What is the differential diagnosis and investigation for a young lady with unilateral numbness and underlying glaucoma and hypothyroidism (underactive thyroid gland)?

Differential Diagnosis and Investigation for Unilateral Numbness in a Young Woman with Glaucoma and Hypothyroidism

This presentation demands urgent neuroimaging with MRI brain and orbits with contrast to rule out compressive lesions, demyelinating disease, or stroke, as unilateral numbness is a neurological red flag that supersedes the significance of her chronic ocular and endocrine conditions.

Critical Differential Diagnoses

Primary Neurological Causes (Most Urgent)

• Stroke or TIA: Unilateral sensory loss in a young woman requires immediate vascular assessment, particularly if accompanied by other focal deficits 1
• Multiple sclerosis or demyelinating disease: Young women are at highest risk; unilateral sensory symptoms are a classic presentation 1
• Compressive lesions: Tumors, schwannomas, or other mass lesions affecting sensory pathways must be excluded with contrast imaging 1
• Migraine with aura: Can present with unilateral numbness, though typically transient 1

Orbital and Neuro-Ophthalmic Causes

• Thyroid eye disease (TED): Despite having hypothyroidism, TED can occur with Hashimoto's thyroiditis and may present with orbital symptoms including sensory changes from nerve compression 1

  • TED affects women 8:1 and typically presents in the fourth to fifth decade 1
  • Can cause restrictive myopathy, proptosis, and compressive optic neuropathy 1
  • Orbital imaging may show extraocular muscle enlargement and increased orbital fat 1

• Orbital inflammatory disease: IgG4-related disease or idiopathic orbital inflammatory syndrome can present with unilateral orbital involvement and sensory changes 1

  • May mimic TED but requires different management 1

• Orbital mass lesions: Including lymphoma, which can present with unilateral symptoms and is associated with autoimmune conditions 1

Systemic Considerations Related to Underlying Conditions

• Central hypothyroidism: If her hypothyroidism is actually central (pituitary/hypothalamic), this could indicate a pituitary mass causing both endocrine dysfunction and neurological symptoms 2, 3

  • Check if her TSH pattern is consistent with primary versus central hypothyroidism 2
  • Pituitary lesions can cause sensory deficits through mass effect 3

• Hypothyroidism-related neuropathy: Peripheral neuropathy can occur with hypothyroidism, though typically bilateral and distal 1

Essential Investigations

Immediate Neuroimaging (Highest Priority)

• MRI brain and orbits with and without contrast: This is the gold standard initial investigation 1

  • Provides optimal soft tissue characterization for demyelinating lesions, masses, and orbital pathology 1
  • Diffusion-weighted imaging helps identify acute stroke and can characterize lymphoma 1
  • Orbital sequences assess for TED, inflammatory disease, and compressive lesions 1

• MRI head with contrast if intracranial extension suspected: Evaluates for distant metastases or intracranial disease extent 1

Complementary Imaging

• CT orbits with contrast: Complementary to MRI, particularly useful if TED is suspected and surgical decompression is being considered 1
  • Provides excellent assessment of orbital bone anatomy and muscle volumes 1

Laboratory Evaluation

• Thyroid function reassessment: Verify TSH, free T4, and free T3 to ensure adequate hypothyroid treatment 1, 2

  • If TSH is low/normal with low free T4, suspect central hypothyroidism requiring pituitary evaluation 2, 3
  • Check thyroid antibodies (anti-TPO, anti-thyroglobulin) as Hashimoto's is associated with TED 1

• Complete pituitary hormone panel if central hypothyroidism suspected: Including morning ACTH and cortisol, as adrenal insufficiency can coexist and requires treatment before thyroid replacement 2, 3

• Inflammatory markers: ESR, CRP, and consider IgG4 levels if orbital inflammatory disease suspected 1

Specialized Neuro-Ophthalmic Assessment

• Comprehensive ophthalmologic examination: Including visual acuity, color vision, pupillary examination, and fundoscopy to screen for optic neuropathy 1
• Exophthalmometry: To measure proptosis if TED suspected 1
• Forced duction testing: May reveal restriction from TED or inflammatory disease 1
• Visual field testing: Humphrey fields to assess for compressive optic neuropathy 1

Vascular Imaging (If Stroke/TIA Suspected)

• MRA or CTA: If vascular etiology is suspected based on acute onset or risk factors 1

Clinical Pitfalls to Avoid

• Do not attribute neurological symptoms to glaucoma alone: Glaucoma causes visual field defects, not unilateral body numbness 1

• Do not assume hypothyroidism is adequately treated: Poorly controlled hypothyroidism has been associated with glaucoma progression, but verify thyroid status and consider central causes 1, 4, 5, 6

• Do not delay neuroimaging: Unilateral numbness is a neurological emergency until proven otherwise; imaging should not be delayed for laboratory results 1

• Consider TED even with hypothyroidism: TED can occur with Hashimoto's thyroiditis and may precede, coincide with, or follow thyroid dysfunction by years 1

• Screen for pituitary pathology: If central hypothyroidism is present, always evaluate other pituitary axes before initiating thyroid replacement to avoid precipitating adrenal crisis 2, 3