Are the acute migraines, low‑grade fever, neck tightness, and vague chest discomfort in a patient with subclinical hyperthyroidism (possible early Graves disease) on low‑dose risperidone and lamotrigine more likely caused by the thyroid condition than by a drug reaction?

Acute Migraines, Fever, Neck Tightness, and Chest Pain in Subclinical Hyperthyroidism: Thyroid vs. Medication Etiology

The constellation of acute-onset migraines, low-grade fever, neck tightness, and vague chest pain in a patient with newly diagnosed subclinical hyperthyroidism (query Graves' disease) is most likely thyroid-related rather than caused by risperidone 0.5mg or lamotrigine 50mg. The symptom cluster—particularly the combination of migraines, fever, and neck discomfort—suggests either thyrotoxicosis-related hypermetabolic effects or a destructive thyroiditis phase, both of which are thyroid-mediated phenomena.

Primary Diagnostic Reasoning

Why Thyroid Dysfunction Is the Likely Culprit

• Subclinical hyperthyroidism with suspected Graves' disease creates a hypermetabolic state that directly causes cardiovascular symptoms (palpitations, chest discomfort), neurological symptoms (migraines, tremor), and systemic symptoms (low-grade fever, anxiety) even when free T4 and T3 remain within normal ranges 1.

• The anxiety-thyroid axis is bidirectional: subclinical hyperthyroidism is associated with heightened interoceptive sensitivity and anxiety symptoms, which can manifest as chest tightness and exacerbate migraine frequency 2.

• Migraines specifically improve with thyroid normalization: a randomized controlled trial demonstrated that levothyroxine treatment in subclinical hypothyroidism significantly reduced migraine frequency, severity, and MIDAS scores at 3 months, establishing a direct thyroid-migraine link 3. While this study addressed hypothyroidism, it confirms that thyroid dysfunction—in either direction—modulates migraine pathophysiology.

• Destructive thyroiditis (including silent or postpartum variants) accounts for 61% of subclinical hyperthyroidism cases and presents with neck discomfort, low-grade fever, and transient thyrotoxic symptoms before progressing to hypothyroidism 4. This self-limited condition would explain the acute symptom onset.

Why Medications Are Unlikely Causes

• Risperidone 0.5mg is a very low dose and the patient tolerated even higher doses previously without these symptoms. NMS was already ruled out by laboratory evaluation. Risperidone does not typically cause migraines, fever, or neck tightness at therapeutic doses.

• Lamotrigine 50mg after gradual titration is below the typical therapeutic range (100–200mg for mood stabilization, 200–400mg for seizures). Lamotrigine's most concerning adverse effect is Stevens-Johnson syndrome (rash, fever, mucositis), which does not match this presentation. Lamotrigine does not cause subclinical hyperthyroidism.

• Neither medication explains the biochemical finding of subclinical hyperthyroidism. The low TSH with normal free T4/T3 is a primary thyroid disorder, not a drug-induced phenomenon.

Immediate Diagnostic Algorithm

Confirm Subclinical Hyperthyroidism Severity and Etiology

1. Repeat TSH, free T4, and free T3 within 2–4 weeks to confirm persistent suppression, as transient TSH suppression can occur during acute illness or recovery from thyroiditis 1, 5.

2. Measure TSH-receptor antibodies (TRAb) to confirm Graves' disease. However, TRAb is positive in only 33% of subclinical Graves' cases, so a negative result does not exclude the diagnosis 4.

3. Obtain radioiodine uptake and scan (unless contraindicated) to distinguish Graves' disease (diffuse increased uptake) from destructive thyroiditis (low uptake) or toxic nodular goiter (focal uptake) 5, 4.

4. Check erythrocyte sedimentation rate (ESR) and serum thyroglobulin if destructive thyroiditis is suspected; ESR is elevated in subacute thyroiditis, and thyroglobulin is elevated in destructive processes 4.

Assess Cardiovascular and Neurological Risk

• Obtain ECG immediately to screen for atrial fibrillation, as subclinical hyperthyroidism with TSH <0.1 mIU/L increases atrial fibrillation risk 3–5 fold, and this patient has chest pain 1, 6, 7.

• Evaluate for cardiac arrhythmias or heart failure symptoms, especially if the patient is over 60 years or has underlying cardiac disease, as subclinical hyperthyroidism increases cardiovascular mortality up to 3-fold 6, 7.

