open access

Vol 89, No 4 (2021)
Review paper
Submitted: 2021-01-01
Accepted: 2021-06-19
Published online: 2021-09-02
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Endocrine paraneoplastic syndromes in lung cancer: a respiratory physician’s perspective

Pratap Upadhya1, Arpitha Ananthraju2, Rohit vadala3, Madhusmita Mohanty Mohapatra1
DOI: 10.5603/ARM.a2021.0075
·
Pubmed: 34494243
·
Adv Respir Med 2021;89(4):403-412.
Affiliations
  1. Department of Pulmonary Medicine, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
  2. Department of Obstetrics and Gynecology, Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India
  3. Department of Pulmonary Medicine, All India Institute of Medical Sciences, New Delhi, India

open access

Vol 89, No 4 (2021)
REVIEWS
Submitted: 2021-01-01
Accepted: 2021-06-19
Published online: 2021-09-02

Abstract

Lung malignancy is known to be one of the leading causes of cancer-related mortality. Endocrine paraneoplastic syndromes in lung cancer are common. These are due to secretion of various substances and not because of direct tumour invasion or me-tastasis. These syndromes have also been associated with lung cancer prognosis. This review describes the many endocrine paraneoplastic syndromes seen in lung cancer and narrates their incidence, biology, clinical features, diagnosis, and management.

Abstract

Lung malignancy is known to be one of the leading causes of cancer-related mortality. Endocrine paraneoplastic syndromes in lung cancer are common. These are due to secretion of various substances and not because of direct tumour invasion or me-tastasis. These syndromes have also been associated with lung cancer prognosis. This review describes the many endocrine paraneoplastic syndromes seen in lung cancer and narrates their incidence, biology, clinical features, diagnosis, and management.

Get Citation

Keywords

endocrine paraneoplastic syndromes, lung cancer, hypercalcaemia, hyponatraemia, small-cell lung carcinoma

About this article
Title

Endocrine paraneoplastic syndromes in lung cancer: a respiratory physician’s perspective

Journal

Advances in Respiratory Medicine

Issue

Vol 89, No 4 (2021)

Article type

Review paper

Pages

403-412

Published online

2021-09-02

DOI

10.5603/ARM.a2021.0075

Pubmed

34494243

Bibliographic record

Adv Respir Med 2021;89(4):403-412.

Keywords

endocrine paraneoplastic syndromes
lung cancer
hypercalcaemia
hyponatraemia
small-cell lung carcinoma

