1 Kennedy BK, Berger SL, Brunet A, et al. Geroscience: linking aging to chronic disease. Cell 2014; 159: 709–13.
2 Cavadas C, Aveleira CA, Souza GF, Velloso LA. The pathophysiology of defective proteostasis in the hypothalamus—from obesity to ageing. Nat Rev Endocrinol 2016; 12: 723–33.
3 Surks MI, Ortiz E, Daniels GH, et al. Subclinical thyroid disease: scientific review and guidelines for diagnosis and management. JAMA 2004; 291: 228–38.
4 Bremner AP, Feddema P, Leedman PJ, et al. Age-related changes in thyroid function: a longitudinal study of a community-based cohort. J Clin Endocrinol Metab 2012; 97: 1554–62.
5 Waring AC, Arnold AM, Newman AB, Buzkova P, Hirsch C, Cappola AR. Longitudinal changes in thyroid function in the oldest old and survival: the cardiovascular health study all-stars study. J Clin Endocrinol Metab 2012; 97: 3944–50.
6 Bjergved L, Jorgensen T, Perrild H, et al. Predictors of change in serum TSH after iodine fortification: an 11-year follow-up to the DanThyr study. J Clin Endocrinol Metab 2012; 97: 4022–29.
7 Chaker L, Korevaar TI, Medici M, et al. Thyroid function characteristics and determinants: the Rotterdam Study. Thyroid 2016; 26: 1195–204.
8 Hoogendoorn EH, Hermus AR, de Vegt F, et al. Thyroid function and prevalence of anti-thyroperoxidase antibodies in a population with borderline sufficient iodine intake: influences of age and sex. Clin Chem 2006; 52: 104–11.
9 Mammen JS, McGready J, Ladenson PW, Simonsick EM. Unstable thyroid function in older adults is caused by alterations in both thyroid and pituitary physiology and is associated with increased mortality. Thyroid 2017; 27: 1370–77.
10 Strich D, Karavani G, Edri S, Gillis D. TSH enhancement of FT4 to FT3 conversion is age dependent. Eur J Endocrinol 2016; 175: 49–54.
11 van den Beld AW, Visser TJ, Feelders RA, Grobbee DE, Lamberts SW. Thyroid hormone concentrations, disease, physical function, and mortality in elderly men. J Clin Endocrinol Metab 2005; 90: 6403–09.
12 Burman KD, Smallridge RC, Osburne R, et al. Nature of suppressed TSH secretion during undernutrition: effect of fasting and refeeding on TSH responses to prolonged TRH infusions. Metabolism 1980; 29: 46–52.
13 Klug TL, Adelman RC. Age-dependent accumulation of an immunoreactive species of thyrotropin (TSH) which inhibits production of thyroid hormones [proceedings]. Adv Exp Med Biol 1978; 97: 259–64.
14 Veltri F, Rocha FO, Willems D, et al. Prevalence of thyroid dysfunction and autoimmunity in the older population and implications of age-specific reference ranges. Clin Chim Acta 2017; 465: 34–39.
15 Biondi B, Bartalena L, Cooper DS, Hegedus L. Laurberg P, Kahaly GJ. The 2015 European Thyroid Association guidelines on diagnosis and treatment of endogenous subclinical hyperthyroidism. Eur Thyroid J 2015; 4: 149–63.
16 Pearce SH, Razvi S, Yadegarfar ME, et al. Serum thyroid function, mortality and disability in advanced old age: the Newcastle 85+study. J Clin Endocrinol Metab 2016; 101: 4385–94.
17 Selmer C, Olesen JB, Hansen ML, et al. The spectrum of thyroid disease and risk of new onset atrial fibrillation: a large population cohort study. BMJ 2012; 345: e7895.
18 Segna D, Bauer DC, Feller M, et al. Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts. J Intern Med 2018; 283: 56–72.
19 Rieben C, Segna D, da Costa BR, et al. Subclinical thyroid dysfunction and the risk of cognitive decline: a meta-analysis of prospective cohort studies. J Clin Endocrinol Metab 2016; 101: 4945–54.
