[Reduced incidence of side-effects of growth hormone substitution in 404 patients with hypophyseal insufficiency. Results of a multicenter indications study].
BACKGROUND
Substitution of pituitary insufficient patients with recombinant human growth hormone (rhGH) in addition to the conventional substitution with glucocorticoids, L-thyroxine and sex hormones has been approved by the regulatory authorities in 1995 with the imposition to conduct surveillance studies to monitor drug safety.


RESULTS
24% of all patients were within their 2nd treatment year, 15% within their 4th year, maximum treatment period was 6 years. There were 2 peaks within the patients age distribution: 30 to 39 years (24%) and 50 to 59 years (24%). The causes for pituitary disease were as follows: pituitary adenomas (47%), idiopathic (16%), craniopharyngeomas (16%) and others (21%). Mean GH dose was 1.5 IU/d s.c. (range 0.4 to 4 IU/d). Serum-IGF-1 increased by 159 and 192% in females and males. Waist circumference decreased by 2% and serum cholesterol was lowered by 5.5% in males. There were 2 cases with new carcinomas, 1 diabetes mellitus II and 1 death. Adverse events (AEs) within KIMS were compared to those of the treatment (GH) and placebo (PI) groups of the previous admission trials (in percent): edema: KIMS 10, GH 37, Pl 3; arthralgia: KIMS 8, GH 19, Pl 2; muscle pain: KIMS 3, GH 16, Pl 3; dizziness: KIMS 2, GH 1, Pl 3; headache: KIMS 2, GH 3, Pl 2; others: KIMS 2, GH 22, Pl 13. The reported incidence of AEs in KIMS was lower than in previous clinical trials. There might be 3 reasons for this: 1. under-reporting, particularly those AEs not likely to be related to GH treatment; 2. doses used in trials were 2-fold higher than in KIMS; 3. dose titration for individual patients.


CONCLUSIONS
Surveillance programs are important for monitoring of drug long-term efficacy and safety.
Wüster
C
C
Abteilung Innere Medizin I, Universität Heidelberg. ChristianWuster@T-Online.de
Melchinger
U
U
Eversmann
T
T
Hensen
J
J
Kann
P
P
von zur Mühlen
A
A
Ranke
M B
MB
Schmeil
H
H
Steinkamp
H
H
Tuschy
U
U
D000293:Adolescent; D000328:Adult; D000368:Aged; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007018:Hypopituitarism / Q000209:etiology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D010901:Pituitary Function Tests; D011358:Product Surveillance, Postmarketing
D013006:Growth Hormone
Verminderte Inzidenz von Nebenwirkungen einer Wachstumshormonsubstitution bei 404 Patienten mit Hypophyseninsuffizienz. Ergebnisse einer Multicenteranwendungsbeobachtung. Deutsche KIMS-Studiengruppe.