The slide says that aldosterone acts in the “distal renal tubule and ascending loop of Henle” ^[1]. The modern physiological description is more precise:

• Aldosterone acts mainly in the late distal nephron and cortical collecting duct.
• In principal cells it increases ENaC, basolateral Na⁺/K⁺-ATPase and K⁺ secretion.
• In α-intercalated cells it promotes H⁺ secretion.
• The result is Na⁺ retention with potential hypokalaemia and metabolic alkalosis.
• Hypokalaemia is not obligatory; many patients with PA are normokalaemic.

The slide also assigns percentages of “mineralocorticoid action” to cortisol and aldosterone ^[1]. Those percentages should not be memorised as a physiological partition. Cortisol can bind the mineralocorticoid receptor, but renal 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) normally converts cortisol to cortisone. Severe cortisol excess can overwhelm this protection; liquorice can inhibit 11β-HSD2.

The slide places the liver, kidney, ACE, adrenal and kidney in order ^[1]. The important distinctions are:

• Renin is an enzyme, released when renal perfusion/NaCl delivery is low or β₁ sympathetic drive is high.
• Angiotensin II causes vasoconstriction and strongly stimulates aldosterone.
• Plasma K⁺ directly regulates aldosterone; ACTH has a smaller, usually transient effect. The slide's “low plasma sodium directly stimulates” line is an oversimplification: sodium depletion acts mainly through reduced effective volume/renal NaCl delivery and the RAAS.
• Upright posture, exercise, sodium depletion, hypovolaemia and diuretics can activate renin/aldosterone; sodium loading and volume expansion suppress them.
• In PA, aldosterone secretion is inappropriately autonomous, so renin is suppressed.

The lecture gives adenoma 60–70%, hyperplasia 20–40%, dexamethasone-suppressible disease 1–2%, and carcinoma as very rare ^[1]. Treat those as slide-era proportions and terminology; current classification is usually unilateral versus bilateral PA because that distinction determines surgery versus medical therapy.

1. Measure plasma aldosterone and renin together, calculate the aldosterone-to-renin ratio (ARR), and check potassium. The 2025 guideline conditionally suggests this for all people with hypertension where implementation is feasible ^[12].
2. Collect in the morning with the patient seated, avoid dietary sodium restriction for the preceding few days, and correct hypokalaemia, because it can lower aldosterone and cause a false negative ^[12].
3. Interpret aldosterone, renin and ARR together using the laboratory's assay and units. A universal “ARR > 30” is unsafe because thresholds are method-dependent.
4. Review interfering medicines. Withdrawal is not an automatic blanket rule: it must be balanced against BP and cardiovascular safety. β-blockers and central α₂-agonists can suppress renin and cause false-positive ratios; ACE inhibitors/ARBs, diuretics, MR antagonists and ENaC blockers can raise renin and cause false negatives. Repeat with a safe minimal- or full-withdrawal strategy when needed ^[12].
5. Aldosterone-suppression testing is useful in selected patients with an intermediate probability who want surgical assessment. It is not required in every screen-positive patient, especially with overt renin-independent aldosterone excess or when the patient will be treated medically ^[12].

The lecture's visual sequence is:

• 08:00 after overnight recumbency: relatively high ACTH drive and low postural angiotensin II drive.
• 12:00 after four hours upright: ACTH has fallen while renin–angiotensin drive has risen.
• An ACTH-responsive adenoma was taught to show a paradoxical fall in aldosterone; bilateral hyperplasia was taught to show an exaggerated rise ^[1].

The percentages above reproduce the slide ^[1], but the postural test is not the contemporary lateralisation test. It is vulnerable to circadian, medication, potassium and subtype effects.

• CT describes adrenal anatomy and helps exclude a large/invasive mass, but a nodule may be nonfunctioning and the aldosterone source may be too small to see.
• For a patient who wants and is suitable for surgery, adrenal venous sampling (AVS) is generally used to distinguish unilateral from bilateral secretion ^[12].
• AVS compares aldosterone after correction for cortisol to confirm successful sampling and assess lateralisation. Cut-offs, cosyntropin use and interpretation are centre/protocol dependent; “> 4:1” is not a universal stand-alone rule.
• A possible exception is a very young patient (for example, < 35 years) with marked PA, spontaneous hypokalaemia and a clear unilateral > 1 cm adenoma, after specialist review ^[12].

