A Novel Treatment for Height Growth in Patients With Growth Hormone Insensitivity Syndrome by Cyproheptadine Hydrochloride

Maryam Razzaghy-Azar; Mitra Nourbakhsh; Mona Nourbakhsh


Clin Endocrinol. 2018;88(6):880-888. 

In This Article

Abstract and Introduction


Background: Cyproheptadine HCl (CyproH) is an appetite–stimulating drug and while it was prescribed for a patient with growth hormone insensitivity syndrome (GHIS) for increasing appetite, his height growth was surprisingly increased. Therefore, the aim of this study was to investigate the effect of CyproH on growth parameters of the patients with GHIS.

Patients and design: Twenty patients were enrolled in two prospective cohorts at two different times. Fifteen cases were observed for 1.17 ± 1.3 years without treatment (observation period, OP). Then, CyproH was administered for 2.2 ± 2.7 years (treatment period, TP), and growth parameters were compared within these two periods. Five patients who did not receive any treatment for 1–8.24 years (4 ± 2.9) were the control group.

Results: Height velocity (HV) increased from 1.88 ± 0.7 to 6.1 ± 0.8 cm/year and HV–SDS reached from −4.5 ± 0.74 to −0.21 ± 1.2 in OP and TP, respectively (P < .001), whereas HV and HV–SDS were 2.2 ± 1.1 cm/yr and −4.2 ± 1.2, respectively, in controls (P < .001). Height SDS was −7.0 ± 1.7 and increased to −6 ± 2.2 after treatment (P = .002). Gain in height was 2.3 ± 0.6 SDS in 5 patients who were treated for 5.4 ± 2.8 years. BMI–SDS was not significantly changed within two time periods and also in cases and controls.

Conclusion: CyproH caused height growth in the patients with GHIS, and therefore, this treatment can be considered as an alternative option to IGF–I injection.


Growth hormone insensitivity syndrome (GHIS) is defined as defects in GH receptor or postreceptor signals which result in resistance to GH and cause severe growth retardation.[1] GH receptor is a water–soluble protein consisting of three extracellular, transmembrane and intracellular domains. Binding of GH to extracellular domain is followed by dimerization of the receptor and activation of a tyrosine kinase (JAK–2), a member of the Janus kinase family. Activated JAK–2 phosphorylates tyrosine molecules in transcription factor proteins, called STATs, leading to the activation of target gene transcription and insulin–like growth factor 1 (IGF–I) production.[2] Growth hormone–binding protein (GHBP) is generated by cleavage of the membrane receptor in humans. Low level of GHBP has been reported in this syndrome, suggesting a defect in the receptor.[3] Insulin–like growth factor 1 (IGF–I) is low in these patients in spite of high GH level.[4] In 1966, Laron and colleagues described this syndrome in three siblings.[5] Liver biopsy was performed on two affected patients after 20 years and showed defect in GH receptor.[6] Mutated GH receptor genes have been shown to be the underlying defect in GH–resistant dwarfism known as Laron syndrome.[7] There are typical clinical features of growth hormone deficiency in this syndrome. In 1993, the clinical and biochemical characteristics of 27 affected patients were described by Savage et al.[8]

Treatment of these children for enhancing growth is performed by one or two daily injections of IGF–I.[9] It is a costly medication which is not affordable for many of these patients and is not available in some countries worldwide. There are several adverse effects for this medicine such as hypoglycaemia.[9]

Cyproheptadine hydrochloride (CyproH) is an antihistamine antiserotonin drug that has an appetite–stimulating effect.[10] This drug has not been previously used for improving height in this disorder. It was prescribed for one of our patients with GHIS to increase his appetite and height growth was surprisingly noticed after a few months of treatment. Therefore, the aim of this study was to evaluate the effect of CyproH on height growth of the patients with GHIS. The hypothesis of this study was that CyproH improves height growth in patients with GHIS.