Garmes HM, Boguszewski CL, Miranda PAC, Martins MRA, da Silva SRC, Abucham JZ Filho, et al. Management of hypopituitarism: a perspective from the Brazilian Society of Endocrinology and Metabolism. Arch Endocrinol Metab. 2021;65(2):212–30. https://doi.org/10.20945/2359-3997000000335.

Regal M, Páramo C, Sierra SM, Garcia-Mayor RV. Prevalence and incidence of hypopituitarism in an adult Caucasian population in northwestern Spain. Clin Endocrinol (Oxf). 2001;6:735–40. https://doi.org/10.1046/j.1365-2265.2001.01406.x.

Article  Google Scholar 

Stochholm K, Gravholt CH, Laursen T, Jørgensen JO, Laurberg P, Andersen M, et al. Incidence of GH deficiency – a nationwide study. Eur J Endocrinol. 2006;155(1):61–71. https://doi.org/10.1530/eje.1.02191.

Article  CAS  PubMed  Google Scholar 

Rosén T, Bengtsson BA. Premature mortality due to cardiovascular disease in hypopituitarism. Lancet. 1990;336(8710):285–8. https://doi.org/10.1016/0140-6736(90)91812-o.

Article  PubMed  Google Scholar 

Pappachan JM, Raskauskiene D, Kutty VR, Clayton RN. Excess mortality associated with hypopituitarism in adults: a meta-analysis of observational studies. J Clin Endocrinol Metab. 2015;100:1405–11. https://doi.org/10.1210/jc.2014-3787.

Article  CAS  PubMed  Google Scholar 

Jasim S, Alahdab F, Ahmed AT, Tamhane S, Prokop LJ, Nippoldt TB, et al. Mortality in adults with hypopituitarism: a systematic review and meta-analysis. Endocrine. 2017;56(1):33–42. https://doi.org/10.1007/s12020-016-1159-3.

Article  CAS  PubMed  Google Scholar 

Gaillard RC, Mattsson AF, Akerblad AC, Bengtsson BÅ, Cara J, Feldt-Rasmussen U, et al. Overall and cause-specific mortality in GH-deficient adults on GH replacement. Eur J Endocrinol. 2012;166(6):1069–77. https://doi.org/10.1530/EJE-11-1028.

Article  CAS  PubMed  Google Scholar 

Fleseriu M, Hashim IA, Karavitaki N, Melmed S, Murad MH, Salvatori R, et al. Hormonal Replacement in Hypopituitarism in Adults: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101:3888–921. https://doi.org/10.1210/jc.2016-2118.

Article  CAS  PubMed  Google Scholar 

Patti M-E, Kahn CR. The Insulin Receptor – A Critical Link in Glucose Homeostasis and Insulin Action. J Basic Clin Physiol Pharmacol. 1998;9:2–4. https://doi.org/10.1515/jbcpp.1998.9.2-4.89.

Article  Google Scholar 

Huang PL. A comprehensive definition for metabolic syndrome. Dis Model Mech. 2009;2:231–7. https://doi.org/10.1242/dmm.001180.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Himsworth HP. RBK. Insulin-sensitive and insulin-insensitive types of diabetes mellitus. Clin Sci. 1939;4:119–52.

Taylor SI, Accili D, Imai Y. Insulin resistance or insulin deficiency. Which is the primary cause of NIDDM? Diabetes. 1994;43:735–40. https://doi.org/10.2337/diab.43.6.735.

Bergman RN, Phillips LS, Cobelli C. Physiologic evaluation of factors controlling glucose tolerance in man: measurement of insulin sensitivity and beta-cell glucose sensitivity from the response to intravenous glucose. J Clin Invest. 1981;68:1456–67. https://doi.org/10.1172/jci110398.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ferrannini E, Mari A. How to measure insulin sensitivity. J Hypertens. 1998;16:895–906. https://doi.org/10.1097/00004872-199816070-00001.

Liu JL, Coschigano KT, Robertson K, Lipsett M, Guo Y, Kopchick JJ, et al. Disruption of growth hormone receptor gene causes diminished pancreatic islet size and increased insulin sensitivity in mice. Am J Physiol Endocrinol Metab. 2004;287:405–13. https://doi.org/10.1152/ajpendo.00423.2003.

Article  Google Scholar 

Ciresi A, Guarnotta V, Pizzolanti G, Giordano C. Comparison between euglycemic hyperinsulinemic clamp and surrogate indices of insulin sensitivity in children with growth hormone deficiency. Growth Horm IGF Res. 2018;39:40–4. https://doi.org/10.1016/j.ghir.2017.12.007.

Article  CAS  PubMed  Google Scholar 

Castillo AR, de Souza AL, Alegre SM, Atala YB, Zantut-Wittmann DE, Garmes HM. Insulin Sensitivity Is Not Decreased in Adult Patients With Hypopituitarism Without Growth Hormone Replacement. Front Endocrinol. 2019;10:534. https://doi.org/10.3389/fendo.2019.00534.

