Background: Altered adrenocortical activity is one suggested mechanism relating small birth size with the metabolic syndrome in adulthood. Adrenal androgen concentrations are higher in children born small (SGA) than appropriate for gestational age (AGA). Aim: To compare adrenocortical hormonal activity between 20-year-old subjects born SGA or AGA. Methods: Seventy 20-year-old subjects (35 SGA and 35 age- and gender-matched AGA controls) were studied. Serum cortisol, cortisone, corticosteroid-binding globulin (CBG), glucocorticoid bioactivity (GBA), aldosterone, dehydroepiandrosterone sulfate (DHEAS) and androstenedione were measured, and the free cortisol index (FCI) was calculated. Results: The mean levels of glucocorticoid parameters, aldosterone, DHEAS or androstenedione did not differ between the SGA and AGA groups. In both groups, the males had lower cortisol (p < 0.05) and CBG levels (p < 0.01) and higher DHEAS (p < 0.01) concentrations than the females. Females who used hormonal contraceptives had higher cortisol and CBG levels (p < 0.01) but similar FCI, GBA and DHEAS levels than females who did not use contraceptives. Conclusion: No differences in adrenocortical activity were found between 20-year-old SGA and AGA subjects. Enhanced peripubertal adrenal androgen secretion seems to disappear by early adulthood in full-term born SGA subjects. FCI and GBA are useful parameters in the evaluation of the glucocorticoid milieu during hormonal contraceptive use.

1.
Phillips DI, Barker DJ, Fall CH, Seckl JR, Whorwood CB, Wood PJ, Walker BR: Elevated plasma cortisol concentrations: a link between low birth weight and the insulin resistance syndrome? J Clin Endocrinol Metab 1998;83:757–760.
2.
Walker BR, Phillips DI, Noon JP, Panarelli M, Andrew R, Edwards HV, Holton DW, Seckl JR, Webb DJ, Watt GC: Increased glucocorticoid activity in men with cardiovascular risk factors. Hypertension 1998;31:891–895.
3.
Benediktsson R, Lindsay RS, Noble J, Seckl JR, Edwards CR: Glucocorticoid exposure in utero: new model for adult hypertension. Lancet 1993;341:339–341.
4.
Seckl JR: Prenatal glucocorticoids and long-term programming. Eur J Endocrinol 2004;151(suppl 3):U49–U62.
5.
Clark PM, Hindmarsh PC, Shiell AW, Law CM, Honour JW, Barker DJ: Size at birth and adrenocortical function in childhood. Clin Endocrinol (Oxf) 1996;45:721–726.
6.
Phillips DI, Walker BR, Reynolds RM, Flanagan DE, Wood PJ, Osmond C, Barker DJ, Whorwood CB: Low birth weight predicts elevated plasma cortisol concentrations in adults from 3 populations. Hypertension 2000;35:1301–1306.
7.
Levitt NS, Lambert EV, Woods D, Hales CN, Andrew R, Seckl JR: Impaired glucose tolerance and elevated blood pressure in low birth weight, nonobese, young south african adults: early programming of cortisol axis. J Clin Endocrinol Metab 2000;85:4611–4618.
8.
Reynolds RM, Walker BR, Syddall HE, Andrew R, Wood PJ, Whorwood CB, Phillips DI: Altered control of cortisol secretion in adult men with low birth weight and cardiovascular risk factors. J Clin Endocrinol Metab 2001;86:245–250.
9.
Reynolds RM, Walker BR, Syddall HE, Andrew R, Wood PJ, Phillips DI: Is there a gender difference in the associations of birthweight and adult hypothalamic-pituitary-adrenal axis activity? Eur J Endocrinol 2005;152:249–253.
10.
Francois I, de Zegher F: Adrenarche and fetal growth. Pediatr Res 1997;41:440–442.
11.
Dahlgren J, Boguszewski M, Rosberg S, Albertsson-Wikland K: Adrenal steroid hormones in short children born small for gestational age. Clin Endocrinol (Oxf) 1998;49:353–361.
12.
Ibáñez L, Potau N, Marcos MV, de Zegher F: Exaggerated adrenarche and hyperinsulinism in adolescent girls born small for gestational age. J Clin Endocrinol Metab 1999;84:4739–4741.
13.
Ghirri P, Bernardini M, Vuerich M, Cuttano AM, Coccoli L, Merusi I, Ciulli C, D’Accavio L, Bottone U, Boldrini A: Adrenarche, pubertal development, age at menarche and final height of full-term, born small for gestational age (SGA) girls. Gynecol Endocrinol 2001;15:91–97.
14.
Tenhola S, Martikainen A, Rahiala E, Parviainen M, Halonen P, Voutilainen R: Increased adrenocortical and adrenomedullary hormonal activity in 12-year-old children born small for gestational age. J Pediatr 2002;141:477–482.
15.
van Montfoort N, Finken MJ, le Cessie S, Dekker FW, Wit JM: Could cortisol explain the association between birth weight and cardiovascular disease in later life? A meta-analysis. Eur J Endocrinol 2005;153:811–817.
16.
Houang M, Morineau G, le Bouc Y, Fiet J, Gourmelen M: The cortisol-cortisone shuttle in children born with intrauterine growth retardation. Pediatr Res 1999;46:189–193.
17.
Radetti G, Renzullo L, Gottardi E, D’Addato G, Messner H: Altered thyroid and adrenal function in children born at term and preterm, small for gestational age. J Clin Endocrinol Metab 2004;89:6320–6324.
18.
