Day 70 MCAT Practice Question

Endocrine System

Ectopic Cushing’s syndrome is a rare condition caused by an ACTH-secreting tumor

outside the pituitary gland, such as in the lungs or pancreas. These tumors, known

as ectopic ACTH-secreting tumors, disrupt the normal functioning of the endocrine

system and lead to a wide range of physiological disturbances.

In a healthy individual, the hypothalamus secretes corticotropin-releasing hormone

(CRH), which stimulates the anterior pituitary gland to produce adrenocorticotropic

hormone (ACTH). ACTH then acts on the adrenal cortex, signaling the release of

cortisol, a glucocorticoid hormone that regulates various metabolic processes.

Cortisol exerts negative feedback on both the hypothalamus and the anterior

pituitary, maintaining homeostasis.

However, in the case of an ectopic ACTH-secreting tumor, the neoplastic cells

continuously produce ACTH, bypassing the normal regulatory mechanisms. The

excessive ACTH stimulation leads to the overproduction of cortisol by the adrenal

glands, resulting in hypercortisolism. The persistently elevated cortisol levels have

systemic effects, including hyperglycemia, muscle wasting, osteoporosis, and

immunosuppression.



One of the most significant consequences of ectopic Cushing’s syndrome is its

impact on the cardiovascular system. Cortisol enhances the sensitivity of vascular

smooth muscle cells to the effects of catecholamines, leading to increased

peripheral vascular resistance and hypertension. Moreover, cortisol promotes

the retention of sodium and water in the kidneys, further contributing to the

development of hypertension and fluid overload.



The diagnosis of ectopic Cushing’s syndrome involves a combination of biochemical

tests and imaging studies. Dexamethasone suppression tests can help differentiate

between pituitary-dependent and ectopic sources of ACTH. Additionally, imaging

techniques such as CT scans, MRI, and PET scans are used to localize the ACTHsecreting tumor.

Treatment of ectopic Cushing’s syndrome primarily focuses on the surgical removal

of the ACTH-secreting tumor. If the tumor cannot be located or is inoperable,

medications such as ketoconazole or metyrapone may be used to inhibit cortisol

synthesis. In some cases, bilateral adrenalectomy may be necessary to control the

excessive cortisol production.

Cortisol exerts its effects on target cells by:

A) Binding to G protein-coupled receptors on the plasma membrane

B) Directly activating ion channels on the plasma membrane

C) Binding to intracellular receptors and regulating gene expression

D) Initiating the phosphorylation cascade of receptor tyrosine kinases