What is the most likely diagnosis for a 55-year-old female showing symptoms of lethargy, constipation, and an enlarged thyroid with a low free T4?

The symptoms presented—lethargy, constipation, and an enlarged thyroid, combined with a low free T4 level—strongly indicate primary hypothyroidism. In this condition, the thyroid gland fails to produce sufficient thyroid hormones, leading to lower levels of free T4 in the bloodstream. The thyroid gland can often become enlarged due to compensatory mechanisms in response to low hormone production, which can be referred to as a goiter.

Lethargy and constipation are common symptoms associated with hypothyroidism due to the decreased metabolic rate and slowed gastrointestinal motility that occur with insufficient thyroid hormone levels. The combination of these clinical signs and laboratory findings points clearly toward primary hypothyroidism as the most likely diagnosis.

In contrast, secondary hypothyroidism typically involves low levels of TSH due to pituitary dysfunction, which would not typically present with an enlarged thyroid. Primary hyperthyroidism would be characterized by high levels of T4 and symptoms such as weight loss and palpitations instead, while secondary hyperthyroidism would also show elevated TSH levels. The clinical picture presented does not align with these conditions, solidifying the diagnosis of primary hypothyroidism as the most definitive choice.