The Diagnosis of Growth Hormone Deficiency in Children and Adults
Stephen Michael Shalet,
Andrew Toogood,
Asad Rahim and
Bernadette M. D. Brennan
Christie Hospital National Health Service Trust, Withington,
Manchester M20 4BX, U.K.
I. Introduction
II. GHD in Children
A. Clinical aspects
B. Radiology
C. GH provocative tests
D. Physiologicalassessment of GH secretion
E. IGFs
F. IGFBPs
G. Newerstrategies for assessment of GH status
H. Practical approachto the diagnosis of GHD
III. GHD in Adults
A. Clinical aspects
B. GH provocative tests
C. Physiological assessment of GHsecretion
D. IGF-I and IGFBP-3
E. Obesity
F. Elderly
G.Childhood onset
H. Newer strategies for assessment of GH status
I. Practical approach to the diagnosis of GHD
This article has been cited by other articles:
M. Tzanela, D. Zianni, K. Bilariki, A. Vezalis, N. Gavalas, A. Szabo, P. Drimala, D. Vassiliadi, and C. Vassilopoulos The effect of body mass index on the diagnosis of GH deficiency in patients at risk due to a pituitary insult
Eur. J. Endocrinol.,
January 1, 2010;
162(1):
29 - 35.
[Abstract][Full Text][PDF]
G Brabant, E M Poll, P Jonsson, D Polydorou, and I Kreitschmann-Andermahr Etiology, baseline characteristics, and biochemical diagnosis of GH deficiency in the adult: are there regional variations?
Eur. J. Endocrinol.,
November 1, 2009;
161(suppl_1):
S25 - S31.
[Abstract][Full Text][PDF]
A Mukherjee and S M Shalet The value of IGF1 estimation in adults with GH deficiency
Eur. J. Endocrinol.,
November 1, 2009;
161(suppl_1):
S33 - S39.
[Abstract][Full Text][PDF]
J. D J Thomas and J. P Monson Adult GH deficiency throughout lifetime
Eur. J. Endocrinol.,
November 1, 2009;
161(suppl_1):
S97 - S106.
[Abstract][Full Text][PDF]
G. Fanciulli, A. Delitala, and G. Delitala Growth hormone, menopause and ageing: no definite evidence for 'rejuvenation' with growth hormone
Hum. Reprod. Update,
May 1, 2009;
15(3):
341 - 358.
[Abstract][Full Text][PDF]
K. A. Mossberg, B. E. Masel, C. R. Gilkison, and R. J. Urban Aerobic Capacity and Growth Hormone Deficiency after Traumatic Brain Injury
J. Clin. Endocrinol. Metab.,
July 1, 2008;
93(7):
2581 - 2587.
[Abstract][Full Text][PDF]
P. M. Janiszewski, K. C. Oeffinger, T. S. Church, A. L. Dunn, D. A. Eshelman, R. G. Victor, S. Brooks, A. J. Turoff, E. Sinclair, J. C. Murray, et al. Abdominal Obesity, Liver Fat, and Muscle Composition in Survivors of Childhood Acute Lymphoblastic Leukemia
J. Clin. Endocrinol. Metab.,
October 1, 2007;
92(10):
3816 - 3821.
[Abstract][Full Text][PDF]
G. Gelwane, C. Garel, D. Chevenne, P. Armoogum, D. Simon, P. Czernichow, and J. Leger Subnormal Serum Insulin-Like Growth Factor-I Levels in Young Adults with Childhood-Onset Nonacquired Growth Hormone (GH) Deficiency Who Recover Normal GH Secretion May Indicate Less Severe but Persistent Pituitary Failure
J. Clin. Endocrinol. Metab.,
October 1, 2007;
92(10):
3788 - 3795.
[Abstract][Full Text][PDF]
K. Chihara, A. Shimatsu, N. Hizuka, T. Tanaka, Y. Seino, Y. Katofor, and the KP-102 Study Group A simple diagnostic test using GH-releasing peptide-2 in adult GH deficiency
Eur. J. Endocrinol.,
July 1, 2007;
157(1):
19 - 27.
