Growth Hormone Deficiency and the Role of the Hypothalamus





Growth Hormone Deficiency and the Role of the Hypothalamus

Hormones play a critical role in function of body organs given that they enable movement of information through the blood stream. Hormones are produced by different endocrine glands in the body and are tasked with regulation of growth metabolism and development. Deficiencies or low levels of hormones usually result in body imbalance, which can have severe effects in metabolic and growth functions within the body. The lack of more than one hormone usually results in a severe medical condition termed as Multiple Pituitary Hormone Deficiency (MPHD).

The hypothalamus plays the critical function of regulation of production of hormones by relaying messages to the pituitary glands. The pituitary gland is tasked with the production of various hormones based on the messages received from the hypothalamus. Hormones produced vary in terms of function given that some have a direct function and role whereas others are for stimulation of other glands to produce hormones in the body such as the thyroid, adrenal, ovaries, and testes (sex hormone glands).

The hypothalamus and the pituitary gland function in a coordinated manner given that one relies on the other for movement of messages for effective bodily functions. The pituitary gland is termed as the master gland given that it is tasked with release of various hormones in response to needs of the body as conveyed by the hypothalamus. The growth hormone assumes an important position in the human body. It is defined as a significant body system metabolic hormone that is tasked with the regulation of lipids (fat), proteins, and subsequent carbohydrate homeostasis.

Growth Hormone Deficiency (GH) arises because of insufficient production of the growth hormone by the pituitary gland. The hypothalamus is tasked with controlling the levels of hormones found in the blood by inducing the production of the needed hormones through the pituitary gland. Low or insufficient production of the growth hormone is associated with problems such as damaged hypothalamus or severed linkage between the pituitary gland and the hypothalamus.

The Growth Hormone assumes the role of an anabolic hormone as well as being a fat mobilizing diabetogenic element that results in the increase in blood sugar levels. The body produces a variety of growth hormones. The primary type or form of the growth hormone within the human body is a complex protein that has 191 types of amino acids and 22 KD (kilodaltons). This type of growth hormone is usually known as somatotrope. Growth Hormones are produced by the growth hormone cells known as the somatotropes that can be found in the anterior lobe of the pituitary gland.

The Growth Hormone somatotropes are tasked with the production and secretion of more than half of the hormone producing cells located in the anterior pituitary gland. The Growth hormone is important for development, growth and subsequent maintenance of the mental and physical functions of human beings at all stages of life from conception until death. The hypothalamus is located above the pituitary gland and is unable to function independently without the pituitary gland. The pituitary gland is divided into two lobes with the connection to the hypothalamus gland being provided by the pituitary stalk.

The pituitary stalk is the avenue for transit that is utilized by the hypothalamus uses for transmission of neuroendocrine signals to the pituitary gland. In addition, the pituitary glands regulate the production of the various hormones in use by different glands. The anterior lobe in the pituitary gland is directed by a hypothalamic neuroendocrine messenger known as the growth hormone releasing hormone (GHRH). The growth hormone is mediated by another hormone known as somatostatin, which is produced by the hypothalamus. The production of somatostatin is on an intermittent basis in relation to the needs of the body. When the somatostatin hormone is absent, the hypothalamus engages in the production of the GHRH whereas the presence of GHRH results in inhibited production of the Growth Hormone (GH). The relationship between the two hormones, the GHRH, and somatostatin is responsible for the random secretions of the growth hormone in the human body.

The secretion of the growth hormone (GH) varies in terms of amplitude, frequency, and duration. In addition the patterns of secretion is primary a function of nutritional state, developmental state, sleep state, exercise, stress and metabolic clearance in the human body. The maximum levels of production of the Growth Hormone usually take place during the first hour of sleep, which is termed as the initial slow-wave of sleep in stages 3 and 4. The GH is usually potent only for several minutes within the human body. During its short life, it is distributed towards the various organs and body tissues such as the liver and lungs. In the live it induces the production of an insulin like growth chemical known as somatomedin-C (IGF-I).

