In the last 50 years there have been great advances in the field of central thyroid disorders. However, despite important developments, such as the introduction of ultrasensitive TSH assays and improvements in pituitary imaging studies, diagnosing and uncovering the aetiology of both central hyper- and hypo-thyroidism remains challenging in many cases. This thesis adds data to the existing literature generated from studies in large cohorts of patients with TSH secreting pituitary tumours (TSHoma) and describes novel methods for pituitary imaging using functional imaging. Lastly, functional studies of a novel mutation in the TRHR gene giving rise to central congenital hypothyroidism (CCH) are presented. In the first chapter, an overview of central disorders of thyroid function are discussed with emphasis on TSHomas and congenital central hypothyroidism. Pituitary imaging modalities are also discussed with emphasis on functional pituitary imaging. The second chapter describes the methods applied during the conduct of the presented research studies and these methods are elucidated in more detail in each subsequent chapter. In the third chapter, results from a prospective observational study involving 31 consecutive patients with TSHoma are presented and contrasted to a large cohort of patients with RTHbeta as well as healthy euthyroid volunteers. In the fourth chapter, phenotypic differences among patients harbouring micro- versus macro-TSHomas are presented. The second part of this chapter discusses the response of TSHomas to primary medical therapy with somatostatin analogues (SSA).
In the fifth chapter, the application and findings of functional pituitary imaging with the radioactive tracer 11C-Methionine are presented; this approach has been applied to all pituitary adenoma subtypes, including TSH secreting adenomas. In the last chapter, functional studies of a novel mutation in the TRHR gene are presented. This mutation was discovered in a child with isolated congenital central hypothyroidism.