What is the diagnosis of a patient with hyperthyroidism, severe jaundice, anemia, hypokalemia, and proteinuria?

Diagnosis: Hyperthyroidism with Severe Cholestatic Jaundice and Associated Complications

The most likely diagnosis is hyperthyroidism (likely Graves' disease) complicated by severe cholestatic jaundice, with the anemia, hypokalemia, and proteinuria representing secondary manifestations of the thyrotoxic state.

Primary Diagnostic Consideration

Hyperthyroidism with severe hepatic dysfunction is the unifying diagnosis. Severe jaundice can occur directly from hyperthyroidism itself, with bilirubin levels reaching as high as 323 μmol/L (approximately 19 mg/dL) documented in hyperthyroid patients without concomitant liver disease 1. This cholestatic pattern represents a rare but well-documented complication of thyrotoxicosis 2.

Key Diagnostic Features Supporting This Diagnosis:

• Severe jaundice in hyperthyroidism occurs through cholestatic mechanisms, though the exact pathophysiology remains unclear 2
• Hepatic dysfunction can present with markedly prolonged prothrombin time and deep jaundice in hyperthyroidism alone, making it difficult to distinguish from unrelated liver disease until thyroid function is controlled 1
• Serum aminotransferase elevations are typically mild (>250 IU/L in only 3% of cases), consistent with cholestatic rather than hepatocellular injury 1

Secondary Manifestations Explained

Anemia

• Anemia in hyperthyroidism can result from multiple mechanisms including increased red cell turnover, nutritional deficiencies from hypermetabolic state, and bone marrow suppression 3
• The severity should prompt evaluation for concurrent causes (iron, B12, folate deficiency) that may be unrelated to thyroid disease 3

Hypokalemia

• Hypokalemia occurs in hyperthyroidism through increased cellular uptake of potassium driven by excess thyroid hormone 3
• This can be severe enough to cause thyrotoxic periodic paralysis in susceptible individuals 4

Proteinuria

• Proteinuria is a recognized manifestation of hyperthyroidism, particularly in autoimmune thyroid disease (Graves' disease) 5
• The proteinuria correlates with thyroid hormone levels and typically resolves with achievement of euthyroid state 5
• Daily protein excretion in documented cases ranged from 11-13.5 mg/m²/h, which can be substantial 5

Diagnostic Workup Algorithm

Confirm Hyperthyroidism:

• Check TSH (expected: suppressed) and free T4/T3 (expected: elevated) 6, 4
• Measure TSH receptor antibodies to confirm Graves' disease if clinically suspected 6, 4
• Thyroid peroxidase antibodies support autoimmune etiology 3, 5

Evaluate Hepatic Dysfunction:

• Obtain complete liver panel including bilirubin (direct/indirect), aminotransferases, alkaline phosphatase, and prothrombin time 1
• Rule out alternative causes of jaundice: viral hepatitis serologies, autoimmune markers (ANA, anti-smooth muscle antibody), drug exposure history 2
• Abdominal ultrasound to exclude biliary obstruction and assess for hepatosplenomegaly 1

Assess Complications:

• Complete blood count to characterize anemia 3
• Serum potassium and electrocardiogram (prolonged QT interval can occur with hypokalemia) 3
• Quantify proteinuria with 24-hour urine collection or spot protein-to-creatinine ratio 5
• Urinalysis to assess for active sediment (should be bland in thyroid-related proteinuria) 7, 5

Critical Pitfall to Avoid

Do not assume the jaundice is drug-induced from antithyroid medications if the patient has not yet been treated. Severe cholestatic jaundice can be the presenting manifestation of hyperthyroidism itself 2, 1. However, if methimazole or propylthiouracil have been initiated, drug-induced hepatotoxicity must be considered, as antithyroid drugs can cause severe hepatic injury requiring immediate discontinuation 4.

Treatment Approach

Immediate Management:

• Initiate antithyroid drug therapy (methimazole preferred unless contraindicated) to control hyperthyroidism 2, 4
• Add beta-blocker for symptomatic relief of adrenergic symptoms 6, 4
• Correct hypokalemia with potassium supplementation 3
• Monitor liver function tests closely during treatment 2, 1

Expected Clinical Course:

• Jaundice should improve with restoration of euthyroid state 2
• Proteinuria typically resolves as thyroid hormone levels normalize 5
• Liver function abnormalities may take weeks to months to fully resolve after achieving euthyroidism 1

Monitoring:

• Recheck thyroid function tests every 2-3 weeks initially during thyrotoxic phase 3
• Serial liver function tests to document improvement 2, 1
• Repeat urinalysis and proteinuria quantification after achieving euthyroid state 5

When to Consider Alternative Diagnoses

If the patient does not improve with antithyroid therapy or if atypical features are present, consider:

• Concomitant unrelated liver disease if jaundice persists despite controlled hyperthyroidism 1
• Primary renal disease if proteinuria persists with active urinary sediment (hematuria, cellular casts) after achieving euthyroid state 7, 5
• Hypophysitis or central hypothyroidism if TSH is low/normal with low free T4 (opposite pattern from hyperthyroidism) 3, 8