Assessment of somatotropic function in children with syndrome of biologically inactive growth hormone against a background of clonidine and insulin stimulation tests

Main Article Content

N.A. Sprinchuk


Background. Growth pathology caused by somatotropic insufficiency is one of the most urgent problems in pediatric endocrinology. An increase in the growth hormone (GH) level less than 10 ng/ml was traditio­nally considered a criterion for diagnosing somatotropic insufficiency in patients with short stature, when performing provocation tests. The purpose is to evaluate the effectiveness of clonidine and insulin provocation tests for the somatotropic hormone (STH) stimulation in diagnosing the syndrome of biologically inactive growth hormone (SBIGH). Materials and methods. A total of 158 patients with SBIGH (47 girls and 111 boys aged 8.30 ± 0.24 years) were examined. The study included patients with delayed growth more than 2 standard deviations. Basal and stimulated STH levels were determined using insulin and clonidine tests. A 4-day growth hormone sensiti­vity test was obligatorily performed for determining insulin-like growth factor 1 levels prior to the first GH injection and the day after the test completion. Results. The maximum increase in STH against a background of insulin and clonidine tests was above 10 ng/ml in all patients with SBIGH. Significantly higher maximum increase of STH parameters (p < 0.01) was noted in clonidine stimulation test than in insulin one. This was proved both in patients with SBIGH (17.79 ± 0.51 ng/ml and 13.83 ± 0.92 ng/ml, respectively) and in children of control group (16.81 ± 1.60 and 11.18 ± 0.70 ng/ml). Standard deviation score of insulin-like growth factor 1 was significantly lower (p < 0.001) in children with SBIGH than in control group. More pronounced changes were observed in prepubertal patients. Conclusions. Clonidine provocation test is more informative than insulin one, and causes a significantly higher stimulating maximum release of GH. It is recommended to start the investigation of STH function with clonidine test, which is safer for patients due to the absence of a risk of severe hypoglycemic conditions.

Article Details

How to Cite
Sprinchuk, N. “Assessment of Somatotropic Function in Children With Syndrome of Biologically Inactive Growth Hormone Against a Background of Clonidine and Insulin Stimulation Tests”. INTERNATIONAL JOURNAL OF ENDOCRINOLOGY (Ukraine), vol. 15, no. 2, May 2019, pp. 148-51, doi:10.22141/2224-0721.15.2.2019.166108.
Pediatric Endocrinology


Rohayem J, Drechsel H, Tittel B, Hahn G, Pfaeffle R, Huebner A. Long-Term Outcomes, Genetics, and Pituitary Morphology in Patients with Isolated Growth Hormone Deficiency and Multiple Pituitary Hormone Deficiencies: A Single-Centre Experience of Four Decades of Growth Hormone Replacement. Horm Res Paediatr. 2016;86(2):106-116. doi: 10.1159/000448098.

Chinoy A, Murray PG. Diagnosis of growth hormone deficiency in the paediatric and transitional age. Best Pract Res Clin Endocrinol Metab. 2016 Dec;30(6):737-747. doi: 10.1016/j.beem.2016.11.002.

Bolshova OV, Pakhomova VH. The content of insulin-like growth factor 1 and essential trace elements in the blood plasma of children with different forms of short stature. Mìžnarodnij endokrinologìčnij žurnal. 2016;(75):70-5. doi: 10.22141/2224-0721.3.75.2016.76639. (in Ukrainian).

Coutant R, Dörr HG, Gleeson H, Argente J. Diagnosis of endocrine disease: limitations of the IGF1 generation test in children with short stature. Eur J Endocrinol. 2012 Mar;166(3):351-7. doi: 10.1530/EJE-11-0618.

Takahashi Y, Kaji H, Okimura Y, Goji K, Abe H, Chihara K. Short stature caused by a mutant growth hormone. N Engl J Med. 1996 Feb 15;334(7):432-6. doi: 10.1056/NEJM199602153340704.

Sprynchuk NA. The role of the somatotropin sensitivity test in the diagnosis of biologically inactive growth hormone syndrome. Endokrynologia. 2010;15(2):287-90. (in Ukrainian).

Argente J. Challenges in the management of short stature. Horm Res Paediatr. 2016;85(1):2-10. doi: 10.1159/000442350.

Zelazowska-Rutkowska B, Trusiak M, Bossowski A, Cylwik B. Diagnostic usefulness of insulin-like growth factor 1 and insulin-like growth factor binding protein 3 in children with suspected pituitary dwarfism. Clin Lab. 2018 May 1;64(5):759-765. doi: 10.7754/Clin.Lab.2018.171126.

Ministry of Нealth of Ukraine. Order on February 03, 2009 № 55. On Adoption of Treatment Protocols for Children with Endocrine Diseases. Available from: Accessed: February 03, 2009. (in Ukrainian).

Ministry of Нealth of Ukraine. Order on April 27, 2006 № 254. On Adoption of Protocols for the Provision of Medical Care for Children in the Specialty Pediatric Endocrinology. Available from: Accessed: April 27, 2006. (in Ukrainian).

Nazarenko KA, Kuznetsova ES, Filina NIu. Structure and clinical features of growth retardation in children. Saratov Journal of Medical Scientific Research. 2016;12(2):231-236. (in Russian).

Devesa J. Clonidine plus GHRH administration for diagnosing growth hormone deficiency in children. J Clin Mol Endocrinol. 2017;2(1):6. doi: 10.21767/2572-5432.10042.

Guo С, Chen L. Diagnostic value of provocative test by insulin combined with clonidine for growth hormone deficiency in children. Iran J Pediatr. 2013 Jun;23(3):315-20.

Domracheva EG, Novokreshchenova AN. Diagnosis of somatotropic insufficiency in children. Informatsionno-analiticheskii zhurnal. 2012;(1):64-66. (in Russian).

Poyrazoğlu Ş, Akçay T, Arslanoğlu İ, et al. Current practice in diagnosis and treatment of growth hormone deficiency in childhood: a survey from Turkey. J Clin Res Pediatr Endocrinol. 2015 Mar;7(1):37-44. doi: 10.4274/jcrpe.1794.

Rhee N, Oh KY, Yang EM, Kim CJ. Growth hormone responses to provocative tests in children with short stature. Chonnam Med J. 2015 Apr;51(1):33-8. doi: 10.4068/cmj.2015.51.1.33.