20 Ceresini G, Morganti S, Rebecchi I, et al. Evaluation of the circadian profiles of serum dehydroepiandrosterone (DHEA), cortisol, and cortisol/DHEA molar ratio after a single oral administration of DHEA in elderly subjects. Metabolism 2000;49: 548–51.
21 Selmer C, Olesen JB, Hansen ML, et al. Subclinical and overt thyroid dysfunction and risk of all-cause mortality and cardiovascular events: a large population study. J Clin Endocrinol Metab 2014; 99: 2372–82.
22 Atzmon G, Barzilai N, Surks MI, Gabriely I. Genetic predisposition to elevated serum thyrotropin is associated with exceptional longevity. J Clin Endocrinol Metab 2009; 94: 4768–75.
23 Hennessey JV, Espaillat R. Diagnosis and management of subclinical hypothyroidism in elderly adults: a review of the literature. J Am Geriatr Soc 2015; 63: 1663–73.
24 Rodondi N, den Elzen WP, Bauer DC, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA 2010; 304: 1365–74.
25 Chaker L, Baumgartner C, den Elzen WP, et al. Thyroid function within the reference range and the risk of stroke: an individual participant data analysis. J Clin Endocrinol Metab 2016; 101: 4270–82.
26 Virgini VS, Rodondi N, Cawthon PM, et al. Subclinical thyroid dysfunction and frailty among older men. J Clin Endocrinol Metab 2015; 100: 4524–32.
27 Bano A, Chaker L, Schoufour J, et al. High circulating free thyroxine levels may increase the risk of frailty: the Rotterdam Study. J Clin Endocrinol Metab 2018; 103: 328–35.
28 Simonsick EM, Chia CW, Mammen JS, Egan JM, Ferrucci L. Free thyroxine and functional mobility, fitness, and fatigue in euthyroid older men and women in the Baltimore longitudinal study of aging. J Gerontol A Biol Sci Med Sci 2016; 71: 961–67.
29 Bowers J, Terrien J, Clerget-Froidevaux MS, et al. Thyroid hormone signaling and homeostasis during aging. Endocr Rev 2013; 34: 556–89.
30 Di Somma C, Brunelli V, Savanelli MC, et al. Somatopause: state of the art. Minerva Endocrinol 2011; 36: 243–55.
31 Ceda GP, Dall’Aglio E, Morganti S, et al. Update on new therapeutic options for the somatopause. Acta Biomed Ateneo Parmense 2010;81 (suppl 1): 67–72.
32 Giordano R, Bonelli L, Marinazzo E, Ghigo E, Arvat E. Growth hormone treatment in human ageing: benefits and risks. Hormones (Athens) 2008; 7: 133–39.
33 Nashiro K, Guevara-Aguirre J, Braskie MN, et al. Brain structure and function associated with younger adults in growth hormone receptor-deficient humans. J Neurosci 2017; 37: 1696–707.
34 Laron Z, Kauli R, Lapkina L, Werner H. IGF-I deficiency, longevity and cancer protection of patients with Laron syndrome. Mutat Res Rev Mutat Res 2017; 772: 123–33.
35 Junnila RK, List EO, Berryman DE, Murrey JW, Kopchick JJ. The GH/IGF-1 axis in ageing and longevity. Nat Rev Endocrinol 2013; 9: 366–76.
36 Cruz-Jentoft AJ, Kiesswetter E, Drey M, Sieber CC. Nutrition, frailty, and sarcopenia. Aging Clin Exp Res 2017; 29: 43–48.
37 Chapman IM. Endocrinology of anorexia of ageing. Best Pract Res Clin Endocrinol Metab 2004; 18: 437–52.
38 MacIntosh CG, Andrews JM, Jones KL, et al. Effects of age on concentrations of plasma cholecystokinin, glucagon-like peptide 1, and peptide YY and their relation to appetite and pyloric motility. Am J Clin Nutr 1999; 69: 999–1006.
39 Fried LP, Tangen CM, Walston J, et al. Frailty in older adults:evidence for a phenotype. J Gerontol A Biol Sci Med Sci 2001;56: M146–56.
