Acromegaly and thyroid cancer: analysis of evolution in a series of patients

Karina Danilowicz1,2, Soledad Sosa2,1, Mariana Soledad Gonzalez Pernas3,1, Elizabeth Bamberger1,4, Sabrina Mara Diez1,5, Patricia Fainstein-Day6,1, Alejandra Furioso7,1, Mariela Glerean1,6, Mirtha Guitelman1,8, Débora Katz3,1, Nicole Lemaitre9, Alicia Lowenstein7, Mariela del Valle Luna9, María Paz Martínez10, Karina Miragaya1,11, Daniel Moncet12, María Victoria Ortuño10, Analía Pignatta13, Constanza Fernanda Ramacciotti14, Adriana Reyes7, Amelia Susana Rogozinski7,1, Patricia Slavinsky1,3, Julieta Tkatch8,1, Fabián Pitoia2
1Neuroendocrine Department, Sociedad Argentina de Endocrinología y Metabolismo, Buenos Aires, Argentina
2Endocrinology Division, Hospital de Clínicas José de San Martín- Universidad de Buenos Aires, Buenos Aires, Argentina
3Endocrinology Division, FLENI, Buenos Aires, Argentina
4Centro Privado de Endocrinología, Mendoza, Argentina
5Endocrinology Division, Hospital Pirovano, Buenos Aires, Argentina
6Department of Endocrinology and Nuclear Medicine, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina
7Endocrinology Division, Hospital Ramos Mejía, Buenos Aires, Argentina
8Endocrinology Division, Hospital Carlos G. Durand, Buenos Aires, Argentina
9Endocrinology Division, Hospital Ángel C. Padilla, Tucumán, Argentina
10Endocrinology Division, Hospital Alemán, Buenos Aires, Argentina
11Endocrinology Division, Sanatorio Güemes, Buenos Aires, Argentina
12Endocrinology Division, Hospital Privado de Comunidad, Mar del Plata, Buenos Aires, Argentina
13Endocrinology Division, Hospital Interzonal San Juan Bautista, San Fernando del Valle de Catamarca, Catamarca, Argentina
14Endocrinology Division, Hospital Privado Universitario de Córdoba, Córdoba, Argentina

Tóm tắt

Acromegaly is associated with higher morbidity and mortality mainly due to cardiovascular disease. Data on the incidence and evolution of thyroid cancer in acromegaly are controversial. Our objective was to describe the characteristics of a group of acromegalic patients with differentiated thyroid carcinoma (DTC) and analyze their evolution. This is a retrospective multicenter study of 24 acromegalic patients with DTC. The AJCC Staging System 8th Edition was used for TNM staging, and the initial risk of recurrence (RR), initial response and response at the end of follow-up (RFU) were defined according to the 2015 ATA Guidelines. As a control group, 92 patients with DTC without acromegaly were randomly included. Statistical analyses were done using SPSS Statistics 20.0. Median age of patients at diagnosis of acromegaly was 49.5 years (range 12–69). The median delay in diagnosis of acromegaly was 3 years (range 0.5–23). Mean baseline IGF-1 level was 2.9 ± 1.1 ULN. Median age at DTC diagnosis was 51.5 years (18–69). At the moment of diagnosis of DTC, 58.3% of the patients had active acromegaly. Median time from DTC diagnosis to acromegaly control was 1.25 years (0.5–7). Mean DTC tumor diameter of the biggest lesion was 14.6 ± 9.2 mm, being multifocal in 37.5%. All tumors were papillary carcinomas, two cases being of an aggressive variety. Lymph node dissection was performed in 8 out of 24 patients and 62.5% had metastases. Only one patient had distant metastases. Radioiodine ablation was given to 87.5% of patients. Nineteen patients (79%) were stage I, four (17%) stage II and one (4%) stage IVb. Initial RR was low in 87% (21/24), intermediate in 9% (2/24) and high in 4% (1/24) patient. RFU was: 83% (19/23) patients with no evidence of disease, 9% (2/23) with indeterminate response, 4% (1/23) with biochemical incomplete response and 4% (1/23) with structural incomplete response, at a median time of FU of 36.5 months. When comparing RFU between acromegalics and controls no statistically significant differences were found. Patients with acromegaly and DTC mostly had a low initial RR. When compared with the control group, we found that DTC patients with acromegaly did not have a worse evolution.

