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The term Cushing's syndrome is generally used while referring to the increased cortisol secretion by the adrenal cortex and is attributed to the external administration of corticosteroids leading to a hypercortisolism condition known as Cushing's syndrome (Tiruneh et al., 2017). When the pituitary oversecretes Adrenocorticotropic hormone (ACTH) leading to hypercortisolism, then this condition is now known as Cushing's disease. For all of these conditions, there are absolute similarities in the clinical conditions. Cushing syndrome in a human occurs in cases where the levels of glucocorticoids are high in the body. There are various factors that could lead to increased glucocorticoid levels in the body, and one of them could be internal cortisol overproduction by the adrenal cortex (Newell-Price et al., 2006). Another factor that could lead to such increased levels is external pharmacological synthetic glucocorticoid administration that may include prednisone or dexamethasone.
Various functional neoplasms could lead to the overproduction of endogenous glucocorticoid, which could include the direct secretion of proteins or cortisol itself, and in most cases, this usually leads to the regulation of the secretion of adrenocortical cortisol. Currently, the majority of the people who are diagnosed with the condition of Cushing's disease are determined to have acquired it through the use of corticosteroid medications, which are used in the treatment of a variety of diseases and conditions such as multiple sclerosis, asthma, and rheumatoid arthritis. Hypercortisolism is not a common condition, and its prevalence in the entire world is very low, with all the causes combined summing up to only 13 cases in every one million people, and an overall estimation of two new cases per year for every one million people (Tiruneh et al., 2017).
Normal Anatomy of the Major Body Systems
The pituitary gland, which is part of the human brain, is the part that majorly leads to the condition. The pituitary gland is a major endocrine system gland and is also known as the hypophysis. It is responsible for the secretion of hormones whose functions include controlling the actions of other organs in the endocrine system as well as various tissues around the body. The pituitary gland has the shape of a pea, and it is located on the underside of the brain where it suspends with the support of the pituitary stalk (Newell-Price et al., 2006). The pituitary is anatomically a two-in-one structure that consists of the posterior pituitary and the anterior pituitary, with all the parts functions differently and has different embryonic origins.
Normally in the absence of Cushing's syndrome, the human body does not have some of the symptoms that are presented by the condition. For example, there is no acne, fatigue, muscle weakness, thinning skin, or weight gain. Women who have the condition tend to develop more hair on their body and face, a condition that does not exist in the normal anatomy of the human body. Most of the hair grows on the chest, neck, face, thighs, and abdomen. Besides, the normal anatomy of a woman calls for regular menstrual cycles, and this is not the case in women who have Cushing's disease as they tend to experience irregular menstruation (Newell-Price et al., 2006).
Normal Physiology of Body System Affected
The primary function of the hypothalamic-pituitary-adrenal axis is to collectively but somehow imprecisely generate a cortisol response and a basal rhythm to a wide variety of stimuli. The axis entails the central integrative control and physiological feedback, and hypothalamus CRH synthesis control, cortisol in the adrenal cortex, and ACTH in the anterior pituitary (Tiruneh et al., 2017). The activity of CRH neurons in the hypothalamus paraventricular nucleus gets altered by stress and circadian inputs. Most of the hypothalamic neurons have multiple tasks as they both synthesize arginine vasopressin and also synthesize CRH, and it is thought that an increase in the release of vasopressin from hypophysiotropic nerves together with CRH is essential for a full ACTH response generation to different stressors or stimuli (Arnaldi et al., 2010). The anterior pituitary gets derived from the embryonic ectoderm and produces five endocrine hormones, all from different epithelial endocrine cell types. The hypothalamic hormone is responsible for the controlling of the release of anterior pituitary hormones, and the hormones get synthesized in neuron cell bodies, which are located in many nuclei found around the third ventricle.
One of the hormones released by the anterior pituitary is the growth hormone, which targets almost all tissues of the body. When the growth hormones bind with the growth hormone receptors, it dimerizes it and activates JAK2 tyrosine kinase, which is associated with GHR, and tyrosyl phosphorylation of both JAK2 and GHR (Newell-Price et al., 2006). As a result of this, it leads to the activation and recruitment of an array of signaling molecules that includes receptor substrates, MAP kinases, phosphatidylinositol 3' phosphate kinase, insulin receptors substrates, Stat transcription factors, intracellular calcium, and protein kinase C (Tiruneh et al., 2017).