• Document migraine characteristics (frequency, severity, aura, triggers) to establish baseline for monitoring response to thyroid treatment 3.

Treatment Decision Based on TSH Level

If TSH <0.1 mIU/L (Severe Subclinical Hyperthyroidism)

• Treat immediately with antithyroid medication (methimazole or carbimazole) if Graves' disease is confirmed by positive TRAb or diffuse uptake on scan, as this degree of suppression carries significantly increased cardiovascular and bone risks 5, 6, 7.

• Start beta-blocker (propranolol 10–40mg TID or atenolol 25–50mg daily) for symptomatic relief of palpitations, tremor, anxiety, and chest discomfort while awaiting definitive thyroid treatment 5.

• If destructive thyroiditis is confirmed (low radioiodine uptake, elevated ESR), do NOT use antithyroid drugs; instead, provide symptomatic treatment with beta-blockers and NSAIDs for neck pain, as the condition is self-limited and will resolve in 2–6 months 5, 4.

If TSH 0.1–0.45 mIU/L (Mild Subclinical Hyperthyroidism)

• Routine antithyroid treatment is NOT recommended for this TSH range, as evidence does not establish clear association with adverse outcomes 5.

• Repeat thyroid function tests every 3–12 months until TSH normalizes or the condition stabilizes 5.

• Consider treatment if:

  • TSH drops below 0.1 mIU/L on repeat testing 5
  • Patient develops atrial fibrillation or cardiac arrhythmias 5, 6
  • Patient is over 60–65 years with cardiovascular risk factors 6, 7
  • Destructive thyroiditis progresses to overt hyperthyroidism (rare) 4

Addressing the Acute Symptom Cluster

Migraine Management

• Migraines will likely improve once thyroid function normalizes, whether through spontaneous resolution of thyroiditis or treatment of Graves' disease 3.

• Continue standard migraine prophylaxis and abortive therapy (triptans, NSAIDs) in the interim, but avoid excessive use of vasoconstrictors if tachycardia or chest pain worsens.

Fever and Neck Tightness

• If subacute thyroiditis is confirmed (tender thyroid, elevated ESR), treat with NSAIDs (ibuprofen 600mg TID or naproxen 500mg BID) or prednisone 40mg daily tapered over 4–6 weeks for severe pain 4.

• If silent thyroiditis (painless thyroid, normal ESR), fever and neck discomfort typically resolve spontaneously within weeks as the thyrotoxic phase ends 4.

Chest Pain

• Rule out cardiac ischemia or arrhythmia with ECG, troponin, and continuous monitoring if chest pain is persistent or worsening 6, 7.

• Beta-blockers will alleviate chest discomfort if it is related to thyrotoxicosis-induced tachycardia or increased cardiac output 5.

Critical Pitfalls to Avoid

• Do not treat based on a single TSH measurement—confirm persistent suppression with repeat testing, as 50% of patients with TSH 0.1–0.45 mIU/L normalize spontaneously 5.

• Do not start antithyroid drugs empirically without establishing etiology—destructive thyroiditis will not respond and may unnecessarily expose the patient to agranulocytosis risk 5.

• Do not ignore cardiac symptoms—even mild palpitations or chest discomfort warrant immediate ECG and consideration for beta-blocker therapy, as subclinical hyperthyroidism significantly increases atrial fibrillation risk 5, 6, 7.

• Do not assume medications are the cause when biochemical thyroid dysfunction is present—the low TSH with normal free T4/T3 is a primary thyroid disorder that explains the symptom constellation far better than low-dose risperidone or lamotrigine.

• Do not delay treatment if TSH <0.1 mIU/L in a patient over 60 or with cardiac disease—this threshold represents significantly higher cardiovascular mortality risk and warrants intervention 6, 7.

Expected Clinical Course

• If Graves' disease: approximately one-third of patients with subclinical Graves' hyperthyroidism progress to overt disease, one-third normalize, and one-third remain subclinical over 32 months of follow-up 8. Older age and positive anti-TPO antibodies predict progression 8.

• If destructive thyroiditis: symptoms typically resolve within 2–6 months as the thyrotoxic phase ends, often followed by transient hypothyroidism before full recovery 4.

• Migraine improvement: expect reduction in headache frequency, severity, and MIDAS scores within 3 months of thyroid normalization, based on the levothyroxine trial in subclinical hypothyroidism 3.