Skip to main content
SpringerLink
Log in

Subjects with isolated GH deficiency due to a null GHRHR mutation eat proportionally more, but healthier than controls

  • Original Article
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

The GH/IGF-I axis has important interactions with the alimentary system and with the balance between energy intake (EI) and energy requirement (ER). Reduced EI has been described in adult-onset acquired GH deficiency (GHD). Individuals from the Brazilian Itabaianinha cohort, with isolated GHD (IGHD) due to a homozygous mutation (c.57+1G→A) in the GHRH receptor gene, are an ideal model to study the consequences of lifetime GHD. The purpose of this study is to evaluate EI and ER in this untreated IGHD cohort. Cross-sectional study of 24 adult IGHD patients and 23 controls from the same region, matched for age and gender. Estimated EI (EEI) was evaluated by dietary recall, and estimated ER (EER) by the equation of the Dietary Reference Intakes. Fat mass was assessed by DXA. Both EEI and EER were lower in IGHD than controls. However, when corrected by body weight, EEI was higher in IGHD (p = 0.005). IGHD individuals consume in percentage more proteins (p < 0.0001), less carbohydrates (p = 0.013), and equal amount of lipids in comparison to controls. The higher EEI per body weight suggests a possible increase of orexigenic mechanisms in untreated IGHD individuals, ensuring greater caloric intake, which would have adaptive advantages for small-sized individuals in environments with limited access to food. IGHD individuals seem to have a healthier dietary pattern than CO.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. N. Moller, J. Gjedsted, L. Gormsen, J. Fuglsang, C. Djurhuus, Effects of growth hormone on lipid metabolism in humans. Growth Horm. IGF Res. 13, 18–21 (2003)

    Article  Google Scholar 

  2. A. Vijayakumar, S. Yakar, D. LeRoith, The intricate role of growth hormone in metabolism. Front Endocrinol. 2, 1–11 (2011)

    Article  Google Scholar 

  3. V.N. Anisimov, A.A. Bartke, The key role of growth hormone–insulin–IGF-1 signaling in aging and cancer. Crit. Rev. Oncol. Hematol. 87, 201–223 (2013)

    Article  PubMed  PubMed Central  Google Scholar 

  4. A.A. Sakharova, J.F. Horowitz, S. Surya, N. Goldenberg, M.P. Harber, K. Symons, Role of growth hormone in regulating lipolysis, proteolysis, and hepatic glucose production during fasting. J. Clin. Endocrinol. Metab. 93, 2755–2759 (2008)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. C.R.P. Oliveira, R.A. Meneguz-Moreno, M.H. Aguiar-Oliveira, J.A.S. Barreto-Filho, Emerging role of the GH/IGF-I on cardiometabolic Control. Arq. Bras. Cardiol. 97, 434–439 (2011)

    Article  CAS  PubMed  Google Scholar 

  6. A.H.O. Souza, R. Salvatori, J.R.C.E. Martinelli, W.M.O. Carvalho, C.A. Menezes, E.S.A. Barretto, J.A.S.B. Filho, M.R.S. Alcântara, C.R.P. Oliveira, P.R.S. Alcântara, R.J.R. Ramalho, H.Á. Oliveira, I.B. Lima, J.N. Carneiro, M.M. Santos, M.S. Gill, P.E. Clayton, M.H.A. Oliveira, Hormônio do crescimento ou somatotrófico: novas perspectivas na deficiência isolada de GH a partir da descrição da mutação no gene do receptor do GHRH nos indivíduos da cidade de Itabaianinha, Brasil. Arq. Bras. Endocrinol. Metab. 48, 406–413 (2004)

    Article  Google Scholar 

  7. M. Kojima, H. Hosoda, Y. Date, M. Nakazato, H. Matsuo, Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656–660 (1999)

    Article  CAS  PubMed  Google Scholar 

  8. A.D. Howard, S.D. Feighner, D.F. Cully, J.P. Arena, P.A. Liberator, A receptor in pituitary and hypothalamus that functions in growth hormone release. Science 273, 974–977 (1996)

