Is central hypothyroidism present given low serum thyroxine (T4), low triiodothyronine (T3), and low thyrotropin (TSH) levels, in a patient with a history of upper thoracic radiation for Hodgkin lymphoma?

Central Hypothyroidism Diagnosis

Yes, Khadija has central hypothyroidism, not primary hypothyroidism or hyperthyroidism, as evidenced by her low T4 (2.2 μg/dL), low T3 (33 ng/dL), and inappropriately low-normal TSH (0.2 μIU/mL) in the setting of upper thoracic radiation for Hodgkin lymphoma. 1, 2

Understanding the Laboratory Pattern

The key diagnostic feature is the inappropriately low TSH in the presence of low thyroid hormones. In primary hypothyroidism, TSH would be markedly elevated (typically >10 mIU/L) as the pituitary attempts to stimulate a failing thyroid gland. 1, 3 However, Khadija's TSH of 0.2 μIU/mL is below the normal range (0.5-5 μIU/mL), indicating the problem originates from inadequate pituitary TSH secretion or hypothalamic dysfunction, not from thyroid gland failure. 1, 2

Why This Is Not Hyperthyroidism

• Low thyroid hormone levels definitively exclude hyperthyroidism. Her T4 of 2.2 μg/dL (normal 5.0-12) and T3 of 33 ng/dL (normal 70-195) are both significantly below normal ranges. 1
• In hyperthyroidism, both TSH would be suppressed AND thyroid hormones would be elevated, which is the opposite of Khadija's pattern. 1
• Her negative thyroid stimulating immunoglobulin (TSI) rules out Graves' disease, the most common autoimmune cause of hyperthyroidism. 1

Why This Is Not Primary Hypothyroidism

• In primary hypothyroidism, TSH elevation precedes and accompanies low thyroid hormones. The pituitary responds to low T4/T3 by dramatically increasing TSH production, often to levels >10 mIU/L. 1, 3
• Khadija's TSH is inappropriately low (0.2 μIU/mL) given her profoundly low thyroid hormones, indicating pituitary or hypothalamic dysfunction rather than thyroid gland failure. 1, 2

Clinical Correlation Supporting Central Hypothyroidism

Her symptoms are classic for hypothyroidism of any etiology:

• Fatigue and increased tiredness despite maintaining regular exercise 1
• Weight gain without dietary changes 1
• Cold intolerance (more uncomfortable in cold weather) 1
• Heavy menstrual periods (menorrhagia is common in hypothyroidism) 1
• Dry, coarse skin on physical examination 1

The critical distinguishing feature is that central hypothyroidism symptoms are typically milder than primary hypothyroidism, which aligns with Khadija's presentation—she remains functional and continues swimming, though with increased fatigue. 2, 4

Radiation-Induced Central Hypothyroidism

Upper thoracic radiation for Hodgkin lymphoma is a well-established cause of central hypothyroidism. 1 The radiation field likely included the hypothalamic-pituitary region, causing:

• Direct damage to pituitary thyrotroph cells that produce TSH 2, 4
• Hypothalamic dysfunction affecting TRH (thyrotropin-releasing hormone) production 2, 5
• Progressive pituitary failure that may evolve over months to years post-radiation 2, 6

Critical Next Steps Before Treatment

Before initiating levothyroxine, you must evaluate for concurrent adrenal insufficiency (secondary adrenal failure). 1, 3

• Measure morning cortisol and ACTH levels immediately. If cortisol is low with low-normal or low ACTH, this indicates secondary adrenal insufficiency. 1
• Starting thyroid hormone before corticosteroid replacement can precipitate life-threatening adrenal crisis by increasing cortisol metabolism. 1, 3
• Hydrocortisone must be initiated first if adrenal insufficiency is present, then levothyroxine can be safely started. 1, 3

Additional Pituitary Hormone Assessment

Evaluate all pituitary axes, as central hypothyroidism rarely occurs in isolation after radiation: 2, 4

• Growth hormone (GH) - measure IGF-1 levels 3, 2
• Gonadotropins (LH/FSH) - though her menstrual changes may reflect hypothyroidism itself 2
• Prolactin levels - to assess lactotroph function 2
• Consider pituitary MRI to evaluate for structural abnormalities, though radiation-induced damage may not show obvious lesions initially 2, 6

Treatment Approach for Central Hypothyroidism

Once adrenal insufficiency is ruled out or treated, initiate levothyroxine replacement:

• Start with 1.6 mcg/kg/day for patients <70 years without cardiac disease, which applies to Khadija at age 48. 1, 3
• Monitor treatment using free T4 levels, NOT TSH, as TSH remains unreliable in central hypothyroidism. 3, 2
• Target free T4 in the upper half of the normal reference range (approximately 1.2-1.8 ng/dL if normal range is 0.8-1.8). 3, 2
• Recheck free T4 every 6-8 weeks during dose titration, then every 6-12 months once stable. 1, 3

Common Diagnostic Pitfalls to Avoid

Do not rely on TSH alone for thyroid screening in patients with pituitary/hypothalamic risk factors. The TSH-reflex strategy (measuring only TSH initially) will miss central hypothyroidism because TSH may be low-normal rather than elevated. 1, 2

Do not misinterpret low TSH with low-normal T4 as subclinical hyperthyroidism. This pattern requires free T4 measurement to distinguish between early hyperthyroidism (elevated T4) and central hypothyroidism (low or low-normal T4). 1, 6

Do not assume normal TSH excludes hypothyroidism in symptomatic patients with radiation history. In central hypothyroidism, TSH can remain within the reference range despite significant hypothyroidism. 1, 2

Never initiate thyroid hormone replacement before confirming adequate cortisol levels in patients with suspected central hypothyroidism, as this represents a medical emergency if adrenal insufficiency coexists. 1, 3