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Horm Metab Res 2014; 46(10): 691-696
DOI: 10.1055/s-0034-1374589
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Male and Female Hypogonadism are Highly Prevalent in South Africans with Addison’s Disease

I. L. Ross
1   Division of Endocrinology, Department of Medicine, University of Cape Town, Cape Town, South Africa
,
N. S. Levitt
1   Division of Endocrinology, Department of Medicine, University of Cape Town, Cape Town, South Africa
,
D. J. Blom
2   Division of Lipidology, Department of Medicine, University of Cape Town, Cape Town, South Africa
,
D. Haarburger
3   Ampath Laboratories, Pomona, Gauteng Province, South Africa
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Publikationsverlauf

received 03. Januar 2014

accepted 26. März 2014

Publikationsdatum:
05. Mai 2014 (online)

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Abstract

Hypogonadism may complicate Addison’s disease (primary hypoadrenalism), but prevalence and metabolic sequelae of hypogonadism in Addison’s disease are poorly described. We recruited patients from the South African Addison’s disease national registry who received stable replacement doses of hydrocortisone and had no acute illness. Male biochemical testosterone deficiency was defined as an early morning basal testosterone<9.9 nmol/l and premature ovarian failure (POF) when menopause occurred before 40 years of age. Cardiometabolic risk variables were measured in males only. Male hypogonadism prevalence was 33% (14/42), and 10 patients had newly diagnosed hypogonadism. Two untreated patients had elevated FSH or LH (>10 or 12 IU/l). Testosterone deficiency did not correlate with age, disease duration or hydrocortisone dose. Untreated male hypogonadal subjects had a higher (mean±standard deviation) BMI compared to eugonadal subjects 29.2±4.9 kg/m2 vs. 24.7±3.4 kg/m2 (p=0.01) and a higher median (interquartile range) high-sensitive-CRP 6.4 (2.5–14.0) mg/l vs. 1.45 (0.6–2.8) mg/l (p=0.002). There were no differences between the 2 groups in lipids, lipoproteins and fasting glucose. The median (interquartile range) DHEAS was lower in the hypogonadal 0.31 (0.27–0.37) μmol/l, compared with the eugonadal group 0.75 (0.50–1.51) μmol/l (p=0.005). POF was documented in 11% of female patients. Male testosterone deficiency was highly prevalent in this cohort and was primarily due to secondary hypogonadism. Only BMI and hs-CRP were increased in untreated male hypogonadal subjects. Male and female hypogonadism appears to be a common complication of Addison’s disease and may contribute to its morbidity.

