Horm Metab Res 2003; 35(2): 114-119
DOI: 10.1055/s-2003-39058
Original Clinical
© Georg Thieme Verlag Stuttgart · New York

Impact of Growth Hormone on Central Nervous Activity, Vigilance, and Tiredness after Short-Term Therapy in Growth Hormone-Deficient Adults

M.  E.  Pavel 1 , T.  Lohmann 1 , E.  G.  Hahn 1 , M.  Hoffmann 2
  • 1 Division of Endocrinology, Department of Internal Medicine I
  • 2 Sleep Disorders Center, Department of Psychiatry, Erlangen-Nuremberg University Hospital, Germany
Further Information

Publication History

Received 23 May 2002

Accepted after revision 9 October 2002

Publication Date:
07 May 2003 (online)

Abstract

Impairment of well-being and cognitive function has been reported in growth hormone-deficient adults, as well as an improvement of these parameters after GH substitution, albeit inconsistently. The effect of growth hormone on central nervous activity, vigilance and sleepiness was studied prospectively in 16 growth hormone-deficient adults (7 females, 9 males, mean age: 36.8 yrs) with multiple pituitary hormone deficiencies before and 3 months after the start of growth hormone substitution using two objective methods of measurement, pupillographic sleepiness test and a choice reaction time test. Significant differences were found for neither pupillary unrest index nor for reaction time, false or missing reactions in 12 evaluable patients (7 females, 5 males, mean age 37.8 years). Because of the known interrelationships between growth hormone, sleep and mood, the visual analogue scale for tiredness and standardized retrospective questionnaires regarding sleep and mood (Pittsburgh sleep quality index, Epworth sleepiness scale, Depression scale) were used as additional methods. After GH substitution, there was no difference in sleep efficiency and daytime sleepiness, but some of the subjective sleep parameters (sleep quality and sleep latency) improved significantly. There was a tendency for mood improvement, too. Although results must be interpreted cautiously due to the small sample size, we conclude that the improved sleep and mood parameters might be caused by other indices of general well-being in our study.

