What could be causing a patient's symptoms of anxiety, paresthesia, and cold sensations in the extremities and face, given normal complete blood count (CBC) and thyroid panel results?

Evaluation of Paresthesias, Cold Sensations, and Anxiety with Normal CBC and Thyroid Panel

Despite normal thyroid function tests, you should pursue further endocrine evaluation focusing on subtle HPT axis dysfunction, vitamin B12/folate deficiency, peripheral neuropathy assessment, and consider anxiety disorder as a primary diagnosis only after excluding all organic causes. 1

Initial Diagnostic Approach

Reassess Thyroid Function Despite Normal Results

• Normal thyroid panels do not exclude subtle thyroid dysfunction that can cause these exact symptoms. 2
• Approximately half of studies demonstrate blunted TSH responses to TRH stimulation in anxiety patients despite normal baseline thyroid tests, suggesting subclinical HPT axis alterations 2
• An inverse relationship exists between self-reported anxiety levels and TSH even within the normal range 2
• Request the specific TSH and free T4 values - subclinical hypothyroidism (TSH 4.5-10 mU/L with normal free T4) can cause cold intolerance, paresthesias, and anxiety 3
• Subclinical thyroid dysfunction significantly increases anxiety scores compared to euthyroid patients, whether hyperthyroid or hypothyroid 3

Critical Vitamin and Metabolic Deficiencies

• Check vitamin B12, folate, and complete metabolic panel immediately - these are common causes of paresthesias with normal CBC 4
• Calcium and magnesium levels must be assessed, as hypocalcemia causes neuromuscular irritability, paresthesias, and tetany 4
• Hypoparathyroidism produces calcium deficiency leading to paresthesias and psychiatric symptoms 4

Peripheral Neuropathy Evaluation

• Paresthesias in extremities and face suggest peripheral nerve involvement requiring specific workup beyond CBC 4
• Consider checking hemoglobin A1c for diabetes screening, even with normal glucose 4
• Thyroid dysfunction itself causes reversible peripheral neuropathy and paresthesias 4

Secondary Endocrine Considerations

Hypophysitis and Central Hypothyroidism

• Central hypothyroidism presents with LOW or normal TSH with low free T4 - this pattern is often missed 2
• If TSH is in the lower-normal range with symptoms, consider pituitary dysfunction 2
• Morning cortisol and ACTH should be checked if central hypothyroidism is suspected 2
• MRI of sella turcica may be warranted if pituitary dysfunction is suspected 2

Pheochromocytoma Screening

• Cold sensations combined with anxiety and paresthesias warrant consideration of pheochromocytoma 1
• Check 24-hour urinary fractionated metanephrines or plasma metanephrines 1
• Associated symptoms include paroxysmal episodes, palpitations, and pallor 1

Anxiety Disorder as Primary Diagnosis

When to Consider Primary Anxiety

• Anxiety should only be diagnosed as primary AFTER comprehensive endocrine evaluation is completed 5, 6
• Hyperthyroidism symptoms (anxiety, palpitations, tremor) overlap extensively with panic disorder, leading to frequent misdiagnosis 5
• A recent case report documented a 10-month misdiagnosis of generalized anxiety disorder in a patient with hypothyroidism who was never tested for thyroid dysfunction 6
• Another case described thyroid storm misdiagnosed as panic attack in a patient with known panic disorder 5

Important Caveat About Psychiatric Medications

• If patient is on SSRIs (like sertraline), these medications themselves cause paresthesias in 2% of patients 7
• SSRIs cause sweating (7-11%), tremor (8%), and autonomic symptoms that overlap with thyroid dysfunction 7
• Up to one-third of psychiatric patients demonstrate thyroid function test abnormalities from medications or psychiatric illness itself (non-thyroidal illness) 8

Recommended Diagnostic Algorithm

Immediate Next Steps:

1. Obtain specific TSH and free T4 values - request the actual numbers, not just "normal" 1, 3
2. Order comprehensive metabolic panel including calcium, magnesium 4
3. Check vitamin B12, folate, and hemoglobin A1c 4
4. If TSH >4.5 mU/L or <0.5 mU/L, consider subclinical thyroid dysfunction 3

If Initial Workup Normal:

1. Consider 24-hour urine metanephrines or plasma metanephrines 1
2. Evaluate for peripheral neuropathy with nerve conduction studies if paresthesias persist 4
3. Morning cortisol and ACTH if fatigue is prominent 2

If All Testing Normal:

1. Refer to endocrinology for TRH stimulation test - this may reveal subtle HPT axis dysfunction not apparent on standard testing 2
2. Only then consider primary anxiety disorder diagnosis 5, 6

Critical Pitfalls to Avoid

• Never accept "normal thyroid panel" without seeing actual values - subclinical dysfunction occurs with TSH 4.5-10 mU/L 3
• Do not diagnose anxiety disorder without excluding organic causes first - multiple case reports document serious misdiagnoses 5, 6
• Remember that psychiatric medications can cause these symptoms - review medication list carefully 7, 8
• Central hypothyroidism has NORMAL or LOW TSH - do not be falsely reassured by normal TSH if free T4 is low-normal 2
• Thyroid function tests can be abnormal in psychiatric patients without true thyroid disease (non-thyroidal illness), but this is a diagnosis of exclusion 8