[Abstract][Full Text][PDF]
G. Brabant, A. Krogh Rasmussen, B. M. K. Biller, M. Buchfelder, U. Feldt-Rasmussen, K. Forssmann, B. Jonsson, M. Koltowska-Haggstrom, D. Maiter, B. Saller, et al. Clinical Implications of Residual Growth Hormone (GH) Response to Provocative Testing in Adults with Severe GH Deficiency
J. Clin. Endocrinol. Metab.,
July 1, 2007;
92(7):
2604 - 2609.
[Abstract][Full Text][PDF]
R. D. Murray, M. Bidlingmaier, C. J. Strasburger, and S. M. Shalet The Diagnosis of Partial Growth Hormone Deficiency in Adults with a Putative Insult to the Hypothalamo-Pituitary Axis
J. Clin. Endocrinol. Metab.,
May 1, 2007;
92(5):
1705 - 1709.
[Abstract][Full Text][PDF]
C. Franco, G. Johannsson, B.-A. Bengtsson, and J. Svensson Baseline Characteristics and Effects of Growth Hormone Therapy over Two Years in Younger and Elderly Adults with Adult Onset GH Deficiency
J. Clin. Endocrinol. Metab.,
November 1, 2006;
91(11):
4408 - 4414.
[Abstract][Full Text][PDF]
A. J Drake and C. J H Kelnar The evaluation of growth and the identification of growth hormone deficiency
Arch. Dis. Child. Ed. Pract.,
October 1, 2006;
91(3):
ep61 - ep67.
[Full Text][PDF]
J. Svensson, G. Johannsson, A. Iranmanesh, K. Albertsson-Wikland, J. D Veldhuis, and B.-A. Bengtsson GH secretory pattern in young adults who discontinued GH treatment for GH deficiency and decreased longitudinal growth in childhood.
Eur. J. Endocrinol.,
July 1, 2006;
155(1):
91 - 99.
[Abstract][Full Text][PDF]
A. Mukherjee, W. D. J. Ryder, A. Jostel, and S. M. Shalet Prolactin Deficiency Is Independently Associated with Reduced Insulin-Like Growth Factor I Status in Severely Growth Hormone-Deficient Adults
J. Clin. Endocrinol. Metab.,
July 1, 2006;
91(7):
2520 - 2525.
[Abstract][Full Text][PDF]
F. Tanriverdi, H. Senyurek, K. Unluhizarci, A. Selcuklu, F. F. Casanueva, and F. Kelestimur High Risk of Hypopituitarism after Traumatic Brain Injury: A Prospective Investigation of Anterior Pituitary Function in the Acute Phase and 12 Months after Trauma
J. Clin. Endocrinol. Metab.,
June 1, 2006;
91(6):
2105 - 2111.
[Abstract][Full Text][PDF]
S Pekic, M Doknic, D Miljic, M Joksimovic, J Glodic, M Djurovic, C Dieguez, F Casanueva, and V Popovic Ghrelin test for the assessment of GH status in successfully treated patients with acromegaly.
Eur. J. Endocrinol.,
May 1, 2006;
154(5):
659 - 666.
[Abstract][Full Text][PDF]
V K B Prabhakar and S M Shalet Aetiology, diagnosis, and management of hypopituitarism in adult life.
Postgrad. Med. J.,
April 1, 2006;
82(966):
259 - 266.
[Abstract][Full Text][PDF]
J Ayuk and M C Sheppard Growth hormone and its disorders
Postgrad. Med. J.,
January 1, 2006;
82(963):
24 - 30.
[Abstract][Full Text][PDF]
A. Agha, M. Sherlock, S. Brennan, S. A. O'Connor, E. O'Sullivan, B. Rogers, C. Faul, D. Rawluk, W. Tormey, and C. J. Thompson Hypothalamic-Pituitary Dysfunction after Irradiation of Nonpituitary Brain Tumors in Adults
J. Clin. Endocrinol. Metab.,
December 1, 2005;
90(12):
6355 - 6360.
