Which manifestation(s) are characteristic of Cushing's syndrome? Select all that apply.
Fragile skin.
Muscle wasting.
Moon face.
Hypoglycemia.
Weight loss.
Correct Answer : A,B,C
Choice A rationale
Fragile skin is a characteristic manifestation of Cushing's syndrome due to the catabolic effects of excess cortisol. Cortisol inhibits the synthesis of collagen and connective tissue, leading to thinning of the dermis. This makes the skin prone to easy bruising, slow wound healing, and the development of wide, purple striae, particularly on the abdomen. The loss of structural integrity in the skin is a direct result of the prolonged hypercortisolemia affecting protein metabolism.
Choice B rationale
Muscle wasting is caused by the high levels of cortisol promoting the breakdown of proteins, especially in the extremities. Cortisol stimulates gluconeogenesis by mobilizing amino acids from skeletal muscle. This leads to the characteristic thin arms and legs seen in patients with Cushing's syndrome. This proximal muscle weakness can make it difficult for patients to perform basic tasks, such as rising from a chair or climbing stairs, due to the significant loss of muscle mass.
Choice C rationale
Moon face refers to the rounded, plethoric facial appearance that occurs in Cushing's syndrome. This is caused by the abnormal redistribution of fat triggered by chronic glucocorticoid excess. Cortisol promotes lipogenesis in specific areas, leading to fat accumulation in the face, the supraclavicular regions, and the posterior cervicodorsal area, often called a buffalo hump. This facial rounding is one of the most recognizable clinical signs used to diagnose the presence of hypercortisolism.
Choice D rationale
Cushing's syndrome does not cause hypoglycemia; instead, it causes hyperglycemia. Cortisol is a counter-regulatory hormone that opposes the action of insulin and increases blood glucose levels by stimulating the liver to produce glucose and decreasing the sensitivity of peripheral tissues to insulin. Therefore, patients with Cushing's syndrome often develop secondary diabetes mellitus or impaired glucose tolerance, with blood sugar levels consistently remaining above the normal fasting range of 70 to 99 mg/dL.
Choice E rationale
Weight loss is not associated with Cushing's syndrome. In fact, generalized weight gain and central obesity are hallmark features of the condition. While the limbs may appear thin due to muscle wasting, the trunk and face accumulate significant adipose tissue. This truncal obesity, combined with a moon face and buffalo hump, creates the classic Cushingoid appearance. Weight loss would be more indicative of adrenal insufficiency, also known as Addison's disease, which is the opposite of Cushing's.
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Correct Answer is C
Explanation
Choice A rationale
Addison's disease involves the destruction of the adrenal cortex, leading to a profound deficiency in mineralocorticoids, primarily aldosterone. Aldosterone normally functions to promote sodium reabsorption and potassium excretion in the distal renal tubules. In its absence, the kidneys fail to excrete potassium effectively, leading to hyperkalemia, not hypokalemia. The normal serum potassium range is 3.5 to 5.0 mEq/L, and patients with Addison's often exceed the 5.0 mEq/L threshold.
Choice B rationale
A deficiency in aldosterone leads to significant renal wasting of sodium and water, resulting in a depleted intravascular volume. Additionally, the lack of cortisol reduces the sensitivity of the vascular smooth muscle to catecholamines, which normally maintain systemic vascular resistance. This combination of hypovolemia and impaired vascular tone leads to chronic hypotension and orthostatic dizziness. Hypertension is not a characteristic of adrenal insufficiency; rather, it is more commonly associated with excess adrenal hormones.
Choice C rationale
Cortisol is a primary glucocorticoid that plays a vital role in maintaining blood glucose levels by stimulating gluconeogenesis in the liver and antagonizing the effects of insulin in peripheral tissues. In Addison's disease, the lack of cortisol impairs these metabolic pathways, especially during periods of fasting or stress. This leads to fasting hypoglycemia. Normal fasting blood glucose ranges between 70 to 99 mg/dL, but Addisonian patients may frequently fall below this level.
Choice D rationale
Due to the lack of aldosterone, the renal tubules cannot adequately reabsorb sodium, which is then lost in the urine along with water. This process results in hyponatremia, characterized by low serum sodium levels. The normal range for serum sodium is 135 to 145 mEq/L. Patients with Addison's disease typically present with levels below 135 mEq/L, often accompanied by salt craving. Hypernatremia is inconsistent with the pathophysiology of primary adrenal insufficiency.
Correct Answer is A
Explanation
Choice A rationale
Addison's disease is a primary adrenal insufficiency caused by the destruction of the adrenal cortex, resulting in a deficiency of cortisol and aldosterone. Cortisol is vital for the stress response and glucose metabolism, while aldosterone regulates sodium and potassium balance. Without these hormones, patients experience hyponatremia, hyperkalemia, and hypotension. The lack of negative feedback leads to increased ACTH production, often causing skin hyperpigmentation. Lifelong hormone replacement is required to prevent an adrenal crisis.
Choice B rationale
The overproduction of growth hormone is associated with the pituitary gland and leads to acromegaly or gigantism, depending on whether the epiphyseal plates have closed. This condition affects bone growth and soft tissue expansion but does not involve the adrenal hormones cortisol or aldosterone. Addison's disease is specifically an adrenal cortex failure. While both are endocrine disorders, their pathophysiology, clinical manifestations, and hormonal pathways are entirely distinct and involve different master regulatory organs.
Choice C rationale
A lack of insulin production is the pathophysiology of type 1 diabetes mellitus, which occurs due to the destruction of beta cells in the islets of Langerhans within the pancreas. Addison's disease involves the adrenal glands, not the pancreas. While Addison's disease can lead to hypoglycemia because cortisol is a counter-regulatory hormone that normally raises blood sugar, the primary defect is not related to insulin secretion or the body's ability to process carbohydrates via the pancreatic pathway.
Choice D rationale
The overproduction of parathyroid hormone is known as hyperparathyroidism, which originates in the parathyroid glands. This condition primarily disturbs calcium and phosphate homeostasis, often leading to hypercalcemia and bone resorption. Addison's disease does not involve the parathyroid glands or calcium regulation as its primary defect. The focus of Addison's disease is the life-threatening deficiency of steroid hormones from the adrenal cortex, which is essential for maintaining hemodynamic stability and electrolyte concentrations.
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