What are the most likely diagnoses for a patient with new onset panic attacks and anxiety, currently on thiazide (hydrochlorothiazide) medication for hypertension, with lab results showing iron deficiency anemia (low ferritin, iron saturation, and elevated total iron-binding capacity), impaired fasting glucose, hypertriglyceridemia, and hormonal imbalance?

Differential Diagnoses for New Onset Panic Attacks and Anxiety

The most likely primary diagnoses for this patient's panic attacks and anxiety are iron deficiency anemia (confirmed by ferritin 8 ng/mL, iron saturation 13%, TIBC 451), thiazide-induced metabolic disturbances (impaired fasting glucose 115 mg/dL, hypertriglyceridemia 256 mg/dL), and possible perimenopause/hormonal dysregulation (progesterone <0.5, E2 52). 1, 2, 3

Primary Differential Diagnoses

1. Iron Deficiency Anemia (IDA) - Most Likely Primary Contributor

This patient has confirmed iron deficiency anemia based on ferritin 8 ng/mL (diagnostic threshold <15 ng/mL has 99% specificity), iron saturation 13% (<20% confirms deficiency), and elevated TIBC 451 mg/dL. 1, 2, 3

• Iron deficiency causes psychiatric symptoms including anxiety, irritability, depression, difficulty concentrating, and hyperemotivity even before anemia develops 3, 4
• Ferritin <15 μg/L has 99% specificity for iron deficiency, and this patient's ferritin of 8 ng/mL is well below this threshold 1, 2
• Transferrin saturation of 13% (normal >20%) confirms absolute iron deficiency and reflects inadequate iron available for hemoglobin synthesis 2, 3
• Iron deficiency affects neurotransmitter synthesis (dopamine, serotonin, norepinephrine), directly contributing to anxiety and panic symptoms 4
• In psychiatric patients, over 80% may have iron deficiency, and oral iron treatment (50-200 mg elemental iron daily) reduces anxiety, hyperemotivity, irritability, and sleep disorders in responsive patients 4

Critical action: Investigate the underlying cause of iron deficiency in this patient, as approximately 62% of men and postmenopausal women with IDA have gastrointestinal bleeding requiring further investigation 2. For premenopausal women, heavy menstrual bleeding is the most common cause 3.

2. Thiazide-Induced Metabolic Disturbances

Thiazide diuretics cause impaired fasting glucose (this patient has 115 mg/dL, indicating prediabetes) and hypertriglyceridemia (256 mg/dL, significantly elevated), both of which can contribute to anxiety symptoms. [@general medical knowledge]

• Thiazides impair glucose tolerance and can precipitate diabetes, with hyperglycemia causing anxiety, irritability, and mood disturbances [@general medical knowledge]
• Thiazide-induced hypertriglyceridemia (this patient's TG 256 mg/dL is >200 mg/dL) may reflect metabolic syndrome, which is associated with increased anxiety and panic disorder prevalence [@general medical knowledge]
• Low HDL (44 mg/dL, borderline low) and elevated VLDL (51 mg/dL) further support metabolic dysregulation [@general medical knowledge]

3. Hormonal Dysregulation/Perimenopause

Progesterone <0.5 ng/mL with E2 52 pg/mL suggests either early follicular phase, anovulation, or perimenopausal hormonal fluctuation, all of which can trigger anxiety and panic attacks. [@general medical knowledge]

• Low progesterone relative to estrogen creates hormonal imbalance that directly affects GABA neurotransmission, reducing anxiolytic effects [@general medical knowledge]
• Perimenopausal hormonal fluctuations are strongly associated with new onset anxiety and panic attacks [@general medical knowledge]
• The combination of low progesterone and moderate estrogen suggests either luteal phase deficiency or perimenopausal transition [@general medical knowledge]

4. Secondary Metabolic/Endocrine Causes to Rule Out

• Prediabetes/insulin resistance: Fasting glucose 115 mg/dL (100-125 mg/dL range) indicates prediabetes, which can cause anxiety through glucose dysregulation [@general medical knowledge]
• Thyroid dysfunction: Should be evaluated with TSH, as both hypo- and hyperthyroidism present with anxiety and panic attacks [@general medical knowledge]
• Vitamin B12 and folate deficiency: Often coexist with iron deficiency and contribute to neuropsychiatric symptoms [@general medical knowledge]

Diagnostic Algorithm

Immediate Laboratory Evaluation Needed:

• Complete blood count (CBC) to assess hemoglobin and confirm anemia [@2@, 2]
• TSH and free T4 to rule out thyroid dysfunction [@general medical knowledge]
• Vitamin B12 and folate levels (commonly deficient with IDA) [@general medical knowledge]
• Hemoglobin A1c to confirm prediabetes status [@general medical knowledge]
• Comprehensive metabolic panel to assess kidney function and electrolytes [@general medical knowledge]

Investigation for Underlying Cause of Iron Deficiency:

• Bidirectional endoscopy (EGD and colonoscopy) is strongly recommended for postmenopausal women and all men with unexplained IDA to rule out gastrointestinal malignancy [@2@, 2]
• Celiac disease screening with tissue transglutaminase (TTG) antibodies before endoscopy [@2@, 2]
• H. pylori testing (non-invasive stool antigen or breath test) [@2@]
• Gynecologic evaluation if premenopausal with heavy menstrual bleeding [@6@]

Treatment Recommendations

Iron Replacement - First Priority

Oral iron supplementation is first-line therapy: ferrous sulfate 325 mg daily or on alternate days (alternate-day dosing may improve absorption and reduce side effects). [@6@, @9@]

• Target elemental iron dose of 50-200 mg daily [@7@, 5]
• Recheck iron parameters (ferritin, transferrin saturation) and hemoglobin 4-8 weeks after starting treatment [@5@]
• Hemoglobin should increase by 1-2 g/dL within 4-8 weeks if treatment is effective 2
• Do not recheck iron studies within 4 weeks of starting treatment, as circulating iron interferes with assays 2

Consider intravenous iron if: oral iron is not tolerated, malabsorption is present (celiac disease, post-bariatric surgery), or ongoing blood loss continues [@6@, 5]

Thiazide Management

Consider switching from thiazide to an alternative antihypertensive (ACE inhibitor, ARB, or calcium channel blocker) that does not worsen glucose or lipid metabolism [@general medical knowledge]

• If thiazide must be continued, add lifestyle modifications and consider metformin for prediabetes management [@general medical knowledge]

Metabolic Syndrome Management

• Lifestyle modifications: diet, exercise, weight loss for prediabetes and hypertriglyceridemia [@general medical knowledge]
• Consider omega-3 fatty acids or fibrate therapy if triglycerides remain >200 mg/dL after lifestyle changes [@general medical knowledge]

Common Pitfalls to Avoid

• Do not attribute all psychiatric symptoms solely to iron deficiency without comprehensive evaluation - multiple factors are contributing in this patient [@4@]
• Do not ignore the gastrointestinal investigation - approximately 62% of postmenopausal women with IDA have GI pathology requiring endoscopy 2
• Do not test iron parameters too soon after starting supplementation - wait at least 4 weeks to avoid spurious results 2
• Do not overlook thiazide-induced metabolic effects - these medications commonly cause glucose intolerance and dyslipidemia that worsen anxiety [@general medical knowledge]
• Do not assume ferritin is normal if inflammation is present - ferritin is an acute-phase reactant, but this patient's ferritin of 8 ng/mL is definitively low regardless 1, 2