In a patient who recently had seizures and now shows low triiodothyronine, low or normal thyroxine, and an inappropriately low or normal thyroid‑stimulating hormone, could hypopituitarism be the underlying cause?

Can Hypopituitarism Explain This Patient's Presentation?

Yes, hypopituitarism (specifically central hypothyroidism) is a strong diagnostic consideration and must be actively excluded in this patient with seizures, low T3, low-normal T4, and inappropriately normal/low TSH.

Why Hypopituitarism Should Be Suspected

The constellation of low T3, low or normal T4, and inappropriately normal or low TSH is the hallmark biochemical pattern of central hypothyroidism due to pituitary or hypothalamic dysfunction 1, 2, 3. In primary hypothyroidism, TSH would be markedly elevated in response to low thyroid hormones—the fact that TSH remains normal or low despite inadequate thyroid hormone levels indicates failure of the pituitary-hypothalamic axis 2, 4.

Seizures can be both a cause and consequence of pituitary dysfunction. Head trauma, subarachnoid hemorrhage, or severe metabolic derangements associated with seizures can damage the hypothalamic-pituitary region, leading to hypopituitarism 5, 4. Conversely, untreated hypopituitarism—particularly adrenal insufficiency—can precipitate seizures through hypoglycemia, hyponatremia, or hypotension 1, 4.

Critical Diagnostic Algorithm

Step 1: Confirm Central Hypothyroidism

• Measure free T4 alongside TSH to distinguish central from primary hypothyroidism 1, 2. Low free T4 with low/normal TSH confirms central hypothyroidism 2, 3.
• Do NOT rely on TSH alone—in central hypothyroidism, TSH may appear "normal" but is inappropriately low given the degree of thyroid hormone deficiency 2, 3.

Step 2: Assess for Panhypopituitarism (Life-Threatening Priority)

Before initiating any thyroid hormone replacement, you must rule out concurrent ACTH deficiency, as starting levothyroxine before corticosteroids can precipitate fatal adrenal crisis 1, 4.

• Measure 8 AM cortisol and ACTH immediately 1, 4
• If cortisol is low (<5 μg/dL) or equivocal (5-15 μg/dL), perform a 1 mcg cosyntropin stimulation test before any treatment 1
• Check other pituitary axes: LH, FSH, testosterone (men) or estradiol (women), prolactin, IGF-1 1, 4

Step 3: Identify the Underlying Cause

• Obtain MRI of the pituitary with dedicated pituitary cuts to evaluate for mass lesions, empty sella, stalk thickening, or infiltrative disease 1, 4
• Screen for infiltrative causes if imaging shows abnormalities: serum ACE and chest imaging for sarcoidosis, ferritin and transferrin saturation for hemochromatosis 5
• Review recent history for head trauma, subarachnoid hemorrhage, meningitis, or postpartum hemorrhage (Sheehan syndrome) 5, 4

Treatment Sequence (Critical Safety Consideration)

If both adrenal insufficiency and central hypothyroidism are present, ALWAYS start hydrocortisone at least 1 week before levothyroxine 1, 4. The physiologic dose is hydrocortisone 20 mg in the morning and 10 mg in the afternoon 1.

Starting thyroid hormone first increases cortisol metabolism and can unmask or worsen adrenal crisis, manifesting as hypotension, shock, or death 1, 4.

Common Pitfalls to Avoid

• Never assume primary hypothyroidism based on low thyroid hormones alone—always check TSH appropriateness 2, 3
• Never start levothyroxine without first excluding or treating adrenal insufficiency in suspected central hypothyroidism 1, 4
• Do not dismiss normal pituitary imaging—9% of hypopituitarism cases have normal MRI, particularly in infiltrative diseases like sarcoidosis or hemochromatosis 5
• Recognize that hypopituitarism after head trauma or seizures can evolve over weeks to months—30-70% of patients with traumatic brain injury develop hypopituitarism 2, 4

When Hypopituitarism Is Less Likely

If TSH is frankly elevated (>10 mIU/L) with low T4, this indicates primary hypothyroidism, not hypopituitarism 6. However, in the acute/subacute phase of critical illness, TSH may be transiently suppressed even in primary hypothyroidism—repeat testing after recovery is essential 7, 3.

In nonthyroidal illness (sick euthyroid syndrome), T3 falls first, followed by T4 in severe cases, but TSH typically remains normal or slightly elevated 7, 3. The key distinction is that free T4 is usually normal or only mildly reduced in nonthyroidal illness, whereas in central hypothyroidism, free T4 is definitively low 3.