What is adrenal insufficiency and its symptoms in a patient with potential hypothyroidism, fatigue, weight gain, and difficulty sleeping, possibly with a history of recent steroid use?

What is Adrenal Insufficiency and Its Symptoms

Adrenal insufficiency is a life-threatening condition caused by inadequate production of cortisol (and sometimes aldosterone), presenting with fatigue, nausea, weight loss, and hypotension—symptoms that overlap significantly with hypothyroidism and are particularly important to recognize in patients with recent steroid use. 1, 2

Definition and Types

Adrenal insufficiency represents a syndrome of cortisol deficiency that occurs in three forms 2, 3:

• Primary adrenal insufficiency (Addison's disease): Destruction of the adrenal gland itself, causing deficiency of both cortisol and aldosterone, with autoimmunity accounting for approximately 85% of cases in Western populations 1
• Secondary adrenal insufficiency: Pituitary disorders causing ACTH deficiency, resulting in cortisol deficiency but preserved aldosterone production 1
• Tertiary/iatrogenic adrenal insufficiency: The most common form, caused by suppression of the hypothalamic-pituitary-adrenal axis from exogenous glucocorticoid therapy—affecting approximately 7 in 1000 people on long-term oral corticosteroids 1, 4

In your clinical context with recent steroid use, tertiary adrenal insufficiency is the most likely diagnosis and must be actively excluded. 1, 4

Cardinal Symptoms

Most Common Presenting Features

• Fatigue and weakness: Occurs in 50-95% of patients, often the most debilitating symptom 2, 5
• Nausea and vomiting: Present in 20-62% of cases, frequently accompanied by poor appetite 5, 2
• Weight loss and anorexia: Affects 43-73% of patients 2
• Postural hypotension: A hallmark feature reflecting insufficient mineralocorticoid therapy in primary adrenal insufficiency or inadequate cortisol replacement 5

Additional Clinical Features

• Morning nausea and lack of appetite: Particularly common symptoms that may indicate glucocorticoid under-replacement 4, 5
• Abdominal pain: Can be periumbilical and may mimic acute abdomen 4, 5
• Muscle pain or cramps: Frequently reported, often accompanied by generalized weakness 5
• Hyperpigmentation: Occurs ONLY in primary adrenal insufficiency due to elevated ACTH stimulating melanocytes; absent in secondary/tertiary forms 4, 5
• Salt craving: Specific to primary adrenal insufficiency due to aldosterone deficiency 6

Laboratory Abnormalities

Key Diagnostic Findings

• Hyponatremia: Present in 90% of newly diagnosed cases, though levels may be only marginally reduced 6, 4, 5
• Hyperkalemia: Occurs in only approximately 50% of primary adrenal insufficiency cases; notably ABSENT in steroid-induced adrenal insufficiency because aldosterone secretion is preserved 6, 4, 5
• Hypoglycemia: May occur, particularly during acute illness or stress 4, 5
• Mild hypercalcemia: Found in 10-20% of patients at presentation 6, 5

Critical pitfall: The absence of hyperkalemia cannot rule out adrenal insufficiency, and the classic combination of hyponatremia plus hyperkalemia occurs in only about half of cases. 6, 5

Acute Presentation: Adrenal Crisis

Adrenal crisis is a medical emergency with high mortality if untreated, requiring immediate recognition and treatment without delay for diagnostic procedures. 1, 6, 5

Features of Adrenal Crisis

• Unexplained collapse and severe hypotension/shock: Often refractory to vasopressors 6, 5
• Severe vomiting and/or diarrhea: Common precipitating events 5
• Altered mental status: Including confusion, loss of consciousness, or coma 5
• Severe weakness and dehydration: With hypovolemic shock 5

Any patient taking ≥20 mg/day prednisone or equivalent for at least 3 weeks who develops unexplained hypotension should be presumed to have adrenal insufficiency until proven otherwise. 6, 4

Special Considerations in Your Clinical Context

Overlap with Hypothyroidism

Approximately half of patients with primary adrenal insufficiency have coexisting autoimmune thyroid disease, creating overlapping symptoms of fatigue, weight changes, and cold intolerance. 1

• Both conditions can cause fatigue, weight gain, difficulty sleeping, and cold intolerance 1
• Critical management principle: When treating concurrent hypothyroidism and adrenal insufficiency, corticosteroids MUST be started several days before initiating thyroid hormone replacement to prevent precipitating adrenal crisis 6, 7
• Annual screening for thyroid function is recommended in all patients with confirmed adrenal insufficiency 6

Steroid-Induced Adrenal Insufficiency Features

Distinguishing features from primary adrenal insufficiency include: 4

• Absence of hyperpigmentation (no elevated ACTH to stimulate melanocytes) 4
• Preserved aldosterone function (no hyperkalemia or significant salt wasting) 4
• Exogenous steroids confound interpretation of cortisol levels and diagnostic tests 6, 4

Associated Autoimmune Conditions

Screen for these conditions as they frequently coexist with autoimmune adrenal insufficiency: 1, 5

• Autoimmune thyroid disease (most common association) 1
• Type 1 diabetes mellitus 1
• Vitamin B12 deficiency due to autoimmune gastritis 1
• Celiac disease (screen if frequent or episodic diarrhea present) 6, 5
• Premature ovarian insufficiency in women 1

When to Suspect Adrenal Insufficiency

High-risk scenarios requiring immediate evaluation: 6, 4

• Recent steroid use (oral, inhaled, topical, intranasal, or intra-articular) with symptom onset after tapering or discontinuation 1, 4
• Unexplained hypotension, especially if requiring vasopressor support 6, 4
• Persistent fatigue with weight loss despite adequate caloric intake 2
• Hyponatremia that mimics SIADH (adrenal insufficiency must be excluded before diagnosing SIADH) 6
• Morning nausea and lack of appetite unresponsive to standard treatments 4

Treatment of suspected acute adrenal insufficiency should NEVER be delayed for diagnostic procedures if the patient is clinically unstable—give 100 mg IV hydrocortisone immediately plus 0.9% saline infusion. 6, 4, 5