What is adrenal insufficiency in a patient with normal thyroid function and persistent cold intolerance?

Adrenal Insufficiency: A Simple Explanation

What Is Adrenal Insufficiency?

Adrenal insufficiency is a condition where your adrenal glands (small organs sitting on top of your kidneys) fail to produce enough cortisol, a vital hormone your body needs to function properly. 1, 2

Think of cortisol as your body's natural stress hormone—it helps regulate blood pressure, blood sugar, immune function, and how your body responds to illness or injury. 2, 3

Types of Adrenal Insufficiency

There are three main types:

• Primary adrenal insufficiency (Addison's disease): The adrenal glands themselves are damaged and cannot produce cortisol or aldosterone (another important hormone). This is most commonly caused by autoimmune destruction, where your immune system mistakenly attacks your adrenal glands. 2, 4

• Secondary adrenal insufficiency: The pituitary gland in your brain fails to produce ACTH (the hormone that tells your adrenal glands to make cortisol). This can result from pituitary tumors, surgery, radiation, or certain medications like opioids. 2, 3

• Glucocorticoid-induced adrenal insufficiency: This is the most common type and occurs when someone takes steroid medications (like prednisone) for a long time, which suppresses the body's natural cortisol production. When the medication is stopped, the adrenal glands may not immediately resume normal function. 2, 3

Common Symptoms

The symptoms develop gradually and are often vague, which is why diagnosis is frequently delayed:

• Profound fatigue and weakness that doesn't improve with rest (occurs in 50-95% of patients) 2, 3
• Unintentional weight loss and poor appetite (43-73% of patients) 2, 3
• Nausea, vomiting, and abdominal pain (20-62% of patients) 2, 5
• Dizziness or lightheadedness when standing (postural hypotension) due to low blood pressure 3, 5
• Salt craving (specific to primary adrenal insufficiency) 3, 1
• Skin darkening or hyperpigmentation (only in primary adrenal insufficiency, due to elevated ACTH) 5, 3
• Low blood sodium (hyponatremia) is present in approximately 90% of newly diagnosed cases 1, 5

How Is It Diagnosed?

The diagnosis requires blood tests, ideally performed in the early morning around 8 AM: 1, 2

• Morning cortisol level: A level below 5 µg/dL (or 250 nmol/L) with high ACTH suggests primary adrenal insufficiency. 1, 2
• ACTH level: High in primary adrenal insufficiency, low or inappropriately normal in secondary adrenal insufficiency. 1, 2
• Cosyntropin stimulation test: If morning cortisol is borderline (5-10 µg/dL), this test involves giving synthetic ACTH and measuring cortisol response. A peak cortisol below 500 nmol/L (18 µg/dL) confirms adrenal insufficiency. 1, 2

Important caveat: Hyperkalemia (high potassium) is only present in about 50% of cases, so its absence does not rule out adrenal insufficiency. 1, 5

Treatment

Treatment involves replacing the missing hormones: 2, 4

• Glucocorticoid replacement: Hydrocortisone 15-25 mg daily (divided into 2-3 doses) or prednisone 3-5 mg daily. 2, 4
• Mineralocorticoid replacement (only for primary adrenal insufficiency): Fludrocortisone 0.05-0.3 mg daily to replace aldosterone. 2, 4

Critical safety point: In patients with both adrenal insufficiency and hypothyroidism, steroids must always be started before thyroid hormone replacement to avoid triggering a life-threatening adrenal crisis. 6, 1

Adrenal Crisis: A Medical Emergency

Adrenal crisis is a life-threatening complication that occurs when cortisol levels drop dangerously low, often triggered by illness, surgery, or physical stress. 5, 2

Symptoms include:

• Severe weakness and confusion 5
• Severe vomiting and diarrhea 5
• Profound low blood pressure and shock 5, 7
• Loss of consciousness 5

Treatment must never be delayed for diagnostic testing—immediate IV hydrocortisone 100 mg and aggressive fluid resuscitation with normal saline are required. 5, 7

Living with Adrenal Insufficiency

All patients must be educated on "stress dosing"—doubling or tripling their glucocorticoid dose during illness, fever, or physical stress. 2, 3

Patients should:

• Wear a medical alert bracelet indicating adrenal insufficiency 6, 4
• Carry an emergency injectable hydrocortisone kit (100 mg IM) with training on self-injection 1, 3
• Carry a steroid emergency card 3, 4
• Understand that even minor illnesses like stomach flu can trigger adrenal crisis if medication cannot be absorbed 5, 3

Addressing Your Specific Scenario: Cold Intolerance with Normal Thyroid Function

In a patient with normal thyroid function but persistent cold intolerance, adrenal insufficiency should be strongly considered as a potential cause. 1

Cold intolerance is a recognized symptom of adrenal insufficiency, though it is more commonly associated with hypothyroidism. 6 When thyroid function tests are normal (normal TSH and free T4), other causes of cold intolerance must be investigated, and adrenal insufficiency is high on that differential diagnosis list. 1

The key diagnostic step is measuring morning (8 AM) cortisol and ACTH levels. 1, 2 If cortisol is low with elevated ACTH, primary adrenal insufficiency is likely. If cortisol is low with low or inappropriately normal ACTH, secondary adrenal insufficiency should be suspected. 1, 2

A cosyntropin stimulation test may be necessary if morning cortisol levels are indeterminate (between 5-10 µg/dL or 140-275 nmol/L). 1, 2 This test definitively confirms or excludes adrenal insufficiency when initial results are unclear.

Important consideration: Adrenal insufficiency can present with a clinical picture nearly identical to other conditions causing fatigue and cold intolerance, making it essential to exclude this diagnosis before attributing symptoms to other causes. 1