Beyond the Dual Paraneoplastic Syndromes of Small-Cell Lung Cancer with ADH and ACTH Secretion: A Case Report with Literature Review and Future Implications

Abstract

We present a case of small-cell lung cancer (SCLC) with syndrome of inappropriate antidiuretic hormone secretion (SIADH) in which serum sodium gradually normalized with the onset of hypertension, refractory hypokalemia, and chloride-resistant metabolic alkalosis due to ectopic adrenocorticotrophic hormone (ACTH) secretion (EAS). In this case report, we discuss the diagnostic challenges of dual paraneoplastic syndromes with SIADH and EAS, management of SCLC with paraneoplastic endocrinopathies, and their prognostic impact on SCLC. In addition, we discuss neuroendocrine differentiation and ectopic hormone production in relation to intratumoral heterogeneity in SCLC and propose tumor microenvironment and hormonal and metabolic dependence as important determinants of tumor growth and survival.

Long-term Survival of a Patient with Small Cell Lung Cancer Secreting ADH and ACTH Simultaneously, Following the Prolonged Use of Amrubicin

“…Paraneoplastic Cushing's syndrome results from the ectopic production of ACTH and affects 1-5% of all patients diagnosed with Cushing's syndrome (2); approximately 50-60% of these cases are neuroendocrine lung tumors [carcinoid tumors (30-46%); SCLC (8-20%)] (3-5). The diagnosis is established under high clinical suspicion based on elevated cortisol and ACTH levels in addition to a positive dexamethasone suppression test.…”

“…It is noteworthy that thus far, there have been only nine reported cases wherein SCLC produced these two hormones simultaneously (2,(6)(7)(8)(9)(10)(11)(12)(13). According to these reports, the opposing effects of cortisol and ADH on renal sodium excre-tion sometimes complicate the diagnosis or result in a misdiagnosis.…”

“…According to these reports, the opposing effects of cortisol and ADH on renal sodium excre-tion sometimes complicate the diagnosis or result in a misdiagnosis. In addition, the presence of these paraneoplastic syndromes is indicative of a poor prognosis in SCLC patients, with overall survival of only 2-4 months (2,(6)(7)(8)(9)13).…”

Electrolyte Derangements when Ectopic Cushing's Is Included in Dual Paraneoplastic Syndrome

“…Although ectopic adrenocorticotropic hormone (ACTH) syndrome is typically characterized by hypokalemia, which may be refractory to treatment, as in the recently reported case, 1 the occasional patient presents with concurrent hyponatremia, as depicted in several case studies. [2][3][4][5] This biochemical association is attributable to the rarely reported paraneoplastic syndrome of coexistence of ectopic ACTH secretion and syndrome of inappropriate antidiuretic hormone secretion. [2][3][4] The underlying cause was small-cell lung cancer in all 11 fully investigated cases.…”

“…[2][3][4][5] This biochemical association is attributable to the rarely reported paraneoplastic syndrome of coexistence of ectopic ACTH secretion and syndrome of inappropriate antidiuretic hormone secretion. [2][3][4] The underlying cause was small-cell lung cancer in all 11 fully investigated cases. [2][3][4] Among patients with this syndrome (the so-called "dual paraneoplastic syndrome"), plasma ACTH levels have ranged from "high normal" 2 to 851 pg/mL.…”