    Article  CAS  PubMed  Google Scholar 

  9. T.R. Castañeda, J. Tong, R. Datta, M. Culler, M.H. Tschöp, Ghrelin in thr regulation of body and metabolism. Front. Neuroendocrinol. 31, 44–46 (2010)

    Article  PubMed  Google Scholar 

  10. H. Iwakura, K. Kangawa, N. Kazuwa, The regulation of circulating ghrelin—with recent updates from cell-based assays. Endocr. J. 62, 107–122 (2015)

    Article  CAS  PubMed  Google Scholar 

  11. R.M. Luque, Q. Lin, J. Córdoba-Chacón, P.V. Subbaiah, T. Buch, A. Waisman, H. Vankelecom, R.D. Kineman, Metabolic impact of adult-onset, isolated, growth hormone deficiency (AOiGHD) due to destruction of pituitary somatotropes. PLoS One 6, 1–11 (2011)

    Google Scholar 

  12. D. Deepak, C. Daousi, E. Boyland, J.H. Pinkney, J.P.H. Wilding, I.A. MacFarlane, Growth hormone and changes in energy balance in growth hormone deficient adults. Eur. J. Clin. Invest. 38, 622–627 (2008)

    Article  CAS  PubMed  Google Scholar 

  13. L. Recinella, R. Shohreh, R. Salvatori, G. Orlando, M. Vacca, L. Brunetti, Effects of isolated GH deficiency on adipose tissue, feeding and adipokines in mice. Growth Horm. IGF Res. 23, 237–242 (2013)

    Article  CAS  PubMed  Google Scholar 

  14. S. Leone, A. Chiavaroli, R. Shohreh, C. Ferrante, A. Ricciuti, F. Manippa, L. Recinella, C.D. Nisio, G. Orlando, R. Salvatori, M. Vacca, L. Brunetti, Increased locomotor and thermogenic activity in mice with targeted ablation of GHRH gene. Growth Horm. IGF Res. 25, 80–84 (2015)

    Article  CAS  PubMed  Google Scholar 

  15. R. Salvatori, C.Y. Hayashida, M.H. Aguiar-Oliveira, R.D.J.A. Phillips, A.H. Souza, R.G. Gondo, S.P. Toledo, M.M. Conceicão, M. Prince, H.G. Maheshwari, G. Baumann, M.A. Levine, Familial dwarfism due to a novel mutation of the growth hormone-releasing hormone receptor gene. J. Clin. Endocrinol. Metab. 84, 917–923 (1999)

    CAS  PubMed  Google Scholar 

  16. E. Gomes-Santos, R. Salvatori, T.O. Ferrão, C.R.P. Oliveira, R.D.C.A. Diniz, J.A.M. Santana, F.A. Pereira, R.A.A. Barbosa, A.H.O. Souza, E.V. Melo, C.C.E. Pereira, A.A.O. Santos-Oliveira, I.A.S. Oliveira, J.Á. Machado, F.J.S. Júnior, J.A.S. Barreto-Filho, M.H. Aguiar-Oliveira, Increased visceral adiposity and cortisol to cortisone ratio in adults with congenital life time isolated GH deficiency. J. Clin. Endocrinol. Metab. 99, 3285–3289 (2014)

    Article  CAS  PubMed  Google Scholar 

  17. C.R.P. Oliveira, R. Salvatori, J.A.S. Barreto-Filho, I.E.S. Rocha, A. Mari, R.M.C. Pereira, V.C. Campos, M. Menezes, E. Gomes, R.M. Meneguz, V.P. Araújo, N.L.T.F. Leite, A.O.C. Nascimento, M.I.T. Farias, T.A.R. Viscente, R.D.C. Araújo, E.V. Melo, M.H. Aguiar-Oliveira, Insulin sensitivity and β-cell function in adults with lifetime, untreated isolated growth hormone deficiency. J. Clin. Endocrinol. Metab. 97, 1–7 (2012)

