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

Published:January 13, 2020DOI:https://doi.org/10.1016/j.amjmed.2019.11.009
      To the Editor:
      Although ectopic adrenocorticotropic hormone (ACTH) syndrome is typically characterized by hypokalemia, which may be refractory to treatment, as in the recently reported case,

      Fanous N, Schwartz C, Gargus N, Casella JL: Ectopic Cushing's syndrome: a rare cause of electrolyte derangements[e-pub ahead of print]. Am J Med. https://doi.org/10.1016/j.amjmed.2019.08.047.

      the occasional patient presents with concurrent hyponatremia, as depicted in several case studies.
      • Stoicescu A
      • Irimie CA
      • Varciu M
      • Irimie M
      Simultaneously presentation of two paraneoplastic syndrome in a patient with lung carcinoma.

      Kosuda A, Shirahata T, Kudo N, et al: Long-term survival of a patient with small cell lung cancer secreting ADH and ACTH simultaneously, following the prolonged use of amrubicin: a case report[e-pub ahead of print]. Intern Med. https://doi.org/10.2169/internalmedicine.2838-19.

      • Agarwal KA
      • Soe MH
      Beyond the dual paraneoplastic syndrome of small-cell lung cancer with ADH and ACTH secretion: a case report with literature review and future implications.
      • Jolobe OM
      Ectopic ACTH syndrome: redefinition and case report.
      This biochemical association is attributable to the rarely reported paraneoplastic syndrome of coexistence of ectopic ACTH secretion and syndrome of inappropriate antidiuretic hormone secretion.
      • Stoicescu A
      • Irimie CA
      • Varciu M
      • Irimie M
      Simultaneously presentation of two paraneoplastic syndrome in a patient with lung carcinoma.

      Kosuda A, Shirahata T, Kudo N, et al: Long-term survival of a patient with small cell lung cancer secreting ADH and ACTH simultaneously, following the prolonged use of amrubicin: a case report[e-pub ahead of print]. Intern Med. https://doi.org/10.2169/internalmedicine.2838-19.

      • Agarwal KA
      • Soe MH
      Beyond the dual paraneoplastic syndrome of small-cell lung cancer with ADH and ACTH secretion: a case report with literature review and future implications.
      The underlying cause was small-cell lung cancer in all 11 fully investigated cases.
      • Stoicescu A
      • Irimie CA
      • Varciu M
      • Irimie M
      Simultaneously presentation of two paraneoplastic syndrome in a patient with lung carcinoma.

      Kosuda A, Shirahata T, Kudo N, et al: Long-term survival of a patient with small cell lung cancer secreting ADH and ACTH simultaneously, following the prolonged use of amrubicin: a case report[e-pub ahead of print]. Intern Med. https://doi.org/10.2169/internalmedicine.2838-19.

      • Agarwal KA
      • Soe MH
      Beyond the dual paraneoplastic syndrome of small-cell lung cancer with ADH and ACTH secretion: a case report with literature review and future implications.
      Among patients with this syndrome (the so-called “dual paraneoplastic syndrome”), plasma ACTH levels have ranged from “high normal”
      • Stoicescu A
      • Irimie CA
      • Varciu M
      • Irimie M
      Simultaneously presentation of two paraneoplastic syndrome in a patient with lung carcinoma.
      to 851 pg/mL.
      • Agarwal KA
      • Soe MH
      Beyond the dual paraneoplastic syndrome of small-cell lung cancer with ADH and ACTH secretion: a case report with literature review and future implications.
      In the 91-year-old patient who presented with hyponatremia and hypokalemia (the latter easily reversed by administration of triamterene),
      • Jolobe OM
      Ectopic ACTH syndrome: redefinition and case report.
      hyponatremia was initially incorrectly attributed to triggering of inappropriate secretion of antidiuretic hormone by congestive heart failure (because chest radiography showed cardiomegaly and pulmonary congestion).
      • Jolobe OM
      Ectopic ACTH syndrome: redefinition and case report.
      When the provisional diagnosis was subsequently revised (again incorrectly) to hypoadrenalism-related hyponatremia, a short synacthen test was performed, which yielded the following results:
      • Basal (9 am) plasma cortisol, 310.7 mcg/dL
      • Plasma cortisol 30 minutes after a 250-mcg dose of intravenous 1-24 tetracosactrin amounted to 464 mcg/dL
      Additionally, plasma osmolality was documented as 259 mOsm/kg, but there was no evaluation of plasma vasopressin or urine osmolality.
      On the afternoon of the short synacthen test, the patient underwent abdominal computed tomography, which revealed bilateral adrenal hyperplasia and hepatic metastases. These findings prompted a revision of the diagnosis to ectopic ACTH syndrome. This time, plasma ACTH was measured, and this registered a level of 64 pg/mL with concurrent plasma cortisol of 609 mcg/dL. The corresponding plasma ACTH precursor level amounted to 2704 pmol/L (reference range 5-34 pmol/L). Repeat chest radiography showed mediastinal lymphadenopathy. She died the following day. No autopsy was performed.

      Comments

      • 1)
        The coexistence of hypokalemia and hyponatremia should raise the index of suspicion for the possibility of dual paraneoplastic syndrome.
      • 2)
        A high ACTH precursor/ACTH ratio of approximately 48 or more supports a diagnosis of ectopic Cushing's
        • Stewart PM
        • Gibson S
        • Crosby SR
        • et al.
        ACTH precursors characterize the ectopic ACTH syndrome.
        if plasma ACTH is only modestly elevated.

      References

      1. Fanous N, Schwartz C, Gargus N, Casella JL: Ectopic Cushing's syndrome: a rare cause of electrolyte derangements[e-pub ahead of print]. Am J Med. https://doi.org/10.1016/j.amjmed.2019.08.047.

        • Stoicescu A
        • Irimie CA
        • Varciu M
        • Irimie M
        Simultaneously presentation of two paraneoplastic syndrome in a patient with lung carcinoma.
        Bulletin Transylvania University of Brasov Series VI: Medical Sciences. 2013; 6: 39-44
      2. Kosuda A, Shirahata T, Kudo N, et al: Long-term survival of a patient with small cell lung cancer secreting ADH and ACTH simultaneously, following the prolonged use of amrubicin: a case report[e-pub ahead of print]. Intern Med. https://doi.org/10.2169/internalmedicine.2838-19.

        • Agarwal KA
        • Soe MH
        Beyond the dual paraneoplastic syndrome of small-cell lung cancer with ADH and ACTH secretion: a case report with literature review and future implications.
        Case Rep Oncol Med. 2018 Oct 18; 20184038397https://doi.org/10.1155/2018/4038397
        • Jolobe OM
        Ectopic ACTH syndrome: redefinition and case report.
        Postgrad Med J. 1996; 72: 174-175
        • Stewart PM
        • Gibson S
        • Crosby SR
        • et al.
        ACTH precursors characterize the ectopic ACTH syndrome.
        Clin Endocrinol (Oxf). 1994; 40: 199-204