[Abstract][Full Text][PDF]
A. R. Hoffman, B. M. K. Biller, D. Cook, J. Baptista, B. L. Silverman, L. Dao, K. M. Attie, P. Fielder, T. Maneatis, B. Lippe, et al. Efficacy of a Long-Acting Growth Hormone (GH) Preparation in Patients with Adult GH Deficiency
J. Clin. Endocrinol. Metab.,
December 1, 2005;
90(12):
6431 - 6440.
[Abstract][Full Text][PDF]
A. Mukherjee, J. E Adams, L. Smethurst, and S. M Shalet Interdependence of lean body mass and total body water, but not quality of life measures, during low dose GH replacement in GH-deficient adults
Eur. J. Endocrinol.,
November 1, 2005;
153(5):
661 - 668.
[Abstract][Full Text][PDF]
S. Cianfarani, A. Liguori, S. Boemi, M. Maghnie, L. Iughetti, M. Wasniewska, M. E. Street, S. Zucchini, G. Aimaretti, and D. Germani Inaccuracy of Insulin-Like Growth Factor (IGF) Binding Protein (IGFBP)-3 Assessment in the Diagnosis of Growth Hormone (GH) Deficiency from Childhood to Young Adulthood: Association to Low GH Dependency of IGF-II and Presence of Circulating IGFBP-3 18-Kilodalton Fragment
J. Clin. Endocrinol. Metab.,
November 1, 2005;
90(11):
6028 - 6034.
[Abstract][Full Text][PDF]
G. Corneli, C. Di Somma, R. Baldelli, S. Rovere, V. Gasco, C. G. Croce, S. Grottoli, M. Maccario, A. Colao, G. Lombardi, et al. The cut-off limits of the GH response to GH-releasing hormone-arginine test related to body mass index
Eur. J. Endocrinol.,
August 1, 2005;
153(2):
257 - 264.
[Abstract][Full Text][PDF]
J. Ayuk, M. C. Sheppard, A. S. Bates, and P. M. Stewart Letter re: Monitoring the Response to Treatment in Acromegaly
J. Clin. Endocrinol. Metab.,
August 1, 2005;
90(8):
4980 - 4980.
[Full Text][PDF]
M. Maghnie, G. Aimaretti, S. Bellone, G. Bona, J. Bellone, R. Baldelli, C. de Sanctis, L. Gargantini, R. Gastaldi, L. Ghizzoni, et al. Diagnosis of GH deficiency in the transition period: accuracy of insulin tolerance test and insulin-like growth factor-I measurement
Eur. J. Endocrinol.,
April 1, 2005;
152(4):
589 - 596.
[Abstract][Full Text][PDF]
A. Mukherjee, S. Tolhurst-Cleaver, W. D. J. Ryder, L. Smethurst, and S. M. Shalet The Characteristics of Quality of Life Impairment in Adult Growth Hormone (GH)-Deficient Survivors of Cancer and Their Response to GH Replacement Therapy
J. Clin. Endocrinol. Metab.,
March 1, 2005;
90(3):
1542 - 1549.
[Abstract][Full Text][PDF]
C. Lofqvist, E. Andersson, L. Gelander, S. Rosberg, L. Hulthen, W. F. Blum, and K. A. Wikland Reference Values for Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) and the Ratio of Insulin-Like Growth Factor-I to IGFBP-3 throughout Childhood and Adolescence
J. Clin. Endocrinol. Metab.,
March 1, 2005;
90(3):
1420 - 1427.
[Abstract][Full Text][PDF]
J. Leger, S. Danner, D. Simon, C. Garel, and P. Czernichow Do All Patients with Childhood-Onset Growth Hormone Deficiency (GHD) and Ectopic Neurohypophysis Have Persistent GHD in Adulthood?
J. Clin. Endocrinol. Metab.,
February 1, 2005;
90(2):
650 - 656.
[Abstract][Full Text][PDF]
J. E. Sanders, K. A. Guthrie, P. A. Hoffmeister, A. E. Woolfrey, P. A. Carpenter, and F. R. Appelbaum Final adult height of patients who received hematopoietic cell transplantation in childhood
Blood,
February 1, 2005;
105(3):
1348 - 1354.