Từ khóa


Tài liệu tham khảo

Melmed S. Acromegaly. N Engl J Med. 1990;322:966–77. Melmed S. Acromegaly. N Engl J Med. 2006;355(24):2558–73. Agustsson TT, Baldvinsdottir T, Jonasson JG, Olafsdottir E, Steinthorsdottir V, Sigurdsson G, Thorson AV, Carroll PV, Korbonits M, Benediktsson R. The epidemiology of pituitary adenomas in Iceland, 1955-2012: a nationwide population-based study. Eur J Endocrinol. 2015;173(5):655–64. Day PF, Loto MG, Glerean M, Picasso MF, Lovazzano S, Giunta DH. Incidence and prevalence of clinically relevant pituitary adenomas: retrospective cohort study in a Health Management Organization in Buenos Aires, Argentina. Arch Endocrinol Metab. 2016;60(6):554–61. https://doi.org/10.1590/2359-3997000000195 PMID: 27982201. Dekkers OMJ, Biermasz NR, Pereira AM, Romijn JA, Vandenbroucke JP. Mortality in acromegaly: a metaanalysis. Clin Endocrinol Metab. 2008;93(1):61–7. Sherlock M, Ayuk J, Tomlinson JW, Toogood AA, Aragon-Alonso A, Sheppard MC, Bates AS, Stewart PM. Mortality in patients with pituitary disease. Endocr Rev. 2010;31(3):301–42. Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. J Clin Endocrinol Metab. 2004;89:667–74. Varadhan L, Reulen RC, Brown M, Clayton RN. The role of cumulative growth hormone exposure in determining mortality and morbidity in acromegaly: a single Centre study. Pituitary. 2016;19:251–61. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, Pathogenesis and Management. Endocr Rev. 2004;25:102–52. Jenkins PJ, Mukherjee A, Shalet SM. Does growth hormone cause cancer? Clin Endocrinol. 2006;64:115–21. Jenkins P, Besser M. Acromegaly and Cancer: A problem. J Clin Endocrinol Metab. 2001;86:2935–41. Boguszewski CL, Ayuk J. Acromegaly and cancer: an old debate revisited. Eur J Endocrinol. 2016;175:R147–56. Melmed S. Acromegaly and cancer: not a problem? J Clin Endocrinol Metab. 2001;86(7):2929–34. Petroff D, Tonjes A, Grussendorf M, Droste M, Dimopoulou CH, Stalla G, Jaursch-Hancke C, Mai M, Schopol J, Schofl CH. The incidence of cancer among acromegaly patients: results from the German acromegaly registry. J Clin Endocrinol Metab. 2015;100:3994–02. Dal J, Leisner MZ, Hermansen K, Farkas DK, Bengtsen M, Kistorp C, Nielsen EH, Andersen M, Feldt-Rasmussen U, Dekkers OM, Sørensen HT, Jørgensen JOL. Cancer incidence in patients with acromegaly: a cohort study and meta-analysis of the literature. J Clin Endocrinol Metab. 2018;103(6):2182–8. Arosio M, Reimondo G, Malchiodi E, Berchialla P, Borraccino A, De Marinis L, Pivonello R, Grottoli S, Losa M, Cannavò S, Minuto F, Montini M, Bondanelli M, De Menis E, Martini C, Angeletti G, Velardo A, Peri A, Faustini-Fustini M, Tita P, Pigliaru F, Borretta G, Scaroni C, Bazzoni N, Bianchi A, Appetecchia M, Cavagnini F, Lombardi G, Ghigo E, Beck-Peccoz P, Colao A, Terzolo M, Italian Study Group of Acromegaly. Predictors of morbidity and mortality in acromegaly: an Italian survey. Eur J Endocrinol. 2012;167(2):189–98. Tirosh A, Shimon I. Complications of acromegaly: thyroid and colon. Pituitary. 2017;20(1):70–5. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid Cancer: the American Thyroid Association guidelines task force on thyroid nodules and differentiated thyroid Cancer. Thyroid. 2016;26(1):1–133. Rajasoorya C, Holdaway IM, Wrightson P, Scott DJ, Ibbertson HK. Determinants of clinical outcome and survival in acromegaly. Clin Endocrinol. 