The growth hormone axis as an aetiological factor in adult inguinal hernia development

Witherspoon, Paul (2006) The growth hormone axis as an aetiological factor in adult inguinal hernia development. MSc(R) thesis, University of Glasgow.

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Adult inguinal hernia development is a common general surgical problem with 85,000 inguinal hernia repairs being performed annually in the United Kingdom. An understanding of the aetiology is important as it may help improve operative repair or identify modifiable factors that could prevent the disease. The current understanding of adult inguinal hernia aetiology is complex and multi-factorial. The inguinal canal is a dynamic structure and paralysis of the deep inguinal ring or variations in parameters of the canal can predispose to hernia development. The presence of a patent processus vaginalis can also result in hernia development but can not alone explain the aetiology. There is a genetic component with a number of hereditary connective tissue and metabolic storage diseases being associated with inguinal hernia development. The extra-cellular matrix is a complex alloy of protein families that provides a structural framework for tissues. It is a dynamic environment whose composition and activity varies between tissues. Control of this environment involves both paracrine and autocrine regulation by a wide spectrum of growth factors, hormones and enzymes. The mechanical properties of tendon and interstisital tissue extra-cellular matrix is defined by the proportion of type I: type III collagen within it. Adult inguinal hernia patients have been found to have reduced ratios of type I: type III collagen caused by elevated expression and production of type III collagen, occurring in both direct and indirect hernias. Levels of matrix metalloproteinases, the degredative enzymes of the matrix, have been found to be variable but may have an influence in younger inguinal hernia patients. The growth hormone axis in adults influences body composition including protein, fat, carbohydrate and bone metabolism. It works directly by the effects of growth hormone and indirectly via the mediator insulin-like growth factor-1. The axis activity declines with age and is associated with many of the changes in body habitus associated with ageing. The peak decline in this activity coincides with the peak incidence of adult male inguinal hernias. A variety of studies in the fields of dermatological, vascular and orthopaedic research have demonstrated that growth hormone, insulin-like growth factor-1 and age can modulate both collagen metabolism and MMP activity. Alterations in the ratio of type I: type III collagen have also been noted. These observations are both time and tissue dependant. This study hypothesized that the growth hormone axis, in particular its age-related decline, could have a role in the aetiology of adult inguinal hernia development. Gonadal axis function also declines with age and this was assessed also. 47 adult male patients were recruited from 100 consecutive patients referred to the Southern General Hospital with inguinal hernias between 2003 and 2005. These were compared to 47 age-matched controls recruited from 850 patients reviewed with benign pathology in the general, orthopaedic and day-case clinics over a similar time period. Patients were excluded if they had any history of endocrine pathology, aneurysmal vascular disease, diabetes, liver or renal pathology or malignancy to exclude factors known to influence growth hormone axis activity. In addition, the control patients were examined by two independent clinical practitioners to exclude occult groin hernia and were also excluded if they had a history of ventral abdominal wall hernias. All other medical history, including smoking history, was noted and height / weight measurements were taken for calculation of body mass index. A single serum blood sample was taken for the analysis of IGF-1 (as a surrogate marker of GH/IGF-1 axis activity), testosterone and sex hormone binding globulin. The free androgen index was calculated from these results in order to exclude gonadal axis activity as a confounding factor. Both groups were similar in baseline characteristics except for mean BMI (mean BMI hernia 25.1 vs control 26.6; p=0.035). IGF-1 negatively correlated with age in both groups. There was a negative correlation with testosterone and age also. Free androgen index displayed a significant negative correlation with age which was maintained when controlling for BMI and IGF-1. There was a no significant difference between the mean IGF-1 concentrations of the hernia cohort compared to controls. The hernia cohort had significantly higher gonadal axis activity but this was within normal limits. These results confirmed the recognized age-related declines in the growth hormone and male gonadal axis within this cohort. It did not show a significant difference between IGF-1 levels in the hernia and control groups. The noted elevated testosterone and free androgen binding index levels in the hernia cohort was unexpected but certainly excluded reduced gonadal axis activity as an aetiological factor. This was the first study to investigate a possible relationship between adult inguinal hernia development and the growth hormone and gonadal axes. It suggests that the recognized hormonal changes associated with adult male ageing are not aetiological factors in adult male inguinal hernia development. Further research in this area is warranted to confirm these findings.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Keywords: Endocrinology
Subjects: Q Science > QH Natural history > QH345 Biochemistry
Colleges/Schools: College of Medical Veterinary and Life Sciences
Supervisor's Name: O'Dwyer, Prof. Patrick J.
Date of Award: 2006
Depositing User: Enlighten Team
Unique ID: glathesis:2006-71431
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 10 May 2019 10:49
Last Modified: 21 May 2021 09:25

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