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Journal of the American College of Nutrition, Vol. 17, No. 5, 405-406 (1998)
Published by the American College of Nutrition

Growth Hormone (GH) Treatment in Non-GH Deficient Chronic Disease

Samuel M. Richton, MD

Division of Pediatric Endocrinology Miami Children’s Hospital Miami, FL


   INTRODUCTION
TOP
 INTRODUCTION
REFERENCES
 
Cystic fibrosis (CF) is the most frequent fatal genetic disorder in the US [1]. At birth, infants with CF have a mean length close to normal, but by age 4 months they have a mean height SDS of only -1.3 SD. After the age of 12 months, they do experience some catch-up growth resulting in a mean height SDS of -0.3 SD by 5 years of age [2]. Further growth is probably largely dependent on the severity of the disease. Data from the registry maintained by the Cystic Fibrosis Foundation suggests that approximately 40% of CF patients are below the 5th percentile for height and 36% are below the 5th percentile for weight [3].

Although generally thought of as a chronic lung disease, there are significant nutritional problems that produce an energy deficit in many CF patients sufficient to limit linear growth and weight gain. These include poor calorie intake related to anorexia, increased nutrient losses through malabsorption and increased energy requirements due to their disease [4]. This energy deficit is associated with increased morbidity and mortality [5].

Is there a role for biosynthetic human growth hormone (HGH) in the treatment of cystic fibrosis? Human growth hormone is well known for its anabolic effects on protein synthesis and cell growth [6]. In patients with other catabotic conditions such as sepsis [7], burns [8] and trauma [9], studies have demonstrated decreased urinary nitrogen excretion, increased protein synthesis and resultant increases in lean-body mass. The study by Alemzadeh, Upchurch and McCarthy in this issue of JACN [10] adds data to the limited experience already reported on the short-term effect of HGH in CF patients [11–13].

At present, HGH is FDA approved as safe and effective for treatment of three very different conditions: pituitary growth hormone deficiency, Turner Syndrome, and chronic renal failure. Turner Syndrome is the prototype for successful HGH treatment of a form of genetic short stature; chronic renal failure is the prototype for successful HGH treatment in a non-HGH deficient chronic disease state. Treatment of CF with HGH would appear to fall into the latter category.

Alemzadeh and his co-authors have shown a significant but short-term increase in both height and weight z scores in five very young patients with CF. The findings suggest that HGH may increase the lean body mass in CF patients. Greater lean body mass has been associated with improved pulmonary function [14] and decreased morbidity [15] in CF. Growth hormone treatment also resulted in significant increases in mean IGF-1 and IGFBP-3 values in this group. A similar increase in growth rate was previously reported in a group of 24 patients enrolled in the National Cooperative Growth Study (NCGS) [16], a large database from a multi-center study.

While the Alemzadeh study adds to our knowledge of the short-term HGH effect in another non-GH deficient disease state, the most important questions about long-term safety and efficacy remain to be addressed. Many of the concerns recently reported about safety of HGH treatment in renal transplant patients (scoliosis, pigmented nevi, pancreatitis, glucose intolerance) [17] could be applicable to HGH treatment in other chronic diseases such as cystic fibrosis.

The ultimate effect of HGH treatment on pulmonary function, nutritional status, adult height and weight, morbidity, mortality and quality of life must still be addressed in cystic fibrosis and the many other currently "unapproved indications" [18] in which growth hormone is being used.

Received July 1, 1998.
   REFERENCES
TOP
 INTRODUCTION
 REFERENCES
 

  1. Matthews LW, Drotar D: Cystic fibrosis—a challenging, long-term chronic disease. Ped Clin North Am 31(1): 133–152, 1984.[Medline]
  2. Karlberg J, Kjellmer I, Kristiansson B: Linear growth in children with cystic fibrosis. Acta Ped 80: 508–514, 1991.
  3. FitzSimmons SC: The changing epidemiology of cystic fibrosis. J Ped 122(1): 1–9, 1993.[Medline]
  4. Clark PA, Rogol AD: Growth, development and critical disease. In Ober KP (ed): "Endocrinology of Critical Disease." Totowa, NJ: Humana Press, 1997.
  5. Preece MA, Law CM, Davies PSW: The growth of children with chronic pediatric disease. Clin Endo Metab 15: 453–477, 1986.[Medline]
  6. Gore DC, Honeycutt D, Jahoor F, Wolfe RR, Herndon DN: Effects of exogenous growth hormone on whole-body and isolated-limb protein kinetics in burned patients. Arch Surg 126: 38–43, 1990.
  7. Douglas R, Humberstone D, Haystead A, Shaw J: Metabolic effects of recombinant human growth hormone: isotopic studies in the post absorptive state and during TPN. Br J Surg 77: 785–90, 1996.
  8. Wilmore DW, Moyland JA, Bristowe BF: Anabolic effects of human growth hormone and high caloric feedings following thermal injury. Surg Gynecol Obstet: 138: 875–878, 1974.[Medline]
  9. Soroff HS, Rozin RR, Mooty J, Lister J, Rabin MS: Role of human growth hormone in the response to trauma. I: Metabolic effects following burns. Ann Surg: 166: 739–752, 1967.[Medline]
  10. Alemzadeh R, Upchurch L, McCarthy V: Anabolic effects of growth hormone (GH) treatment in cystic fibrosis (CF). J Am Coll Nutr 17(5): 419–424, 1998.[Abstract/Free Full Text]
  11. Meacham LR, Wilson DP, Kramer JC, Culler FL: Growth hormone (rhGH) treatment of children with cystic fibrosis (CF) does not result in significant insulin resistance. (Abstract). Ped Res 29: 82A, 1991.
  12. Sackey AH, Taylor CJ, Barraclough M, Wales JKH, Pichering M: Growth hormone as a nutritional adjunct in patients with cystic fibrosis: results of a pilot study. J Hum Nutr Diet 8: 185–191, 1995.
  13. Huseman CA, Colombo JL, Brooks MA, Smay JR, Gregor NG, Sammut PH, Bier DM: Anabolic effect of biosynthetic growth hormone in children with cystic fibrosis. Ped Pulmonol 22: 90–95, 1996.
  14. Steinkamp G, von der Hardt H: Improvement of nutritional status and lung function after long-term nocturnal gastrostomy feedings in cystic fibrosis. J Pediatr: 124: 244–249, 1994.[Medline]
  15. Sheperd R, Cooksley WGE, Cooke WDD: Improved growth and clinical, nutritional and respiratory changes in response to nutritional therapy in cystic fibrosis. J Pediatr 97: 351–357, 1980.[Medline]
  16. Hardin DS, Sy JP: Effects of growth hormone treatment in children with cystic fibrosis: The National Cooperative Growth Study experience. J Pediatr 131: 565–569, 1997.[Medline]
  17. Friedman AL: Growth hormone is not safe for children with renal transplant. J Pediatr 131: 525–527, 1997.[Medline]
  18. Rosenfeld RG: The spectrum of uses for growth hormone in children. Growth Genetics and Hormones 14(1): 1–4, 1998.




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