40 Veldhuis JD, Sharma A, Roelfsema F. Age-dependent and gender-dependent regulation of hypothalamic-adrenocorticotropicadrenal axis. Endocrinol Metab Clin North Am 2013; 42: 201–25.
41 Nater UM, Hoppmann CA, Scott SB. Diurnal profiles of salivary cortisol and alpha-amylase change across the adult lifespan: evidence from repeated daily life assessments. Psychoneuroendocrinology 2013; 38: 3167–71.
42 Almeida DM, Piazza JR, Stawski RS. Interindividual differences and intraindividual variability in the cortisol awakening response: an examination of age and gender. Psychol Aging 2009;24: 819–27.
43 Dmitrieva NO, Almeida DM, Dmitrieva J, Loken E, Pieper CF. A day-centered approach to modeling cortisol: diurnal cortisol profiles and their associations among U.S. adults. Psychoneuroendocrinology 2013; 38: 2354–65.
44 Gardner MP, Lightman S, Sayer AA, et al. Dysregulation of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages: an individual participant meta-analysis. Psychoneuroendocrinology 2013; 38: 40–49.
45 Dijckmans B, Tortosa-Martinez J, Caus N, et al. Does the diurnal cycle of cortisol explain the relationship between physical performance and cognitive function in older adults? Eur Rev Aging Phys Act 2017; 14: 6.
46 Ennis GE, An Y, Resnick SM, Ferrucci L, O’Brien RJ, Moffat SD. Long-term cortisol measures predict Alzheimer disease risk. Neurology 2017; 88: 371–78.
47 Schoorlemmer RM, Peeters GM, van Schoor NM, Lips P. Relationships between cortisol level, mortality and chronic diseases in older persons. Clin Endocrinol (Oxf) 2009;71: 779–86.
48 Tiganescu A, Walker EA, Hardy RS, Mayes AE, Stewart PM. Localization, age- and site-dependent expression, and regulation of 11beta-hydroxysteroid dehydrogenase type 1 in skin. J Invest Dermatol 2011; 131: 30–36.
49 Kilgour AH, Gallagher IJ, MacLullich AM, et al. Increased skeletal muscle 11betaHSD1 mRNA is associated with lower muscle strength in ageing. PLoS One 2013; 8: e84057.
50 Herbert J. The age of dehydroepiandrosterone. Lancet 1995;345: 1193–94.
51 Ferrari E, Arcaini A, Gornati R, et al. Pineal and pituitary-adrenocortical function in physiological aging and in senile dementia. Exp Gerontol 2000; 35: 1239–50.
52 Ravaglia G, Forti P, Maioli F, et al. The relationship of dehydroepiandrosterone sulfate (DHEAS) to endocrine-metabolic parameters and functional status in the oldest-old. Results from an Italian study on healthy free-living over-ninety-year-olds. J Clin Endocrinol Metab 1996; 81: 1173–78.
53 Ohlsson C, Vandenput L, Tivesten A. DHEA and mortality: what is the nature of the association? J Steroid Biochem Mol Biol 2015;145: 248–53.
54 Baulieu EE, Thomas G, Legrain S, et al. Dehydroepiandrosterone (DHEA), DHEA sulfate, and aging: contribution of the DHEAge Study to a sociobiomedical issue. Proc Natl Acad Sci USA 2000;97: 4279–84.
55 Elraiyah T, Sonbol MB, Wang Z, et al. The benefits and harms of systemic dehydroepiandrosterone (DHEA) in postmenopausal women with normal adrenal function: a systematic review and meta-analysis. J Clin Endocrinol Metab 2014; 99: 3536–42.
56 Broekmans FJ, Soules MR, Fauser BC. Ovarian aging: mechanisms and clinical consequences. Endocr Rev 2009;30: 465–93.
57 Hale GE, Zhao X, Hughes CL, Burger HG, Robertson DM, Fraser IS. Endocrine features of menstrual cycles in middle and late reproductive age and the menopausal transition classified according to the Staging of Reproductive Aging Workshop (STRAW) staging system. J Clin Endocrinol Metab 2007;92: 3060–67.
58 Santoro N, Randolph JF Jr. Reproductive hormones and the menopause transition. Obstet Gynecol Clin North Am 2011; 38: 455–66.