Authors

Pratap Upadhya
Arpitha Ananthraju
Rohit vadala
Madhusmita Mohanty Mohapatra

References (77)
  1. Gaga M, Powell CA, Schraufnagel DE, et al. ATS/ERS Task Force on the Role of the Pulmonologist in the Management of Lung Cancer. An official American Thoracic Society/European Respiratory Society statement: the role of the pulmonologist in the diagnosis and management of lung cancer. Am J Respir Crit Care Med. 2013; 188(4): 503–507.
  2. Beckles MA, Spiro SG, Colice GL, et al. Initial evaluation of the patient with lung cancer: symptoms, signs, laboratory tests, and paraneoplastic syndromes. Chest. 2003; 123(1 Suppl): 97S–104S.
  3. Dela Cruz CS, Tanoue LT, Matthay RA. Lung cancer: epidemiology, etiology, and prevention. Clin Chest Med. 2011; 32(4): 605–644.
  4. Früh M, De Ruysscher D, Popat S, et al. ESMO Guidelines Working Group. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 Suppl 6: vi99–v105.
  5. Li Xu, Bie Z, Zhang Z, et al. Clinical analysis of 64 patients with lung-cancer-associated hypercalcemia. J Cancer Res Ther. 2015; 11 Suppl: C275–C279.
  6. Reisch N, Reincke M. [Endocrine paraneoplastic syndromes]. Internist (Berl). 2018; 59(2): 125–133.
  7. Detterbeck FC, Lewis SZ, Diekemper R, et al. Executive summary: diagnosis and management of lung cancer, 3rd ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2013; 143(5 Suppl): 7S–37S.
  8. Ramos RE, Perez Mak M, Alves MF, et al. Malignancy-related hypercalcemia in advanced solid tumors: survival outcomes. J Glob Oncol. 2017; 3(6): 728–733.
  9. Mirrakhimov AE. Hypercalcemia of malignancy: an update on pathogenesis and management. N Am J Med Sci. 2015; 7(11): 483–493.
  10. Bender RA, Hansen H. Hypercalcemia in bronchogenic carcinoma. A prospective study of 200 patients. Ann Intern Med. 1974; 80(2): 205–208.
  11. Hiraki A, Ueoka H, Takata I, et al. Hypercalcemia-leukocytosis syndrome associated with lung cancer. Lung Cancer. 2004; 43(3): 301–307.
  12. Nielsen PK, Rasmussen AK, Feldt-Rasmussen U, et al. Ectopic production of intact parathyroid hormone by a squamous cell lung carcinoma in vivo and in vitro. J Clin Endocrinol Metab. 1996; 81(10): 3793–3796.
  13. Goldner W. Cancer-related hypercalcemia. J Oncol Pract. 2016; 12(5): 426–432.
  14. Kasper DL, Fauci AS, Hauser SL. Harrison’s principles of internal medicine. Mc Graw Hill Education, New York 2015.
  15. Yoshimoto K, Yamasaki R, Sakai H, et al. Ectopic production of parathyroid hormone by small cell lung cancer in a patient with hypercalcemia. J Clin Endocrinol Metab. 1989; 68(5): 976–981.
  16. Hiraki A, Ueoka H, Bessho A, et al. Parathyroid hormone-related protein measured at the time of first visit is an indicator of bone metastases and survival in lung carcinoma patients with hypercalcemia. Cancer. 2002; 95(8): 1706–1713.
  17. Ma Xt, Yu Lw, Fu J. Paraneoplastic syndromes of hypercalcemia and leukocytosis associated with colonic metastases from squamous cell carcinoma of the lung. Int J Colorectal Dis. 2008; 23(1): 129–130.
  18. Van den Eynden GG, Neyret A, Fumey G, et al. PTHrP, calcitonin and calcitriol in a case of severe, protracted and refractory hypercalcemia due to a pancreatic neuroendocrine tumor. Bone. 2007; 40(4): 1166–1171.
  19. Gilmore JL, Gonterman RM, Menon K, et al. Reconstitution of amphiregulin-epidermal growth factor receptor signaling in lung squamous cell carcinomas activates PTHrP gene expression and contributes to cancer-mediated diseases of the bone. Mol Cancer Res. 2009; 7(10): 1714–1728.
  20. Kandil E, Noureldine S, Khalek M, et al. Ectopic secretion of parathyroid hormone in a neuroendocrine tumor: a case report and review of the literature. Int J Clin Exp Med. 2011; 4(3): 234–240.
  21. Strewler GJ. The physiology of parathyroid hormone-related protein. N Engl J Med. 2000; 342(3): 177–185.
  22. McClelland MT. Paraneoplastic syndromes related to lung cancer. Clin J Oncol Nurs. 2010; 14(3): 357–364.
  23. Ricciardi S, de Marinis F. Treatment of bone metastases in lung cancer: the actual role of zoledronic acid. Rev Recent Clin Trials. 2009; 4(3): 205–211.
  24. Stewart AF. Clinical practice. Hypercalcemia associated with cancer. N Engl J Med. 2005; 352(4): 373–379.
  25. Takeuchi Y, Takahashi S, Miura D, et al. Cinacalcet hydrochloride relieves hypercalcemia in Japanese patients with parathyroid cancer and intractable primary hyperparathyroidism. J Bone Miner Metab. 2017; 35(6): 616–622.