    Article  Google Scholar 

  18. J.A.S. Barreto-Filho, M.R.S. Alcântara, M.A. Barreto, A.C.S. Sousa, V. Bastos, A.H. Souza, R.M.C. Pereira, P.E. Clayton, M.S. Gill, M.H. Aguiar-Oliveira, Familial isolated growth hormone deficiency is associated with increased systolic blood pressure, central obesity, and dyslipidemia. J. Clin. Endocrinol. Metab. 87, 2018–2023 (2002)

    Article  CAS  PubMed  Google Scholar 

  19. H. Kanety, R. Hemi, S. Ginsberg, C. Pariente, E. Issachar, E. Barhod, T. Funahashi, Z. Laron, Total and high molecular weight adiponectin are elevated in patients with Laron syndrome despite marked obesity. Eur. J. Endocrinol. 161, 837–844 (2009)

    Article  CAS  PubMed  Google Scholar 

  20. M.H. Aguiar-Oliveira, R. Salvatori, Lifetime Growth Hormone (GH) Deficiency: impact on growth, metabolism, body composition, and survival capacity Chapter ID 160, in Handbook of Growth and Growth Monitoring in Health and Disease, ed. by V.R. Preedy (Springer Science + Business Media, LLC, New York, 2011)

    Google Scholar 

  21. C.G. Salvador, L. Serra-Majem, L. Ribas-Barba, What and how much do we eat? 24-hour dietary recall method. Nutr. Hosp. 31, 46–48 (2015)

    Google Scholar 

  22. IOM/Food and Nutrition Board, Dietary Reference Intakes for energy, carbohydrate, fiber, fat, fatty acids, cholesterol, protein, and amino acids (Macronutrients), vol. 1 (The National Academies Press, Washington, DC, 2005), pp. 1–1358

    Google Scholar 

  23. F. Salomon, R.C. Cuneo, R. Hesp, P.H. Sonksen, The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N. Engl. J. Med. 321, 1797–1803 (1989)

    Article  CAS  PubMed  Google Scholar 

  24. Y.E. Snel, M.E. Doerga, R.J. Brummer, P.M. Zelissen, M.L. Zonderland, H.P. Koppeschaar, Resting metabolic rate, body composition and related hormonal parameters in growth hormone-deficient adults before and after growth hormone replacement therapy. Eur. J. Endocrinol. 133, 445–450 (1995)

    Article  CAS  PubMed  Google Scholar 

  25. J.A.R. Barbosa, R. Salvatori, C.R.P. Oliveira, R.M.C. Pereira, C.T. Farias, A.V.O. Britto, N.T. Farias, A. Blackford, M.H. Aguiar-Oliveira, Quality of life in congenital, untreated, lifetime isolated growth hormone deficiency. Psychoneuroendocrinology 34, 894–900 (2009)

    Article  CAS  PubMed  Google Scholar 

  26. Z. Laron, S. Ginsberg, N. Vaisman, Investigations to determine the cause of obesity in patients with Laron syndrome, in Laron syndrome—from man to mouse, ed. by Z. Laron, J.J. Kopchick (Springer, Berlin, 2011), pp. 135–142

    Chapter  Google Scholar 

  27. S. Ginsberg, Z. Laron, M.A. Bed, N. Vaisman, The obesity of patients with Laron syndrome is not associated with excessive nutritional intake. Obes. Res. Clin. Pract. 3, 3–8 (2009)

    Article  Google Scholar 

  28. R. Salvatori, M.G. Serpa, G. Parmigiani, A.V. Britto, J.L. Oliveira, C.R. Oliveira, C.M. Prado, C.T. Farias, J.C. Almeida, T.A. Vicente, M.H. Aguiar-Oliveira, Growth hormone (GH) response to hypoglycemia and clonidine in the GH-releasing hormone resistance syndrome. J. Endocrinol. Invest. 29, 805–808 (2006)

