Figure 17-3: Mild iodine deficiency associated or not with smoking, presence of natural goitrogenic, drugs, familial goiter, genetic markers and gender (women) will decrease the inhibition of serum T4 on the pituitary thyrotrophs. Increased TSH production will cause Diffuse goiter followed by nodule formation. Finally, after decades of life, a large multinodular goiter is present with cystic areas, hemorrhage, fibrosis and calcium deposits.