References

  • 1 Bengtsson B A, Eden S, Lönn L, Kvist H, Stokland A, Lindstedt G, Bosaeus I, Tölli J, Sjöström L, Isaksson O GP. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH.  J Clin Endocrinol Metab. 1993;  76 309-317
  • 2 Björk S, Jönsson B, Westphal O, Levin J E. Quality of life of adults with growth hormone deficiency: a controlled study.  Acta Paediatr Scand. 1989;  356 (suppl) 55-59
  • 3 Aström C, Pedersen S A, Lindholm J. The influence of growth hormone on sleep in adults with growth hormone deficiency.  Clin Endocrinol. 1990;  33 496-500
  • 4 Deijen J B, de Boer H, Blok G J, van der Veen E A. Cognitive impairments and mood disturbances in growth hormone deficient men.  Psychoneuroendocrinology. 1996;  21(3) 313-322
  • 5 Rosen T, Wiren L, Wilhelmsen L, Wiklund I, Bengtsson B A. Decreased psychological well-being in adult patients with growth hormone deficiency.  Clin Endocrinol. 1994;  40 111- 116
  • 6 Wallymahmed M E, Foy P, MacFarlane I A. The quality of life of adults with growth hormone deficiency: comparison with diabetic patients and control subjects.  Clin Endocrinol. 1999;  51 (3) 333-338
  • 7 Cuneo R C, Salomon G A, Mc Gauley G A, Sonksen P H. The growth hormone deficiency syndrome in adults.  Clin Endocrinol. 1992;  37 387-397
  • 8 Wiren L, Wilhelmsen L, McKenna S P, Hernberg-Stahl E. The quality of life of adult growth hormone deficient patients in Sweden compared to a random population sample assessed by QoL-AGHDA.  Endocrinol Metab. 1997;  4 (Suppl B) 167
  • 9 Verhelst J, Abs R, Vandeweghe M, Mockel J, Legros J, Kopinschi G, Mahler C, Velkeniers B, Vanhaelst L, van Aelst A, de Rijdt D, Stevenaert A, Beckers A. Two years of replacement therapy in adults with growth hormone deficiency.  Clin Endocrinol. 1997;  47 485-494
  • 10 Holmes S J, Shalet S M. Factors influencing the desire for long-term GH replacement in adults.  Clin Endocrinol. 1995;  43 151-157
  • 11 Whitehead H M, Boreham C, McIlrath E M, Sheridan B, Kennedy L, Atkinson A B, Hadden D R. Growth hormone treatment of adults with growth hormone deficiency: results of a 13 month placebo controlled cross-over study.  Clin Endocrinol. 1992;  36 45-52
  • 12 Florkowski C M, Stevens I, Joyce P, Espiner E A, Donald R A. Growth hormone replacement does not improve psychological well-being in adult hypopituitarism: a randomized crossover trial.  Psychoneuroendocrinology. 1998;  23 (1) 57-63
  • 13 Murray R D, Skillicorn C J, Howell S J, Lisset C A, Rahim A, Smethurst L E, Shalet S M. Influences on quality of life in GH deficient adults and their effect on response to treatment.  Clin Endocrinol. 1999;  51 (5) 565-573
  • 14 Baum H BA, Katznelson L, Sherman J C, Biller B MK, Hayden D L, Schoenfeld D A, Cannistraro K E, Klibanski A. Effects of physiological growth hormone (GH) therapy on cognition and quality of life in patients with adult-onset GH deficiency.  J Clin Endocrinol Metab. 1998;  83 3184-3189
  • 15 Deijen J B, de Boer H, van der Veen E A. Cognitive changes during growth hormone replacement in adults.  Psychoneuroendocrinology. 1998;  23 (1) 45-55
  • 16 Posner M, Rafal R. Cognitive theories of attention at rehabilitation of attentional deficits. In: Meier M, Benton A, Diller L [eds]: Neuropsychological rehabilitation Churchil Livingstone Edinburgh; 1987: 182-201
  • 17 Wilhelm B, Wilhelm H, Streicher P, Lüdtke H, Adler M. Pupillographie als objektiver Vigilanztest.  Wien Med Wschr. 1996;  13 387-389
  • 18 Weeß HG, Sauter C, Geisler P, Böhning W, Wilhelm B, Rotte M, Gresele C, Schneider C, Schulz H, Lund R, Steinberg R. Vigilance, tendency to fall asleep, sustained attention, tiredness, sleepiness - diagnostic tools for the measurement of sleepiness related processes and their criteria of quality.  Somnology. 2000;  1 20-38
  • 19 Wilhelm B, Wilhelm H, Lüdtke H, Streicher P, Adler M. Pupillographic assessment of sleepiness in sleep-deprived healthy subjects.  Sleep. 1998;  22(3) 258-265
  • 20 Wilhelm B, Giedke H, Lüdtke H, Bittner E, Hofmann A, Wilhelm H. Daytime variations in central nervous system activation measured by a pupillographic sleepiness test.  J Sleep Res. 2001;  10 1-7
  • 21 Wilhelm B, Körner A, Heldmaier K, Moll K, Wilhelm H, Lüdtke H. Normal values of the pupillographic sleepiness test in male and female subjects aged 20 to 60 years.  Somnology. 2001;  3 115-120