1994;41(1):95–102. Wright AD, Hill DM, Lowy C, Fraser TR. Mortality in acromegaly. Q J Med. 1970;39(153):1–16 PMID: 5427331. Ayuk J, Clayton RN, Holder G, Sheppard MC, Stewart PM, Bates AS. Growth hormone and pituitary radiotherapy, but not serum insulin-like growth factor-I concentrations, predict excess mortality in patients with acromegaly. J Clin Endocrinol Metab. 2004;89(4):1613–7. Beauregard C, Truong U, Hardy J, Serri O. Long-term outcome and mortality after transsphenoidal adenomectomy for acromegaly. Clin Endocrinol. 2003;58(1):86–91. Bates AS, Van't Hoff W, Jones JM, Clayton RN. An audit of outcome of treatment in acromegaly. Q J Med. 1993;86(5):293–9 PMID: 8327647. Mercado M, Gonzalez B, Vargas G, Ramirez C, de los Monteros AL, Sosa E, Jervis P, Roldan P, Mendoza V, López-Félix B, Guinto G. Successful mortality reduction and control of comorbidities in patients with acromegaly followed at a highly specialized multidisciplinary clinic. J Clin Endocrinol Metab. 2014;99(12):4438–46. Shevah O, Laron Z. Patients with congenital deficiency of IGF-I seem protected from the development of malignancies: a preliminary report. Growth Hormon IGF Res. 2007;17(1):54–7. Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363(9418):1346–53. Chan JM, Stampfer MJ, Giovannucci E, Gann PH, Ma J, Wilkinson P, Hennekens CH, Pollak M. Plasma insulin-like growth factor-I and prostate cancer risk: a prospective study. Science. 1998;279(5350):563–6. Tramontano D, Cushing GW, Moses AC, Ingbar SH. Insulin like growth factor-I stimulates the growth of rat thyroid cells in culture and synergizes the stimulation of DNA synthesis induced by TSH and graves’-IgG. Endocrinology. 1986;119:940–2. Chanson P, Salenave S. Acromegaly. Orphanet J Rare Dis. 2008;3:17. https://doi.org/10.1186/1750-1172-3-17. Miyakawa M, Saji M, Tsushima T, Wakai K, Shizume K. Thyroid volume and serum thyroglobulin levels in patients with acromegaly: correlation with plasma insulin-like growth factor I levels. J Clin Endocrinol Metab. 1988;67(5):973–8. Wolinski K, Czarnywojtek A, Ruchala M. Risk of thyroid nodular disease and thyroid cancer in patients with acromegaly--meta-analysis and systematic review. PLoS One. 2014;9(2):e88787. Rogozinski A, Furioso A, Glikman P, Junco M, Laudi R, Reyes A, Lowenstein A. Thyroid nodules in acromegaly. Arq Bras Endocrinol Metab. 2012;56(5):300–4. Gasperi M, Martino E, Manetti L, Arosio M, Porretti S, Faglia G, Mariotti S, Colao AM, Lombardi G, Baldelli R, Camanni F, Liuzzi A, Acromegaly study Group of the Italian Society of endocrinology. Prevalence of thyroid diseases in patients with acromegaly: results of an Italian multi-center study. J Endocrinol Investig. 2002;25(3):240–5. Dagdelen S, Cinar N, Erbas T. Increased thyroid cancer risk in acromegaly. Pituitary. 2014;17(4):299–306. Dogansen SC, Salmaslioglu A, Yalin GY, Tanrikulu S, Yarman S. Evaluation of natural course of thyroid nodules in patients with acromegaly. Pituitary. 2019;22:29–36. dos Santos MC, Nascimento GC, Nascimento AG, Carvalho VC, Lopes MH, Montenegro R, Montenegro R Jr, Vilar L, Albano MF, Alves AR, Parente CV, dos Santos Faria M. Thyroid cancer in patients with acromegaly: a case-control study. Pituitary. 2013;16(1):109–14. Gullu BE, Celik O, Gazioglu N, Kadioglu P. Thyroid cancer is the most common cancer associated with acromegaly. Pituitary. 2010;13(3):242–8. Gul N, Soyluk O, Dogansen SC, Kurtulmus N, Yarman S. Disease activity may not affect the prognosis of coexisting thyroid cancer in acromegalic patients. Exp Clin Endocrinol Diabetes. 2019. https://doi.org/10.1055/a-0915-1982 [Epub ahead of print].