Untoward Events in Patients Treated with Growth Hormone in the USA

Abstract

Since 1960 more than 30,000 children have been treated with growth hormone (GH) in the USA. Ten cases of Creutzfeldt-Jakob disease have been associated with the use of GH purified from pituitaries in the USA, and more cases may appear in the future. Ten cases of leukemia or preleukemia have been reported in patients undergoing GH treatment in the US. Eight of these patients had previously diagnosed tumors of the central nervous system. As the indications for GH treatment broaden, and the dosages of GH increase, more unfavorable clinical events linked directly to the biological actions of GH can be expected to occur. Continued surveillance for clinically important GH-associated events is important.

A Novel Non-Peptidyl Growth Hormone Secretagogue

“…There is no doubt that GH replacement therapy is effective in promoting linear growth in hypopituitary chil dren. However, several unfavourable side-effects which are common to both pituitary and synthetic GHs have been reported after the commencement of GH treatment, such as GH antibody formation, insulin resistance and others [2], Some of these side-effects are clearly associated with the use of exogenous GH.…”

Design and biological activities of L-163,191 (MK-0677): a potent, orally active growth hormone secretagogue.

“…However, the utility of recombinant GH is limited by the need to administer it by injection. In addition, side effects, including carpal tunnel syndrome, have been reported during treatment (1). It has been suggested that secretagogues may offer an advantage by stimulating a more physiologically relevant, pulsatile release of GH (2).…”

“…The spiropiperidine part structure of this compound is a privileged structure in the terminology of Evans et al (11), since it is also found, for example, in oxytocin (15) and sigma receptor ligands (16). We derivatized the spiropiperidine core of 1 and from this approach lead compound 2 was discovered. It is remarkably potent, with ED50 = 50 nM, even as a mixture of four diastereomers, although, unfortunately, it also was poorly active to release GH in dogs after oral administration.…”

Acute Promyelocytic Leukemia in the Course of Acromegaly: A Case Report.

“…Especially in women, benign and malignant tumors are also increased in the course of acromegaly [1,5,6,[9][10][11][12][13][14][15]18,20,23,24,26]. Firstly, the cause/result association with GH and tumor development is defined because of the effects of GH on hypophisectomized and healthy animals.…”

“…It is a clinical entity due to a pituitary adenoma secreting excessive amounts of GH or, rarely, with the stimulation of GH by ectopic production of growth hormone releasing factor [2]. Patients with acromegaly have reduced life expectancy and various authors have reported that malignancies may increase the overall mortality of acromegalic patients [1,5,6,[9][10][11][12][13][14][15]18,20,23,24,26].…”