[Abstract][Full Text][PDF]
J. Ayuk, M. C. Sheppard, R. N. Clayton, A. S. Bates, and P. M. Stewart Evidence for the Use of IGF-I as a Predictor of Mortality in Acromegaly Is Lacking
J. Clin. Endocrinol. Metab.,
November 1, 2004;
89(11):
5867 - 5868.
[Full Text][PDF]
A. Agha, B. Rogers, M. Sherlock, P. O'Kelly, W. Tormey, J. Phillips, and C. J. Thompson Anterior Pituitary Dysfunction in Survivors of Traumatic Brain Injury
J. Clin. Endocrinol. Metab.,
October 1, 2004;
89(10):
4929 - 4936.
[Abstract][Full Text][PDF]
V. S. Bonert, J. D. Elashoff, P. Barnett, and S. Melmed Body Mass Index Determines Evoked Growth Hormone (GH) Responsiveness in Normal Healthy Male Subjects: Diagnostic Caveat for Adult GH Deficiency
J. Clin. Endocrinol. Metab.,
July 1, 2004;
89(7):
3397 - 3401.
[Abstract][Full Text][PDF]
A. J. van der Lely, M. Tschop, M. L. Heiman, and E. Ghigo Biological, Physiological, Pathophysiological, and Pharmacological Aspects of Ghrelin
Endocr. Rev.,
June 1, 2004;
25(3):
426 - 457.
[Abstract][Full Text][PDF]
R Ayling More guidance on growth hormone deficiency
J. Clin. Pathol.,
February 1, 2004;
57(2):
123 - 125.
[Full Text][PDF]
A. Mukherjee, J. P. Monson, P. J. Jonsson, P. J. Trainer, and S. M. Shalet Seeking the Optimal Target Range for Insulin-Like Growth Factor I during the Treatment of Adult Growth Hormone Disorders
J. Clin. Endocrinol. Metab.,
December 1, 2003;
88(12):
5865 - 5870.
[Abstract][Full Text][PDF]
H. R. Boquete, P. G. V. Sobrado, H. L. Fideleff, A. M. Sequera, A. V. Giaccio, M. G. Suarez, G. F. Ruibal, and M. Miras Evaluation of Diagnostic Accuracy of Insulin-Like Growth Factor (IGF)-I and IGF-Binding Protein-3 in Growth Hormone-Deficient Children and Adults Using ROC Plot Analysis
J. Clin. Endocrinol. Metab.,
October 1, 2003;
88(10):
4702 - 4708.
[Abstract][Full Text][PDF]
I Kreitschmann-Andermahr, C Hoff, S Niggemeier, S Pruemper, M Bruegmann, D Kunz, S Matern, and J M Gilsbach Pituitary deficiency following aneurysmal subarachnoid haemorrhage
J. Neurol. Neurosurg. Psychiatry,
August 1, 2003;
74(8):
1133 - 1135.
[Abstract][Full Text][PDF]
K. H. Darzy, G. Aimaretti, G. Wieringa, H. R. Gattamaneni, E. Ghigo, and S. M. Shalet The Usefulness of the Combined Growth Hormone (GH)-Releasing Hormone and Arginine Stimulation Test in the Diagnosis of Radiation-Induced GH Deficiency Is Dependent on the Post-Irradiation Time Interval
J. Clin. Endocrinol. Metab.,
January 1, 2003;
88(1):
95 - 102.
[Abstract][Full Text][PDF]
J. J. Kopchick, C. Parkinson, E. C. Stevens, and P. J. Trainer Growth Hormone Receptor Antagonists: Discovery, Development, and Use in Patients with Acromegaly
Endocr. Rev.,
October 1, 2002;
23(5):
623 - 646.
[Abstract][Full Text][PDF]
M. Maghnie, F. Cavigioli, C. Tinelli, M. Autelli, M. Arico, G. Aimaretti, and E. Ghigo GHRH Plus Arginine in the Diagnosis of Acquired GH Deficiency of Childhood-Onset
J. Clin. Endocrinol. Metab.,
June 1, 2002;
87(6):
2740 - 2744.