Article  Google Scholar 

Guevara-Aguirre J, Teran E, Lescano D, Guevara C, Guevara A, Saavedra J, et al. Assessing insulin sensitivity and resistance in syndromes of severe short stature. Growth Horm IGF Res. 2020;53–54: 101339. https://doi.org/10.1016/j.ghir.2020.101339.

Article  CAS  PubMed  Google Scholar 

Johansson JO, Fowelin J, Landin K, Lager I, Bengtsson BA. Growth hormone-deficient adults are insulin resistant. Metabolism. 1995;44:1126–9. [PubMed] [Google Scholar]. https://doi.org/10.1016/0026-0495(95)90004-7.

Hew FL, Koschmann M, Christopher M, Rantzau C, Vaag A, Ward G, et al. Insulin resistance in growth hormone-deficient adults: defects in glucose utilization and glycogen synthase activity. J Clin Endocrinol Metab. 1996;81:555–64. https://doi.org/10.1210/jcem.81.2.8636267.

Article  CAS  PubMed  Google Scholar 

Ukropec J, Penesová A, Skopková M, Pura M, Vlcek M, Rádiková Z, et al. Adipokine protein expression pattern in growth hormone deficiency predisposes to the increased fat cell size and the whole body metabolic derangements. J Clin Endocrinol Metab. 2008;93:2255–62. https://doi.org/10.1210/jc.2007-2188.

Article  CAS  PubMed  Google Scholar 

Balaž M, Ukropcova B, Kurdiova T, Vlcek M, Surova M, Krumpolec P, et al. Improved adipose tissue metabolism after 5-year growth hormone replacement therapy in growth hormone deficient adults: The role of zinc-α2-glycoprotein. Adipocyte. 2014;4:113–22. https://doi.org/10.4161/21623945.2014.973772.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Pincelli AI, Brunani A, Scacchi M, Dubini A, Borsotti R, Tibaldi A, et al. The serum concentration of tumor necrosis factor alpha is not an index of growth-hormone- or obesity-induced insulin resistance. Horm Res. 2001;55:57–64. https://doi.org/10.1159/000049971.

Article  CAS  PubMed  Google Scholar 

Bülow B, Link K, Ahrén B, Nilsson AS, Erfurth EM. Survivors of childhood acute lymphoblastic leukaemia, with radiation-induced GH deficiency, exhibit hyperleptinaemia and impaired insulin sensitivity, unaffected by 12 months of GH treatment. Clin Endocrinol (Oxf). 2004;61:683–91. https://doi.org/10.1111/j.1365-2265.2004.02149.x.

Article  CAS  PubMed  Google Scholar 

Krusenstjerna-Hafstrøm T, Clasen BF, Møller N, Jessen N, Pedersen SB, Christiansen JS, et al. Growth hormone (GH)-induced insulin resistance is rapidly reversible: an experimental study in GH-deficient adults. J Clin Endocrinol Metab. 2011;96:2548–57. https://doi.org/10.1210/jc.2011-0273.

Article  CAS  PubMed  Google Scholar 

Garmes HM, Castillo AR, Monte Alegre S, de Souza AL, Atala YB, Zantut-Wittmann DE. Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity. Metabolites. 2022;12(12):1251. https://doi.org/10.3390/metabo12121251.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wijnen M, Olsson DS, van den Heuvel-Eibrink MM, Hammarstrand C, Janssen JAMJL, van der Lely AJ, et al. The metabolic syndrome and its components in 178 patients treated for craniopharyngioma after 16 years of follow-up. Eur J Endocrinol. 2018;178:11–22. https://doi.org/10.1530/EJE-17-0387.

Al-Shoumer KAS, Beshyah SA, Niththyananthan R, Johnston DG. Effect of glucocorticoid replacement therapy on glucose tolerance and intermediary metabolites in hypopituitary adults. Clin Endocrinol (Oxf). 1995;42:85–90. https://doi.org/10.1111/j.1365-2265.1995.tb02602.x.

Article  CAS  PubMed  Google Scholar 

Masternak MM, Bartke A, Wang F, Spong A, Gesing A, Fang Y, et al. Metabolic effects of intra-abdominal fat in GHRKO mice. Aging Cell. 2012;11:73–81. https://doi.org/10.1111/j.1474-9726.2011.00763.x.

Article  CAS  PubMed  Google Scholar 

Bennis MT, Schneider A, Victoria B, Do A, Wiesenborn DS, Spinel L, et al. The role of transplanted visceral fat from the long-lived growth hormone receptor knockout mice on insulin signaling. Geroscience. 2017;39:51–9. https://doi.org/10.1007/s11357-017-9957-y.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Casanueva FF, Camiña JP, Carreira MC, Pazos Y, Varga JL, Schally AV. Growth hormone-releasing hormone as an agonist of the ghrelin receptor GHS-R1a. Proc Natl Acad Sci U S A. 2008;105:20452–7. https://doi.org/10.1073/pnas.0811680106.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Yamashita S, Melmed S. Insulin-like growth factor I action on rat anterior pituitary cells: suppression of growth hormone secretion and messenger ribonucleic acid levels. Endocrinology. 1986;118:176–82. https://doi.org/10.1210/endo-118-1-176.