HIGH GROWTH HORMONE LEVELS IN CLINICALLY SHORT STATURE CHILDREN

Authors

  • Tariq Mahmood Awan
  • Abdus Sattar
  • Ihsan Gul Khattak

Abstract

Background: Growth Hormone (GH) is secreted from the anterior pituitary gland. It binds toreceptors on the surface of target cells, stimulates production of Insulin-like growth factor-I (IGFI) leading to growth of almost all tissues of the body capable of growing. Growth failure (heightbelow 3rd centile) occurs in children who do not secrete sufficient amount of GH. In somechildren, however, short stature is present in the presence of high levels of GH in their blood andthey also secrete normal to increased amounts of GH in response to stimulation tests when testedfor possible deficiency of GH. This condition is known as GH resistance syndrome or Laronssyndrome (LS). Methods: All patients after a thorough clinical evaluation underwent GHevaluation protocol as follows. On arrival in the lab a blood sample was collected for basal GHlevel in each patient. Screening was performed by subjecting the patients to exercise stimulationtest and/or L-dopa stimulation test. Patients with GH deficiency underwent insulin tolerance test(ITT) after one week for confirmation. All the basal and post-stimulation samples were analyzedfor GH levels. A level below 10mIU/L indicated GH deficiency, between 10-20mIU/L asborderline and an adequate response was defined as a GH >20mIU/L. Patients with a basal GHlevel of >20mIU/L and/or a post-stimulation level of >40mIU/L were arbitrarily considered ashaving exaggerated GH levels. This article evaluates the high plasma growth hormone levelsamong clinically short stature children undergoing growth hormone stimulation tests. Results:Two hundred ninty-three patients reported for GH evaluation. Twenty were excluded for variousreasons. Thus 273 patients were included for GH evaluation out of which 66(24.2%) showed GHdeficiency, 89(32.6%) were borderline while 118(43.2%) patients exhibited adequate response,with GH levels of >20mIU/L. A number of patients unexpectedly showed very high GH levels onscreening tests. Out of 118 patients, 21 showed either very high basal levels of >20mIU/L and/or amuch-exaggerated response to stimulation tests with levels more than about 40mIU/L. Closeconsanguinity was found in 67% of patients showing very high GH levels. Conclusion: Somechildren with idiopathic short stature may show high levels of GH during their evaluation for GHdeficiency. We identified a considerable number of such patients. These patients require furtherinvestigations.KEY WORDS: Growth Hormone, Resistance Syndrome, Short Stature, Exercise, L-dopa, InsulinTolerance Test (ITT).

References

Martin JB. Neural Regulation of Growth Hormone Secretion.

N Eng J Med 1973; 188: 1384-1393.

Rappaport R, Souberbielle JC. Growth Disorders In: Soldin

SJ, Rifai N, Hicks JMB ed. Biochemical Basis of Pediatric

Disease. Washington: American Association for Clinical

Chemistry 1992; 141-64.

Hintz RL. Symptoms of Growth Disorders. In: Finberg L ed.

Saunders Manual of Pediatric Practice. Philadelphia: WB.

Saunders Company 1998; 727 – 731.

Rudd BT. Growth, Growth Hormone and the Somatomedins:

A historical perspective and current concepts. Ann Clin

Biochem 1991: 28; 542-555.

Gunn I. Growth Hormone Deficiency. Ann Clin Biochem

; 24: 429 –434.

Guyton and Hall. The Pituitary Hormone and their Control

by the Hypothalamus. In: Guyton and Hall. Eds. Textbook of

Medical Physiology. Philadelphia: W.B. Saunders Company

; 846-857.

Rosenfeld RG, Reiter OE. Normal and aberrant Growth. In:

Wilson JD, Foster DW, Kronenberg HM, Larsen PR eds.

Williams Text Book of Endocrinology, 9th edition.

Philadelphia: W.B.Saunders Company 1998; 1427-1507.

Rosenbloom AL, Aguirre JG, Rosenfeld RG, Fielder PJ. The

Little Women of Loja- Growth Hormone Receptor

Deficiency in an Inbred Population of Southern Ecuador. N

Eng J Med 1990; 323: 1365-1374.

Laron Z. Laron Syndrome (Primary Growth Hormone

Resistance or Insensitivity): The Personel Experience 1958-

J Clin Endocrinol Metab 2004: 89; 1031-1044

Andrey DG et al. Mutations of Growth Hormone Receptor in

Children with Idiopathic Short Stature. N Eng J Med 1995;

: 1093-1098.

