSIS — steroid-induced psychiatric effects; monitor mental status - PEPTIC ULCER DISEASE — take with food, use GI protectants - CUSHING'S APPEARANCE (moon face, buffalo hump) — warn patient these are expected side effects, reversible on tapering 6. MEDICAL ALERT BRACELET Patients on chronic steroid therapy should wear a medical alert bracelet so that emergency providers know to give stress-dose steroids during emergencies. 7. MEDICATION ADHERENCE NEVER skip doses; carry medications while traveling; have extra supply available.

The clinical picture clearly matches iatrogenic Cushing's syndrome — all classic signs are present (moon face, buffalo hump, truncal obesity, purple striae) with the expected lab pattern (hypokalemia, hyperglycemia, hypertension, hypernatremia). Nursing priorities follow Maslow's hierarchy: physiological threats (hypokalemia → cardiac arrhythmia) are addressed before psychosocial concerns (body image). The most critical nursing safety point: NEVER stop prednisone abruptly, as this can cause acute adrenal crisis. Dietary interventions directly counter the metabolic effects of excess cortisol.

This is a classic Addisonian crisis scenario triggered by TWO factors: non-compliance with steroid medications (most critical) AND physiological stress from vomiting/diarrhea illness (which requires increased — not normal — cortisol dosing). The K+ of 6.7 with peaked T waves represents a life-threatening cardiac emergency — the cardiac monitor is first to allow early detection of fatal arrhythmia. IV hydrocortisone is the definitive treatment addressing the root cause. D5NSS corrects three deficits simultaneously. This scenario also illustrates the critical teaching point about sick-day rules: even if Mr. Reyes had been taking his medications, the illness would still have required INCREASED dosing — non-compliance plus illness combined to create a perfect storm for crisis.

This problem tests both pharmacological knowledge (alpha before beta — a NLE classic) and clinical nursing judgment (safety precautions for pheochromocytoma). The NLE Board of Nursing frequently presents pheochromocytoma scenarios that test whether the candidate knows the dangerous consequence of giving beta-blockers alone. Under RA 9173, clarifying unsafe medication orders is both a right and a professional duty of the nurse.

Reading electrolytes alone can tell you which disorder you are dealing with — a key NLE exam strategy. Cushing's = HYPER-glycemia, HYPER-tension, HYPO-kalemia. Addison's = HYPO-glycemia, HYPO-tension, HYPER-kalemia. The skin changes also differentiate: purple striae point to Cushing's; bronze hyperpigmentation points to primary Addison's. The ACTH stimulation test is the definitive diagnostic tool — in Addison's, the adrenal cortex cannot respond because it is destroyed.