Should adults with growth hormone deficiency be treated with hormone replacement?
Growth hormone deficiency (GHD) is a medical condition that can occur in any living human being. Causes for this clinical syndrome are wide, but mainly due to the damaged of the pituitary gland. Since anterior pituitary gland is the site where growth hormone is made, damaged of the anterior lobe of the pituitary gland could cause GHD; inadequate secretion of growth hormone (Ayuk, 2006). On the other hand, question asking if an adult with growth hormone deficiency should be treated with hormone replacement stays as an open question. There are no right or wrong answers to this question even at this point of time as research and investigations regarding this topic are still ongoing. Although there will be pros and cons regarding this topic, however, in this essay I will discuss on whether hormone replacement is suitable for GHD patients, and should they be more widely suggested to an adult with GHD.
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In children, GHD mostly obtained by birth (de Zegher et al.,2000). But, in adults, GHD could be because of various reasons such as pituitary gland damage, which is caused by severe head injury, autoimmune disease or even irradiation. Numerous numbers of organs and systems are involved in the action of growth hormone. Longitudinal growth and development are all relying on the normal secretion of growth hormone. Apart from these, carbohydrate metabolism, changes in protein and lipid are also dependent on the secretion of growth hormone (Ayuk, 2006). Apart from all of these complications, there are other factors associated with GHD, such as cardiovascular disease, neuropsychiatric-abnormalities, neuromuscular and skeletal abnormalities (Gupta, 2011). This condition, growth hormone deficiency is a very important topic in research as this can affect the general well-being of one’s life.
Unlike GHD in children which can be easily detected such as short stature, hypothyroidism, delay in growth and puberty (Stanley, 2012), acquired GHD in adults can be a little more complicated. A work by (Carroll et al., 1998) states that lean body mass (LBM) in an adult with GHD decreased significantly to 7-8% from a 4kg lean tissue mass. Further studies do also suggest that fat mass in a person with GHD was greater by a mean of 7% compared to the normal values of a healthy person based on age, sex and gender. These deductions derived from investigations by using various methods.
Waist/hip ratio and skinfold thickness on fat mass distribution supported by CT scans and MRI are reliable as studies gave a consistent result. Furthermore, the research has shown that in a central (abdominal) distribution particularly the visceral components, it is where excess fat accumulates (Carroll et al., 1998). This further supports the arguments that states complication of GHD could lead to cardiovascular disease. In the same study done, it also states that excess fat accumulating in the abdominal distribution has been associated with cardiovascular mortality and morbidity.
Although there is still a lot of ongoing research and debate regarding cardiovascular morbidity and mortality associated with GHD, (Gupta, 2011) works have suggested reason in the increase of cardiovascular mortality. his work suggests that GHD causes a higher level of plasminogen activator inhibitor-I levels (prothrombotic), whereby this promotes blood clotting, suggesting endothelial dysfunction. This give rises to the total cholesterol, low-density lipoprotein-C (LDL) and resulting in an increased risk of hypertension. All of these conditions eventually directed to the progression of cardiovascular mortality (Gupta, 2011). This is also a way in diagnosing if one is a potential patient with GHD.
Other studies deduced that GHD patients are more prone to having cardiovascular disease compared to healthy individuals due to the low level of growth hormone (GH)-insulin-like growth factor I (IGF-I) (Colao et al., 2006). The result has shown that the increase in ischemic heart disease is because of low IGF-I compared to the normal range. A study has also shown that GHD gives a negative impact on cardiovascular function with a direct effect on the heart and endothelium. It also gives an indirect effect on abdominal obesity; high total body fat and insulin resistance (Colao et al., 2006).
Adding on to insulin resistance, an adult with GHD have been defined as having increased insulin sensitivity (low blood sugar level) with a high risk of fasting hypoglycaemia (Johansson et al., 1995). Supporting evidence on insulin resistance, an experiment with 30 patients suffering from GHD was called as participants. Age, gender and BMI were matched with those in healthy controls. Using insulin stimulation, a deduction was made that those participants with GHD were indeed insulin resistant (Murray and Shalet, 2005). The rise in insulin sensitivity is also another important indication of metabolic syndrome with the presence of cardiovascular mortality (Colao et al., 2006).
There are a lot more ways to diagnose GHD. Since GHD could be associated with neuropsychiatric-cognitive abnormalities, patients with GHD would complain about having mental fatigue, low energy level, etc. (Gupta, 2011) With this, clinicians would narrow down if the problem that the patient experiencing is due to GHD. Apart from all of these, adults that went through surgery to the hypothalamic or pituitary and irradiation should be tested for GHD, as there may be chances that this could cause acquired GHD in adults (Gupta, 2011).
The possibility of using human growth hormone replacement has led to wide and intense research of not only the consequences to those with GHD but also the effects of growth hormone replacement, (Carroll, Christ and Sönksen, 2000). Supporting the claim about the effect of GH replacement, continuous treatment of GH replacement for about 6–12 months can lead to significant improvements in body composition, emotional reactions (Gupta, 2011) and thus the quality of life of individuals (Radcliffe et al., 2004).
