European Journal of Ageing

, Volume 16, Issue 4, pp 405–414 | Cite as

Association of endemic goitre and exceptional longevity in Sardinia: evidence from an ecological study

  • Francesco ToluEmail author
  • Mario Palermo
  • Maria Pina Dore
  • Alessandra Errigo
  • Ana Canelada
  • Michel Poulain
  • Giovanni Mario Pes
Original Investigation


This study aims to test the hypothesis that a high prevalence of endemic goitre, considered as a proxy measure for subclinically reduced thyroid function in the population, is geographically associated with exceptional longevity. Using historical data available for 377 Sardinian municipalities in the first half of the twentieth century, we performed an ecological study to investigate the geographic distribution of goitre and its spatial association with demographic indicators of population longevity. This analysis was conducted by using both conventional ordinary least square and geographically weighted regression models to take into account spatial autocorrelation and included other longevity-associated factors previously identified in Sardinia. The spatial analysis revealed that the goitre rate (p < 0.0001), the proportion of inhabitants involved in pastoralism (p = 0.016), the terrain inclination (p = 0.008), and the distance from the workplace as a proxy for physical activity (p = 0.023) were consistently associated with population longevity at an aggregated level in the 377 municipalities. Within the limits of an ecological study design, our findings support the existence of a significant association between high goitre prevalence and increased probability to survive into old age. The present study confirms previous results and is consistent with animal studies and epidemiological surveys in other long-lived areas known as Blue Zones. Potential mechanisms underlying this association need to be further investigated.


Sardinia Extreme longevity Centenarians Endemic goitre Iodine deficiency 



The authors thank Dr Marianna Tosi for help in retrieving demographic data.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

10433_2019_510_MOESM1_ESM.doc (90 kb)
Supplementary material 1 (DOC 89 kb)


