Mefenamic Acid vs Tolfenamic Acid

1. Chemical Structure

2. Mechanism of Action

3. Pharmacokinetics

4. Clinical Uses

5. Dosing

6. Adverse Effects

7. Contraindications & Precautions

• Active peptic ulcer disease
• Severe renal/hepatic impairment
• Third trimester pregnancy (risk of premature closure of ductus arteriosus)
• Aspirin-exacerbated respiratory disease
• Children/adolescents for mefenamic acid specifically (not recommended)

8. Key Distinguishing Points

Summary

Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics (fenamate pharmacology and PK table); EMA tolfenamic acid summary report; clinical trial data from PubMed.

Imaging to Rule Out Prolactinoma

The Modality: MRI of the Pituitary with Gadolinium

• Cumulative radiation dose from repeated scans can cause cataracts
• "Coned-down" views and tomograms of the sella are very insensitive
• MRI far outperforms CT in soft tissue resolution for small tumors

• Berek & Novak's Gynecology; Textbook of Family Medicine 9e

When to Image

What MRI Shows: Micro vs Macroadenoma

Important caveat: up to half of all prolactin-secreting microadenomas are too small to be detected by any imaging method. A normal MRI does not exclude a microadenoma - it may represent a very small adenoma, prolactin-cell hyperplasia, or idiopathic hyperprolactinemia. - Tietz Textbook of Laboratory Medicine, 7th ed.

Key Diagnostic Pitfalls

1. The "Stalk Effect" (Pseudoprolactinoma)

• A dopamine agonist (bromocriptine/cabergoline) will reduce prolactin in a true prolactinoma but not in stalk effect.

2. The Hook Effect

3. Macroprolactinemia

4. Pituitary Incidentaloma

Prolactin Level and Its Correlation with Imaging Findings

• Swanson's Family Medicine Review; Smith & Tanagho's General Urology

Clinical Workup Flowchart

Follow-up Imaging After Diagnosis

Summary

• MRI pituitary with gadolinium = gold standard for prolactinoma
• Image when prolactin is persistently elevated without a clear drug/physiological cause, or when mass symptoms exist
• A normal MRI does not exclude a small microadenoma
• Always rule out macroprolactinemia (PEG test) and the hook effect before concluding imaging findings
• Distinguish true prolactinoma from stalk effect (the latter won't respond to dopamine agonists)
• Macroadenoma always requires formal visual field testing and neurosurgical consultation

Tests for Hyperthyroidism

Step-by-Step Diagnostic Approach

Step 1 - TSH (First-Line / Best Initial Test)

• Normal range: ~0.5-4.5 mIU/L
• In hyperthyroidism: TSH is suppressed (typically < 0.1 μU/mL in overt disease)
• A normal TSH virtually excludes clinical hyperthyroidism - no further thyroid testing is needed
• TSH is sensitive because even small rises in free T4 suppress TSH through negative feedback

Important caveat: TSH can be falsely suppressed by severe non-thyroidal illness, dopamine infusions, and high-dose glucocorticoids. TSH also remains suppressed for 6-8 weeks after hyperthyroidism is corrected, so it is not useful for monitoring early treatment response. - Washington Manual of Medical Therapeutics

Step 2 - Free T4 (If TSH is Low)

Step 3 - Free T3 (Selected Cases)

• T3 toxicosis occurs in ~5% of hyperthyroid patients - elevated free T3 with normal free T4. Seen early in hyperthyroidism and in iodine-deficient states combined with Graves disease.
• Free T3 also confirms severity of hyperthyroidism when TSH is low.
• Total T3 is sometimes used instead because accurate fT3 measurement is technically challenging at low concentrations.
• Free T3 is not useful for diagnosing hypothyroidism. - Rosen's Emergency Medicine; Harrison's Principles of Internal Medicine 22e

Reverse pattern - elevated fT4 with normal T3 (T4 toxicosis): suggests thyroiditis, exogenous levothyroxine ingestion, or hyperthyroidism in elderly patients with suppressed T4-to-T3 conversion.

Summary: Pattern Recognition

Additional Tests to Establish the Cause

4. TSH Receptor Antibodies (TRAb / TSI)

• Highly sensitive and specific for Graves disease
• TRAb (TSH receptor antibodies) act as TSH agonists, stimulating uncontrolled thyroid hormone production
• Elevated TRAb essentially confirms Graves disease and has largely replaced radioiodine scanning for this purpose in most centres
• Also called TSI (thyroid-stimulating immunoglobulin) or LATS (long-acting thyroid stimulator)
• A 2024 Practice Guideline (Kalra et al., PMID: 39707289) highlights TRAb as the best laboratory marker for Graves disease diagnosis, prognosis, and monitoring

5. Anti-TPO and Anti-Thyroglobulin Antibodies

• Anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin antibodies are elevated in autoimmune thyroid disease (both Graves and Hashimoto's)
• They are not specific to Graves disease - more strongly associated with Hashimoto's thyroiditis
• Useful to confirm autoimmune aetiology but not to distinguish Graves from thyroiditis in isolation

6. ESR (Erythrocyte Sedimentation Rate)

• Used in the diagnosis of subacute (de Quervain's) thyroiditis - typically very elevated (often > 50 mm/hr)
• Thyroiditis causes transient hyperthyroidism (release of stored hormone) followed by hypothyroidism

7. Radioactive Iodine Uptake (RAIU) Scan with I-123

Note: RAIU is contraindicated in pregnancy. If a patient had recent iodinated contrast exposure, the gland is iodine-saturated - use pertechnetate scanning as an alternative. - Goldman-Cecil Medicine; Washington Manual

8. Thyroid Ultrasound with Doppler

• Best modality for thyroid structure
• In Graves disease: diffuse enlargement, heterogeneous echotexture, markedly increased vascularity on Doppler ("thyroid inferno")
• In thyroiditis: decreased or absent vascularity on Doppler (helpful to distinguish from Graves when RAIU is not done)
• Characterises nodules in toxic multinodular goiter or toxic adenoma
• Useful when TRAb is negative but Graves is still suspected, or when RAIU is contraindicated

9. Other Associated Tests

Common Causes and Their Diagnostic Fingerprint

Pitfalls: False Thyroid Function Tests

• Biotin supplements (>100 mg/day): falsely decreased TSH, increased fT4/fT3 - stop biotin for 2-3 days before testing
• Heterophile antibodies: artificially increased TSH
• Thyroid hormone autoantibodies: falsely increased total and free T4/T3
• Macro-TSH: artificially elevated TSH (can be ruled out with PEG precipitation)
• Severe non-thyroidal illness (euthyroid sick syndrome): low T3 (low conversion), and in severe illness low T4 too - TSH may be transiently suppressed mimicking hyperthyroidism