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It is discussed earlier in the essay that GHD influence the protein metabolism in a person’s body and with experimental studies regarding GH replacement therapy, it has proven that the metabolism in GHD patients improved remarkably (Russell-Jones et al., 1993). The experiment has also deduced that due to growth hormone treatments, there is a rise in the amount of LBM in GHD patients as a result of increased protein synthesis (Russell-Jones et al., 1993). This further supported by another experiment stating that the LBM level in an adult with GHD increase by a mean of 2-5.5kg (Carroll et al., 1998). Furthermore, observations based on the skeletal muscle, which is the most important components of LBM has also increased alongside with overall increase in LBM. In addition to the positive effect of GH replacement therapy, studies also shown that with GH replacement therapy, fat mass in the body decrease to about 4-6kh in GHD patients. Measurements have shown that changes were noticed in the abdominal area. Although it is primarily due to the reduction of the visceral fat mass, with the help of diagnostic images attained from using a CT scans and an MRI, the result has shown that there is a definite decrease in the abdominal fat mass (Carroll et al., 1998). This result was also supported by the study of (Colao et al., 2006), where GH replacement gives a positive result such as an increase in LBM by 2-5kg and a decrease in body fat mass by 30% which is about 4-6kg of VAT.
By treating patients with GH replacement, other studies have also shown that it leads to an increase in lean body mass and reduced body fat mass. Since the vascular risk associated with body composition, improvement in body composition is a major factor in the reduction of cardiovascular disease (Colao et al., 2006). reducing total cholesterol levels by 10%, there could be a 30% reduction in the incidence of symptomatic coronary heart disease (Salomon et al., 1989). an investigation had shown that concerning cardiovascular disease, nitric oxide (NO) production decreased in an adult with GHD. However, this experiment had also demonstrated that with the introduction of GH replacement NO production can be seen to increase. The method behind this study was by assessing forearm blood flow using an ultrasonographic technique and venous occlusion strain gauge plethysmography(Carroll, Christ and Sönksen, 2000). In an adult, with GHD it was proven that adult with this illness has impaired endothelium-dependent vasodilatation but with the presence of treatment, there is an improvement in the endothelium-dependent vasodilatation thus reducing the risk of cardiovascular disease (Carroll, Christ and Sönksen, 2000).
Another experiment with 30 GHD participants has also shown a positive effect of using a GH replacement. In this case, participants were allocated randomly to either recombinant human growth hormone or the placebo-controlled trial for 12 months. To determine the NO production index, urine and plasma samples of the participants in both groups were measured at different times of the year. Urinary nitrate and cyclic guanosine monophosphate (GMP) excretion were found to be low in as GHD patients. But the result has shown a great improvement in the NO production index in those treated with growth hormone and those in the placebo-controlled group. Treatment with recombinant human growth hormone fixes the problem of urinary nitrate and cyclic GMP excretion problem. Investigator claimed that this might be due to the stimulation of IGF-1 of endothelial NO formation and thus resulting in the decrease of the peripheral arterial resistance. The increase in the production of NO is the reason for the improvement of cardiovascular disease (Böger et al., 1996).
Many tissues in our body secrete IGF-1 and its secretory site regulates its actions. IGF-1 can acts as an endocrine hormone, as paracrine hormone and also acts as an autocrine hormone (Laron, 2001). With the recombinant human growth hormone, the mean plasma concentration of insulin-like growth factor-1 increased from 0.41±0.05 to 1.53±0.16 U per litre (Salomon et al., 1989). This further supported by the measurement done by another research which indicates that insulin-like growth factor-1 (P<0 01) and insulin (P<0.02) were significantly increased at 2 months in the treatment group (Russell-Jones et al., 1993). These pieces of evidence show the positivity of having GH treatment.
Adding on to the positive effect of GH treatment, significant improvements in the Hamilton Depression Scale (HDS) scores for the GH-treated group was also seen. The quality of life, as measured by the CPRS, improved significantly in the GH-treated group (Radcliffe et al., 2004). In 9 years, another investigation by (Gilchrist, Murray and Shalet, 2002) has demonstrated that the well-being of a patient with untreated GHD was observed to decline in some areas. Whereby in the same period, the well-being of a treated GHD patient was observed to improve notably. Some studies have addressed the importance of psychological well-being and one’s quality of life in GHD patients and how GH replacement affect those. A study using validated questionnaires and comparisons between healthy control of similar age, gender and socioeconomic status was generated. Results have shown enhancement in psychological well-being. However, another possible conclusion was made that indicates patients with the greatest psychological morbidity were the ones that benefit from the GH replacement the most (Carroll, Christ and Sönksen, 2000).
Investigation and further studies on this topic are never-ending. Trial to find a better therapeutic method will always be ongoing. since a patient with GHD is as a result of the changes in body composition, psychological well-being and also substrate metabolism. A method such as GH replacement is introduced, and it was found that it brings more positivity and benefit in one’s overall well-being. This is supported by the more positive pieces of evidence shown in this essay. With this great success at this point, it will be possible in the future that further ambitious steps will be taken such as using GH replacement more widely and reachable to almost everyone who needs it https://doi.org/10.1210/jcem.83.2.4594. Since till date research on partial GHD patient is not addressed intensively, there has no definite answer if GH replacement is beneficial to them. However, the answer to the general question to should adults with growth hormone deficiency be treated with hormone replacement is yes, they should be treated with hormone replacement and it should be actively introduced to patients.
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