Ong KK, Potau N, Petry CJ, Jones R, Ness AR, Honour JW, de Zegher F, Ibáñez L, Dunger DB; Avon Longitudinal Study of Parents and Children Study Team: Opposing influences of prenatal and postnatal weight gain on adrenarche in normal boys and girls. J Clin Endocrinol Metab 2004;89:2647–2651.
19.
Plank C, Meissner U, Rauh M, Wollmann H, Dörr HG, Rascher W, Dötsch J: Cortisol-cortisone ratios in small for gestational age (SGA) children without postnatal catch-up growth. Clin Endocrinol (Oxf) 2007;67:304–309.
20.
Tenhola S, Martikainen A, Rahiala E, Herrgård E, Halonen P, Voutilainen R: Serum lipid concentrations and growth characteristics in 12-year-old children born small for gestational age. Pediatr Res 2000;48:623–628.
21.
Salonen M, Tenhola S, Laitinen T, Lyyra-Laitinen T, Romppanen J, Jääskeläinen J, Voutilainen R: Tracking serum lipid levels and the association of cholesterol concentrations, blood pressure and cigarette smoking with carotid artery intima-media thickness in young adults born small for gestational age. Circ J 2010;74:2419–2425.
22.
Szathmári M, Vásárhelyi B, Tulassay T: Effect of low birth weight on adrenal steroids and carbohydrate metabolism in early adulthood. Horm Res 2001;55:172–178.
23.
Meuwese CL, Euser AM, Ballieux BE, van Vliet HA, Finken MJ, Walther FJ, Dekker FW, Wit JM: Growth-restricted preterm newborns are predisposed to functional adrenal hyperandrogenism in adult life. Eur J Endocrinol 2010;163:681–689.
24.
Pihkala J, Hakala T, Voutilainen P, Raivio K: New Finnish fetal growth charts (in Finnish). Duodecim 1989;105:1540–1546.
25.
le Roux CW, Sivakumaran S, Alaghband-Zadeh J, Dhillo W, Kong WM, Wheeler MJ: Free cortisol index as a surrogate marker for serum free cortisol. Ann Clin Biochem 2002;39:406–408.
26.
Tenhola S, Turpeinen U, Halonen P, Hämäläinen E, Voutilainen R: Association of serum lipid concentrations, insulin resistance index and catch-up growth with serum cortisol/cortisone ratio by liquid chromatography tandem mass spectrometry in children born small for gestational age. Pediatr Res 2005;58:467–471.
27.
Raivio T, Palvimo JJ, Kannisto S, Voutilainen R, Jänne OA: Transactivation assay for determination of glucocorticoid bioactivity in human serum. J Clin Endocrinol Metab 2002;87:3740–3744.
28.
Moilanen AM, Karvonen U, Poukka H, Jänne OA, Palvimo JJ: Activation of androgen receptor function by a novel nuclear protein kinase. Mol Biol Cell 1998;9:2527–2543.
29.
Aarnisalo P, Palvimo JJ, Jänne OA: CREB-binding protein in androgen receptor-mediated signaling. Proc Natl Acad Sci USA 1998;95:2122–2127.
30.
Rosenthal N: Identification of regulatory elements of cloned genes with functional assays. Methods Enzymol 1987;152:704–720.
31.
Palvimo JJ, Partanen M, Jänne OA: Characterization of cell-specific modulatory element in the murine ornithine decarboxylase promoter. Biochem J 1996;316:993–998.
32.
Phillips DI: Programming of the stress response: a fundamental mechanism underlying the long-term effects of the fetal environment? J Intern Med 2007;261:453–460.
33.
Kajantie E, Feldt K, Räikkönen K, Phillips DI, Osmond C, Heinonen K, Pesonen AK, Andersson S, Barker DJ, Eriksson JG: Body size at birth predicts hypothalamic-pituitary-adrenal axis response to psychosocial stress at age 60 to 70 years. J Clin Endocrinol Metab 2007;92:4094–4100.
34.
Miller WL: The adrenal cortex and its disorders; in Brook CGD, Hindmarsh PC, (eds): Clinical Pediatric Endocrinology, ed 4. Oxford, Blackwell Science, 2001, pp 321–376.
35.
Boonstra VH, Mulder PG, de Jong FH, Hokken-Koelega AC: Serum dehydroepiandrosterone sulfate levels and pubarche in short children born small for gestational age before and during growth hormone treatment. J Clin Endocrinol Metab 2004;89:712–717.
36.
Jensen RB, Vielwerth S, Larsen T, Hilsted L, Cohen A, Hougaard DM, Jensen LT, Greisen G, Juul A: Influence of fetal growth velocity and smallness at birth on adrenal function in adolescence. Horm Res Paediatr 2011;75:2–7.
37.
Utriainen P, Voutilainen R, Jääskeläinen J: Girls with premature adrenarche have accelerated early childhood growth. J Pediatr 2009;154:882–887.
38.
Allvin K, Ankarberg-Lindgren C, Fors H, Dahlgren J: Elevated serum levels of estradiol, dihydrotestosterone, and inhibin B in adult males born small for gestational age. J Clin Endocrinol Metab 2008;93:1464–1469.
39.
Jaquet D, Leger J, Chevenne D, Czernichow P, Levy-Marchal C: Intrauterine growth retardation predisposes to insulin resistance but not to hyperandrogenism in young women. J Clin Endocrinol Metab 1999;84:3945–3949.
40.
Pere A, Perheentupa J, Peter M, Voutilainen R: A follow-up of growth and steroids in premature adrenarche. Eur J Pediatr 1995;154:346–352.
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