• Spironolactone is widely used; anti-androgen/progestogenic adverse effects may favour a more selective MRA such as eplerenone.
• Monitor BP, potassium and renal function; renin response may help dose titration when BP remains uncontrolled ^[12].
• Amiloride blocks ENaC and is an alternative when an MRA is unsuitable, but current guidance generally prefers an MRA for PA-specific therapy ^[12].

The slide labels Cushing disease “pituitary/hypothalamic” ^[1]. Cushing disease specifically means a pituitary corticotroph tumour; a hypothalamic source is not part of the definition. Exogenous glucocorticoid exposure is the commonest overall cause, so obtain a complete oral, inhaled, topical, injected and complementary-product history before biochemical testing ^[13].

Features with relatively greater discriminatory value include:

• wide violaceous striae, thin skin and easy bruising;
• proximal muscle weakness;
• facial plethora;
• unexplained osteoporosis or fractures;
• progressive, clustered features or unusual hypertension/diabetes for age.

Central weight gain, depression, diabetes and hypertension are common but nonspecific. Severe cortisol excess may also cause hypokalaemic alkalosis, infection, thrombosis and psychiatric disturbance.

Recommended initial options ^[13]:

• 24-hour urinary free cortisol, usually at least two collections;
• late-night salivary cortisol, usually two samples;
• 1 mg overnight dexamethasone suppression test (DST); or
• longer 2 mg/48-hour low-dose DST.

For the overnight DST, 1 mg dexamethasone is taken around 23:00–24:00 and serum cortisol is measured around 08:00–09:00. Cortisol > 50 nmol/L (> 1.8 μg/dL) is an abnormal screen, not by itself a complete aetiological diagnosis. Consider adherence, CYP3A4-inducing drugs, oestrogen-related changes in cortisol-binding globulin, alcohol, major depression, severe illness and sleep pattern when interpreting results. The lecture's 09:00 and midnight random plasma cortisol/ACTH pair does not substitute for a validated late-night salivary/serum protocol.

If one appropriate test is abnormal, repeat or use another suitable high-accuracy test under endocrinology supervision. Concordant positive tests justify investigation of the cause; concordant negative tests usually stop the work-up unless cyclic disease or very high clinical suspicion remains ^[13].

1. Measure ACTH: suppressed suggests an adrenal source; detectable/inappropriately normal or high suggests ACTH-dependent disease.
2. For ACTH-independent disease, image the adrenals.
3. For ACTH-dependent disease, obtain pituitary MRI and evaluate for ectopic sources according to the biochemical/imaging pattern.
4. High-dose DST and CRH testing reflect slide-era physiological reasoning: pituitary tumours may suppress with high-dose dexamethasone or respond to CRH, while ectopic sources often do not ^[1]. They are supportive, imperfect tests, not definitive binary classifiers, and routine high-dose DST is absent from many contemporary diagnostic pathways ^[17].
5. Bilateral inferior petrosal sinus sampling (IPSS) is an expert invasive test for distinguishing pituitary from ectopic ACTH when biochemical and imaging findings are inconclusive. It must be done while hypercortisolism is established; it does not diagnose Cushing syndrome itself ^[14]. Basal central:peripheral ACTH > 2 or stimulated > 3 supports a pituitary source, subject to technical adequacy and expert interpretation.

• Treat the source when possible: transsphenoidal surgery for resectable Cushing disease and adrenalectomy for an autonomous adrenal tumour.
• Steroidogenesis inhibitors such as metyrapone, osilodrostat, ketoconazole/levoketoconazole, or other centre-specific agents may control cortisol when surgery is delayed, contraindicated or insufficient; pituitary-directed and glucocorticoid-receptor–blocking drugs have selected roles. Choice depends on speed required, sex/pregnancy potential, liver/QT/electrolyte risk, tumour behaviour, availability and monitoring. Preoperative medical control is individualised, not mandatory in every patient ^[17].
• Optimise hypertension, diabetes, potassium and infection risk; assess and actively manage the markedly increased venous thromboembolism risk.
• After successful removal of a cortisol source, the HPA axis may remain suppressed. Perioperative glucocorticoid strategy and subsequent replacement/taper depend on the operation, biochemical response and local protocol; monitor for adrenal insufficiency.

The early pathway is shared by sympathetic neurons and adrenal medulla. High local cortisol exposure in the adrenal promotes PNMT, so adrenal tumours more often have an adrenergic component, while many sympathetic paragangliomas are predominantly noradrenergic. “Extra-adrenal tumours lack PNMT” is a useful lecture simplification, not an absolute biological rule.

