What is the appropriate diagnosis and treatment for a patient presenting with fatigue, brain fog, cold intolerance, poor stamina, palpitations, and dizziness?

Diagnostic Approach: Primary Hypothyroidism vs. Central Hypothyroidism

This symptom constellation—fatigue, brain fog, cold intolerance, poor exercise stamina, palpitations, and dizziness—strongly suggests thyroid dysfunction, and you must immediately check TSH and free T4 to differentiate between primary hypothyroidism (high TSH, low free T4) and central hypothyroidism (low/normal TSH with low free T4). 1

Initial Laboratory Evaluation

Order these tests immediately, preferably at 8 AM: 1

• TSH and free T4 (essential first-line tests) 1
• Morning ACTH and cortisol (or 1 mcg cosyntropin stimulation test) 1, 2
• Complete metabolic panel (glucose, electrolytes, creatinine) 1
• Complete blood count (to assess for anemia) 1
• Thyroid peroxidase (TPO) antibody if hypothyroidism confirmed 1

Critical Diagnostic Distinction

If TSH is HIGH and free T4 is LOW:

• This is primary hypothyroidism (most commonly Hashimoto's thyroiditis in iodine-sufficient areas) 3, 4
• Proceed directly to levothyroxine treatment 3, 4

If TSH is LOW/NORMAL and free T4 is LOW:

• This is central hypothyroidism from pituitary/hypothalamic dysfunction (hypophysitis) 1, 2
• You MUST evaluate other pituitary hormones before starting treatment: 1, 2
  • Gonadal hormones (testosterone in men, estradiol in women) 1
  • FSH and LH 1
  • MRI of sella with pituitary cuts 1

Critical pitfall: In central hypothyroidism with concurrent adrenal insufficiency, you must ALWAYS start corticosteroids BEFORE thyroid hormone replacement to avoid precipitating an adrenal crisis. 1

Treatment Protocol

For Primary Hypothyroidism:

• Start levothyroxine 1.5-1.8 mcg/kg/day in most patients 4, 5
• Use lower starting dose (12.5-50 mcg/day) if patient is >60 years old or has known/suspected coronary artery disease 4, 5
• Target TSH: 0.5-2.0 mIU/L 5
• Recheck TSH and free T4 in 6-8 weeks, then annually once stable 3

For Central Hypothyroidism (Hypophysitis):

• Replace deficient hormones in this specific order: 1
  1. Corticosteroids FIRST (physiologic doses of hydrocortisone) 1
  2. Then thyroid hormone (levothyroxine) 1
• Monitor with free T4 levels (not TSH), targeting upper half of normal range 5
• Both adrenal insufficiency and hypothyroidism are typically permanent, requiring lifelong replacement 1
• All patients with adrenal insufficiency must obtain and carry a medical alert bracelet 1

Additional Considerations

If palpitations are prominent: The symptom pattern could also suggest thyrotoxicosis from thyroiditis (which can precede hypothyroidism), particularly if the patient is on immune checkpoint inhibitors. 1 In this case, you would see high free T4 or T3 with low/normal TSH. 1

If TSH and free T4 are both normal: Consider adrenal insufficiency as the primary diagnosis, as fatigue and cold intolerance overlap significantly with hypothyroid symptoms. 2 Morning cortisol <3 mcg/dL or failure to respond to cosyntropin stimulation confirms adrenal insufficiency. 1

Common pitfall: Symptoms of hypothyroidism are non-specific and extremely prevalent in the general population. 6 However, given this specific constellation with cold intolerance and poor stamina, thyroid dysfunction remains the most likely diagnosis requiring immediate biochemical confirmation. 1, 3