What is the difference in diagnosis and treatment between central hypothyroidism and acquired hypothyroidism in patients presenting with hypothyroidism?

Central vs Acquired (Primary) Hypothyroidism: Diagnosis and Treatment

Central hypothyroidism is diagnosed by low free T4 with low or inappropriately normal TSH, while acquired primary hypothyroidism presents with elevated TSH and low free T4; critically, in central hypothyroidism, corticosteroids must always be initiated before thyroid hormone replacement to prevent adrenal crisis. 1

Diagnostic Differentiation

Laboratory Findings

Primary (Acquired) Hypothyroidism:

• Elevated TSH with low free T4 2
• TSH typically >10 mIU/L in cases requiring treatment 2
• Most commonly caused by Hashimoto thyroiditis in iodine-sufficient regions 3

Central Hypothyroidism:

• Low or inappropriately normal TSH with low free T4 1, 4
• TSH may appear "normal" on screening, leading to missed or delayed diagnosis 5, 4
• Results from pituitary or hypothalamic dysfunction 2, 4

Critical Diagnostic Pitfall

The TSH-reflex strategy (measuring TSH alone without free T4) will miss central hypothyroidism entirely because TSH levels are not elevated 4. When central hypothyroidism is suspected clinically, both TSH and free T4 must be measured simultaneously, preferably around 8 AM 1.

Additional Workup for Central Hypothyroidism

All patients with suspected central hypothyroidism require comprehensive evaluation for other pituitary hormone deficiencies 1:

• ACTH and cortisol (or 1 mcg cosyntropin stimulation test) - critical to identify adrenal insufficiency 1
• Gonadal hormones: testosterone (men), estradiol (premenopausal women), FSH, LH 1
• Pituitary MRI with dedicated pituitary cuts 1
• TRH stimulation test can confirm diagnosis when biochemistry is equivocal 5

Approximately 50% of patients with central hypothyroidism present with panhypopituitarism (adrenal insufficiency plus hypothyroidism plus hypogonadism), and >75% have both adrenal insufficiency and hypothyroidism 1.

Treatment Differences

Primary Hypothyroidism Treatment

• Levothyroxine monotherapy is standard 2
• Monitor with TSH, targeting 0.5-2.0 mIU/L 2
• Check TSH and free T4 every 6-8 weeks while titrating 1
• Once stable, repeat every 6-12 months 1
• Start with full calculated dose in young healthy patients 2
• Start low dose in elderly, coronary artery disease, or long-standing severe hypothyroidism 2

Central Hypothyroidism Treatment

Critical Treatment Sequence: When both adrenal insufficiency and central hypothyroidism coexist, steroids MUST be initiated before thyroid hormone to avoid precipitating adrenal crisis 1, 3, 2. Thyroid hormone accelerates cortisol clearance, which can unmask or worsen adrenal insufficiency 3.

Monitoring Strategy:

• TSH is NOT a reliable marker for treatment monitoring in central hypothyroidism 1, 2
• Monitor free T4 or total T4 levels, maintaining them in the upper half of the normal range for age 1, 2
• Check every 6-8 weeks while titrating, then every 6-12 months once stable 1

Replacement Regimen:

• Physiologic doses of hydrocortisone (15-20 mg in divided doses) for adrenal insufficiency 3
• Levothyroxine for hypothyroidism, initiated only after steroid replacement 1, 2
• Other hormone replacement as indicated (testosterone, estrogen) 3

Common Treatment Pitfall

Approximately 25% of patients with central hypothyroidism are inadvertently maintained on sufficiently high levothyroxine doses to completely suppress TSH, increasing risk of atrial fibrillation and osteoporosis 1. This occurs because providers mistakenly use TSH as the treatment target rather than free T4 levels.

Clinical Presentation Differences

Primary hypothyroidism typically presents with more pronounced symptoms: bradycardia, mild hypertension, narrowed pulse pressure, potential pericardial effusions and myxedema in severe cases 3.

Central hypothyroidism usually has milder clinical manifestations 4, 6. Common symptoms include headache (85%) and fatigue (66%), though visual changes are uncommon 1. Goiter is always absent in central hypothyroidism 6.

Imaging Considerations

There is no role for thyroid imaging (ultrasound, CT, MRI, or radionuclide scans) in the workup of primary hypothyroidism in adults 3. All causes of hypothyroidism show decreased radioiodine uptake, and imaging does not differentiate etiologies 3.

For central hypothyroidism, pituitary MRI is essential to evaluate for structural lesions 1.

Long-term Management

Both adrenal insufficiency and hypothyroidism from hypophysitis typically require lifelong hormonal replacement 1. All patients need education on stress dosing for sick days, emergency injectable steroids, and should wear medical alert identification 3, 1.