Key words

testosterone - oestrogen - primary hypoadrenalism
 

  • References

  • 1 Arlt W, Allolio B. Adrenal insufficiency. Lancet 2003; 361: 1881-1893
    CrossrefPubMedSuche in Google Scholar
  • 2 Valivullah HM, Aruldhas MM, Govindarajulu P. Testicular lipogenic enzymes–direct effects of dexamethasone in vivo. Biochem Biophys Res Commun 1985; 131: 726-730
    CrossrefPubMedSuche in Google Scholar
  • 3 Bambino TH, Hsueh AJ. Direct inhibitory effect of glucocorticoids upon testicular luteinizing hormone receptor and steroidogenesis in vivo and in vitro. Endocrinology 1981; 108: 2142-2148
    CrossrefPubMedSuche in Google Scholar
  • 4 Saketos M, Sharma N, Santoro NF. Suppression of the hypothalamic-pituitary-ovarian axis in normal women by glucocorticoids. Biol Reprod 1993; 49: 1270-1276
    CrossrefPubMedSuche in Google Scholar
  • 5 Sekiguchi Y, Hara Y, Matsuoka H, Hayashi Y, Katsumata N, Hirata Y. Sibling cases of Addison’s disease caused by DAX-1 gene mutations. Intern Med 2007; 46: 35-39
    CrossrefPubMedSuche in Google Scholar
  • 6 Soderbergh A, Myhre AG, Ekwall O, Gebre-Medhin G, Hedstrand H, Landgren E, Miettinen A, Eskelin P, Halonen M, Tuomi T, Gustafsson J, Husebye ES, Perheentupa J, Gylling M, Manns MP, Rorsman F, Kampe O, Nilsson T. Prevalence and clinical associations of 10 defined autoantibodies in autoimmune polyendocrine syndrome type I. J Clin Endocrinol Metab 2004; 89: 557-562
    CrossrefPubMedSuche in Google Scholar
  • 7 Aversa A, Palleschi S, Cruccu G, Silvestroni L, Isidori A, Fabbri A. Rapid decline of fertility in a case of adrenoleukodystrophy. Hum Reprod 1998; 13: 2474-2479
    CrossrefPubMedSuche in Google Scholar
  • 8 Braatvedt GD, Joyce M, Evans M, Clearwater J, Reid IR. Bone mineral density in patients with treated Addison’s disease. Osteoporos Int. 1999; 10: 435-440
    CrossrefPubMedSuche in Google Scholar
  • 9 Reato G, Morlin L, Chen S, Furmaniak J, Smith BR, Masiero S, Albergoni MP, Cervato S, Zanchetta R, Betterle C. Premature ovarian failure in patients with autoimmune Addison’s disease: clinical, genetic, and immunological evaluation. J Clin Endocrinol Metab 2011; 96: E1255-E1261
    CrossrefPubMedSuche in Google Scholar
  • 10 Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. Int J Clin Pract 2006; 60: 762-769
    CrossrefPubMedSuche in Google Scholar
  • 11 Travison TG, Shackelton R, Araujo AB, Hall SA, Williams RE, Clark RV, O’Donnell AB, McKinlay JB. The natural history of symptomatic androgen deficiency in men: onset, progression, and spontaneous remission. J Am Geriatr Soc 2008; 56: 831-839
    CrossrefPubMedSuche in Google Scholar
  • 12 Agledahl I, Skjaerpe PA, Hansen JB, Svartberg J. Low serum testosterone in men is inversely associated with non-fasting serum triglycerides: the Tromso study. Nutr Metab Cardiovasc Dis 2008; 18: 256-262
    CrossrefPubMedSuche in Google Scholar
  • 13 Jones RD, Nettleship JE, Kapoor D, Jones HT, Channer KS. Testosterone and atherosclerosis in aging men: purported association and clinical implications. Am J Cardiovasc Drugs 2005; 5: 141-154
    CrossrefPubMedSuche in Google Scholar
  • 14 Bleicken B, Hahner S, Loeffler M, Ventz M, Allolio B, Quinkler M. Impaired subjective health status in chronic adrenal insufficiency: impact of different glucocorticoid replacement regimens. Eur J Endocrinol 2008; 159: 811-817
    CrossrefPubMedSuche in Google Scholar
