What is the differential diagnosis and initial management for a patient presenting with cold intolerance, headache, and lightheadedness?

Differential Diagnosis for Cold Intolerance, Headache, and Lightheadedness

The most critical diagnosis to consider first is hypothyroidism, particularly from hypophysitis or primary thyroid dysfunction, as this triad of symptoms directly matches the classic presentation and requires urgent hormonal evaluation and replacement therapy to prevent life-threatening complications.

Primary Endocrine Etiologies

Hypothyroidism (Most Likely)

Hypothyroidism should be the leading diagnosis when cold intolerance presents with headache and lightheadedness. 1

• Cold intolerance is a cardinal symptom of hypothyroidism, along with fatigue, weight gain, constipation, and depression 1
• Headache occurs as a common manifestation of thyroid dysfunction 1
• Lightheadedness can result from the cardiovascular effects of low thyroid hormone 1

Diagnostic workup:

• Morning (8 AM) thyroid function tests: TSH and free T4 1
• High TSH with low free T4 confirms primary hypothyroidism 1
• Additional thyroid peroxidase (TPO) antibody testing if biochemical hypothyroidism confirmed 1

Hypophysitis (Critical to Rule Out)

This immune-mediated pituitary inflammation presents with the exact symptom triad and requires immediate recognition. 1

• Headache and fatigue are the primary clinical findings 1
• Low free T4 with low/normal TSH (not elevated TSH) distinguishes this from primary hypothyroidism 1
• Cold intolerance develops from secondary hypothyroidism 1

Required testing before steroid administration:

• Morning thyroid function (TSH, free T4) 1
• Adrenal function (ACTH, cortisol or cosyntropin stimulation test) 1
• Gonadal hormones (testosterone/estradiol, FSH, LH) 1
• MRI of sella with pituitary cuts 1

Critical management principle: In combined adrenal insufficiency and hypothyroidism, always start steroids before thyroid hormone to avoid precipitating adrenal crisis 1

Cardiovascular/Autonomic Etiologies

Orthostatic Hypotension

Lightheadedness is the predominant feature, with headache as a secondary symptom 1

• Sustained BP drop ≥20 mmHg systolic or ≥10 mmHg diastolic within 3 minutes of standing defines classic orthostatic hypotension 1
• Associated symptoms include extreme lightheadedness, visual changes ("tunnel vision"), tremulousness, and weakness 1
• Cold intolerance is not a typical feature, making this less likely as the primary diagnosis 1

Vasovagal Syncope/Presyncope

• Characterized by diaphoresis, warmth, nausea, and pallor preceding lightheadedness 1
• Typically triggered by upright posture, emotional stress, or medical settings 1
• Cold intolerance is not part of this syndrome 1

Acute Coronary Syndrome (Must Exclude in High-Risk Patients)

Lightheadedness is a recognized anginal equivalent that must be considered in appropriate clinical contexts. 1

• Lightheadedness, cold sweats, and nausea are commonly associated symptoms of ACS 1
• Headache is not a typical ACS feature 1
• Cold intolerance is not associated with ACS 1
• Consider in patients with known coronary disease, diabetes, or >20% 10-year Framingham risk 1

Primary Headache Disorders (Less Likely Given Symptom Constellation)

Migraine

While headache is the primary feature, the presence of cold intolerance and persistent lightheadedness makes isolated migraine unlikely 1, 2

• Migraine requires ≥5 attacks lasting 4-72 hours with specific characteristics (unilateral, pulsating, moderate-severe intensity, aggravated by activity) 2
• Associated symptoms include nausea/vomiting, photophobia, and phonophobia—not cold intolerance 2
• Lightheadedness may occur during attacks but is not a defining feature 1

Chronic Migraine

• Requires headache ≥15 days/month for >3 months, with ≥8 days meeting migraine criteria 1, 2
• Cold intolerance is not part of the diagnostic criteria 1

Secondary Headache Red Flags to Exclude

Always evaluate for dangerous secondary causes before confirming primary headache diagnosis. 1, 3

Critical red flags requiring immediate neuroimaging:

• Thunderclap headache (sudden onset, maximum intensity within seconds) 3
• "Worst headache of life" 3
• New headache after age 50 3
• Progressive worsening headache 3
• Headache awakening patient from sleep 3
• Focal neurological signs 3
• Neck stiffness (meningitis/subarachnoid hemorrhage) 3
• Unexplained fever 3
• Altered consciousness 3

Recommended Diagnostic Algorithm

Step 1: Urgent thyroid function testing

• Morning TSH and free T4 1
• If low free T4 with low/normal TSH: proceed to full pituitary workup and MRI 1
• If low free T4 with high TSH: diagnose primary hypothyroidism and check TPO antibodies 1

Step 2: Assess for red flag features

• Perform complete neurological examination 1, 3
• If any red flags present: obtain neuroimaging (MRI preferred, CT if acute hemorrhage suspected) 3

Step 3: Orthostatic vital signs

• Measure BP and heart rate supine and after 3 minutes standing 1
• Document BP drop ≥20/10 mmHg for orthostatic hypotension 1
• Document heart rate increase ≥30 bpm for orthostatic tachycardia 1

Step 4: If thyroid testing normal and no red flags

• Consider headache diary for 2-4 weeks to characterize pattern 1, 2
• Use ID-Migraine or MS-Q screening questionnaire 1, 2
• Reassess for primary headache disorder diagnosis 1

Common Pitfalls to Avoid

• Never start thyroid hormone before steroids in suspected hypophysitis with adrenal insufficiency—this precipitates adrenal crisis 1
• Do not attribute all symptoms to migraine without checking thyroid function—hypothyroidism is easily missed 1
• Do not order routine neuroimaging for hypothyroidism workup—imaging does not differentiate causes and is not indicated 1
• Do not dismiss lightheadedness as "just anxiety"—it may represent serious cardiovascular or endocrine pathology 1
• Avoid relying solely on imaging without complete clinical assessment—history and examination guide appropriate testing 1, 3