The IGF-I is solely responsible for inducing a variety of metabolic functions in the human body that culminate in the building of bone structures, tissues, muscle tone and the linear growth evident in children. The growth hormone performs independent endocrine functions as well as the primary function of producing the IGF-I. Hormone secretion and utilization is regulated by the binding proteins, which vary from IGFBP-1 to IGFBP-6). IGFBP levels in the human body are different in quantity from other hormones such as insulin, the growth hormone, thyroxin, testosterone, sleep, diet, and estrogen.

Growth Hormone Deficiency (GHD) is classified into four primary categories based on the source of the deficiency. The four classifications are:

  1. Classic or pituitary Growth Hormone Deficiency (GHD)

This is defined as the incapacity in the pituitary gland to produce the Growth Hormone (GH).

  1. Hypothalamic Growth Hormone Deficiency (GHD)

This is defined as the incapacity of the hypothalamus to produce and ensure transmission of the neuroendocrine hormone GHRH that is tasked with the direction of the pituitary gland to produce the Growth hormone (GH).

  • Functional Growth Hormone Deficiency (GHD)

This is termed as the incapacity and failure of metabolic and hormonal functions that is brought about by various unknown etiologies, which culminate in the failure of the pituitary gland to produce and utilize the Growth Hormone (GH).

  1. Idiopathic Growth Hormone Deficiency (GHD)

This is an unknown form of GHD.


Adult GHD is classified into three groups based on the stage of progression of the deficiency. The three groups are child onset, adult onset and child onset idiopathic GHD that is divided into causes namely idiopathic and organic causes. Child Onset GHD is associated with various genetic defects and different genetic components. It is associated with Prader-Willi syndrome which is define as a congenital disorder brought about by hypothalamic dysfunction and is characterized by short stature, obesity, absence of muscle tone, central nervous system dysfunction and hypogonadism.

In addition, it is associated with structural defects of the brain, and midline facial defects. Children with brain tumors are highly susceptible to developing GHD because of cranial radiation that may be focused on the pituitary and hypothalamus axis. It is also possible that a large number of patients usually develop hypothalamic radiation induced conditions on the GHRH secreting neurons that arise in the pituitary gland. This results in decline in the response levels to the GHRH after CI therapy during childhood.

The GH during the transition period from childhood to adulthood, the focus function is on muscle tone and bone development. Research indicates the importance for continued GH therapy amongst young adults with severe levels of GHD. The adult onset GHD is usually associated with trauma during or after birth. It is marked by infection in the central nervous system, tumors in the hypothalamus or in the pituitary glands, granulomatous or infiltrative disease, surgery, cranial irradiation and other idiopathic cases. Some of the primary concerns associated with this deficient include high risks of cardiovascular diseases, increase in fats mass, and reduction in sensitivity to insulin, high mortality markers for women than for other population and GHD-related dyslipidemia.

Amongst the elderly, GHD is manifested in the decline in the quality of life, alteration in body composition and fatigue. In addition GHD amongst the elderly is also exhibited in the form of abnormal body composition, lipid profile and bone metabolism. The Growth Hormone has a special role in adults ailing with GHD hypopituitarism in their adult life. Over the years, research has brought to light the role of growth hormone deficiency in the high levels of morbidity, cardiovascular incidents, osteoporosis, metabolic syndrome, muscle wasting, impaired quality of life.

GHD amongst adults is primarily brought about by onset and treatment of Pituitary adenomas. The diagnosis of GHD initially used biochemical tests such as the growth hormone stimulation test (GHST) which evaluated the ability and capacity of the pituitary gland to produce growth hormones. This test has become questionable given its variability and the growth of validity of IGF-I as a primary and significant diagnostic measure when combined with GHST. In addition, this is also combined with phenotype evaluations that are made up of mental and physical traits, patient medical history, and considerations of unique patient physiology.