  • 15 Ross I, Boulle A, Soule S, Levitt N, Pirie F, Karlsson A, Mienie J, Yang P, Wang H, She JX, Winter W, Schatz D. Autoimmunity predominates in a large South African cohort with Addison’s disease of mainly European descent despite long-standing disease and is associated with HLA DQB*0201. Clin Endocrinol (Oxf) 2010; 73: 291-298
    CrossrefPubMedSuche in Google Scholar
  • 16 Ross IL, Levitt NS. Addison’s disease symptoms – a cross sectional study in urban South Africa. PLoS One 2013; 8: e53526
    CrossrefPubMedSuche in Google Scholar
  • 17 Winqvist O, Karlsson FA, Kampe O. 21-Hydroxylase, a major auto­antigen in idiopathic Addison’s disease. Lancet 1992; 339: 1559-1562
    CrossrefPubMedSuche in Google Scholar
  • 18 Ketchum CH, Riley WJ, Maclaren NK. Adrenal dysfunction in asymptomatic patients with adrenocortical autoantibodies. J Clin Endocrinol Metab 1984; 58: 1166-1170
    CrossrefPubMedSuche in Google Scholar
  • 19 Vermeulen A, Verdonck L, Kaufman JM. A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 1999; 84: 3666-3672
    CrossrefPubMedSuche in Google Scholar
  • 20 Gidez LI, Miller GJ, Burstein M, Slagle S, Eder HA. Separation and quantitation of subclasses of human plasma high density lipoproteins by a simple precipitation procedure. J Lipid Res 1982; 23: 1206-1223
    PubMedSuche in Google Scholar
  • 21 Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 1972; 18: 499-502
    CrossrefPubMedSuche in Google Scholar
  • 22 Elder M, Maclaren N, Riley W. Gonadal autoantibodies in patients with hypogonadism and/or Addison’s disease. J Clin Endocrinol Metab 1981; 52: 1137-1142
    CrossrefPubMedSuche in Google Scholar
  • 23 Maclaran K, Panay N. Premature ovarian failure. J Fam Plann Reprod Health Care 2011; 37: 35-42
    CrossrefPubMedSuche in Google Scholar
  • 24 Post FA, Soule SG, Willcox PA, Levitt NS. The spectrum of endocrine dysfunction in active pulmonary tuberculosis. Clin Endocrinol (Oxf) 1994; 40: 367-371
    PubMedSuche in Google Scholar
  • 25 Garg SK, Bandyopadhyay PK, Dash RJ. Hypogonadotropic hypogonadism. An unusual complication of tuberculous meningitis. Trop Geogr Med 1987; 39: 296-298
    PubMedSuche in Google Scholar
  • 26 Gautier A, Bonnet F, Dubois S, Massart C, Grosheny C, Bachelot A, Aube C, Balkau B, Ducluzeau PH. Associations between visceral adipose tissue, inflammation and sex steroid concentrations in men. Clin Endocrinol (Oxf) 2013; 78: 373-378
    CrossrefPubMedSuche in Google Scholar
  • 27 Grossmann M. Testosterone and glucose metabolism in men: current concepts and controversies. J Endocrinol 2014; 220: R37-R55
    CrossrefPubMedSuche in Google Scholar
  • 28 Ding EL, Song Y, Malik VS, Liu S. Sex differences of endogenous sex hormones and risk of type 2 diabetes: a systematic review and meta-analysis. JAMA 2006; 295: 1288-1299
    CrossrefPubMedSuche in Google Scholar
  • 29 Singh R, Artaza JN, Taylor WE, Gonzalez-Cadavid NF, Bhasin S. Androgens stimulate myogenic differentiation and inhibit adipogenesis in C3H 10T1/2 pluripotent cells through an androgen receptor-mediated pathway. Endocrinology 2003; 144: 5081-5088
    CrossrefPubMedSuche in Google Scholar
  • 30 Kupelian V, Page ST, Araujo AB, Travison TG, Bremner WJ, McKinlay JB. Low sex hormone-binding globulin, total testosterone, and symptomatic androgen deficiency are associated with development of the metabolic syndrome in nonobese men. J Clin Endocrinol Metab 2006; 91: 843-850
    CrossrefPubMedSuche in Google Scholar
