Is the patient's thyroid functioning properly and if not, is she experiencing hypothyroidism or hyperthyroidism?

Khadija's Thyroid is NOT Functioning Properly: She Has Central (Secondary) Hypothyroidism

Khadija has central hypothyroidism, a rare but critical diagnosis characterized by low T4 (2.2 ug/dl), low T3 (33 ng/dl), AND inappropriately low-normal TSH (0.2 μIU/mL) that fails to rise despite profound hypothyroidism. This pattern indicates pituitary or hypothalamic dysfunction, likely radiation-induced from her upper thoracic radiation therapy for Hodgkin lymphoma. 1, 2

Why This is Central Hypothyroidism, Not Primary

Laboratory Pattern Analysis

• Low T4 (2.2 ug/dl; normal 5.0-12) combined with low TSH (0.2 μIU/mL; normal 0.5-5) is the hallmark of central hypothyroidism 1, 2
• In primary hypothyroidism, TSH would be markedly elevated (typically >10 mIU/L) in response to low thyroid hormones 3, 4
• The TSH is inappropriately low for the degree of hypothyroidism present - this is pathognomonic for pituitary/hypothalamic failure 2, 5
• Low T3 (33 ng/dl; normal 70-195) confirms severe thyroid hormone deficiency 4
• Normal TSI rules out Graves' disease or other autoimmune hyperthyroidism 1

Clinical Symptom Correlation

Khadija's symptoms are classic for hypothyroidism, not hyperthyroidism:

• Fatigue and increased tiredness - cardinal hypothyroid symptom 6
• Cold intolerance - reflects decreased metabolic rate 6
• Weight gain despite unchanged diet and continued exercise - metabolic slowing 6
• Heavy menstrual periods - hypothyroidism causes menorrhagia 4
• Coarse, dry skin on physical exam - pathognomonic for hypothyroidism 6

These symptoms would be opposite in hyperthyroidism (heat intolerance, weight loss, light periods, warm moist skin). 4

Critical Radiation-Induced Etiology

Upper thoracic radiation for Hodgkin lymphoma is a well-established cause of central hypothyroidism through pituitary damage. 1 The radiation field likely included the hypothalamic-pituitary axis, causing TSH deficiency that manifested months to years post-treatment. 2

Immediate Management Priorities

CRITICAL: Rule Out Adrenal Insufficiency FIRST

Before initiating any thyroid hormone replacement, Khadija MUST be evaluated for secondary adrenal insufficiency. 1, 6, 4

• Measure morning cortisol and ACTH levels immediately 1
• If cortisol is low with low/normal ACTH, this confirms hypopituitarism 1
• Starting levothyroxine before corticosteroid replacement can precipitate life-threatening adrenal crisis by increasing cortisol metabolism 1, 6
• If adrenal insufficiency is present, initiate hydrocortisone 15-20 mg daily (divided doses) BEFORE starting levothyroxine 1, 4

Comprehensive Pituitary Hormone Evaluation

Since central hypothyroidism rarely occurs in isolation, evaluate all pituitary axes: 1, 2

• ACTH/cortisol (most critical - see above)
• LH/FSH and estradiol (may explain heavy periods if deficient)
• Prolactin (can be elevated or low in hypopituitarism)
• IGF-1 (growth hormone axis)
• Pituitary MRI with contrast to assess for structural damage, mass, or empty sella from radiation 2, 5

Levothyroxine Initiation Protocol for Central Hypothyroidism

After confirming adequate cortisol or initiating hydrocortisone replacement: 4

• Start levothyroxine at full replacement dose of 1.6 mcg/kg/day (Khadija is 48 years old without cardiac disease) 3, 7
• Monitor free T4 levels, NOT TSH - TSH is unreliable in central hypothyroidism 1, 7, 2
• Target free T4 in the upper half of normal range 7, 2, 4
• Recheck free T4 in 6-8 weeks and adjust dose by 12.5-25 mcg increments 3, 7
• Once stable, monitor free T4 every 6-12 months 7, 4

Common Diagnostic Pitfalls to Avoid

Misdiagnosing as Subclinical Hyperthyroidism

The low TSH could mislead clinicians into thinking this is hyperthyroidism, but the low T4 and T3 definitively exclude this. 8 A case report describes exactly this error - treating presumed hyperthyroidism with radioiodine in a patient who actually had central hypothyroidism, causing severe iatrogenic hypothyroidism. 8

Treating Based on TSH Alone

In central hypothyroidism, TSH can be low, normal, or even slightly elevated - it is the combination with low free T4 that makes the diagnosis. 1, 2, 9 Drawing both TSH and free T4 together is essential when hypothyroidism is suspected clinically. 1

Missing the Adrenal Crisis Risk

This is the most dangerous pitfall - approximately 50% of patients with central hypothyroidism have concurrent ACTH deficiency. 1, 2 Starting thyroid hormone without addressing adrenal insufficiency can be fatal. 1, 6

Long-Term Monitoring Considerations

• Annual pituitary hormone panel to detect progressive hypopituitarism 2
• Free T4 monitoring (not TSH) every 6-12 months once stable 7, 4
• Bone density screening given estrogen deficiency risk and hypothyroidism 4
• Cardiovascular risk assessment as untreated hypothyroidism increases cardiac morbidity 4
• Endocrinology referral is strongly recommended for complex central hypothyroidism management 6, 2