Cortisol is a very integral component in human physiology as it plays a key role in the control of many physiological systems. When there is the overuse of exogenous glucocorticoids or when endogenous cortisol is in excess, it presents devastating effects that are wide-ranging on most organ systems (Arnaldi et al., 2010). On the other hand, when there is a deficiency of cortisol secretion, the condition can become fatal if it goes untreated.
Mechanism of Pathophysiology
There are several anatomical and physiological changes contributing to Cushing's disease. The condition majorly affects women who are in their reproductive age, but it can affect females and males of any age (Arnaldi et al., 2010). In Cushing's disease, the pituitary tumors are normally microadenomas, implying that their diameters are 10 mm or less. As a result of this, they do not cause symptoms by local mass effect, but rather, the tumors are in most cases discovered when hypercortisolism clinical manifestation that results from ACTH hypersecretion prompt an appropriate diagnostic work-up (Newell-Price et al., 2006). There are occasions where microadenomas are accidentally found while performing imaging for other reasons.
In patients with Cushing's disease, microadenomas are not common, and when the size of the tumors exceeds 15 mm, they cause a mass effect (Arnaldi et al., 2010). With the enlargement of a macroadenoma, it may result in optic chiasm compression, suprasellar extension, cavernous sinus compression, local bone erosion, and panhypopituitarism. One of the most common symptoms of Cushing's disease is weight gain, and the most frequent sign is obesity, which presents itself in a central distribution. Any other symptoms or signs of excess cortisol can develop initially, but bruising, muscle weakness, facial rounding, hypertension, and plethora will have to occur eventually (Arnaldi et al., 2010).
Cushing's syndrome is majorly caused by the use of steroid medicines in the treatment of other conditions. Therefore, to prevent this condition, the best way out is to avoid or reduce the use of steroid medicines. A patient should first talk with their doctors if they plan to treat their conditions using steroid medicines. The patient should be open and free to ask their doctor to explain and make it clear to them how long they plan to have them take such medicines and the possibility that the medicines will cause Cushing's disease (Newell-Price et al., 2006). It is important to note that Cushing's is as a result of pituitary gland tumor and that there is no other way to prevent such tumors.
In the event where a corticosteroid medicine is causing the Cushing's syndrome, then the doctor should lower the dose of such medication over time to help in curbing the disease. When the use of corticosteroid medicine is abruptly stopped, then this could lead to a dangerous drop in the levels of cortisol in the body of the individual. A patient should never stop taking these medicines without the guidance or approval of the doctor, as it is the responsibility of the doctor to prescribe a non-corticosteroid medicine that can be used in place of the corticosteroid that leads to Cushing's syndrome.
If Cushing's syndrome is caused by a tumor, the doctor will remove the tumor from the pituitary gland through a surgical process, a surgery that is usually successful. Sometimes, doctors use radiation treatments after surgery so as to lower the risk of the turmoil returning. After the removal of the turmoil, a patient will need to take a cortisol replacement medicine. The significance of the medicine is that it helps maintain the levels of cortisol as the body will take some time before it can begin producing normal amounts of cortisol (Newell-Price et al., 2006). In most cases, the patients only need to take medicine for a few months, but there are cases where this could take up to a year.
Arnaldi, G., Scandali, V. M., Trementino, L., Cardinaletti, M., Appolloni, G., & Boscaro, M. (2010). Pathophysiology of dyslipidemia in Cushing's syndrome. Neuroendocrinology, 92(Suppl. 1), 86-90. https://www.karger.com/Article/Abstract/314213
Newell-Price, J., Bertagna, X., Grossman, A. B., & Nieman, L. K. (2006). Cushing's syndrome. The Lancet, 367(9522), 1605-1617. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4953010/pdf/204.pdf
Tiruneh, F., Awan, A., Didana, A., & Doshi, S. (2017). Preventing Cushing: Iatrogenic Cushing Syndrome due to Ritonavir-Fluticasone Interaction. Cureus, 9(7). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5602273/
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