[Abstract][Full Text][PDF]
J. Svensson, J. D. Veldhuis, A. Iranmanesh, B.-A. Bengtsson, and G. Johannsson Increased Orderliness of Growth Hormone (GH) Secretion in GH-Deficient Adults with Low Serum Insulin-Like Growth Factor I
J. Clin. Endocrinol. Metab.,
June 1, 2002;
87(6):
2863 - 2869.
[Abstract][Full Text][PDF]
B. M. K. Biller, M. H. Samuels, A. Zagar, D. M. Cook, B. M. Arafah, V. Bonert, S. Stavrou, D. L. Kleinberg, J. J. Chipman, and M. L. Hartman Sensitivity and Specificity of Six Tests for the Diagnosis of Adult GH Deficiency
J. Clin. Endocrinol. Metab.,
May 1, 2002;
87(5):
2067 - 2079.
[Abstract][Full Text][PDF]
M. L. Hartman, B. J. Crowe, B. M. K. Biller, K. K. Y. Ho, D. R. Clemmons, and J. J. Chipman Which Patients Do Not Require a GH Stimulation Test for the Diagnosis of Adult GH Deficiency?
J. Clin. Endocrinol. Metab.,
February 1, 2002;
87(2):
477 - 485.
[Abstract][Full Text][PDF]
J. Koranyi, J. Svensson, G. Gotherstrom, K. S. Sunnerhagen, B.-A. Bengtsson, and G. Johannsson Baseline Characteristics and the Effects of Five Years of GH Replacement Therapy in Adults with GH Deficiency of Childhood or Adulthood Onset: A Comparative, Prospective Study
J. Clin. Endocrinol. Metab.,
October 1, 2001;
86(10):
4693 - 4699.
[Abstract][Full Text][PDF]
P. Marzullo, C. Di Somma, K. L. Pratt, J. Khosravi, A. Diamandis, G. Lombardi, A. Colao, and R. G. Rosenfeld Usefulness of Different Biochemical Markers of the Insulin-Like Growth Factor (IGF) Family in Diagnosing Growth Hormone Excess and Deficiency in Adults
J. Clin. Endocrinol. Metab.,
July 1, 2001;
86(7):
3001 - 3008.
[Abstract][Full Text][PDF]
M. Maghnie, B. Salati, S. Bianchi, M. Rallo, C. Tinelli, M. Autelli, G. Aimaretti, and E. Ghigo Relationship between the Morphological Evaluation of the Pituitary and the Growth Hormone (GH) Response to GH-Releasing Hormone Plus Arginine in Children and Adults with Congenital Hypopituitarism
J. Clin. Endocrinol. Metab.,
April 1, 2001;
86(4):
1574 - 1579.
[Abstract][Full Text]
C. Deal, J. Ma, F. Wilkin, J. Paquette, F. Rozen, B. Ge, T. Hudson, M. Stampfer, and M. Pollak Novel Promoter Polymorphism in Insulin-Like Growth Factor-Binding Protein-3: Correlation with Serum Levels and Interaction with Known Regulators
J. Clin. Endocrinol. Metab.,
March 1, 2001;
86(3):
1274 - 1280.
[Abstract][Full Text]
C. A. Lissett, S. Saleem, A. Rahim, B. M. D. Brennan, and S. M. Shalet The Impact of Irradiation on Growth Hormone Responsiveness to Provocative Agents Is Stimulus Dependent: Results in 161 Individuals with Radiation Damage to the Somatotropic Axis
J. Clin. Endocrinol. Metab.,
February 1, 2001;
86(2):
663 - 668.
[Abstract][Full Text]
R. Vanhala, U. Turpeinen, and R. Riikonen Insulin-Like Growth Factor-I in Cerebrospinal Fluid and Serum in Rett Syndrome
J Child Neurol,
December 1, 2000;
15(12):
797 - 802.
[Abstract][PDF]
A. S. MartÍnez, H. M. Domené, M. G. Ropelato, H. G. Jasper, P. A. Pennisi, M. E. Escobar, and J. J. Heinrich Estrogen Priming Effect on Growth Hormone (GH) Provocative Test: A Useful Tool for the Diagnosis of GH Deficiency
J. Clin. Endocrinol. Metab.,
November 1, 2000;
85(11):
4168 - 4172.
