What are the symptoms of adrenal disorders such as adrenal insufficiency, Cushing's syndrome, primary hyperaldosteronism, and pheochromocytoma?

Symptoms of Adrenal Disorders

Adrenal Insufficiency (Addison's Disease)

The most common presenting symptoms of adrenal insufficiency are fatigue (50-95% of cases), nausea and vomiting (20-62%), and weight loss with anorexia (43-73%), often accompanied by hypotension and salt craving in primary disease. 1

Primary Adrenal Insufficiency Symptoms

• Fatigue and weakness are nearly universal, affecting 50-95% of patients, with proximal muscle weakness being particularly prominent 2, 1
• Gastrointestinal symptoms including nausea, vomiting, abdominal pain, and diarrhea occur in 20-62% of cases 2, 1
• Weight loss and anorexia develop in 43-73% of patients 1
• Hyperpigmentation of skin and mucous membranes is a distinguishing feature of primary adrenal insufficiency due to elevated ACTH, with uneven distribution 2, 3
• Salt craving is a specific clinical clue for primary adrenal insufficiency due to aldosterone deficiency 3
• Orthostatic hypotension and dizziness reflect mineralocorticoid deficiency 3
• Psychiatric disturbances including depression are common 4

Secondary Adrenal Insufficiency Symptoms

• Normal skin color distinguishes secondary from primary disease, as ACTH levels are low 3
• Fatigue, weakness, and weight loss occur similarly to primary disease 1, 5
• Hypotension may be present but is typically less severe than in primary disease 5
• No salt craving as mineralocorticoid function remains intact 3

Acute Adrenal Crisis Symptoms

• Severe hypotension and shock with dehydration are hallmark features requiring immediate recognition 3
• Severe vomiting and/or diarrhea often precipitate the crisis 3
• Altered mental status including confusion, loss of consciousness, and coma 3
• Severe weakness and muscle cramps with abdominal pain and peritoneal irritation 3
• Unexplained collapse should immediately raise suspicion for adrenal crisis 2

Laboratory Manifestations

• Hyponatremia is present in 90% of newly diagnosed cases 2, 3
• Hyperkalemia occurs in only ~50% of cases, so its absence does not exclude the diagnosis 2, 3
• Hypoglycemia may occur, particularly in children 2
• Mild hypercalcemia is present in 10-20% of patients at presentation 2

---

Cushing Syndrome (Hypercortisolism)

Cushing syndrome presents with weight gain, proximal muscle weakness, hypertension, and characteristic physical changes including centripetal obesity, purple striae, and buffalo hump. 2

Classic Physical Features

• Weight gain with centripetal obesity and redistribution of fat to trunk and face 2
• Purple striae on abdomen, thighs, and breasts 2
• Buffalo hump and supraclavicular fat pad enlargement 2
• Moon facies with facial plethora 2
• Proximal muscle weakness affecting primarily hip and shoulder girdle muscles 2
• Hirsutism and acne from androgen excess 2

Metabolic and Cardiovascular Symptoms

• Hypertension is common and may be severe 2
• Hyperglycemia and diabetes mellitus develop frequently 2
• Hypokalemia from mineralocorticoid effects of excess cortisol 2

Neuropsychiatric Symptoms

• Psychiatric disturbances including depression, anxiety, and emotional lability 2
• Cognitive impairment may occur in severe cases 4

Other Manifestations

• Easy bruising and thin skin 2
• Osteoporosis with increased fracture risk 2
• Menstrual irregularities in women 2

---

Primary Hyperaldosteronism (Conn's Syndrome)

Primary hyperaldosteronism typically presents with hypertension, often accompanied by hypokalemia and muscle weakness. 2

Cardinal Symptoms

• Hypertension is the primary manifestation, often resistant to standard antihypertensive therapy 2, 6
• Muscle weakness from hypokalemia 2
• Hypokalemia causes potassium wasting, though not all patients are hypokalemic 2

Additional Features

• Fatigue related to electrolyte disturbances 2
• Polyuria and polydipsia from hypokalemia-induced nephrogenic diabetes insipidus 2
• Muscle cramps from electrolyte abnormalities 2
• Headaches from hypertension 2

---

Pheochromocytoma

Pheochromocytoma presents with episodic or sustained hypertension accompanied by the classic triad of headaches, palpitations, and diaphoresis. 2

Classic Triad

• Headaches are severe and episodic 2
• Palpitations with tachycardia 2
• Profuse sweating (diaphoresis) 2

Additional Symptoms

• Hypertension may be paroxysmal or sustained 2
• Pallor during episodes 2
• Tremor and anxiety 2
• Chest or abdominal pain 2
• Nausea 2

Important Clinical Pitfall

• Screening should be performed in patients with adrenal incidentalomas displaying >10 HU on non-contrast CT or those with signs/symptoms of catecholamine excess, but can be omitted in patients with unequivocal adrenocortical adenomas (<10 HU) without adrenergic symptoms. 2

---

Adrenocortical Carcinoma

Approximately 60% of adrenocortical carcinomas present with symptoms of hormone excess (Cushing syndrome, virilization, or feminization), while hormonally inactive tumors cause symptoms from tumor burden. 2

Hormone-Secreting Tumors

• Cushing syndrome symptoms as described above when cortisol-secreting 2
• Virilization in women including hirsutism, deepening of voice, and oligo/amenorrhea from androgen excess 2
• Feminization in men with gynecomastia and testicular atrophy from estrogen excess 2
• Hypertension from aldosterone or cortisol excess 2

Non-Functional Tumors

• Abdominal pain from mass effect 2
• Back pain 2
• Early satiety 2
• Weight loss 2

---

Critical Diagnostic Considerations

• Treatment of suspected acute adrenal insufficiency should never be delayed by diagnostic procedures—if clinical suspicion is high, administer 100 mg IV hydrocortisone immediately plus 0.9% saline infusion. 2, 3, 1
• The absence of hyperkalemia cannot rule out adrenal insufficiency, as it is present in only ~50% of cases at diagnosis. 2, 3
• Hyponatremia with hypo-osmolality requires exclusion of adrenal insufficiency before diagnosing SIADH, as both conditions present with nearly identical laboratory findings. 3