What is the next step for a 57-year-old female patient taking Monjaro (tirzepatide) for 2 months, now experiencing food intolerance, feeling cold, dizziness, and inability to focus?

Immediate Evaluation for Hypothyroidism and Medication-Related Adverse Effects

This patient requires immediate thyroid function testing (TSH, free T4) and assessment for GLP-1 receptor agonist-related complications, as her constellation of symptoms—food intolerance, cold intolerance, dizziness, and cognitive impairment—strongly suggests either hypothyroidism or severe gastrointestinal adverse effects from Monjaro (tirzepatide) leading to volume depletion.

Critical Diagnostic Workup

Thyroid Function Assessment

• Order TSH and free T4 immediately to evaluate for hypothyroidism, which presents with fatigue, cold intolerance, weight gain, cognitive dysfunction ("brain fog"), and constipation 1
• Cold intolerance combined with inability to focus are classic hypothyroid symptoms that require urgent evaluation 1
• If TSH is elevated and free T4 is low, check thyroid peroxidase (TPO) antibodies to confirm autoimmune thyroiditis 1

Volume Depletion and Renal Function

• Monitor renal function immediately as GLP-1 receptor agonists including tirzepatide can cause acute kidney injury due to volume depletion from gastrointestinal adverse reactions 2
• The majority of reported acute kidney injury cases with GLP-1 receptor agonists occurred in patients with nausea, vomiting, or diarrhea leading to dehydration 2
• Check orthostatic vital signs to assess for volume depletion, as dizziness may indicate orthostatic hypotension from dehydration 3

Gastrointestinal Complications

• Severe gastrointestinal adverse reactions occur more frequently with Monjaro (5 mg: 1.3%, 10 mg: 0.4%, 15 mg: 1.2%) compared to placebo (0.9%) 2
• Food intolerance in this context likely represents gastroparesis or severe nausea/vomiting from the medication 2
• Monjaro is not recommended in patients with severe gastroparesis 2

Immediate Management Algorithm

Step 1: Laboratory Evaluation (Within 24-48 Hours)

• TSH, free T4, TPO antibodies
• Basic metabolic panel (assess renal function and electrolytes)
• Complete blood count
• Consider hemoglobin A1c to assess glycemic control

Step 2: Medication Management

• Temporarily hold Monjaro until evaluation is complete, especially if severe gastrointestinal symptoms are present 2
• Severe gastrointestinal adverse reactions warrant discontinuation or dose reduction 2
• Ensure adequate hydration to prevent volume depletion and acute kidney injury 2

Step 3: Symptomatic Treatment

For Food Intolerance/Gastroparesis:

• If gastroparesis is confirmed, initiate metoclopramide 5-20 mg three to four times daily 1, 4
• Consider ondansetron 4-8 mg twice or three times daily for nausea 1
• Implement dietary modifications: small, frequent meals, low-fat, low-fiber content 4

For Hypothyroidism (if confirmed):

• Start levothyroxine replacement therapy at physiologic doses 1
• Critical: If both adrenal insufficiency and hypothyroidism are present, always start steroids before thyroid hormone to avoid adrenal crisis 1
• Lifelong hormonal replacement is typically needed 1

Step 4: Dizziness Management

• Ensure adequate hydration to minimize orthostatic hypotension 3
• Instruct patient to rise slowly from sitting or lying positions 3
• Warn about potential impairment when driving or operating machinery 3

Common Pitfalls to Avoid

• Do not restart thyroid hormone before ruling out adrenal insufficiency if hypophysitis is suspected, as this can precipitate adrenal crisis 1
• Do not continue Monjaro at current dose if severe gastrointestinal symptoms persist, as this increases risk of acute kidney injury 2
• Do not attribute all symptoms to medication side effects without ruling out thyroid dysfunction, which can be coincidental or medication-related 1
• Food intolerance may represent true gastroparesis requiring prokinetic therapy rather than simple dietary modification 1, 5

Follow-Up Strategy

• If hypothyroidism is confirmed, recheck TSH and free T4 in 6-8 weeks after initiating replacement
• If symptoms are purely medication-related, consider dose reduction or alternative diabetes therapy once acute symptoms resolve
• Monitor renal function during dosage initiation and escalation if Monjaro is restarted 2
• Consider endocrinology referral if hypophysitis or complex thyroid dysfunction is suspected 1