  • 22 Danker-Hopfe H, Kraemer S, Dorn H, Schmidt A, Ehlert I, Herrmann W M. Time-of day variations in different measures of sleepiness (MSLT, pupillography, and SSS) and their interrelations.  Psychophysiology. 2001;  38 (5) 828-835
  • 23 Wilhelm B, Neugebauer P, Lüdtke H, Hohenstein E, Ederle H, Wilhelm H. Pupillographic sleepiness test for therapy control in obstructive sleep apnea syndrome after three months nCPAP.  Somnology. 1999;  3 53-56
  • 24 Conradt R, Brandenburg U, Cassel W, Penzel T, Peter J H. Veränderungen der Vigilanz während Reaktionszeit-Test bei Patienten mit OSA und unter nCPAP-Therapie.  Somnology. 1997;  suppl 1 4
  • 25 Cassel W, Niess D, Dugnus T, Pooch T, Peter J H. Vigilanz bei Patienten mit SBAS und Kontrollpersonen.  Somnology. 1999;  suppl 1 55
  • 26 Aimaretti G, Corneli G, Razzore P, Bellone S, Baffoni C, Arvat E, Camanni F, Ghigo E. Comparison between insulin-induced hypoglycemia and growth hormone (gh) - releasing hormone + arginine as provocative tests for the diagnosis of gh deficiency in adults.  J Clin Endocrinol Metab. 1998;  83 1615-1618
  • 27 Wilhelm B. Die Rolle der zentralen Hemmung - sympathische Tricks in der Steuerung der Pupillenweite.  Somnology. 2001;  suppl 2 61-62
  • 28 Carpenter J S, Andrykowski M A. Psychometric evaluation of the Pittsburgh Sleep Quality Index.  J Psychosom Res. 1998;  45 5-13
  • 29 Johns M W. Sensitivity and specificity of the multiple sleep latency test (MSLT), the maintenance of wakefulness test and the Epworth sleepiness scale: failure of the MSLT as a gold standard.  J Sleep Res. 2000;  9 (1) 5-14
  • 30 Giusti M, Meineri I, Malagamba D, Cuttica C M, Fattaciu G, Menichini U, Rasore E, Giordano G. Impact of recombinant human growth hormone treatment on psychological profiles in hypopititary patients with adult-onset growth hormone deficiency.  Europ J Clin Invest. 1998;  28 (1) 13-19
  • 31 Von Zerssen D, Koeller D M. Depressivitäts-Skala in klinischen Selbstbeurteilungsskalen (Ksb-S) aus dem Münchner Psychiatrischen Informations-System (PSYCHIS München). Weinheim; Beltz 1975
  • 32 Mc Gauley G A. Quality of life assessment before and after growth hormone treatment in adults with growth hormone deficiency.  Acta Paediatr Scand Suppl. 1989;  356 70-72
  • 33 Burman P, Deijen J. Quality of life and cognitive function in patients with pituitary insufficiency.  Psychother Psychosom. 1998;  67 154-167
  • 34 Nyberg F. Growth hormone in the brain: Characteristics of specific brain targets for the hormone and their functional significance.  Front Neuroendocrinol. 2000;  21 330-348
  • 35 Attanasio AF, Lamberts S WJ, Matranga A MC. et al . Adult growth hormone deficient patients demonstrate heterogeneity between childhood onset and adult onset before and during GH treatment.  J Clin Endocrinol Metab.. 1997;  82 82-88
  • 36 Almqvist O, Thoren M, Sääf M, Eriksson O. Effects of growth hormone substitution on mental performance in adults with growth hormone deficiency.  Psychoneuroendocrinology. 1986;  11 347-352
  • 37 Aström C, Lindholm J. Growth hormone deficient young adults have decreased deep sleep.  Neuroendocrinology. 1999;  51 82-84
  • 38 Lai Z, Entner M, Ross P, Nyberg F. Characterisation of putative growth hormone receptors in human choroid plexus.  Brain Research. 1991;  546 222-226
  • 39 Andersson K, Fuxe K, Eneroth P, Isaksson O, Nyberg F, Roos P. Rat growth hormone and hypothalamic catecholamine nerve terminal systems. Evidence for rapid and discrete reductions in dopamine and noradrenaline levels and turnover in the median eminence of the hypophysectomized male rat.  Europ J Pharmacol. 1983;  95 271-275
  • 40 Stern W C, Miller M, Jalowiec J E, Forbes W B, Morgane P J. Effects of growth hormone on brain biogenic amine levels.  Pharmacol Biochem Behav. 1975;  3 1115-1118
  • 41 Johansson J O, Larson G, Andersson M, Elmgren A, Hynsjö L, Lindahl A, Isaksson O GP, Lindstedt S, Bengtsson B A. Treatment of growth hormone deficient adults with recombinant human growth hormone increases the concentration of growth hormone in the cerebrospinal fluid and affects neurotransmitters.  Neuroendocrinology. 1995;  61 57-66

M. E. Pavel

Department of Internal Medicine I · Division of Endocrinology

University of Erlangen-Nürnberg · Ulmenweg 18 · 91054 Erlangen · Germany

Fax: + 49 (91 31) 853 50 66

Email: marianne.pavel@med1.imed.uni-erlangen.de