[Abstract][Full Text]
G. Aimaretti, C. Baffoni, S. Bellone, L. Di Vito, G. Corneli, E. Arvat, L. Benso, F. Camanni, and E. Ghigo Retesting Young Adults with Childhood-Onset Growth Hormone (GH) Deficiency with GH-Releasing-Hormone-Plus-Arginine Test
J. Clin. Endocrinol. Metab.,
October 1, 2000;
85(10):
3693 - 3699.
[Abstract][Full Text]
H. C. Hoeck, P. Vestergaard, P. E. Jakobsen, J. Falhof, and P. Laurberg Diagnosis of Growth Hormone (GH) Deficiency in Adults with Hypothalamic-Pituitary Disorders: Comparison of Test Results Using Pyridostigmine Plus GH-Releasing Hormone (GHRH), Clonidine Plus GHRH, and Insulin-Induced Hypoglycemia as GH Secretagogues
J. Clin. Endocrinol. Metab.,
April 1, 2000;
85(4):
1467 - 1472.
[Abstract][Full Text]
M. H. Aguiar-Oliveira, M. S. Gill, E. S. de, A. Barretto, M. R. S. Alcântara, F. Miraki-Moud, C. A. Menezes, A. H. O. Souza, C. E. Martinelli, F. A. Pereira, et al. Effect of Severe Growth Hormone (GH) Deficiency due to a Mutation in the GH-Releasing Hormone Receptor on Insulin-Like Growth Factors (IGFs), IGF-Binding Proteins, and Ternary Complex Formation Throughout Life
J. Clin. Endocrinol. Metab.,
November 1, 1999;
84(11):
4118 - 4126.
[Abstract][Full Text]
M. Gasperi, G. Aimaretti, G. Scarcello, G. Corneli, C. Cosci, E. Arvat, E. Martino, and E. Ghigo Low Dose Hexarelin and Growth Hormone (GH)-Releasing Hormone as a Diagnostic Tool for the Diagnosis of GH Deficiency in Adults: Comparison with Insulin-Induced Hypoglycemia Test
J. Clin. Endocrinol. Metab.,
August 1, 1999;
84(8):
2633 - 2637.
[Abstract][Full Text]
A. Colao, P. Marzullo, S. Spiezia, D. Ferone, A. Giaccio, G. Cerbone, R. Pivonello, C. Di Somma, and G. Lombardi Effect of Growth Hormone (GH) and Insulin-Like Growth Factor I on Prostate Diseases: An Ultrasonographic and Endocrine Study in Acromegaly, GH Deficiency, and Healthy Subjects
J. Clin. Endocrinol. Metab.,
June 1, 1999;
84(6):
1986 - 1991.
[Abstract][Full Text]
A. Hilding, K. Hall, I.-L. Wivall-Helleryd, M. Sääf, A.-L. Melin, and M. Thorén Serum Levels of Insulin-Like Growth Factor I in 152 Patients with Growth Hormone Deficiency, Aged 19-82 Years, in Relation to Those in Healthy Subjects
J. Clin. Endocrinol. Metab.,
June 1, 1999;
84(6):
2013 - 2019.
[Abstract][Full Text]
M. Maghnie, C. Strigazzi, C. Tinelli, M. Autelli, M. Cisternino, S. Loche, and F. Severi Growth Hormone (GH) Deficiency (GHD) of Childhood Onset: Reassessment of GH Status and Evaluation of the Predictive Criteria for Permanent GHD in Young Adults
J. Clin. Endocrinol. Metab.,
April 1, 1999;
84(4):
1324 - 1328.
[Abstract][Full Text]
A. A. Toogood and S. M. Shalet Growth Hormone Replacement Therapy in the Elderly with Hypothalamic-Pituitary Disease: A Dose-Finding Study
J. Clin. Endocrinol. Metab.,
January 1, 1999;
84(1):
131 - 136.
[Abstract][Full Text]