  26. Sternlicht H, Glezerman IG. Hypercalcemia of malignancy and new treatment options. Ther Clin Risk Manag. 2015; 11: 1779–1788.
  27. Ling PJ, A'Hern RP, Hardy JR. Analysis of survival following treatment of tumour-induced hypercalcaemia with intravenous pamidronate (APD). Br J Cancer. 1995; 72(1): 206–209.
  28. Gurney H, Grill V, Martin TJ. Parathyroid hormone-related protein and response to pamidronate in tumour-induced hypercalcaemia. Lancet. 1993; 341(8861): 1611–1613.
  29. Schwartz WB, Bennett W, Curelop S, et al. syndrome of renal sodium loss and hyponatremia probably resulting from inappropriate secretion of antidiuretic hormone. Am J Med. 1957; 23(4): 529–542.
  30. Amatruda TT, Mulrow PJ, Gallagher JC, et al. Carcinoma of the lung with inappropriate antidiuresis. Demonstration of antidiuretic-hormone-like activity in tumor extract. N Engl J Med. 1963; 269: 544–549.
  31. Raftopoulos H. Diagnosis and management of hyponatremia in cancer patients. Support Care Cancer. 2007; 15(12): 1341–1347.
  32. Grohé C, Berardi R, Burst V. Hyponatraemia — SIADH in lung cancer diagnostic and treatment algorithms. Crit Rev Oncol Hematol. 2015; 96(1): 1–8.
  33. Iyer P, Ibrahim M, Siddiqui W, et al. Syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) as an initial presenting sign of non small cell lung cancer-case report and literature review. Respir Med Case Rep. 2017; 22: 164–167.
  34. Fiordoliva I, Meletani T, Baleani MG, et al. Managing hyponatremia in lung cancer: latest evidence and clinical implications. Ther Adv Med Oncol. 2017; 9(11): 711–719.
  35. Anderson RJ, Chung HM, Kluge R, et al. Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med. 1985; 102(2): 164–168.
  36. Johnson BE, Chute JP, Rushin J, et al. A prospective study of patients with lung cancer and hyponatremia of malignancy. Am J Respir Crit Care Med. 1997; 156(5): 1669–1678.
  37. Lee CR, Watkins ML, Patterson JH, et al. Vasopressin: a new target for the treatment of heart failure. Am Heart J. 2003; 146(1): 9–18.
  38. Verzicco I, Regolisti G, Quaini F, et al. Electrolyte disorders induced by antineoplastic drugs. Front Oncol. 2020; 10: 779.
  39. Hermes A, Waschki B, Reck M. Hyponatremia as prognostic factor in small cell lung cancer--a retrospective single institution analysis. Respir Med. 2012; 106(6): 900–904.
  40. Hansen O, Sørensen P, Hansen KH. The occurrence of hyponatremia in SCLC and the influence on prognosis: a retrospective study of 453 patients treated in a single institution in a 10-year period. Lung Cancer. 2010; 68(1): 111–114.
  41. Meador CK, Liddle GW, Island DP, et al. Cause of Cushing's syndrome in patients with tumors arising from "nonendocrine" tissue. J Clin Endocrinol Metab. 1962; 22: 693–703.
  42. Boddaert G, Grand B, Le Pimpec-Barthes F, et al. Bronchial carcinoid tumors causing Cushing's syndrome: more aggressive behavior and the need for early diagnosis. Ann Thorac Surg. 2012; 94(6): 1823–1829.
  43. Kenchaiah M, Hyer S. Cushing's syndrome due to ectopic ACTH from bronchial carcinoid: a case report and review. Case Rep Endocrinol. 2012; 2012: 215038.
  44. Young J, Haissaguerre M, Viera-Pinto O, et al. Management of endocrine disease: Cushing's syndrome due to ectopic ACTH secretion: an expert operational opinion. Eur J Endocrinol. 2020; 182(4): R29–R58.
  45. Sarid N, Osher E, Gat A, et al. Cushing's syndrome as a harbinger of relapsed nonsmall cell lung cancer. Isr Med Assoc J. 2012; 14(8): 523–524.
  46. Yarbro CH, Wujcik D, Gobel BH. Cancer nursing: principles and practice. Jones & Bartlett Publishers, Burlington 2010.
  47. Shahani S, Nudelman RJ, Nalini R, et al. Ectopic corticotropin-releasing hormone (CRH) syndrome from metastatic small cell carcinoma: a case report and review of the literature. Diagn Pathol. 2010; 5: 56.
  48. Delisle L, Boyer MJ, Warr D, et al. Ectopic corticotropin syndrome and small-cell carcinoma of the lung. Clinical features, outcome, and complications. Arch Intern Med. 1993; 153(6): 746–752.
  49. Shepherd FA, Laskey J, Evans WK, et al. Cushing's syndrome associated with ectopic corticotropin production and small-cell lung cancer. J Clin Oncol. 1992; 10(1): 21–27.
  50. Imura H, Matsukura S, Yamamoto H, et al. Studies on ectopic ACTH-producing tumors. II. Clinical and biochemical features of 30 cases. Cancer. 1975; 35(5): 1430–1437, doi: 10.1002/1097-0142(197505)35:5<1430::aid-cncr2820350529>3.0.co;2-o.
  51. Sarlis NJ, Chanock SJ, Nieman LK. Cortisolemic indices predict severe infections in Cushing syndrome due to ectopic production of adrenocorticotropin. J Clin Endocrinol Metab. 2000; 85(1): 42–47.
