To assesses the frequency and degree of pituitary hyperplasia in patients with primary hypothyroidism, the association of pituitary enlargement with disease severity, and the response to treatment. Between April 2002 and August 2004 at the National Center for Diabetes, Endocrinology and Genetics in Amman, Jordan, 53 patients (49 female and 4 male subjects) with primary hypothyroidism and serum thyrotropin (thyroid-stimulating hormone or TSH) levels of > or = 50 microIU/mL were encountered. Initial and follow-up investigations included thyroid function tests, serum prolactin levels, and magnetic resonance imaging (MRI) of the pituitary. Visual field examination was requested for all patients with pituitary enlargement (and adequately completed in 24). Pituitary enlargement on MRI was found in 37 of the 53 patients (70%), with 31 of the 37 patients (84%) having TSH levels of > or = 100 microIU/mL. After thyroxine treatment, 85% of the patients with pituitary enlargement who underwent a follow-up MRI showed a decrease in size of the gland. About half of the patients were referred to our facility with the diagnosis of hypothyroidism; presenting features in the rest of the patients included galactorrhea, menstrual irregularities, learning disability, short stature, precocious puberty, ovarian hyperstimulation syndrome, headaches, visual field defects, and dry ichthyotic skin. The association between pituitary gland enlargement and primary hypothyroidism should be kept in mind when pituitary hyperplasia is detected on MRI, before unwarranted and drastic interventions are initiated.