Najjar SS, Khachadurian AK, Ilbawi MN, Blizzard RM.

Dwarfism with Elevated Levels of Growth Hormone. N Eng

J Med 1971; 284: 809-812.

Technical Instructions IMMULITE for HGH Assay,

Diagnostic Products Corporation (DPC), Los Angeles, USA

: 1 – 6.

Dattani MT, Pringle PJ, Hindmarsh PC, Brook CG. What is a

normal stimulated growth hormone concentration? J

Endocrinol 1992; 133: 447-450.

Bjarnson R, Savage MO. Growth Hormone Insensitivity: a

widening diagnosis. Arch Dis Child 1999; 8(5): 378-379.

Hull KL, Harvey S. Growth Hormone Resistance: clinical

states and animal models. J Endo1999; 163:165-172

Woods KA, Dastot F, Pierce MA, Clark AJ, Postel-Vinay

MC, Chatelain PG, Ranke MB, Rosenfeld RG, Amselem S

and Savage MO. Phenotype: phenotype relationships in

J Ayub Med Coll Abbottabad 2006;18(2)

growth hormone insensitivity syndrome. J Clin Endo Metab

: 82:3529-3535.

Baumbach L, Schiavi A, Bartlett R, Perera E, Day J, Brown

MR et al. Clinical, biochemical, and molecular investigations

of a genetic isolate of growth hormone insensitivity (Laron’s

Syndrome). J Clin Endocrinol Metab 1997; 82(2): 444-451.

Laron Z. Prismatic cases: Laron syndrome (primary growth

hormone resistance) from patients to laboratory to patient. J

Clin Endo Metab 1995; 80: 1526-1531 25. Walker JL, Ginalska-Malinowska M, Romer TE, Pucilowska

JB Underwood LE. Effects of the Infusion of Insulin-like

growth factor I in a child with growth hormone insensitivity

syndrome (Laron Dwarfism). N Eng J Med 1991; 324: 1483-

Johnston LB, Woods KA, Rose SJ, Clark AJL and Savage

MO. The broad spectrum of inherited growth hormone

insensitivity syndrome. Trends in Endocrinology and Metab

; 9:228-232.

Kowarski AA, Schneider J, Ben-Galim E, Weldon VV,

Daughaday WH. Dwarfism due to inactivity of endogenous

growth hormone. J Clin Endocrinol Metab 1978; 47: 461-3

Mariani P, Gourmelen M, Carnot JF, Saignes F, Cayroche P.

Severe dwarfism with high plasma hGH levels and no

somatomedin activity: Laron’s Syndrome. Sem Hosp 1980;

Frazer T, Gavin JR, Daughaday WH, Hillman RE, Weldon 1853-1856.

VV. Growth hormone dependent growth failure. J Pediatr

; 10: 12-15

Laron Z, Klinger B, Erster B, Anin S. Effect of acute

administration of insulin-like growth factor I in patients with

Daughaday WH, Trivedi B. Absence of serum growth Laron-type dwarfism. Lancet 1988;ii: 1170-2

hormone binding protein in patients with growth hormone

receptor deficiency (Laron dwarfism). Proc Natl Acad Sci

USA 1987; 84: 4636-40.

Mauras N, Martinez V, Rini A, Guevara-Aguirre J.

Recombinant human Insulin-like growth factor I has

significant anabolic effects in adults with growth hormone

receptor deficiency: studies on protein, glucose and lipid

metabolism. J Clin Endocrinol Metab 2000; 85(9): 3036-42.

Maclean DB, Jackson IMD. Molecular Biology and

Regulation of the Hypothalamic Hormones.In. Sheppard MC

ed. Bailliere’s Clinical Endocrinology and Metabolism.

London: Baillier Tindall 1988; 835-868.

Ferrandez A, Nengual J, Bastaros JC, Gonzalvo N, Laron Z,

Silbergeld A. Nanism with high values of GH and no

generation of Somatomedin after hGH (Laron’s Syndrome).

Clinico-biochemic Study of 8 Cases. An Esp Pediatr 1985;

(2): 113-122

Kastrup KW, Andersen, Hanssen AI. Increased

immunoreactive plasma and urinary growth hormone in

growth retardation with defective generation of somatomedin

(Laron’s Syndrome). Acta Paediatr Scand 1975; 64(4): 613-

Downloads

Most read articles by the same author(s)