Adult GHD is a multi-factorial ailment whereby the pituitary glands dysfunction that is linked to pituitary adenomas with the treatment of the latter being a major contributor to the disorder. Adults may show a variety of signs such as, extra-cellular fluid volume, impaired cognitive function, and depression, lack of motivation, lethargy, and decline in muscle mass, muscle strength, physical stamina, and energy. In addition, biochemical tests indicate the presence of other signs such as atherosclerosis, lipid imbalance, and enhanced levels of LDL cholesterol, metabolic syndrome, and obesity.

Biochemical tests usually include a variety of activities such as blood count (CBC) with various platelets, thyroid panel, IGF-I, metabolic panel, lutenizing hormone, estrogen, HbA1c, testosterone, androstenedione, DHEAS, and follicle stimulating hormone. In addition, such tests may also be indicative of deficiencies in other hormones such as testosterone, thyroxin, androgenic steroids such as androstenedione and DHEAS. In addition, they may also indicate diseases, disorders with metabolic function, genetic defects that impede the secretion and utilization of Growth Hormones and insulin related IGF-I hormone.

In the event of low IGF-I levels in the body, further studies should be conducted to make a determination of the cause of such low IGF-I. This is can be achieved by testing for IGF-II levels, and any IGF binding proteins. Secondly, this can also be achieved through growth hormone stimulation tests as a means of determination of the capacity of the pituitary gland to produce the growth hormone (GH). The third procedure is to evaluate the levels of zinc, selenium and magnesium which are the primary minerals in the proper functional capabilities of the metabolic functions of the IGF-I. Diagnosis of AGHD is usually a challenge given that the absence of growth boundaries as primary diagnostic actors. Current treatment strategies for AGHD include the use of rhGH, which is an approved drug by the United States Food and Drug Administration (FDA).

A majority of Growth Hormone Deficiency cause are termed as idiopathic given that the reasons are usually unknown. In addition, the various causes are usually associated with the connections of the pituitary gland to other body organs. Severe damage during birth or because of head injuries, may impede the functionality of the hypothalamus and the pituitary gland thus inhibiting the production of the Growth Hormone.

This condition is considered as hereditary, and affects an estimated 3% of children around the world. The deficiency, without any reason, is seen to be highly common in boys as opposed to girls. Additionally, because of specific pituitary or brain tumors, the treatment of such using irradiation and surgery may impede and affect the functionality of the pituitary gland. This in turn results in hormonal deficiencies with the GHD being the most prevalent hormonal deficiency.

The treatment of leukemia, which focuses on radiation procedures on the entire head, usually has a significant effect on the pituitary gland. Studies indicate that this has a significant effect on functional capabilities of the pituitary gland in secretion of the Growth Hormone (GH). Deficiency associated with the growth hormone may take place independently or in association with other hormonal deficiencies in the human body. In essence, a majority of sex hormones is usually affected but minimal treatment and diagnosis is required until the patient attains the age of puberty.

Furthermore, the thyroid stimulating hormones (TSH) is also affected, despite being a low incidence, together with the adrenal gland (ACTH). Such hormonal imbalances are usually remedied using regular medication. It is noted that more than 30% of children suffering from growth hormone deficiency are obese. Recent studies indicate these over weight children do not engage in the consumption of high calories on a daily but rather consumer low intakes than recommended daily levels. Furthermore, it is also noted that a high level of growth hormone deficiency usually leads to higher incidences of obesity.

There is also a high correlation between low energy expenditure when active or inactive amongst children with growth hormone deficiency. This is largely attributed to the fact that the lack of this hormone impedes effective and normal body function resulting in fatigue and high levels of inactivity and obesity. It is important for parents to note that the potential problem is usually to ensure that the child is able to lead a relativity active life and observing a balanced diet with caution against obsessive consumption of foods.

Daily regimens of healthy diets and activity are important for children to ensure that they achieve normal body function. Furthermore, it ensures that they are able to move away from incidences of obesity, cardiovascular diseases, and diabetic disorders. Deficiencies or low levels of hormones usually result in body imbalance, which can have severe effects in metabolic and growth functions within the body. The lack of more than one hormone usually results in a severe medical condition termed as Multiple Pituitary Hormone Deficiency (MPHD).






















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