Likely Diagnosis: Central (Secondary) Hypothyroidism

This patient's laboratory pattern—suppressed TSH (0.27 mIU/L) combined with low free T4 (0.30 ng/dL)—is diagnostic of central hypothyroidism caused by pituitary or hypothalamic dysfunction, not primary thyroid disease. 1

Understanding the Biochemical Pattern

Why This Is NOT Primary Hypothyroidism or Overtreatment

In primary hypothyroidism, TSH would be markedly elevated (>10 mIU/L) when free T4 is low—the pituitary attempts to compensate for thyroid failure by secreting more TSH 1
In levothyroxine overtreatment, TSH would be suppressed BUT free T4 would be elevated or high-normal—not low as in this case 2
The combination of low TSH with low free T4 indicates the pituitary is failing to produce adequate TSH despite insufficient thyroid hormone, which is the hallmark of central hypothyroidism 1

The Diagnostic Trap of "Normal" TSH in Central Disease

TSH may appear "normal" (within reference range 0.45–4.5 mIU/L) in central hypothyroidism, yet be inappropriately low relative to the degree of thyroid hormone deficiency 1
TSH alone is unreliable for screening central hypothyroidism—free T4 must always be measured alongside TSH to detect this pattern 1, 3
In this patient, TSH 0.27 mIU/L is technically within some laboratory ranges but is inappropriately low given the severely depressed free T4 of 0.30 ng/dL 1

Critical Next Steps: Life-Threatening Priorities BEFORE Thyroid Treatment

1. Immediately Assess for Adrenal Insufficiency (ACTH Deficiency)

DO NOT start levothyroxine until adrenal function is evaluated and treated if deficient—this can trigger fatal adrenal crisis. 1

Required Testing (Obtain Urgently):

8 AM serum cortisol and ACTH measurement 1
If cortisol <5 µg/dL or equivocal (5–15 µg/dL), perform 1 µg cosyntropin stimulation test before any thyroid therapy 1

Why This Is Life-Threatening:

Levothyroxine accelerates cortisol metabolism—if the patient has concurrent ACTH deficiency, starting thyroid hormone first will unmask or precipitate adrenal crisis (hypotension, shock, death) 1, 2
In hypopituitarism, ACTH deficiency frequently coexists with TSH deficiency 1

Treatment Sequencing:

If adrenal insufficiency is confirmed, start physiologic hydrocortisone (20 mg morning, 10 mg afternoon) at least one week BEFORE initiating levothyroxine 1, 2

2. Evaluate the Entire Pituitary Axis (Screen for Panhypopituitarism)

Central hypothyroidism is rarely isolated—assess all pituitary hormones to identify additional deficiencies: 1

LH, FSH, and sex hormones (testosterone in males, estradiol in females) to detect gonadotropin deficiency 1
Prolactin (may be elevated with stalk compression or low with pituitary destruction) 1
IGF-1 to screen for growth hormone deficiency 1
Morning cortisol and ACTH (as above—highest priority) 1

3. Obtain Dedicated Pituitary MRI

Imaging is essential to identify the underlying cause of pituitary dysfunction: 1

Look for mass lesions (adenoma, craniopharyngioma), empty sella, stalk thickening, or infiltrative disease 1
If abnormalities are found, screen for infiltrative etiologies:
- Serum ACE and chest imaging for sarcoidosis 1
- Ferritin and transferrin saturation for hemochromatosis 1

4. Review Recent Medical History for Pituitary Injury

Ask specifically about events that can damage the hypothalamic-pituitary axis: 1

Head trauma 1
Subarachnoid hemorrhage 1
Meningitis 1
Postpartum hemorrhage (Sheehan syndrome) 1
Recent neurosurgery 1

Once Adrenal Function Is Secured: Levothyroxine Initiation

Dosing Strategy for Central Hypothyroidism

Unlike primary hypothyroidism, TSH cannot be used to monitor treatment adequacy in central disease—dose adjustments are guided by free T4 levels. 3

Target Free T4 Range:

Aim for free T4 in the upper half of the reference range (e.g., 1.3–1.6 ng/dL if normal range is 0.9–1.7 ng/dL) 3
Patients with central hypothyroidism require higher free T4 levels than euthyroid controls to achieve clinical euthyroidism 3

Starting Dose:

For patients <70 years without cardiac disease: start levothyroxine 1.6 µg/kg/day (approximately 100–125 µg daily for average-weight adults) 2
For patients >70 years or with cardiac disease: start 25–50 µg daily and titrate slowly by 12.5–25 µg every 6–8 weeks 2

Monitoring Protocol:

Recheck free T4 (NOT TSH) every 6–8 weeks during dose titration 2, 3
TSH will often remain suppressed or low-normal even with adequate replacement—this is expected and does not indicate overtreatment 4, 3
Once stable, monitor free T4 every 6–12 months 2

Common Pitfalls to Avoid

Pitfall #1: Misinterpreting Low TSH as Hyperthyroidism

A low TSH with low (not elevated) free T4 rules out hyperthyroidism 5, 6
In hyperthyroidism, TSH would be suppressed BUT free T4 and T3 would be elevated 5

Pitfall #2: Starting Levothyroxine Before Ruling Out Adrenal Insufficiency

This is the most dangerous error—always assess cortisol FIRST in suspected central hypothyroidism 1, 2

Pitfall #3: Using TSH to Monitor Treatment in Central Hypothyroidism

TSH remains unreliable even during treatment—free T4 is the only valid monitoring parameter 3, 4
TSH may paradoxically suppress further with levothyroxine replacement, mimicking overtreatment when the patient is actually euthyroid 4

Pitfall #4: Assuming Isolated TSH Deficiency

Central hypothyroidism is rarely isolated—failure to screen for panhypopituitarism can miss life-threatening ACTH or gonadotropin deficiency 1

Why This Diagnosis Matters for Morbidity and Mortality

Untreated Central Hypothyroidism Causes:

Cardiovascular dysfunction (delayed myocardial relaxation, reduced cardiac output, increased vascular resistance) 2
Adverse lipid profiles (elevated LDL cholesterol, hypertriglyceridemia) 2
Cognitive impairment and psychiatric symptoms 2
Increased mortality if concurrent adrenal insufficiency is missed 1

Untreated Adrenal Insufficiency (if coexistent) Causes:

Hypotension, shock, and death during physiologic stress 1
Hypoglycemia and hyponatremia 1
Seizures (which can both result from and contribute to pituitary dysfunction) 1

Summary Algorithm

Confirm diagnosis: Low TSH + low free T4 = central hypothyroidism 1
STOP—do NOT start levothyroxine yet 1
Obtain 8 AM cortisol and ACTH immediately 1
If cortisol low/equivocal, perform cosyntropin stimulation test 1
If adrenal insufficiency confirmed, start hydrocortisone ≥1 week before levothyroxine 1
Evaluate remaining pituitary axes (LH, FSH, sex hormones, prolactin, IGF-1) 1
Obtain pituitary MRI to identify structural cause 1
Once adrenal function secured, start levothyroxine targeting upper-normal free T4 3
Monitor with free T4 (NOT TSH) every 6–8 weeks during titration 3, 2

Female patient with suppressed thyroid‑stimulating hormone and low free thyroxine—what is the likely diagnosis and recommended next management?

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