59 Broer SL, Eijkemans MJ, Scheffer GJ, et al. Anti-mullerian hormone predicts menopause: a long-term follow-up study in normoovulatory women. J Clin Endocrinol Metab 2011; 96: 2532–39.
60 Vanden Brink H, Robertson DM, Lim H, et al. Associations between antral ovarian follicle dynamics and hormone production throughout the menstrual cycle as women age. J Clin Endocrinol Metab 2015; 100: 4553–62.
61 Shaw ND, Srouji SS, Histed SN, Hall JE. Differential effects of aging on estrogen negative and positive feedback. Am J Physiol Endocrinol Metab 2011; 301: E351–55.
62 Davison SL, Bell R, Donath S, Montalto JG, Davis SR. Androgen levels in adult females: changes with age, menopause, and oophorectomy. J Clin Endocrinol Metab 2005;90: 3847–53.
63 Fogle RH, Stanczyk FZ, Zhang X, Paulson RJ. Ovarian androgen production in postmenopausal women. J Clin Endocrinol Metab 2007; 92: 3040–43.
64 Lonning PE, Eikesdal HP. Aromatase inhibition 2013: clinical state of the art and questions that remain to be solved. Endocr Relat Cancer 2013; 20: R183–201.
65 Stuenkel CA, Davis SR, Gompel A, et al. Treatment of symptoms of the menopause: an endocrine society clinical practice guideline. J Clin Endocrinol Metab 2015; 100: 3975–4011.
66 Kaufman JM, Vermeulen A. The decline of androgen levels in elderly men and its clinical and therapeutic implications. Endocr Rev 2005; 26: 833–76.
67 Basaria S. Reproductive aging in men. Endocrinol Metab Clin North Am 2013; 42: 255–70.
68 Mahmoud AM, Goemaere S, El-Garem Y, Van Pottelbergh I, Comhaire FH, Kaufman JM. Testicular volume in relation to hormonal indices of gonadal function in community-dwelling elderly men. J Clin Endocrinol Metab 2003; 88: 179–84.
69 Sartorius GA, Nieschlag E. Paternal age and reproduction. Hum Reprod Update 2010; 16: 65–79.
70 Wu FC, Tajar A, Pye SR, et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab 2008; 93: 2737–45.
71 Hsu B, Cumming RG, Hirani V, et al. Temporal trend in androgen status and androgen-sensitive outcomes in older men. J Clin Endocrinol Metab 2016; 101: 1836–46.
72 Araujo AB, Dixon JM, Suarez EA, Murad MH, Guey LT, Wittert GA. Clinical review: endogenous testosterone and mortality in men: a systematic review and meta-analysis. J Clin Endocrinol Metab 2011;96: 3007–19.
73 Snyder PJ, Bhasin S, Cunningham GR, et al. Effects of testosterone treatment in older men. N Engl J Med 2016; 374: 611–24.
74 Manolagas SC, O’Brien CA, Almeida M. The role of estrogen and androgen receptors in bone health and disease. Nat Rev Endocrinol 2013; 9: 699–712.
75 Orwoll ES. Establishing a framework—does testosterone supplementation help older men? N Engl J Med 2016; 374: 682–83.
76 Seeman E, Delmas PD. Bone quality—the material and structural basis of bone strength and fragility. N Engl J Med 2006;354: 2250–61.
77 Manolagas SC. From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev 2010; 31: 266–300.
78 Onal M, Piemontese M, Xiong J, et al. Suppression of autophagy in osteocytes mimics skeletal aging. J Biol Chem 2013;288: 17432–40.
79 Kassem M, Marie PJ. Senescence-associated intrinsic mechanisms of osteoblast dysfunctions. Aging Cell 2011; 10: 191–97.
80 Almeida M, Laurent MR, Dubois V, et al. Estrogens and androgens in skeletal physiology and pathophysiology. Physiol Rev 2017;97: 135–87.
81 Khosla S. Pathogenesis of age-related bone loss in humans. J Gerontol A Biol Sci Med Sci 2013; 68: 1226–35.
82 Falahati-Nini A, Riggs BL, Atkinson EJ, O’Fallon WM, Eastell R, Khosla S. Relative contributions of testosterone and estrogen in regulating bone resorption and formation in normal elderly men. J Clin Invest 2000; 106: 1553–60.