Catecholamines are metabolised by COMT and MAO. Metanephrine and normetanephrine are produced continuously within chromaffin tumours, including between paroxysms; this is why they outperform episodically released catecholamines and VMA as diagnostic markers ^[15].

The slide lists paroxysmal or sustained hypertension, headache, palpitations, diaphoresis, dizziness, anxiety, pallor, weight loss, fever, angina, heart failure, stroke and glucose intolerance ^[1]. The classic exam triad is:

Episodic headache + palpitations + sweating, especially with paroxysmal hypertension.

The old “rule of 10” is obsolete. At least one-third of patients have a disease-causing germline variant, and important associations include RET/MEN2, VHL, NF1, SDHx-related syndromes, TMEM127 and MAX. Current guidance supports shared decision-making and genetic counselling/testing for every patient with proven PPGL, using phenotype, family history and tumour features to guide prioritisation ^[15][18].

Avoid calling a lesion benign or malignant solely from histology. Metastatic PPGL is established by tumour in a site where normal chromaffin tissue is absent; the slide's “up to 36% malignant” is a heterogeneous historical figure, not an individual prediction. All PPGLs have metastatic potential and require risk-aware long-term follow-up. ^[15][18]

• First-line testing is plasma free metanephrines or 24-hour urinary fractionated metanephrines, not urinary VMA or catecholamines alone ^[15].
• If plasma testing is chosen, a fully supine patient should rest for at least 30 minutes and be interpreted against supine reference intervals; otherwise false positives increase ^[15].
• LC-MS/MS or another validated liquid-chromatography method is preferred where available.
• Stress, illness, obstructive sleep apnoea, posture and several drugs can interfere. Dietary restrictions depend on the analyte and local method; the lecture's blanket banana/chocolate/coffee/vanilla list should not be applied uncritically.
• Borderline results require pre-test probability, sampling quality and medication review before imaging or provocative testing.

Proceed to imaging after clear biochemical evidence in most secretory cases. CT is usually first-line; MRI is useful when radiation should be limited, for head/neck paraganglioma, contrast allergy or selected metastatic disease ^[15].

MIBG is taken up through catecholamine transport machinery, but it is not a routine scan for every localised tumour. Its major roles include selected high-risk/multifocal/recurrent or metastatic disease and determining suitability for therapeutic ¹³¹I-MIBG; PET tracers may be preferable depending on genotype, site, biochemical phenotype and treatment question ^[15][18].

1. Prepare every hormonally functional PPGL in a specialist multidisciplinary team, commonly with 7–14 days of α-adrenergic blockade.
2. Restore salt and fluid cautiously after α-blockade to reverse catecholamine-associated volume contraction; modify in heart or kidney failure.
3. Add a β-blocker only after adequate α-blockade if tachycardia requires it.
4. β-blockade first can remove β₂ vasodilation while α₁ vasoconstriction remains, provoking a severe hypertensive crisis.
5. During and after resection, anticipate haemodynamic swings; after removal monitor especially for hypotension and rebound hypoglycaemia ^[15].

The lecture gives a phenoxybenzamine/propranolol regimen ^[1]. Exact agent, dose and target are local specialist decisions; the durable exam principle is α first, β only if needed afterwards.

The open-surgery slide surrounds the operative approaches with five decision factors ^[1]:

• tumour size;
• tumour location and anatomic relationships;
• suspected pathology/invasion;
• need for a concomitant procedure; and
• surgical expertise.

Open approaches shown are anterior transabdominal, lateral extraperitoneal and posterior lumbar. Minimally invasive adrenalectomy is recommended for most adrenal phaeochromocytomas and usually reduces pain and hospital stay. Open surgery is favoured for a large (the guideline gives > 6 cm as an example) or invasive phaeochromocytoma when en-bloc resection and avoidance of tumour rupture are priorities; paraganglioma approach depends strongly on site and invasion. Size informs judgement but is not a universal stand-alone cut-off for every adrenal pathology. ^[15]

• PA biochemistry: inappropriately high aldosterone with suppressed renin; interpret ARR with assay, potassium, posture, sodium and drugs.
• PA lateralisation: CT is anatomy; AVS is usually functional lateralisation before surgery.
• Cushing sequence: establish endogenous hypercortisolism first, then ACTH, then source localisation.
• Cushing disease: pituitary ACTH-secreting tumour, not a synonym for all Cushing syndrome.
• PPGL triad: episodic headache, palpitations and diaphoresis with paroxysmal or sustained hypertension.
• PPGL pharmacology: α-blockade precedes any β-blockade needed for tachycardia.