Paraneoplastic ACTH-Dependent Hypercortisolism and Non-Refractory SIADH Associated with Small Cell Lung Cancer

Paraneoplastic endocrine syndromes are often from the remote effects that are not related to the direct invasion or metastasis. Ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS) accounts for 10-15% of all Cushing Syndromes. Syndrome of inappropriate antidiuretic hormone (SIADH) is found in up to 10% of small cell lung cancer (SCLC). However, their presentation together is seldomly reported in other case reports. Our main goal is to report the highlights of presentation, diagnosis, treatment and rapid progression of the disease.

Case Description:

A 61-year-old Caucasian female with history of active smoking, chronic obstructive pulmonary disease, Hashimoto thyroiditis, and remote cervical cancer history status post hysterectomy and radiation presented with generalized weakness and progressive lightheadedness. She was initially found to be severely hyponatremic with altered mentation and elevated D-dimer. A computed tomography scan demonstrated a left hilar mass with subcarinal lymphadenopathy. She underwent endobronchial ultrasound-guided transbronchial fine needle aspiration with biopsy results showing SCLC. A brief course of Tolvaptan was attempted with normalization of her sodium needing no further treatments. She was also found to have significantly high ACTH, serum and 24-hour urinary cortisol levels. A high dose dexamethasone suppression test failed to suppress her cortisol levels. She was treated with Ketoconazole with rapid normalization of her serum cortisol levels without elevation of her liver enzymes, hypercortisolism or significant improvement in her mentation. Her pituitary work up was consistent with mild subclinical hypothyroidism in addition to suppressed gonadotropin levels. Pituitary magnetic resonance imaging showed an anterior pituitary gland microadenoma without mass effect. Her SCLC staging was consistent with osseous metastatic disease and underwent chemotherapy but developed pancytopenia and sepsis secondary to urinary tract infection. She became severely agitated not able to protect her airways and was transitioned to comfort measures.

Discussion:

Paraneoplastic syndromes occur in < 1% of cancers. EAS occur in as high as 5% of SCLC and except in bronchial carcinoid tumors, it is not inhibited by glucocorticoids. In some rare cases, steroids may even suppress gonadotropins. SIADH is rarely seen with extrapulmonary small cell cancers. SCLC often responds to chemotherapy/radiation but with occult or metastatic disease adjunct treatments may be needed. SIADH may be self-limited or improve after a short course of an ADH antagonist. Adrenal steroidogenesis inhibitors may improve cortisol short-term with or without improvement in mentation.