What are the differential diagnoses and recommended further work‑up for a 34‑year‑old man presenting with severe epigastric burning pain, daily watery diarrhea, daily ethanol consumption, mood instability and anxiety, hyperferritinemia, mild transaminitis, borderline elevated blood urea nitrogen, normal serum calcium, mild hyperkalemia, low‑normal total testosterone with elevated sex hormone‑binding globulin, and dyslipidemia (elevated total cholesterol and LDL)?

Differential Diagnoses and Diagnostic Work-Up

This 34-year-old man with daily alcohol consumption, severe epigastric burning pain, and diarrhea most likely has alcohol-related gastritis or peptic ulcer disease, but you must urgently exclude acute pancreatitis, alcoholic hepatitis, and hemochromatosis given the constellation of elevated transaminases, hyperferritinemia, and low testosterone.

Immediate Life-Threatening Conditions to Exclude

Acute Pancreatitis

• Order serum lipase or amylase immediately (≥2× normal for lipase, ≥4× normal for amylase), as acute pancreatitis characteristically presents with epigastric pain and has 80-90% sensitivity and specificity, with overall mortality <10% but reaching 30-40% in necrotizing pancreatitis 1, 2.
• The combination of daily alcohol use, severe epigastric pain, and diarrhea makes this a critical diagnosis not to miss 2.

Acute Coronary Syndrome

• Obtain an ECG within 10 minutes to exclude myocardial infarction, which can present atypically with isolated epigastric pain in younger patients with risk factors (alcohol use, dyslipidemia), carrying 10-20% mortality if missed 1, 2.
• Serial troponins at 0 and 6 hours are required to definitively exclude acute coronary syndrome 1, 2.

Primary Gastrointestinal Differential Diagnoses

Alcohol-Related Peptic Ulcer Disease (Most Likely)

• Peptic ulcer disease presents with constant epigastric burning pain and has an incidence of 0.1-0.3%, with perforation risk of 2-10% and mortality up to 30% if perforated 1.
• The patient's epigastric burning pain, daily alcohol consumption, and elevated transaminases strongly suggest this diagnosis 1.
• Order H. pylori testing immediately using ^13C-urea breath test or stool antigen (not serology), as H. pylori is the principal cause of peptic ulcers not related to NSAID use 3, 2.

Alcoholic Gastritis

• Gastritis manifests as epigastric burning pain and can be alcohol-induced, appearing on imaging as enlarged areae gastricae, thickened gastric folds, or erosions 4, 3.
• The British Society of Gastroenterology notes that burning sensation starting in the epigastrium helps differentiate dyspepsia from GERD 4.

Functional Dyspepsia with Overlapping IBS

• Functional dyspepsia is characterized by bothersome epigastric pain and burning occurring at least 1 day per week, with symptoms present for at least 8 weeks 4, 1.
• Up to 50% of patients with functional dyspepsia have overlapping IBS, which can present with diarrhea and is reported to occur in 9-23% of the population 4, 1.
• The patient's multi-episode daily diarrhea suggests possible IBS overlap, though pain unrelated to defecation favors functional dyspepsia over IBS 2.

Chronic Pancreatitis

• Chronic pancreatitis presents with epigastric pain, nausea, and post-prandial symptoms due to pancreatic enzyme insufficiency 1.
• Order fecal elastase testing to evaluate for pancreatic insufficiency in this patient with chronic alcohol use 1.

Critical Laboratory Abnormalities Requiring Further Investigation

Hyperferritinemia (Ferritin 656 μg/L)

• The most frequent causes of hyperferritinemia at this level are infection, liver dysfunction (from alcohol), and inflammation 5.
• Ferritin levels of 656 μg/L are typically associated with multiple underlying causes, and 41% of patients with hyperferritinemia have multiple etiologies 5.
• Isolated iron-overload syndromes (hemochromatosis) never exceed ferritin levels >15,000 μg/L, making primary hemochromatosis less likely at this level 6.
• However, order iron studies (serum iron, TIBC, transferrin saturation) and consider HFE gene testing to exclude hereditary hemochromatosis, as the combination of hyperferritinemia, elevated transaminases, and low testosterone raises concern 6, 7.

Elevated Transaminases (AST 43, ALT 92)

• The ALT-predominant pattern (ALT > AST) with ALT 92 suggests alcoholic hepatitis or fatty liver disease 1.
• Order hepatitis panel (HBsAg, anti-HCV), complete metabolic panel, and consider abdominal ultrasound to evaluate for chronic liver disease 4, 1.
• The elevated ferritin combined with transaminitis in the setting of daily alcohol use strongly suggests alcohol-related liver injury 5, 6.

