What is the most likely treatment for a 49-year-old male with a 30 pack-year smoking history, presenting with a 4-cm irregular right-sided perihilar mass on computed tomography (CT) scan, and symptoms suggestive of Cushing's syndrome, such as purple striae and buffalo hump, without enlarged lymph nodes?

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From the Guidelines

The most appropriate treatment for this 49-year-old male with a right-sided perihilar mass and signs of paraneoplastic Cushing's syndrome would be surgical resection (option C). The patient presents with clinical features highly suggestive of ectopic ACTH production from a lung tumor, including weight loss, purple abdominal striae, and posterior neck fat accumulation (buffalo hump) 1. These findings, combined with his significant smoking history and the 4-cm irregular mass without lymph node involvement, point to a likely ACTH-producing lung cancer, most commonly small cell lung cancer or bronchial carcinoid. For such localized tumors without evidence of metastasis, surgical resection offers the best chance for both removing the primary tumor and addressing the paraneoplastic syndrome by eliminating the source of ectopic ACTH.

Key Considerations

  • The presence of ectopic Cushing's syndrome significantly impacts the patient's prognosis and increases the risk of therapy-induced complications, making prompt treatment crucial 1.
  • Surgical resection is preferred over other options as it directly addresses both the tumor and the hormonal imbalance caused by ectopic ACTH production.
  • The patient's symptoms, such as weight loss and purple striae, are indicative of Cushing's syndrome, which can be palliated with treatment of the underlying cause, in this case, the lung tumor 1.

Treatment Approach

  • Surgical resection is the recommended approach for localized tumors without metastasis, as it offers the best chance for cure and resolution of paraneoplastic symptoms.
  • Medical management of hypercortisolism may be necessary preoperatively or if surgical resection is not feasible, using agents such as ketoconazole or mitotane to control cortisol levels 1.
  • The goal of treatment is to remove the source of ectopic ACTH, thereby resolving the Cushing's syndrome symptoms and improving the patient's overall prognosis and quality of life.

From the Research

Treatment Options for Lung Cancer with Cushing's Syndrome

The patient's symptoms, such as purple striae on the abdomen and prominent fat on the posterior neck, suggest Cushing's syndrome, which can be caused by ectopic adrenocorticotropin (ACTH) production by a lung tumor 2, 3, 4. The treatment of Cushing's syndrome due to endogenous overproduction of cortisol typically involves surgery to remove the source of excess cortisol production, followed by medication or radiation therapy if necessary 2, 5, 6.

Surgical Resection and Mediastinoscopy

Given the patient's 4-cm irregular mass without enlarged lymph nodes, surgical resection is a likely treatment option. Mediastinoscopy may be performed to assess lymph node status, and if node-negative, surgical resection can proceed 3, 6.

Key Considerations

  • The patient's 30 pack-year smoking history increases the risk of lung cancer, and the presence of Cushing's syndrome suggests an aggressive tumor 3, 4.
  • Surgical resection, possibly combined with mediastinoscopy, is a common approach for treating lung cancer with Cushing's syndrome 3, 6.
  • Radiation therapy may be considered as a second-line treatment or for patients who are not candidates for surgery 5, 6.

Possible Treatment Approaches

  • Surgical resection with or without mediastinoscopy
  • Combination chemotherapy and radiation (although not directly supported by the provided evidence)
  • Radiation therapy alone (not the most likely option, given the patient's tumor size and Cushing's syndrome)

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Treatment of adrenocorticotropin-dependent Cushing's syndrome: a consensus statement.

The Journal of clinical endocrinology and metabolism, 2008

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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