Thyroid stimulating hormone (TSH) levels are now commonly used as the initial screening lab to assess thyroid function in patients. However, it is important for the clinician to remember that not all abnormal serum TSH values are due to common causes of primary hypothyroidism or thyrotoxicosis. Some are due to normal physiology, like TSH level variability due to age and ethnicity, or due to issues surrounding laboratory measurement of serum TSH. Other abnormal values can be transient and do not require thyroid replacement or ablative treatment, such as nonthyroidal illness. Still other causes, such as central hypothyroidism or a TSH secreting pituitary adenoma, once diagnosed will require further hormonal evaluation and possible genetic workup. It is important to have the correct differential diagnosis so that the appropriate diagnostic workup and treatment plan can be pursued. This chapter will give an overview of the different causes of abnormal serum TSH values not due to primary thyroid dysfunction (several of which are outlined in Fig. 6.1). It will also briefly discuss the clinical symptoms, biochemical findings, and treatment for these conditions.