    Article  CAS  PubMed  Google Scholar 

  29. J. Galganiand, E. Ravussin, Energy metabolism, fuel selection and body weight regulation. Int. J. Obes. (Lond). 32, S109–S119 (2008)

    Article  Google Scholar 

  30. J. Stubbs, D.A. Hughes, A.M. Johnstonel, E. Rowley, C. Reid, M. Elia, R. Stratton, H. Delargy, N. King, J.E. Blundell, The use of visual analogue scales to assess motivation to eat in human subjects: a review of their reliability and validity with an evaluation of new hand-held computerized systems for temporal tracking of appetite ratings. Br. J. Nutr. 84, 405–415 (2000)

    Article  CAS  PubMed  Google Scholar 

  31. B. Sarter, K.S. Kelsey, T.A. Schwartz, W.S. Harris, Blood docosahexaenoic acid and eicosapentaenoic acid in vegans: Associations with age and gender and effects of an algal-derived omega-3 fatty acid supplement. Clin. Nutr. 34, 212–218 (2015)

    Article  CAS  PubMed  Google Scholar 

  32. L. Liu, P.P. Wang, B. Roebothan, A. Ryan, C.S. Tucker, J. Colbourne, N. Baker, M. Cotterchio, Y. Yi, G. Sun, Assessing the validy of a self-administered food-frequency questionnaire (FFQ) in the adult population of newfoundland and labrador. Canada. Nutr J. 12, 1–9 (2013)

    Google Scholar 

  33. M.H. Aguiar-Oliveira, F.T. Oliveira, R.M. Pereira, C.R. Oliveira, A. Blackford, E.H. Valenca, E.G. Santos, M.B. Gois-Junior, R.A. Meneguz-Moreno, V.P. Araujo, L.A. Oliveira-Neto, R.P. Almeida, M.A. Santos, N.T. Farias, D.C. Silveira, G.W. Cabral, F.R. Calazans, J.D. Seabra, T.F. Lopes, E.O. Rodrigues, L.A. Porto, I.P. Oliveira, E.V. Melo, M. Martari, R. Salvatori, Longevity in untreated congenital growth hormone deficiency due to a homozygous mutation in the GHRH receptor gene. J. Clin. Endocrinol. Metab. 95, 714–721 (2010)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. L.G. Bandini, K. Lividini, S.M. Phillips, A. Must, Accuracy of Dietary Reference Intakes for determining energy requirements in girls 1–3 Linda. Am. J. Clin. Nutr. 98, 700–704 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

We thank the Clinic CLIMEDI (Aracaju, SE) for the DXA measurements.

Conflict of interest

The authors have no conflict of interest to disclose.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Federal University of Sergipe, Aracaju, SE, 49060-100, Brazil

    Alécia A. Oliveira-Santos, Elenilde Gomes-Santos, João A. M. Santana, Ângela C. G. B. Leal, Rita A. A. Barbosa, Carla R. P. Oliveira, Anita H. O. Souza, Eugênia H. O. Valença & Manuel H. Aguiar-Oliveira

  2. Division of Endocrinology, Diabetes and Metabolism, Johns Hopkins University School of Medicine, 1830 East Monument Street Suite #333, Baltimore, MD, 21287, USA

    Roberto Salvatori

Authors
  1. Alécia A. Oliveira-Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Roberto Salvatori
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elenilde Gomes-Santos
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. João A. M. Santana
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ângela C. G. B. Leal
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Rita A. A. Barbosa
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Carla R. P. Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anita H. O. Souza
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Eugênia H. O. Valença
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Manuel H. Aguiar-Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Roberto Salvatori.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Oliveira-Santos, A.A., Salvatori, R., Gomes-Santos, E. et al. Subjects with isolated GH deficiency due to a null GHRHR mutation eat proportionally more, but healthier than controls. Endocrine 51, 317–322 (2016). https://doi.org/10.1007/s12020-015-0670-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-015-0670-2

Keywords

Search

Navigation