Adrenal Gland Atrophy in ACTH-Independent Cushing’s Syndrome Essay Example

Introduction

Cushing’s Syndrome (CS) is a disease that resulting from issues with the adrenal gland or systems that affect it, such as pituitary adenoma (tumors). This is mainly associated with the excess secretion of Adrenocorticotropic hormone (ACTH) which leads to the overproduction of the cortisol hormone. This will lead to negative health concerns like obesity, diabetes mellitus, bacterial infections, and more. There are different types of Cushing’s Syndrome depending on where in the body the tumors are growing. For example, ACTH-dependent will usually be caused by an abnormal source, like a tumor, that will over secrete the ACTH hormone and ACTH-independent will usually be caused by an issue with the adrenal gland that won’t stop production of the cortisol hormone (Columbia 2021). 

In order to fix this issue, treatment may include the removal of part or all of the adrenal gland, and in turn can result in impaired function. This seems to be a result of adrenal tissue atrophy that is initiated by low ACTH levels and suppression of the gland. Those that have suffered with this disease and its “cures” may be impaired the rest of their lives because there isn’t necessarily a great treatment plan without severe problems. By trying to find a method to overcome this atrophy and its subsequent disfunction, we could possibly reduce the postoperative insufficiency. This means that people that have Cushing’s Syndrome can live a mostly normal life without the debilitating side effects after diagnosis and treatment. 

The Hypothalamus-Pituitary Axis (HPA) is directly associated with the adrenal gland and produces ACTH, which then tells the adrenal gland to secrete cortisol. After removing most of the adrenal gland in response to CS, the surrounding tissue is compromised due to hypercortisolism. This is when the tissues are consistently exposed to glucocorticoids like cortisol. As a result, the HPA decreases the secretion of ACTH and therefore the residual adrenal tissues become atrophied and dysfunctional. There are many medications that have been developed to try and reduce this effect such as glucocorticoid receptor (GR) antagonists. One specific medication that includes the GR antagonist is Mifepristone (MIF). MIF can block the receptors for glucocorticoids so ACTH can continue to be produced, therefore avoiding tissue atrophy. 

Experimental

It was hypothesized that by treating postoperative patients with MIF, it will increase the activity of the HPA, produce ACTH, and stimulate the remaining adrenal tissue so it can grow. With that, we could see increased function and preservation of the tissue and potentially control diabetes mellitus and hypertension. Using rat models, DEX tests were administered to rats with CS. Some of the rats were treated with MIF and some were not in order to monitor the residual tissue function and response. An unspecified number of 10-week-old male Sprague-Dawley rats were randomly divided into four groups and all housed under the same ethical, controlled conditions. Two experiments were performed: one to determine if ACTH-independent CS rats treated with MIF would experience suppression of the HPA axis and another to determine the appropriate dosage of MIF for the rats. For the first experiment, each group was administered DEX at the same dosage. After 8-14 days, three groups were administered different dosages of DEX and then had blood samples taken to measure their ACTH levels each week for three weeks. For the second experiment, the same thing was done but blood glucose and electrolytes were also measured. After the initial treatments, the rats were placed under anesthesia and their adrenal glands were removed. 

Results

In experiment one, the first group of rats (control) that had only a DEX test done, showed decreased levels of ACTH after each test. All of the other groups that were also administered MIF along with DEX tests showed increased levels of ACTH. The results also indicated that higher doses of MIF increased levels of ACTH, which therefore implied that the higher levels would also stimulate the HPA axis. The third group of rats showed the best dose-response relationship and it was determined that the given amount to that group, 6mg/100g MIF was the best dosage of MIF. In the second experiment, the DEX group showed normal symptoms of hypercortisolism, while the DEX+MIF treated rats showed higher ACTH levels, normal blood glucose levels and blood pressure. This implies that the MIF treated rat showed an improvement in adrenal tissue function after removal surgery. Conclusion

This study was done in hopes of finding a solution to the treatment of ACTH-Independent Cushing’s Syndrome, which is generally an adrenalectomy. Due to the removal of the adrenal glands and hypercortisolism, the surrounding adrenal tissue can deteriorate and cause adverse effects. Other effects like hypoglycemia and diabetes mellitus caused by CS decrease the quality of life. MIF treatment was hypothesized to help all these symptoms and the study results show that the hypothesis was correct. Other studies will be needed to determine if this treatment can be effective on humans and help increase the quality of life for those affected by CS.  

Works Cited

Columbia , S. (2021). Cushing's Syndrome. Columbia Surgery. https://columbiasurgery.org/conditions-and-treatments/cushings-syndrome. 

Kirk, L. F., Hash, R. B., Katner, H. P., & Jones, T. (2000, September 1). Cushing's disease: Clinical manifestations and diagnostic evaluation. American Family Physician. https://www.aafp.org/afp/2000/0901/p1119.html.