**Core Concept**
Thyrotoxicosis is a clinical syndrome resulting from excessive levels of thyroid hormones in the body, which can be caused by various conditions such as Graves' disease, thyroiditis, or excessive intake of thyroid hormone medication. The primary pathophysiological mechanism involves the overproduction of thyroid hormones, leading to increased metabolic rate, cardiovascular effects, and various systemic symptoms.

**Why the Correct Answer is Right**
The most common symptom of thyrotoxicosis is weight loss, despite increased appetite, due to the accelerated metabolic rate caused by elevated levels of triiodothyronine (T3) and thyroxine (T4). This increased metabolic rate leads to enhanced cellular activity, resulting in increased energy expenditure and subsequent weight loss. The heightened metabolic rate also contributes to other symptoms such as palpitations, tremors, and heat intolerance.

**Why Each Wrong Option is Incorrect**
**Option A:** Although palpitations are a common symptom of thyrotoxicosis, they are not the most frequent symptom. Palpitations are primarily related to the increased heart rate and contractility caused by the high levels of thyroid hormones.
**Option B:** Heat intolerance is a symptom of thyrotoxicosis, but it is not the most common symptom. Heat intolerance is related to the increased metabolic rate and is often accompanied by sweating and flushing.
**Option C:** Fatigue is not typically associated with thyrotoxicosis; instead, patients often report increased energy and activity levels due to the elevated metabolic rate.

**Clinical Pearl / High-Yield Fact**
It's essential to remember that weight loss in the context of thyrotoxicosis is often accompanied by other symptoms such as increased appetite, heat intolerance, and tremors, which can help distinguish it from other conditions causing weight loss.

**Correct Answer: D. Weight loss**