  1. Aggarwal N, Razvi S (2013) Thyroid and aging or the aging thyroid? An evidence-based analysis of the literature. J Thyr Res 2013:481287Google Scholar
  2. Aghini-Lombardi F, Antonangeli L, Vitti P (1998) Epidemiologia del gozzo endemico in Italia. Ann Sup Sanità 34:311–314Google Scholar
  3. Ambrosi V (1941) Policlinico. Sez Prat 48:1606Google Scholar
  4. Anwar K, Rehman H, Khan M, Shahabi I, Aslam R, Evaluation of goiters (2015) A comparison of palpation and ultrasonography in assessment of enlarged thyroid gland. KJMS 8:197–201Google Scholar
  5. Atzeni E, Alba ML, Loviselli A, Velluzzi F, Martino E, Balestrieri A (1989) Iodine content in drinking water in the middle south Sardinia Italy. Rassegna Med Sarda 92:323–332Google Scholar
  6. Atzmon G, Barzilai N, Surks MI, Gabriely I (2009a) Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity. Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab 94:4768–4775Google Scholar
  7. Atzmon G, Barzilai N, Hollowell JG, Surks MI, Gabriely I (2009b) Extreme longevity is associated with increased serum thyrotropin. J Clin Endocrinol Metab 94:1251–1254Google Scholar
  8. Boyle JA, Greig WR, Fulton S, Dalakos TG (1966) Excess dietary calcium and human thyroid function. J Endocrinol 34:531–532Google Scholar
  9. Buffenstein R (2005) The naked mole-rat: a new long-living model for human aging research. J Geron Biol Sci Med Sci 60:1369–1377Google Scholar
  10. Chen Y (2013) New approaches for calculating moran’s index of spatial autocorrelation. PLoS ONE 8(7):e68336Google Scholar
  11. Corda D (1935) Osservazioni sulla frequenza e sulle manifestazioni del gozzismo frusto o conclamato su 5000 alunni delle scuole elementari di Cagliari. La Clin Pediatrica 17:725–752Google Scholar
  12. Costa A (1973) The iodine content of drinking water in Sardinia. Folia Endocrinol 26:134–138Google Scholar
  13. Desogus V (1938) Di un particolare aspetto della teoria geologica del gozzismo con speciale riguardo all’isola di Sardegna. Rassegna Med Sarda 5:173–191Google Scholar
  14. Etling N, Fouque F, Garabedian M (1986) Effect of dietary supply of calcium on thyroid function in rats. Reprod Nutr Dev 26:841–847Google Scholar
  15. Fastame MC, Hitchcott PK, Penna MP (2018) The impact of leisure on mental health of Sardinian elderly from the ‘blue zone’: evidence for ageing well. Aging Clin Exp Res 30:169–180Google Scholar
  16. Feller M, Snel M, Moutzouri E, Bauer DC, de Montmollin M, Aujesky D, Ford I, Gussekloo J, Kearney PM, Mooijaart S, Quinn T, Stott D, Westendorp R, Rodondi N, Dekkers OM (2018) Association of thyroid hormone therapy with quality of life and thyroid-related symptoms in patients with subclinical hypothyroidism: a systematic review and meta-analysis. JAMA 320:1349–1359Google Scholar
  17. Fermi C (1934) Regioni malariche, decadenza risanamento e spesa. Voll. 1–3. “Sardegna”. Roma: Tip. Editrice di RomaGoogle Scholar
  18. Fiore E, Tonacchera M, Vitti P (2014) Influence of iodization programmes on the epidemiology of nodular goitre. Best Pract Res Clin Endocrinol Metab 28:577–588Google Scholar
  19. Fotheringham AS, Brunsdon C, Charlton ME (2002) Geographically weighted regression: the analysis of spatially varying relationships. Wiley, ChichesterGoogle Scholar
  20. Greenland S (2001) Ecologic versus individual level sources of bias in ecologic estimates of contextual health effects. Int J Epidemiol 30:1343Google Scholar
  21. Greenland S, Morgenstern H (1989) Ecological bias, confounding, and effect modification. Int J Epidemiol 18:269Google Scholar
  22. Haining R, Law J (2011) Geographical Information Systems models and spatial data analysis. In: Batabyal A, Nijkamp P (eds) Research tools in natural resource and environmental economics. World Scientific Publishing, Singapore, pp 377–402Google Scholar
  23. Ladenson PW (2008) Cardiovascular consequences of subclinical thyroid dysfunction: more smoke but no fire. Ann Intern Med 148:880–881Google Scholar
  24. Laulund AS, Nybo M, Brix TH, Abrahamsen B, Jørgensen HL, Hegedüs L (2014) Duration of thyroid dysfunction correlates with all-cause mortality. The OPENTHYRO register cohort. PLoS ONE 9:e110437Google Scholar
  25. Loviselli A, Velluzzi F, Mossa P, Cambosu MA, Secci G, Atzeni F, Taberlet A, Balestrieri A, Martino E, Grasso L, Songini M, Bottazzo GF, Mariotti S (2001) Sardinian Schoolchildren Study Group. The Sardinian Autoimmunity Study: 3. Studies on circulating antithyroid antibodies in Sardinian schoolchildren: relationship to goiter prevalence and thyroid function. Thyroid 11:849–857Google Scholar
  26. Martino E, Loviselli A, Velluzzi F, Murtas ML, Carta M, Lampis M, Murru R, Mastinu A, Arba ML, Sica V et al (1994) Endemic goitre and thyroid function in central-southern Sardinia. Report on an extensive epidemiological survey. J Endocrinol Invest 17:653–657Google Scholar
  27. Moran PAP (1950) Notes on continuous stochastic phenomena. Biometrika 37:17–23Google Scholar
  28. Nordmeyer JP, Simons M, Wenzel C, Scholten T (1997) How accurate is the assessment of thyroid volume by palpation? A prospective study of 316 patients. Exp Clin Endocrinol Diabete 6:366–371. CrossRefGoogle Scholar
  29. Nudda A, Battacone G, Decandia M, Acciaro M, Aghini-Lombardi F, Frigeri M, Pulina G (2009) The effect of dietary iodine supplementation in dairy goats on milk production traits and milk iodine content. J Dairy Sci 92:5133–5138Google Scholar
  30. Olivieri A, Vitti P (Ed.) (2014) Attività di monitoraggio del programma nazionale per la prevenzione dei disordini da carenza iodica. Roma: Istituto Superiore di Sanità. (Rapporti ISTISAN 14/6)Google Scholar
  31. Ooka H, Shinkai T (1986) Effects of hyperthyroidism on the life span of the rat. Mech Age Dev 33:275–282Google Scholar
