What could be causing a patient to feel hot in cold temperatures and cold in hot temperatures?

Paradoxical Temperature Perception: Diagnostic Approach

Primary Differential Diagnosis

This patient's symptoms of feeling hot in cold environments and cold in hot environments strongly suggest autonomic thermoregulatory dysfunction, most commonly seen in peripheral neuropathy affecting small sensory and autonomic fibers. 1, 2

The hypothalamus controls body temperature through input from sensory receptors throughout the body, and disruption at any level—from peripheral sensory receptors to central integration—can cause paradoxical temperature perception 1, 2.

Key Diagnostic Considerations

Peripheral Neuropathy with Autonomic Involvement

• Peripheral neuropathy affecting autonomic and small sensory fibers is the most likely cause of abnormal thermoregulation with paradoxical temperature sensations 3
• Small fiber neuropathy disrupts both autonomic thermoregulation (sweating, vasoconstriction) and behavioral thermoregulation (temperature perception) 3
• Common etiologies include:
  • Diabetes mellitus (most common) 3
  • Immune-mediated autonomic neuropathy 3
  • Primary systemic amyloidosis 3
  • Erythromelalgia 3

Multiple Sclerosis

• MS affects 60-80% of patients with heat intolerance (Uhthoff's phenomenon), though this typically manifests as worsening symptoms with heat rather than paradoxical cold sensations 4
• MS lesions in hypothalamic regions responsible for temperature control can impair thermoregulatory effector responses 4
• Demyelination produces altered neural integration within the CNS affecting temperature perception 4

Central Dysautonomia

• Hypothalamic dysfunction can cause disrupted temperature regulation with abnormal set points 2
• This may result from structural lesions, inflammatory conditions, or degenerative disorders 2

Essential Diagnostic Workup

Neurophysiologic Testing

• Quantitative sudomotor axon reflex test (QSART) to assess postganglionic sudomotor function 3
• Thermoregulatory sweat test (TST) to quantify anhidrosis distribution—patients with ≥25% body surface anhidrosis show significantly impaired core temperature regulation 3
• Quantitative sensory testing for small fiber function 3

Skin Biopsy

• Intraepidermal nerve fiber density measurement is the gold standard for diagnosing small fiber neuropathy 3
• Reduced linear density of intraepidermal nerve fibers correlates with impaired thermoregulation 3

Laboratory Evaluation

• Hemoglobin A1c and fasting glucose (diabetes screening) 3
• Thyroid function tests (hyperthyroidism can affect thermoregulation) 5
• Serum protein electrophoresis and immunofixation (amyloidosis) 3
• Autoimmune panel including ganglionic acetylcholine receptor antibodies (autoimmune autonomic neuropathy) 3

Imaging

• Brain and spinal cord MRI if MS or central lesions suspected 4

Management Approach

Symptomatic Treatment

• Avoid extreme temperature environments—stay indoors during temperature extremes 5
• Use layered clothing that can be adjusted regardless of ambient temperature 5
• In hot weather: regular water spraying, cooling devices (air conditioning, fans) 5
• In cold weather: appropriate insulation and gradual acclimatization over 2 weeks 6

Underlying Condition Treatment

• Optimize glycemic control if diabetic neuropathy identified 3
• Immunotherapy for immune-mediated autonomic neuropathy 3
• Disease-modifying therapy if MS diagnosed 4

Monitoring and Safety

• Patients with ≥25% body surface anhidrosis on TST are at significantly higher risk for heat-related illness and require close monitoring during heat exposure 3
• Educate on recognition of heat exhaustion symptoms: nausea, dizziness, muscle cramps, headache, fatigue 7
• Immediate cooling and electrolyte-carbohydrate fluids if heat exhaustion develops 7

Critical Pitfalls to Avoid

• Do not dismiss these symptoms as psychological—they represent objective autonomic dysfunction requiring neurologic evaluation 2, 3
• Avoid medications that impair thermoregulation (anticholinergics, diuretics) in patients with confirmed autonomic dysfunction 5
• Do not delay diagnostic workup—progressive autonomic neuropathy can lead to life-threatening thermoregulatory failure 2
• Recognize that normal routine nerve conduction studies do not exclude small fiber neuropathy—specialized autonomic testing is required 3