Objective: We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes. Methods: 22 GHD patients were investigated in a double-blind randomized study and 90 GHD patients in an open study at baseline and after 6 and 12 months of GH replacement therapy. Results: In the placebo-controlled trial, the FT3 levels increased after 6 months in the GH-treated group, and in the open study the FT3 levels tended to increase. Other hormone concentrations did not change in either part of the study. Four patients required an increase in thyroxine dose, while 2 patients needed dose reduction. One originally euthyroid patient required thyroxine replacement. Two patients with originally conserved pituitary-adrenal function developed ACTH insufficiency. The hydrocortisone dose was increased in 1 and decreased in 1 of the 66 patients with secondary hypocortisolism. None of the females required any adjustment of sex hormone replacement therapy. Two of 37 males needed dose increase of testosterone, while 1 needed dose reduction. Conclusion: GH replacement therapy required dose adjustments regarding other hormone replacement therapies in 12.2% (n = 11), while initiation of new hormone replacement was performed in 3.3% (n = 3) of the 90 patients during the 1-year follow-up. Monitoring of pituitary hormone axes is advisable after commencement of GH replacement therapy, since changes of hormone replacement therapy was observed in a small but clinically significant number of patients.

1.
Grunfeld C, Sherman BM, Cavalieri RR: The acute effects of human growth hormone administration on thyroid function in normal men. J Clin Endocrinol Metab 1988;67:1111–1114.
2.
Wolthers T, Grofte T, Moller N, Christiansen JS, Orskov H, Weeke J, Jorgensen JOL: Calorigenic effects of growth hormone: The role of thyroid hormones. J Clin Endocrinol Metab 1996;81:1416–1419.
3.
Binnerts A, Swart GR, Wilson JH, Hoogerbrugge N, Pols HA, Birkenhager JC, Lamberts SW: The effect of growth hormone administration in growth hormone-deficient adults on bone, protein, carbohydrate and lipid homeostasis, as well as on body composition. Clin Endocrinol 1992;37:79–87.
4.
Jorgensen JO, Moller J, Skakkebaek NE, Week J, Christiansen JS: Thyroid function during growth hormone therapy. Horm Res 1992;38:S63–S67.
5.
Gacs G, Banos C: The effect of growth hormone on plasma levels of T4, free-T4, T3, reverse T3 and TBG in hypopituitary patients. Acta Endocrinol 1981;96:475–479.
6.
Pirazzoli P, Cacciari E, Mandini M, Sganga T, Capelli M, Cicognani A, Gualandi S: Growth and thyroid function in children treated with growth hormone. J Pediatr 1992;121:210–213.
7.
Trainer PJ, Holly J, Medback S, Rees LH, Besser GM: The effect of recombinant IGF-I on anterior pituitary function in healthy volunteers. Clin Endocrinol 1994;41:801–807.
8.
Moore JS, Monson JP, Kaltsas G, Putignano P, Wood PJ, Sheppard MC, Besser GM, Taylor NF, Stewart PM: Modulation of 11β-hydroxysteroid dehydrogenase isoenzymes by growth hormone and insulin-like growth factor: In vivo and in vitro studies. J Clin Endocrinol Metab 1999;84:4172–4177.
9.
Stewart PM, Toogood AA, Tomlinson JW: Growth hormone, insulin-like growth factor-I and the cortisol-cortisone shuttle. Horm Res 2001;56:S1–S6.
10.
L’Allemand D, Penhoat A, Lebrethom MC, Ardevol R, Baehr V, Oelkers W, Saez JM: Insulin-like growth factors enhance steroidogenic enzyme and corticotropin receptor messenger ribonucleic acid levels and corticotropin steroidogenic responsiveness in cultured human adrenocortical cells. J Clin Endocrinol Metab 1996;81:3892–3897.
11.
Gianotti L, Ramunni J, Lanfrancol F, Maccagno B, Giordano R, Broglio F, Maccario M, Muller EE, Chigo E, Arvat E: Recombinant human IGF-I does not modify the ACTH and cortisol responses to hCRH and hexarelin, a peptidyl GH secretagogue, in humans. J Endocrinol Invest 2001;24:67–71.
12.
Hull KL, Harvey S: Growth hormone: Roles in female reproduction. J Endocrinol 2001;168:1–23.
13.
Carani C, Granata ARM, De Rosa M, Garau C, Zarrilli S, Paesano L, Colao A, Marrama P, Lombardi G: The effect of chronic treatment with GH on gonadal function in men with isolated GH deficiency. Eur J Endocrinol 1999;140:224–230.
14.
