Correspondence

Acute Pancreatitis Associated with Growth Hormone Therapy for Short Stature

N Engl J Med 1995; 332:401-402February 9, 1995

Article

To the Editor:

We report the occurrence of acute pancreatitis in children being treated with recombinant growth hormone for short stature.

The index patient was a 12-year-old boy with pseudohypoparathyroidism who was receiving thyroxine and vitamin D. The patient was short and had biochemical evidence of growth hormone deficiency, for which he was treated with growth hormone at a dose of 0.05 mg per kilogram of body weight per day. After the sixth dose, nausea, vomiting, and severe abdominal pain developed in the absence of prodromal symptoms of infection or any history of abdominal trauma. When admitted to the hospital, the patient was afebrile and his abdomen was slightly distended and tender but otherwise normal. Serum amylase and lipase concentrations were 798 U per liter (normal range, 25 to 115) and 320 U per liter (normal range, 4 to 24), respectively. The complete blood count and results of liver-function studies were normal, as were serum glucose, creatinine, calcium, and phosphate concentrations. The findings on abdominal computed tomography were consistent with a diagnosis of pancreatitis. The growth hormone therapy was stopped. The patient's symptoms improved over a period of three days, and his serum amylase and lipase concentrations declined to normal within nine days. Three weeks later growth hormone therapy was resumed, but after the second injection his abdominal symptoms recurred and his serum amylase and lipase concentrations increased to 248 and 107 U per liter, respectively. Growth hormone therapy was again stopped, and he recovered in three days. Fecal fat and trypsin and serum glucose concentrations were normal.

The patient has been symptom-free for more than three years. None of his clinical problems or medications, with the exception of vitamin D,1 have been associated with acute pancreatitis, a rare ailment in children.2-5 His sister also has pseudohypoparathyroidism and is receiving growth hormone therapy but has had no complications.

Ten other cases of acute pancreatitis in children (six girls and four boys) receiving growth hormone therapy have been reported to the Food and Drug Administration. All the children had short stature. Three had growth hormone deficiency, three chronic renal insufficiency, two Turner's syndrome, and two short stature of unknown cause. Their mean age was 11 years (range, 2 to 15). Abdominal symptoms developed in nine of these children during the first six months of growth hormone therapy, and six were reported to have elevated serum amylase and lipase concentrations. In one patient the pancreatitis subsided despite the continuation of growth hormone therapy. In two other patients growth hormone therapy was resumed successfully after the pancreatitis subsided. Chronic renal insufficiency, diabetes mellitus, and valproate therapy (which two of the three patients with chronic renal insufficiency were receiving) have been associated with pancreatitis. Although the extent of the association of growth hormone therapy with pancreatitis and the mechanisms by which growth hormone may cause pancreatitis are not known, pancreatitis should be considered in any patient in whom abdominal symptoms develop during treatment with growth hormone.

(This letter represents the views of the authors and does not constitute an official position of the Food and Drug Administration.)

Saul Malozowski, M.D., Ph.D.
Food and Drug Administration, Rockville, MD 20857

Wellington Hung, M.D., Ph.D.
Denise C. Scott, M.D.
Georgetown University Medical Center, Washington, DC 20007

Bruce V. Stadel, M.D., M.P.H.
Food and Drug Administration, Rockville, MD 20857

5 References

1. 1

   Waele BD, Smitz J, Willems G. Recurrent pancreatitis secondary to hypercalcemia following vitamin D poisoning. Pancreas 1989;4:378-380
   CrossRef | Web of Science | Medline

2. 2

   Sibert JR. Pancreatitis in childhood. Postgrad Med J 1979;55:171-175
   CrossRef | Web of Science | Medline

3. 3

   Steinberg W, Tenner S. Acute pancreatitis. N Engl J Med 1994;330:1198-1210
   Full Text | Web of Science | Medline

4. 4

   Tam PK, Saing H, Irving IM, Lister J. Acute pancreatitis in children. J Pediatr Surg 1985;20:58-60
   CrossRef | Web of Science | Medline

5. 5

   Weizman Z, Durie PR. Acute pancreatitis in childhood. J Pediatr 1988;113:24-29
   CrossRef | Web of Science | Medline

Citing Articles (10)

Citing Articles

1. 1

   2012. Human Growth Hormone and Insulin-Like Growth Factor. , 334-350.
   CrossRef

2. 2

   Jolanta Jaworek, Anna Leja-Szpak, Artur Dembiński, Romana Tomaszewska, Joanna Szklarczyk, Michalina Kot, Katarzyna Nawrot-Porąbka, Joanna Bonior, Zygmunt Warzecha, Wiesław W. Pawlik. (2009) Involvement of sensory nerves in the protective effect of growth hormone on acute pancreatitis. Growth Hormone & IGF Research 19:6, 517-522
   CrossRef

3. 3

   Jan-Paul Rutten, Martijn Poeze, Cornelis H.C. Dejong. (2008) Acute Pancreatitis Caused by Excessive Use of Growth Hormone in a 40-Year-Old Man. Pancreas 36:2, 217
   CrossRef

4. 4

   M Wilson. (2003) Acute pancreatitis complicating 50% full-thickness burns in a 5-year-old child. Burns 29:6, 619-621
   CrossRef

5. 5

   Scott A. Chapman, G. Paulina Wacksman, Betty D. Patterson. (2001) Pancreatitis Associated with Valproic Acid: A Review of the Literature. Pharmacotherapy 21:12, 1549-1560
   CrossRef

6. 6

   N Tritos. (1998) Recombinant human growth hormone: old and novel uses. The American Journal of Medicine 105:1, 44-57
   CrossRef

7. 7

   H. Vierhapper. (1998) Role, sensitivity and validity of GH stimulation tests in the diagnosis of growth hormone deficiency in adults. Growth Hormone & IGF Research 8, 37-40
   CrossRef

8. 8

   H. Vierhapper, P. Nowotny, T. Czech, C. Bieglmayer, W. Raber, W. Waldhäusl. (1997) How (not) to diagnose growth hormone deficiency in adults: Stimulated serum concentrations of growth hormone in healthy subjects and in patients with pituitary macroadenomas. Metabolism 46:6, 680-683
   CrossRef

9. 9

   Richard N Fine, Edward Kohaut, Douglas Brown, Joyce Kuntze, Kenneth M Attie. (1996) Long-term treatment of growth retarded children with chronic renal insufficiency, with recombinant human growth hormone. Kidney International 49:3, 781-785
   CrossRef

10. 10

    D C. Scott,, W. Hung,. (1995) Pseudohypoparathyroidism Type la and GH Deficiency in Two Siblings. Journal of Pediatric Endocrinology and Metabolism 8:3, 205-208
    CrossRef