  52. Small M, Lowe GD, Forbes CD, et al. Thromboembolic complications in Cushing's syndrome. Clin Endocrinol (Oxf). 1983; 19(4): 503–511.
  53. Van Zaane B, Nur E, Squizzato A, et al. Hypercoagulable state in Cushing's syndrome: a systematic review. J Clin Endocrinol Metab. 2009; 94(8): 2743–2750.
  54. Guignat L, Bertherat J. The diagnosis of Cushing's syndrome: an Endocrine Society Clinical Practice Guideline: commentary from a European perspective. Eur J Endocrinol. 2010; 163(1): 9–13.
  55. Limper AH, Carpenter PC, Scheithauer B, et al. The Cushing syndrome induced by bronchial carcinoid tumors. Ann Intern Med. 1992; 117(3): 209–214.
  56. Nagy-Mignotte H, Shestaeva O, Vignoud L, et al. Multidisciplinary Thoracic Oncology Group at Grenoble University Hospital, France. Prognostic impact of paraneoplastic cushing's syndrome in small-cell lung cancer. J Thorac Oncol. 2014; 9(4): 497–505.
  57. Nieman LK. Recent updates on the diagnosis and management of Cushing's syndrome. Endocrinol Metab (Seoul). 2018; 33(2): 139–146.
  58. Torniai M, Scortichini L, Tronconi F, et al. Systemic treatment for lung carcinoids: from bench to bedside. Clin Transl Med. 2019; 8(1): 22.
  59. Hendifar AE, Marchevsky AM, Tuli R. Neuroendocrine tumors of the lung: current challenges and advances in the diagnosis and management of well-differentiated disease. J Thorac Oncol. 2017; 12(3): 425–436.
  60. Fischer S, Kruger M, McRae K, et al. Giant bronchial carcinoid tumors: a multidisciplinary approach. Ann Thorac Surg. 2001; 71(1): 386–393.
  61. İkizoğlu G. Red face revisited: flushing. Clin Dermatol. 2014; 32(6): 800–808.
  62. Cogen JD, Swanson J, Ong T. Endobronchial carcinoid and concurrent carcinoid syndrome in an adolescent female. Case Rep Pediatr. 2016; 2016: 2074970.
  63. Soga J, Yakuwa Y, Osaka M. Carcinoid syndrome: a statistical evaluation of 748 reported cases. J Exp Clin Cancer Res. 1999; 18(2): 133–141.
  64. Rubin de Celis Ferrari AC, Glasberg J, Riechelmann RP. Carcinoid syndrome: update on the pathophysiology and treatment. Clinics (Sao Paulo). 2018; 73(Suppl 1): e490s.
  65. Tormey WP, FitzGerald RJ. The clinical and laboratory correlates of an increased urinary 5-hydroxyindoleacetic acid. Postgrad Med J. 1995; 71(839): 542–545.
  66. Yeung SCJ, Habra MA, Thosani SN. Lung cancer-induced paraneoplastic syndromes. Curr Opin Pulm Med. 2011; 17(4): 260–268.
  67. Ahmadieh H, Arabi A. Endocrine paraneoplastic syndromes: a review. Endocrinol Metab Int J. 2015; 1(1): 15–25.
  68. Iglesias P, Díez JJ. Management of endocrine disease: a clinical update on tumor-induced hypoglycemia. Eur J Endocrinol. 2014; 170(4): R147–R157.
  69. Kim SW, Lee SE, Oh YL, et al. Nonislet cell tumor hypoglycemia in a patient with adrenal cortical carcinoma. Case Rep Endocrinol. 2016; 2016: 5731417.
  70. Kanaji N, Watanabe N, Kita N, et al. Paraneoplastic syndromes associated with lung cancer. World J Clin Oncol. 2014; 5(3): 197–223.
  71. Nauck MA, Reinecke M, Perren A, et al. Hypoglycemia due to paraneoplastic secretion of insulin-like growth factor-I in a patient with metastasizing large-cell carcinoma of the lung. J Clin Endocrinol Metab. 2007; 92(5): 1600–1605.
  72. Faglia G, Arosio M, Bazzoni N. Ectopic acromegaly. Endocrinol Metab Clin North Am. 1992; 21(3): 575–595.
  73. Doga M, Bonadonna S, Burattin A, et al. Ectopic secretion of growth hormone-releasing hormone (GHRH) in neuroendocrine tumors: relevant clinical aspects. Ann Oncol. 2001; 12 Suppl 2: S89–S94.
  74. Oberg K, Norheim I, Wide L. Serum growth hormone in patients with carcinoid tumours; basal levels and response to glucose and thyrotrophin releasing hormone. Acta Endocrinol (Copenh). 1985; 109(1): 13–18.
  75. Ghazi AA, Amirbaigloo A, Dezfooli AA, et al. Ectopic acromegaly due to growth hormone releasing hormone. Endocrine. 2013; 43(2): 293–302.
  76. Butler PW, Cochran CS, Merino MJ, et al. Ectopic growth hormone-releasing hormone secretion by a bronchial carcinoid tumor: clinical experience following tumor resection and long-acting octreotide therapy. Pituitary. 2012; 15(2): 260–265.
  77. Metz SA, Weintraub B, Rosen SW, et al. Ectopic secretion of chorionic gonadotropin by a lung carcinoma. Pituitary gonadotropin and subunit secretion and prolonged chemotherapeutic remission. Am J Med. 1978; 65(2): 325–333.

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