Hull KL, Harvey S: Growth hormone: A reproductive endocrine-paracrine regulator? Rev Reprod 2000;5:175–182.
15.
Ovesen P, Moller J, Jorgensen JO, Moller N, Christiansen JS: Lack of impact of pharmacological growth hormone administration on circulating levels of reproductive hormones during the menstrual cycle in normal women. Fertil Steril 1993;59:311–314.
16.
Ovesen P, Moller J, Jorgensen JO, Moller N, Christiansen JS: Effect of growth hormone administration on circulating levels of luteinizing hormone, follicle-stimulating hormone and testosterone in normal healthy men. Hum Reprod 1993;8:1869–1872.
17.
Juul A, Andersson AM, Pedersen SA, Jorgensen JO, Christiansen JS, Groome NP, Skakkebaek NE: Effects of growth hormone replacement therapy on IGF-related parameters and on the pituitary-gonadal axis in GH-deficient males. A double-blind, placebo-controlled crossover study. Horm Res 1998;49:269–278.
18.
Lara JI, Lorenzo MJ, Cacicedo L, Tolon RM, Balsa JA, Lopez-Fernandez J, Sanchez-Franco F: Induction of vasoactive intestinal peptide gene expression and prolactin secretion by insulin-like growth factor I in rat pituitary cells: Evidence for an autoparacrine regulatory system. Endocrinology 1994;135:2526–2532.
19.
Fruchtman S, Jackson L, Borski R: Insulin-like growth factor I disparately regulates prolactin and growth hormone synthesis and secretion: Studies using the teleost pituitary model. Endocrinology 2000;141:2886–2894.
20.
Fruchtman S, Gift B, Howes B, Borski R: Insulin-like growth factor-I augments prolactin and inhibits growth hormone release through distinct as well as overlapping cellular signalling pathways. Comp Biochem Physiol B Biochem Mol Biol 2001;129:237–242.
21.
Atkin SL, Landolt AM, Foy P, Jeffreys RV, Hipkin L, White MC: Effects of insulin-like growth factor-I on growth hormone and prolactin secretion and cell proliferation of human somatotrophinomas and prolactinomas in vitro. Clin Endocrinol 1994;41:503–509.
22.
Invited Report of the Growth Hormone Research Society Workshop: Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency. J Clin Endocrinol Metab 1998;83:379–381.
23.
Trainer JP, Besser M: The Bart’s Endocrine Protocols. London, Longman Group Ltd, 1995, pp 27–28.
24.
Juul A, Bang P, Hertel NT, Main K, Dalgaard P, Jorgensen K, Muller J, Hall K, Skakkebaek NE: Serum insulin-like growth factor-I in 1,030 healthy children, adolescents, and adults: Relation to age, sex, stage of puberty, testicular size and body mass index. J Clin Endocrinol Metab 1994;78:744–752.
25.
Jorgensen JO, Ovesen P, Juul A, Hansen TK, Skakkebaek NE, Christiansen JS: Impact of growth hormone administration on other hormonal axes. Horm Res 1999;51:S121–S126.
26.
Jorgensen JO, Moller J, Laursen T, Orskov H, Christiansen JS, Weeke J: Growth hormone administration stimulates energy expenditure and extrathyroidal conversion of thyroxine to triiodothyronine in a dose-dependent manner and suppresses circadian thyrotropin levels: Studies in GH-deficient adults. Clin Endocrinol 1994;41:609–614.
27.
Amato G, Izzo G, Salzano I, Bellastella A: Recombinant human growth hormone treatment at low doses does not significantly change thyroid function in growth hormone-deficient adults. J Endocrinol Invest 1996;19:563–566.
28.
Bengtsson BA, Eden S, Lonn L, Kvist H, Stokland A, Lindstedt G, Bosaeus I, Tolli J, Sjorstom L, Isaksson OG: Treatment of adults with growth hormone deficiency with recombinant human growth hormone. J Clin Endocrinol Metabol 1993;76:309–317.
29.
Jorgensen JO, Pedersen SA, Lauberg P, Weeke J, Skakkeback NE, Christiansen JS: Effect of growth hormone therapy on thyroid function of growth hormone-deficient adults with and without concomitant thyroxine-substituted central hypothyroidism. J Clin Endocrinol Metab 1989;69:1127–1132.
30.
Carroll PV, Christ ER, Bengtsson BA, Carlsson L, Christiansen JS, Clemmons D, Hintz R, Ho K, Laron Z, Sizonenko P, Sonksen PH, Tanaka T, Thorner M: Growth hormone deficiency in adulthood and the effects of growth hormone replacement: A review. Growth Hormone Research Society Scientific Committee. J Clin Endocrinol Metab 1998;83:382–395.
