Review Question - QID 216995

This patient with an extensive past smoking history presents with hemoptysis, fatigue, temporal muscle wasting, and a history of chronic non-productive cough in the setting of signs of hypercortisolism (recent diagnosis of diabetes indicative of poor glucose tolerance, skin atrophy, and proximal muscle weakness), which is suggestive of small cell lung cancer (a neuroendocrine tumor) causing Cushing syndrome via ectopic ACTH production.

Small cell lung cancers are the most common neuroendocrine lung cancers and can result in ectopic production of adrenocorticotropic hormone (ACTH), which stimulates cortisol synthesis and secretion by the adrenal cortex. This results in a state of hypercortisolism, which can present with menstrual irregularities, signs of androgen excess (e.g., oily skin, virilization), skin atrophy, glucose intolerance, abdominal striae, and proximal muscle wasting/weakness. Ectopic ACTH production secondary to small cell lung cancer should be considered in patients with signs of Cushing syndrome and lung cancer symptoms (e.g., chronic cough, hemoptysis, muscle wasting). The diagnosis of ectopic ACTH production can be secured with serum cortisol, 24-hour urine free cortisol, and ACTH measurements. The initial imaging work-up of lung cancer includes chest radiographs and computed tomography scans.

Deldycke et al. review the incidence of paraneoplastic Cushing syndrome, finding that bronchial carcinoids and small cell lung cancers are the most common etiologies. They state that no overt tumor is found in 10-20% of cases.

Incorrect Answers:
Answer 1: Lung parenchymal infection by a Gram positive organism (e.g., Streptococcus pneumoniae) refers to pneumonia, which should be considered in any patient with a cough and concern for infection. However, pneumonia usually presents acutely with productive sputum and signs of infection, including fever and chills. This patient is afebrile, and her symptoms are chronic.

Answer 2: Malignancy of keratin-producing lung cells with metastasis refers to squamous cell carcinoma. Squamous cell lung cancer can cause a non-productive cough with hemoptysis. However, it is associated with hypercalcemia as a paraneoplastic syndrome, mediated through production of parathyroid hormone-related peptide. Symptoms of hypercalcemia include constipation, polyuria, bone pain, muscle weakness, or depression.

Answer 3: Malignancy of skin pigment-producing cells with metastasis refers to metastatic melanoma. Melanoma can metastasize to the lungs, causing a cough and hemoptysis. While this patient does have several skin lesions on her torso, the lesions do not have typical concerning features for melanoma (asymmetry, border irregularity, color variation, diameter >6mm, and/or evolution over time). Additionally, metastatic melanoma is not typically associated with Cushing syndrome as a paraneoplastic syndrome.

Answer 5: Pulmonary infection by acid-fast bacilli refers to pulmonary tuberculosis, which should be considered in any patient presenting with a cough and hemoptysis. Pulmonary tuberculosis can also present with constitutional symptoms such as chills and night sweats. This patient’s travel to an area where tuberculosis is endemic puts her at risk for contracting this condition. However, pulmonary tuberculosis would not explain this patient’s signs of hypercortisolism.

Bullet Summary:
Small cell lung cancer can cause Cushing syndrome as a paraneoplastic syndrome due to ectopic ACTH production, presenting with signs of cortisol excess such as glucose intolerance, skin atrophy, abdominal striae, and proximal muscle weakness.