Low-Normal Testosterone (294 ng/dL) with Elevated SHBG (21.5 nmol/L)

• Chronic alcohol use causes hypogonadism through multiple mechanisms, including direct testicular toxicity and increased SHBG from liver dysfunction 1.
• The combination of low-normal testosterone, elevated SHBG, mood instability, and anxiety is consistent with alcohol-related hypogonadism 1.
• Calculate free testosterone to assess true androgen status, as elevated SHBG reduces bioavailable testosterone 1.

Mild Hyperkalemia (Potassium 5.2 mEq/L)

• Repeat potassium measurement to exclude pseudohyperkalemia from hemolysis 1.
• If confirmed, evaluate for renal dysfunction (BUN 22 is borderline elevated), hypoaldosteronism, or medication effects 1.

Essential Diagnostic Work-Up

Immediate Laboratory Tests

• Complete blood count to assess for anemia (alarm feature requiring urgent endoscopy) 4, 1.
• Complete metabolic panel including liver function tests, renal function, and electrolytes 1, 2.
• Serum lipase or amylase to exclude acute pancreatitis 1, 2.
• C-reactive protein and serum lactate to assess for serious organic pathology 2.
• H. pylori breath test or stool antigen (not serology) 3, 2.
• Iron studies (serum iron, TIBC, transferrin saturation) to evaluate hyperferritinemia 6.
• Hepatitis panel (HBsAg, anti-HCV) given elevated transaminases 1.
• Fecal elastase to evaluate for pancreatic insufficiency 1.

Imaging Studies

• CT abdomen and pelvis with IV contrast is the gold standard when diagnosis is unclear, identifying pancreatitis, perforation (showing extraluminal gas in 97%, fluid/fat stranding in 89%), liver disease, and vascular emergencies 4, 2.
• Abdominal ultrasound to evaluate liver parenchyma, biliary tree, and pancreas 4.

Endoscopic Evaluation

• Upper endoscopy is indicated because this patient is <40 years but has treatment-resistant symptoms, daily alcohol use (risk factor), and multiple alarm features including epigastric tenderness on examination 4, 1.
• The British Society of Gastroenterology recommends non-urgent endoscopy for treatment-resistant dyspepsia in patients ≥25 years 4.
• Endoscopy with mucosal biopsies remains the gold standard for diagnosing peptic ulcer disease, gastritis, and excluding malignancy 1, 3.

Psychiatric and Systemic Considerations

Mood Instability and Anxiety

• Mood instability and anxiety are common in functional dyspepsia and are part of the gut-brain axis dysfunction 4.
• However, these symptoms may also reflect alcohol withdrawal, hypogonadism, or chronic illness 1.
• Screen for alcohol use disorder using validated tools (AUDIT-C) and assess for withdrawal symptoms 1.

Critical Pitfalls to Avoid

• Never dismiss cardiac causes in patients with epigastric pain regardless of age—obtain ECG and serial troponins 1, 2.
• Do not attribute persistent diarrhea to functional dyspepsia alone—Rome IV criteria state that symptoms relieved by evacuation of feces should not be considered part of dyspepsia 4.
• Do not delay endoscopy in patients with alarm features (epigastric tenderness, treatment-resistant symptoms, daily alcohol use), as missing peptic ulcer disease or malignancy leads to poor outcomes 4, 1.
• Do not use H. pylori serology for test-and-treat strategy—use breath or stool testing only 3, 2.
• Do not assume hyperferritinemia at 656 μg/L indicates hemochromatosis—it is more commonly due to inflammation, infection, or liver dysfunction in this context 5, 6.

Initial Management While Awaiting Diagnostic Results

• Start high-dose proton pump inhibitor therapy immediately with omeprazole 40 mg once daily before meals, achieving ulcer healing rates of 80-90% for duodenal ulcers and 70-80% for gastric ulcers 1, 2.
• Counsel on alcohol cessation, as continued alcohol use worsens peptic ulcer disease, gastritis, liver dysfunction, and hypogonadism 1, 2.
• For symptomatic relief of nausea, consider ondansetron 8 mg sublingual every 4-6 hours (obtain baseline ECG due to QTc prolongation risk) 1, 2.
• Avoid NSAIDs, which worsen peptic ulcer disease 2.