  32. Ottonello P (1927) Nuove indagini sulla distribuzione dell’endemia gozzigena in Sardegna. Rivista di Patol Nerv e Mentale 32:13Google Scholar
  33. Pastorelli AA, Stacchini P, Olivieri A (2015) Daily iodine intake and the impact of salt reduction on iodine prophylaxis in the Italian population. Eur J Clin Nutr 69:211–215Google Scholar
  34. Peretti G (1943) Rapporti tra alimentazione e caratteri antropometrici. Studio statistico-biometrico in Sardegna. Quad Della Nutr 9:69–130Google Scholar
  35. Perez C, Salazar-Baldioceda A, Tandon OB, Srimshaw NS (1956) Endemic goiter in in costa rican school children. Institute of Nutrition in Central America and Panama (INCAP). Am J Public Health Nations Health 46:1283–1286Google Scholar
  36. Pes GM, Poulain M (2014) Longevità e identità in Sardegna. L’identificazione della “Zona Blu” dei centenari in Ogliastra. Franco Angeli Ed., Milano, Italy, ISBN 9788891708076Google Scholar
  37. Pes GM, Poulain M (2016) Blue zones. In: Pachana NA (ed) Encyclopedia of geropsychology. Springer, Singapore. CrossRefGoogle Scholar
  38. Pes GM, Lio D, Carru C, Deiana L, Baggio G, Franceschi C, Ferrucci L, Oliveri F, Scola L, Crivello A, Candore G, Colonna-Romano G, Caruso C (2004) Association between longevity and cytokine gene polymorphisms. A study in Sardinian centenarians. Aging Clin Exp Res 16:244–248Google Scholar
  39. Pes GM, Tolu F, Poulain M, Errigo A, Masala S, Pietrobelli A, Battistini NC, Maioli M (2013) Lifestyle and nutrition related to male longevity in Sardinia: an ecological study. Nutr Metab Cardiovasc Dis 23:212–219Google Scholar
  40. Pes GM, Tolu F, Dore MP, Sechi GP, Errigo A, Canelada A, Poulain M (2015) Male longevity in Sardinia, a review of historical sources supporting a causal link with dietary factors. Eur J Clin Nutr 69:411–418Google Scholar
  41. Pes GM, Dore MP, Errigo A, Poulain M (2018) Analysis of physical activity among free-living nonagenarians from a sardinian longevous population. J Aging Phys Act 26:254–258Google Scholar
  42. Pinchera A, Rago T, Vitti P (1998) Physiopathology of iodine deficiency. Ann Ist Sup Sanità 34:301–305Google Scholar
  43. Poulain M, Pes GM, Grasland C, Carru C, Ferrucci L, Baggio G et al (2004) Identification of a geographic area characterized by extreme longevity in the Sardinia island: the AKEA study. Exp Gerontol 39:1423–1429Google Scholar
  44. Poulain M, Pes G, Salaris L (2011) A population where men live as long as women: villagrande Strisaili Sardinia. J Aging Res 2011:153756Google Scholar
  45. Poulain M, Herm A, Pes GM (2013) The blue zones: areas of exceptional longevity around the world. Vienna Yearb Popul Res 11:83–102Google Scholar
  46. Poulain M, Chambre D, Herm A, Pes GM (2017) Anthropometric traits at military medical examination associated with demographic family characteristics. Hist Fam 22:310–332Google Scholar
  47. Pulina G, Aghini-Lombardi F, Frigeri M, Battaccone G, Rubattu R, Garzella G, Grasso L, Nudda A (2008) Iodine content in sheep and goat cheese produced in Sardinia (Italy). J Dairy Sci 91, E-Suppl. 1Google Scholar
  48. Putzu F (1928) Il gozzo in Sardegna. Arch Ital Chir 20:1–42Google Scholar
  49. Rosero-Bixby L (2008) The Exceptionally High Life Expectancy of Costa Rican Nonagenarians. Demography 45:673–691Google Scholar
  50. Rozing MP, Westendorp RG, de Craen AJ, Frölich M, Heijmans BT, Beekman M, Wijsman C, Mooijaart SP, Blauw GJ, Slagboom PE, van Heemst D, Leiden Longevity Study (LLS) Group (2010a) Low serum free triiodothyronine levels mark familial longevity: the Leiden Longevity Study. J Gerontol A Biol Sci Med Sci 65:365–368Google Scholar
  51. Rozing MP, Houwing-Duistermaat JJ, Slagboom PE, Beekman M, Frölich M, de Craen AJ, Westendorp RG, van Heemst D (2010b) Familial longevity is associated with decreased thyroid function. J Clin Endocrinol Metab 95:4979–4984Google Scholar
  52. Salaris L, Poulain M, Samaras TT (2012) Height and survival at older ages among men born in an inland village in Sardinia (Italy), 1866–2006. Biodemography Soc Biol 58:1–13Google Scholar
  53. Sørensen JR, Hegedüs L, Kruse-Andersen S, Godballe C, Bonnema SJ (2014) The impact of goitre and its treatment on the trachea, airflow, oesophagus and swallowing function. A systematic review. Best Pract Res Clin Endocrinol Metab 28:481–494Google Scholar
  54. Speller E, Brodribb W (2012) Breastfeeding and thyroid disease: a literature review. Breastfeed Rev 20:41–47Google Scholar
  55. Tentoni S, Lisa A, Fiorani O, Lipsi RM, Caselli G, Astolfi P (2012) Spatial analysis of the aptitude to late maternity on the island of Sardinia. J Biosoc Sci 44:257–272Google Scholar
  56. Van den Beld A, Visser TJ, Feelders RA, Grobbee DE, Lamberts SW (2005) Thyroid hormone concentrations, disease, physical function and mortality in elderly men. J Clin Endocrinol Metab 90:6403–6409Google Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  • Francesco Tolu
    • 1
    Email author
  • Mario Palermo
    • 1
  • Maria Pina Dore
    • 2
  • Alessandra Errigo
    • 3
  • Ana Canelada
    • 4
  • Michel Poulain
    • 5
  • Giovanni Mario Pes
    • 2
    • 6
  1. 1.S.C. di EndocrinologiaMalattie della Nutrizione e del Ricambio - Azienda Ospedaliero-Universitaria di SassariSassariItaly
  2. 2.Department of Medical, Surgical and Experimental MedicineUniversity of SassariSassariItaly
  3. 3.Azienda Ospedaliero-Universitaria di SassariSassariItaly
  4. 4.Departamento de Medicina Preventiva y Salud Pública e Historia de la CienciaUniversidad de MàlagaMàlagaSpain
  5. 5.Estonian Institute for Population StudiesTallinn UniversityTallinnEstonia
  6. 6.Sardinia Blue Zone ObservatorySardiniaItaly

Personalised recommendations