  • 31 Cattabiani C, Basaria S, Ceda GP, Luci M, Vignali A, Lauretani F, Valenti G, Volpi R, Maggio M. Relationship between testosterone deficiency and cardiovascular risk and mortality in adult men. J Endocrinol Invest 2012; 35: 104-120
    PubMedSuche in Google Scholar
  • 32 Kaplan SA, Johnson-Levonas AO, Lin J, Shah AK, Meehan AG. Elevated high sensitivity C-reactive protein levels in aging men with low testosterone. Aging Male 2010; 13: 108-112
    CrossrefPubMedSuche in Google Scholar
  • 33 Bergthorsdottir R, Leonsson-Zachrisson M, Oden A, Johannsson G. Premature mortality in patients with Addison’s disease: a population-based study. J Clin Endocrinol Metab 2006; 91: 4849-4853
    CrossrefPubMedSuche in Google Scholar
  • 34 Martinez-Jabaloyas JM. Hipogonadism. Global epidemiology and transversal relationships. Arch Esp Urol 2013; 66: 632-638
    PubMedSuche in Google Scholar
  • 35 Reisch N, Hahner S, Bleicken B, Flade L, Pedrosa Gil F, Loeffler M, Ventz M, Hinz A, Beuschlein F, Allolio B, Reincke M, Quinkler M. Quality of life is less impaired in adults with congenital adrenal hyperplasia because of 21-hydroxylase deficiency than in patients with primary adrenal insufficiency. Clin Endocrinol (Oxf) 2011; 74: 166-173
    CrossrefPubMedSuche in Google Scholar
  • 36 Erichsen MM, Lovas K, Fougner KJ, Svartberg J, Hauge ER, Bollerslev J, Berg JP, Mella B, Husebye ES. Normal overall mortality rate in Addison’s disease, but young patients are at risk of premature death. Eur J Endocrinol 2009; 160: 233-237
    CrossrefPubMedSuche in Google Scholar
  • 37 Leelarathna L, Breen L, Powrie JK, Thomas SM, Guzder R, McGowan B, Carroll PV. Co-morbidities, management and clinical outcome of auto-immune Addison’s disease. Endocrine 2010; 38: 113-117
    CrossrefPubMedSuche in Google Scholar
  • 38 Nelson LM. Clinical practice. Primary ovarian insufficiency. N Engl J Med 2009; 360: 606-614
    CrossrefPubMedSuche in Google Scholar
  • 39 Reato G, Morlin L, Chen S, Furmaniak J, Smith BR, Masiero S, Albergoni MP, Cervato S, Zanchetta R, Betterle C. Premature ovarian failure in patients with autoimmune Addison’s disease: clinical, genetic, and immunological evaluation. J Clin Endocrinol Metab 2011; 96: E1255-E1261
    CrossrefPubMedSuche in Google Scholar
  • 40 Yorgun H, Tokgozoglu L, Canpolat U, Gurses KM, Bozdag G, Yapici Z, Sahiner L, Kaya EB, Kabakci G, Oto A, Tuncer M, Aytemir K. The cardiovascular effects of premature ovarian failure. Int J Cardiol 2013; 168: 506-510
    CrossrefPubMedSuche in Google Scholar
  • 41 Brambilla DJ, O’Donnell AB, Matsumoto AM, McKinlay JB. Intraindividual variation in levels of serum testosterone and other reproductive and adrenal hormones in men. Clin Endocrinol (Oxf) 2007; 67: 853-862
    CrossrefPubMedSuche in Google Scholar
  • 42 Bhasin S, Zhang A, Coviello A, Jasuja R, Ulloor J, Singh R, Vesper H, Vasan RS. The impact of assay quality and reference ranges on clinical decision making in the diagnosis of androgen disorders. Steroids 2008; 73: 1311-1317
    CrossrefPubMedSuche in Google Scholar
  • 43 Rosner W, Auchus RJ, Azziz R, Sluss PM, Raff H. Position statement: Utility, limitations, and pitfalls in measuring testosterone: an Endocrine Society position statement. J Clin Endocrinol Metab 2007; 92: 405-413
    CrossrefPubMedSuche in Google Scholar
  • 44 Betterle C, Dal Pra C, Mantero F, Zanchetta R. Autoimmune adrenal insufficiency and autoimmune polyendocrine syndromes: autoantibodies, autoantigens, and their applicability in diagnosis and disease prediction. Endocr Rev 2002; 23: 327-364
    CrossrefPubMedSuche in Google Scholar