31.
Tschop M, Lahner H, Feldmeier H, Grasberger H, Morrison KM, Janssen OE, Attanasio AF, Strasburger CJ. Effects of growth hormone replacement therapy on levels of cortisol and cortisol-binding globulin in hypopituitary adults. Eur J Endocrinol 2000;143:769–773.
32.
Lippe BM, Van Herle AJ, LaFranchi SH, Uller RP, Lavin N, Kaplan SA: Reversible hypothyroidism in growth hormone-deficient children treated with human growth hormone. J Clin Endocrinol Metab 1975;40:612–618.
33.
Laurberg P, Jakobsen PE, Hoeck HC, Vestergaard P: Growth hormone and thyroid function: Is secondary thyroid failure underdiagnosed in growth hormone-deficient patients? Thyroidology 1994;6:73–79.
34.
Porretti S, Giavoli C, Ronchi C, Lombardi MZ, Valle D, Arosio M, Beck-Peccoz P: Recombinant human GH replacement therapy and thyroid function in a large group of adult GH-deficient patients: When does L-T4 therapy become mandatory? J Clin Endocrinol Metab 2002;87:2042–2045.
35.
Cacciari E, Cicognani A, Pirazzoli P, Bernardi F, Zappulla F, Salardi S, Mazzanti L, Biasini A, Valenti E: Effect of long-term GH administration on pituitary-thyroid function in idiopathic hypopituitarism. Acta Paediatr 1979;68:405–409.
36.
Municchi G, Malozowski S, Nisula BC, Cristiano A, Rose SR: Noctural thyrotropin surge in growth hormone-deficient children. J Pediatr 1992;121:214–220.
37.
Wyatt DT, Gesundheit N, Sherman B: Changes in thyroid hormone levels during growth hormone therapy in initially euthyroid patients: Lack of need for thyroxine supplementation. J Clin Endocrinol Metabol 1998;83:3493–3497.
38.
Rosenbloom AL, Riley WJ, Silverstein JH, Garnica AD, Netzloff ML, Weber FT: Low-dose single weekly injections of growth hormone: Response during first year of therapy of hypopituitarism. Pediatrics 1980;66:272–276.
39.
Portes ES, Oliveira JH, MacCagnan P, Abucham J: Changes in serum thyroid hormone levels and their mechanisms during long-term growth hormone replacement therapy in growth hormone-deficient children. Clin Endocrinol 2000;53:183–189.
40.
Rasmussen AK, Feldt-Rasmussen U, Skakkebaek NE, Jorgensen JO, Christiansen JS, Muller J: Autoimmune thyrotoxicosis developed during growth hormone treatment of an adult with childhood onset growth hormone deficiency. A causal relationship? Autoimmunity 1998;27:57–61.
41.
Weaver JU, Thaventhiran L, Noonan K, Burrin JM, Taylor NF, Norman MR, Monson JP: The effect of growth hormone replacement on cortisol metabolism and glucocorticoid sensitivity in hypopituitary adults. Clin Endocrinol 1994;41:639–648.
42.
Walker BR, Andrew R, MacLeod KM, Padfield PL: Growth hormone replacement inhibits renal and hepatic 11β-hydroxysteroid dehydrogenases in ACTH-deficient patients. Clin Endocrinol 1998;49:257–263.
43.
Gelding SV, Taylor NF, Wood PJ, Noonan K, Weawe JU, Wood DF, Monson JP: The effect of growth hormone replacement therapy on cortisol-cortisone interconversion in hypopituitary adults: Evidence for growth hormone modulation of extrarenal 11β-hydroxysteroid dehydrogenase activity. Clin Endocrinol 1998;48:153–162.
44.
Rodrigues-Arnao J, Perry L, Besser GM, Ross RJ: Growth hormone treatment in hypopituitary growth hormone-deficient adults reduces circulating cortisol levels during hydrocortisone replacement therapy. Clin Endocrinol 1996;45:33–37.
45.
Toogood AA, Taylor NF, Shalet SM, Monson JP: Modulation of cortisol metabolism by low-dose growth hormone replacement in elderly hypopituitary patients. J Clin Endocrinol Metab 2000;85:1727–1730.
46.
Balducci R, Toscano V, Mangiantini A, Bianchi P, Guglielmi R, Boscherini B: The effect of growth hormone administration on testicular response during gonadotropin therapy in subjects with combined gonadotropin and growth hormone deficiencies. Acta Endocrinol 1993;128:19–23.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.