What is the best course of action for a patient with progressive numbness and tingling, initially in the hand and now generalized, and a history of acromegaly (with normal hormone levels) and anxiety?

Progressive Numbness and Tingling with History of Acromegaly

This patient requires urgent neurological evaluation to rule out carpal tunnel syndrome, peripheral neuropathy, or functional neurological disorder, with immediate assessment for contributing metabolic and structural causes related to their acromegaly history.

Immediate Diagnostic Approach

Neurological Assessment

• Perform comprehensive neurological examination focusing on:

  • Pattern of sensory loss (distal vs. proximal, symmetric vs. asymmetric) 1
  • Muscle weakness assessment, particularly distal muscle groups 1
  • Deep tendon reflexes (reduced or absent reflexes suggest polyneuropathy) 1
  • Gait assessment for wide-based unsteady pattern 1
  • Assessment for numbness and tingling characteristics in hands and feet 1, 2

• Distinguish between neuropathy patterns as this critically affects management:

  • Classic polyneuropathy begins distally in toes/feet, progressing to fingertips symmetrically 1
  • Carpal tunnel syndrome (common in acromegaly, often preceding polyneuropathy by years) presents with D1-3 distribution 1
  • Generalized spreading suggests either progression of polyneuropathy or functional neurological disorder 1

Critical Acromegaly-Related Considerations

Acromegaly creates specific neurological risks even with controlled hormone levels:

• Up to 50% of acromegalic patients have complex ventricular arrhythmias, with strong correlation to left ventricular mass and disease duration (not hormone levels) 1
• Carpal tunnel syndrome is extremely common in acromegaly due to soft tissue overgrowth 1
• Structural cardiac changes may be reversible with treatment but neurological complications can persist 1

Essential Laboratory and Diagnostic Testing

First-Line Laboratory Tests

• Fasting blood glucose and hemoglobin A1c to assess for diabetes (common in acromegaly and major cause of peripheral neuropathy) 2, 3
• Thyroid function tests (TSH, free T4) as hypothyroidism causes neuropathy and is an endocrine comorbidity 3
• Vitamin B12 level to evaluate for deficiency-related neuropathy 2, 3
• Complete blood count to assess for anemia 3
• Electrolytes to rule out metabolic disturbances that can occur with endocrinopathies 1

Confirmatory Neurophysiological Testing

• Nerve conduction studies and electromyography are confirmatory for polyneuropathy 1
• Important caveat: Conventional nerve conduction studies will NOT detect small-fiber neuropathy 1
• If nerve conduction studies are normal but symptoms persist, consider skin biopsy for epidermal nerve fiber density 1

Cardiac Evaluation Given Acromegaly History

• ECG to assess for QT prolongation and arrhythmias (life-threatening arrhythmias are an established manifestation of acromegaly) 1
• 24-hour Holter monitoring if any cardiac symptoms or ECG abnormalities 1
• Echocardiogram to assess left ventricular mass (correlates with ventricular arrhythmias in acromegaly) 1

Addressing the Anxiety Component

The anxiety history is clinically significant and may represent:

• Psychopathology associated with acromegaly itself: Approximately two-thirds of acromegaly patients display anxiety, which tends to be more prevalent in younger patients with shorter disease duration 4, 5
• Depression and anxiety significantly predict quality of life in acromegaly (more so than biochemical control) and are modifiable treatment targets 5
• Functional neurological disorder possibility: Progressive spreading of sensory symptoms from focal to generalized can occur with functional disorders 1

Management Algorithm

If Carpal Tunnel Syndrome Confirmed

• Refer to hand surgery for consideration of carpal tunnel release (especially common in acromegaly patients) 1
• This often precedes polyneuropathy by many years in acromegaly patients 1

If Peripheral Neuropathy Confirmed

• Duloxetine 60 mg once daily is first-line pharmacological treatment for neuropathic pain, with option to increase to 120 mg daily 1, 2
• Physical activity has been shown to improve neuropathy symptoms 1, 2
• Optimize glucose control if diabetes is present (foundational step to prevent progression) 2

If Functional Neurological Disorder Suspected

• Refer to neurologist with expertise in functional disorders 1
• Avoid aids and equipment in acute phase as they can interrupt normal automatic movement patterns 1
• Consider occupational therapy with focus on normalizing movement patterns 1

Addressing Psychopathology

• Screen for depression and anxiety formally as these are highly prevalent in acromegaly and significantly impact quality of life 4, 5, 6
• Consider psychiatric referral as treating depression and anxiety may improve overall outcomes more than focusing solely on biochemical control 5

Common Pitfalls to Avoid

• Do not assume normal hormone levels exclude acromegaly-related complications: Cardiac changes, neuropathy, and quality of life issues correlate with disease duration and left ventricular mass, NOT current hormone levels 1, 5, 6
• Do not rely on single test for neuropathy diagnosis: At least two tests should be performed 3
• Do not overlook small-fiber neuropathy: Requires skin biopsy if conventional nerve conduction studies are normal 1
• Do not dismiss anxiety as purely psychological: It may represent functional neurological disorder requiring specific neurological management 1
• Do not focus exclusively on biochemical control: Psychopathology (depression/anxiety) is a stronger predictor of quality of life than hormone levels in treated acromegaly 5