83 Orwoll ES, Lapidus J, Wang PY, et al. The limited clinical utility of testosterone, estradiol, and sex hormone binding globulin measurements in the prediction of fracture risk and bone loss in older men. J Bone Miner Res 2017; 32: 633–40.
84 Faroqui S, Levi M, Soleimani M, Amlal H. Estrogen downregulates the proximal tubule type IIa sodium phosphate cotransporter causing phosphate wasting and hypophosphatemia. Kidney Int 2008; 73: 1141–50.
85 Dick IM, Devine A, Beilby J, Prince RL. Effects of endogenous estrogen on renal calcium and phosphate handling in elderly women. Am J Physiol Endocrinol Metab 2005; 288: E430–35.
86 Sato AY, Richardson D, Cregor M, et al. Glucocorticoids induce bone and muscle atrophy by tissue-specific mechanisms upstream of E3 ubiquitin ligases. Endocrinology 2017; 158: 664–77.
87 Almeida M, O’Brien CA. Basic biology of skeletal aging: role of stress response pathways. J Gerontol A Biol Sci Med Sci 2013;68: 1197–208.
88 Weinstein RS, Manolagas SC. Apoptosis and osteoporosis. Am J Med 2000; 108: 153–64.
89 Fleet JC. The role of vitamin D in the endocrinology controlling calcium homeostasis. Mol Cell Endocrinol 2017; 453: 36–45.
90 Bruce DG, St John A, Nicklason F, Goldswain PR. Secondary hyperparathyroidism in patients from Western Australia with hip fracture: relationship to type of hip fracture, renal function, and vitamin D deficiency. J Am Geriatr Soc 1999; 47: 354–59.
91 Carrivick SJ, Walsh JP, Brown SJ, Wardrop R, Hadlow NC. Brief report: does PTH increase with age, independent of 25-hydroxyvitamin D, phosphate, renal function, and ionized calcium? J Clin Endocrinol Metab 2015; 100: 2131–34.
92 Campos-Obando N, Koek WNH, Hooker ER, et al. Serum phosphate is associated with fracture risk: the Rotterdam Study and MrOS. J Bone Miner Res 2017; 32: 1182–93.
93 Martin A, David V, Quarles LD. Regulation and function of the FGF23/klotho endocrine pathways. Physiol Rev 2012; 92: 131–55.
94 Seck T, Scheppach B, Scharla S, et al. Concentration of insulin-like growth factor (IGF)-I and -II in iliac crest bone matrix from pre- and postmenopausal women: relationship to age, menopause, bone turnover, bone volume, and circulating IGFs. J Clin Endocrinol Metab 1998; 83: 2331–37.
95 Garnero P, Sornay-Rendu E, Delmas PD. Low serum IGF-1 and occurrence of osteoporotic fractures in postmenopausal women. Lancet 2000; 355: 898–99.
96 Manson JE, Aragaki AK, Rossouw JE, et al. Menopausal hormone therapy and long-term all-cause and cause-specific mortality:the Women’s Health Initiative Randomized Trials. JAMA 2017;318: 927–38.
97 The NAMS 2017 Hormone Therapy Position Statement Advisory Panel. The 2017 hormone therapy position statement of The North American Menopause Society. Menopause 2017;24: 728–53.
98 Reaven GM, Chen N, Hollenbeck C, Chen YD. Effect of age on glucose tolerance and glucose uptake in healthy individuals. J Am Geriatr Soc 1989; 37: 735–40.
99 Broughton DL, Taylor R. Review: deterioration of glucose tolerance with age: the role of insulin resistance. Age Ageing 1991; 20: 221–25.
100 Polonsky KS, Given BD, Van Cauter E. Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. J Clin Invest 1988; 81: 442–48.
101 Lang DA, Matthews DR, Peto J, Turner RC. Cyclic oscillations of basal plasma glucose and insulin concentrations in human beings. N Engl J Med 1979; 301: 1023–27.
