What are reported adverse effects of medications used in the treatment of growth hormone receptor deficiency (GHRD)?

Updated: Jan 15, 2019
  • Author: Arlan L Rosenbloom, MD; Chief Editor: Robert P Hoffman, MD  more...
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Episodes of hypoglycemia, which may be severe, are common in infants and children with GHRD. In contrast to the hypoglycemia of GHD, which is corrected by GH replacement therapy, IGF-I treatment enhances the risk in children with GHRD. Hypoglycemia has been the most common early adverse event, reported in 49% of subjects in the largest series, including 5% with seizures. [46]

In a 6-month placebo-controlled study, hypoglycemia was reported in 67% of those receiving placebo and 86% of those treated with rhIGF-I, an insignificant difference. [40] Fingerstick blood glucose measurements in 23 subjects residing on a research unit documented frequent hypoglycemia before breakfast and lunch, which did not increase in frequency with rhIGF-I administration. Five of the subjects participated in a crossover placebo-controlled study for 6 months with a 3-month washout period with fasting glucose determinations done thrice daily by caregivers for the entire 15-month study. The percentage of glucose values < 50 mg/dL was 2.6% on placebo and 5.5% on rhIGF-I—not a significant difference. [46] In practice, hypoglycemia appears reasonably controllable with adequate food intake.

Pain at the injection site is common. Injection site lipohypertrophy is frequent, affecting at least one third of subjects; this is the result of failure to rotate injections, and injection into the lumps can attenuate growth response.

The inotropic effect of IGF-I results in asymptomatic tachycardia in all treated patients, which clears after several months of continued use.

Benign intracranial hypertension or papilledema has been noted in approximately 5% of IGF-treated subjects. While headache is frequent, the placebo-controlled study found no difference between those receiving placebo injections and those receiving IGF-I.

Parotid swelling and facial nerve palsy have been described.

Lymphoid tissue hypertrophy occurs in upwards of one fourth of patients, with hypoacusis, snoring, and tonsillar/adenoidal hypertrophy that required surgical intervention in more than 10% of patients. Thymic hypertrophy was noted in 35% of subjects having regular chest radiographs. Some of these side effects may be more frequent than reported because they take time to develop; for example, snoring incidence in the first year for the 25 subjects treated longest in the mecasermin study was only 4%, but increased to 65% for the entire period. [46]

Anti-IGF-I antibodies have developed in approximately half of the patients treated with IGF-I during the first year of treatment, but these have had no effect on response. [40, 46]

Transient elevation of liver enzymes has also been noted.

Anaphylaxis has been reported. [49]

Coarsening of facial features reminiscent of acromegaly has been noted in many patients, particularly those of pubertal age.

In contrast to the increase in lean body mass and decreasing percentage of body fat that occurs with GH treatment of GHD, both lean and fat mass increase with rhIGF-I therapy, particularly at the higher dosages given. [43, 48] Mean body mass index (BMI) increased from +0.6 SDS to +1.8 SDS during 4-7 years of treatment with rhIGF-I in the European multicenter trial, and severe obesity has occasionally occurred. [45] BMI measurement may not accurately reflect the degree of obesity, which can be a doubling or tripling of body fat as demonstrated by dual energy x-ray absorptiometry. [9]

Whether there might be long-term mitogenic effects of extended therapy with rhIGF-I in growing children is not known. The role of IGF-I in carcinogenesis as an anti-apoptotic agent favoring the survival of precancerous cells, increased cancer risk in hypersomatotropic states, and the evidence for aberrant tissue effects in patients treated with rhIGF-I dictate a need for long-term follow-up of these patients. [50, 51]

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