What is the diagnosis and treatment for a patient with hypothyroidism and prediabetes, taking levothyroxine 25mg daily, presenting with left gluteal pain, numbness, tingling, and burning sensations in the left leg and feet, and persistent left arm pain?

Clinical Assessment and Diagnosis

This patient presents with three distinct neurological syndromes requiring separate evaluation: lumbosacral plexopathy/radiculopathy (left gluteal pain radiating down the leg), possible brachial plexopathy or complex regional pain syndrome (persistent left arm pain from IV infiltration), and length-dependent peripheral neuropathy (bilateral foot burning and tingling). The bilateral foot symptoms are most consistent with diabetic peripheral neuropathy given the prediabetes history, while the unilateral extremity pains require different diagnostic approaches 1, 2, 3.

Primary Concern: Bilateral Foot Neuropathy

The bilateral burning and tingling sensations on the soles of both feet that worsen at night are classic hallmarks of small fiber neuropathy, most likely related to prediabetes. 2, 4

Key Diagnostic Features Supporting Small Fiber Neuropathy:

• Burning pain and "electrical shock" sensations are pathognomonic for small fiber dysfunction affecting unmyelinated C-fibers and thinly myelinated Aδ-fibers 4
• Symptoms worsening at night while at rest is characteristic of neuropathic pain and occurs in the majority of symptomatic patients 4
• Bilateral symmetric distribution starting distally (feet) indicates length-dependent neuropathy, the prototypical pattern in diabetic/prediabetic neuropathy 3
• Up to 50% of diabetic peripheral neuropathy may be asymptomatic initially, but this patient has progressed to symptomatic disease 1, 2, 3

Critical Diagnostic Workup Required:

• Fasting glucose and HbA1c immediately - impaired glucose tolerance can cause small fiber damage even before overt diabetes develops 2
• TSH and free T4 - the current levothyroxine 25mg daily dose is likely inadequate (full replacement is typically 1.6 mcg/kg/day), and undertreated hypothyroidism can worsen neuropathy 5, 6
• Vitamin B12 level - deficiency causes both symptomatic and asymptomatic small fiber loss histologically identical to diabetes 2
• Comprehensive metabolic panel including renal function - chronic kidney disease contributes to small fiber neuropathy 2
• 10-g monofilament testing at multiple plantar sites to assess for loss of protective sensation (LOPS), which dramatically increases ulceration risk 1, 3
• 128-Hz tuning fork at dorsum of great toe to assess vibration sense (large fiber function) 1, 3
• Pinprick and temperature sensation testing to evaluate small fiber function 1, 3
• Comprehensive foot inspection for skin integrity, calluses, deformities, pre-ulcerative signs 3
• Vascular assessment including dorsalis pedis and posterior tibial pulses, as peripheral arterial disease is present in up to 50% of diabetic foot complications 3

Note: Standard nerve conduction studies may be completely normal in small fiber neuropathy, as these tests only evaluate large myelinated fibers - do not rely on electrophysiology alone 4

Secondary Concern: Left Gluteal Pain with Radiation

The left gluteal pain radiating down the left leg with numbness and tingling suggests either lumbosacral plexopathy or L5-S1 radiculopathy. 1

Distinguishing Features to Assess:

• Radiculopathy presents with dermatomal pain distribution, while plexopathy affects multiple peripheral nerve distributions 1
• The sacral plexus supplies motor and sensory innervation to gluteal (motor only), peroneal, and tibial nerve territories 1
• Pain rated 10/10 with no relief from activity, rest, or sitting is atypical and raises concern for structural pathology requiring imaging 1

Imaging Recommendation:

MRI of the lumbosacral plexus is usually appropriate for initial imaging when plexopathy is suspected clinically. 1 This must include:

• Orthogonal views through the oblique planes of the plexus 1
• T1-weighted, T2-weighted, fat-saturated T2-weighted or STIR sequences 1
• High-resolution T2-weighted sequences (MR neurography) 1

Electrodiagnostic studies should be performed to confirm the clinical diagnosis of plexopathy versus radiculopathy. 1

Tertiary Concern: Left Arm Pain from IV Infiltration

Persistent constant achy left arm pain rated 9/10 one year after IV infiltration with difficulty grasping objects suggests either complex regional pain syndrome, brachial plexopathy, or peripheral nerve injury. 1

Required Evaluation:

• MRI of the brachial plexus if symptoms localize to multiple peripheral nerve distributions rather than a single nerve 1
• Electrodiagnostic studies to differentiate plexopathy from isolated peripheral nerve injury 1
• Referral to pain management or neurology for specialized evaluation given chronicity and severity 1

Treatment Plan

Immediate Management of Foot Neuropathy

Initiate duloxetine 30 mg daily, titrating to 60 mg daily after one week for neuropathic pain management. 4 Alternative first-line options include pregabalin starting at 75 mg twice daily or gabapentin starting at 300 mg daily 4. At optimal dosing, 38% of patients achieve ≥50% pain reduction. 4

Glycemic Control Optimization:

Target HbA1c <7% to slow neuropathy progression - tight glycemic control effectively prevents diabetic peripheral neuropathy in type 1 diabetes and modestly slows progression in type 2 diabetes 1, 3, 4

Hypothyroidism Management:

The current levothyroxine 25 mg daily dose is grossly inadequate. 5

• Full replacement dose for primary hypothyroidism is 1.6 mcg/kg/day 5
• Titrate dosage by 12.5 to 25 mcg increments every 4 to 6 weeks until the patient is clinically euthyroid and serum TSH returns to normal 5
• The peak therapeutic effect may not be attained for 4 to 6 weeks 5
• Undertreated hypothyroidism can worsen peripheral neuropathy and must be corrected 6, 7

Foot Care Education (Critical to Prevent Ulceration):

• Never walk barefoot, even indoors 3
• Check inside shoes before wearing for foreign objects 3
• Daily foot self-examination using a mirror to inspect plantar surfaces for cuts, blisters, redness, or calluses 3
• Avoid extreme temperatures - test bath water with elbow, not the foot 3
• Cut nails straight across and not too short 3
• Report any skin breaks, color changes, swelling, or warmth immediately 3
• Prescribe therapeutic footwear with adequate cushioning and depth to redistribute plantar pressures 3, 4

Monitoring and Referrals:

• Referral to podiatry or foot care specialist for ongoing preventive care given LOPS if confirmed 3
• Screen for cardiac autonomic neuropathy (resting tachycardia >100 bpm, orthostatic hypotension), as this often coexists with peripheral neuropathy 1, 3
• Monitor for depression and anxiety, as over two-thirds of patients with painful neuropathy develop these comorbidities, which worsen pain outcomes 4
• Blood pressure control target <130/80 mmHg to slow neuropathy progression 3
• Statin therapy for cardiovascular risk reduction 3
• Smoking cessation is crucial, as smoking significantly increases amputation risk 3

Common Pitfalls to Avoid:

• Do not rely solely on nerve conduction studies - they miss small fiber neuropathy 4
• Do not use prolonged cold water immersion or ice application for symptom relief, as this can lead to immersion foot, skin ulceration, and infection 4
• Do not assume adequate thyroid replacement without checking TSH - this patient's dose is far below standard replacement 5, 6
• Do not dismiss the unilateral extremity pains as "just neuropathy" - they require separate structural evaluation with imaging and electrodiagnostics 1
• Diabetic neuropathy is a diagnosis of exclusion - nondiabetic neuropathies may be present and treatable 1, 2