102 Matveyenko AV, Liuwantara D, Gurlo T, et al. Pulsatile portal vein insulin delivery enhances hepatic insulin action and signaling. Diabetes 2012; 61: 2269–79.
103 Porksen N, Munn S, Steers J, Vore S, Veldhuis J, Butler P. Pulsatile insulin secretion accounts for 70% of total insulin secretion during fasting. Am J Physiol 1995; 269: E478–88.
104 Lang DA, Matthews DR, Burnett M, Turner RC. Brief, irregular oscillations of basal plasma insulin and glucose concentrations in diabetic man. Diabetes 1981; 30: 435–39.
105 Meneilly GS, Ryan AS, Veldhuis JD, Elahi D. Increased disorderliness of basal insulin release, attenuated insulin secretory burst mass, and reduced ultradian rhythmicity of insulin secretion in older individuals. J Clin Endocrinol Metab 1997; 82: 4088–93.
106 Meneilly GS, Veldhuis JD, Elahi D. Disruption of the pulsatile and entropic modes of insulin release during an unvarying glucose stimulus in elderly individuals. J Clin Endocrinol Metab 1999;84: 1938–43.
107 Hori SS, Kurland IJ, DiStefano JJ 3rd. Role of endosomal trafficking dynamics on the regulation of hepatic insulin receptor activity:models for Fao cells. Ann Biomed Eng 2006; 34: 879–92.
108 Basu R, Dalla Man C, Campioni M, et al. Effects of age and sex on postprandial glucose metabolism: differences in glucose turnover, insulin secretion, insulin action, and hepatic insulin extraction. Diabetes 2006; 55: 2001–14.
109 Elahi D, Muller DC, McAloon-Dyke M, Tobin JD, Andres R. The effect of age on insulin response and glucose utilization during four hyperglycemic plateaus. Exp Gerontol 1993; 28: 393–409.
110 Cefalu WT, Wang ZQ, Werbel S, et al. Contribution of visceral fat mass to the insulin resistance of aging. Metabolism 1995;44: 954–59.
111 Coon PJ, Rogus EM, Drinkwater D, Muller DC, Goldberg AP. Role of body fat distribution in the decline in insulin sensitivity and glucose tolerance with age. J Clin Endocrinol Metab 1992;75: 1125–32.
112 Kahn SE, Larson VG, Beard JC, et al. Effect of exercise on insulin action, glucose tolerance, and insulin secretion in aging. Am J Physiol 1990; 258: E937–43.
113 McBean AM, Li S, Gilbertson DT, Collins AJ. Differences in diabetes prevalence, incidence, and mortality among the elderly of four racial/ethnic groups: whites, blacks, hispanics, and asians. Diabetes Care 2004; 27: 2317–24.
114 Petersen KF, Befroy D, Dufour S, et al. Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 2003;300: 1140–42.
115 Meneilly GS, Elahi D. Metabolic alterations in middle-aged andelderly lean patients with type 2 diabetes. Diabetes Care 2005;28: 1498–99.
116 Centers for Disease Control and Prevention. National diabetes statistics report, 2017. https://www.cdc.gov/diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf (accessed Sept 1, 2017).
117 Diabetes UK. Facts and stats. 2016. https://diabetes-resourcesproduction. s3-eu-west-1.amazonaws.com/diabetes-storage/migration/pdf/DiabetesUK_Facts_Stats_Oct16.pdf (accessed Sept 1, 2017).
118 Cowie CC, Rust KF, Byrd-Holt DD, et al. Prevalence of diabetes and high risk for diabetes using A1C criteria in the U.S. population in 1988–2006. Diabetes Care 2010; 33: 562–68.
119 Chia CW, Ferrucci L. A look at the trend in diabetes-related complications in the U.S. over the past two decades: looking ahead. Ann Trans Med 2014; 2: 121.
120 American Diabetes Association. Classification and diagnosis of diabetes. Diabetes Care 2018; 40 (suppl 1): S13–27.
121 Diabetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002; 346: 393–403.
Usted debe ingresar al sitio con su cuenta de usuario IntraMed para ver los comentarios de sus colegas o para expresar su opinión. Si ya tiene una cuenta IntraMed o desea registrase, ingrese aquí