What workup is needed for a patient with Chronic Obstructive Pulmonary Disease (COPD) and pulmonary hypertension, thyroid nodules with thyroid enlargement, leukopenia, and low neutrophil count, with normal liver and renal function?

Workup for 71-Year-Old with COPD, Pulmonary Hypertension, Thyroid Nodules, and Leukopenia

This patient requires a comprehensive evaluation addressing three distinct but potentially interconnected issues: pulmonary hypertension assessment, thyroid disease characterization, and investigation of the mild leukopenia with neutropenia.

Immediate Priority: Pulmonary Hypertension Workup

Basic Laboratory Assessment

• Complete blood count (already done, shows leukopenia 3.7 and neutrophils 1.81) 1
• BNP or NT-proBNP to assess cardiac strain and prognosis in pulmonary hypertension 1, 2
• Comprehensive metabolic panel including serum sodium, potassium, creatinine, uric acid, AST, ALT, and bilirubin 1
• Troponin for cardiac risk stratification 1
• Iron studies as iron deficiency can worsen pulmonary hypertension 1
• Arterial blood gas analysis to assess hypoxemia and hypercapnia, which have prognostic implications and affect thyroid function 1

Cardiovascular Evaluation

• ECG to detect arrhythmias and right ventricular strain patterns 1, 2
• Echocardiography to evaluate right ventricular systolic pressure, right and left ventricular function, pericardial effusion, and right atrial size 1, 2, 3
• Six-minute walk test with Borg dyspnea score for objective functional assessment 1, 2

Pulmonary Assessment

• Pulmonary function tests with DLCO to characterize COPD severity and exclude restrictive lung disease 3
• High-resolution chest CT to evaluate parenchymal lung disease and exclude chronic thromboembolic disease 3
• Ventilation-perfusion scan is mandatory to exclude chronic thromboembolic pulmonary hypertension, as this is potentially surgically correctable 1, 3

Definitive Hemodynamic Assessment

• Right heart catheterization should be considered if pulmonary hypertension management will be altered, particularly if mean PAP ≥25 mmHg is confirmed and pulmonary vascular resistance needs quantification 1, 3

Thyroid Evaluation

Thyroid Function and Autoimmune Testing

• Complete thyroid panel (TSH, free T4, free T3) to assess thyroid function status, as thyroid dysfunction is common in COPD (22% prevalence) and can be associated with pulmonary hypertension 2, 4, 5, 6
• Thyroid antibodies (anti-TPO, anti-thyroglobulin) given the association between autoimmune thyroid disease and neutropenia 5, 7
• Thyroid ultrasound to characterize nodules and assess for multinodular goiter, which is the most common thyroid pathology in COPD patients 4, 6

Important consideration: Hypoxemia and hypercapnia from COPD exacerbations can cause non-thyroidal illness syndrome (NTIS), with prevalence up to 55% in hospitalized COPD patients 8. PaCO2 negatively correlates with free T4 and free T3 levels 8.

Leukopenia and Neutropenia Investigation

Hematologic Workup

• Peripheral blood smear to evaluate cell morphology and exclude dysplasia 7
• Antineutrophil antibodies as 37.2% of thyroid disease patients with neutropenia have positive antineutrophil antibodies 7
• Lymphocyte immunophenotyping (CD4+, CD8+, B cells, NK cells) to evaluate for T-large granular lymphocyte proliferation, which occurs in 20% of neutropenic patients with thyroid disease 7
• Vitamin B12 and folate levels to exclude nutritional causes
• Reticulocyte count to assess bone marrow response

Critical pitfall: The neutrophil count of 1.81 × 10⁹/L represents mild neutropenia. Thyroid disorders have a high frequency (43.6%) in neutropenic patients, with Hashimoto thyroiditis being most common (23.4%) 7. Anti-TPO titers are significantly higher in patients with positive antineutrophil antibodies 7.

Autoimmune Screening

• ANA panel to screen for connective tissue diseases, as autoimmune thyroid disease often coexists with other autoimmune conditions 2, 3
• Complement levels (C3, C4) as these negatively correlate with thyroid antibody titers 7

Additional Investigations Based on Clinical Context

If Pulmonary Hypertension is Severe or Progressive

• HIV testing as part of standard pulmonary arterial hypertension workup 1, 3
• Hepatitis serology if liver function abnormalities are present 1
• Abdominal ultrasound to screen for portal hypertension 1, 3

If Thyroid Nodules Require Further Characterization

• Fine needle aspiration biopsy of suspicious nodules based on ultrasound characteristics and size criteria

Follow-up Timeline

• Reassess within 2-4 weeks after initial testing to review results and determine if specialty referral is needed 2
• Cardiology consultation if echocardiography shows significant pulmonary hypertension or right ventricular dysfunction 2, 3
• Pulmonology consultation for COPD optimization and pulmonary hypertension management 2, 3
• Endocrinology consultation if thyroid dysfunction is confirmed or nodules require intervention 2
• Hematology consultation if neutropenia persists, worsens, or if T-LGL proliferation is detected 7

Key Clinical Correlations

The triad of COPD, pulmonary hypertension, and thyroid disease is not coincidental: Thyroid dysfunction occurs in 22% of COPD patients 4, and hyperthyroidism can directly cause pulmonary hypertension through enhanced catecholamine sensitivity and altered metabolism of vasoactive substances 5. The neutropenia may be autoimmune-mediated, particularly if thyroid antibodies are elevated 7. Hypoxemia correlates negatively with thyroid function (PaO2 positively correlates with free T4, r=0.313) 8, making arterial blood gas analysis essential for interpretation of thyroid tests.