Prolactinomas account for approximately 40% of all pituitary adenomas and are an important cause of hypogonadism and infertility. The ultimate goal of therapy for prolactinomas is restoration or achievement of eugonadism through the normalization of hyperprolactinemia and control of tumor mass. Medical therapy with dopamine agonists is highly effective in the majority of cases and represents the mainstay of therapy. Recent data indicating successful withdrawal of these agents in a subset of patients challenge the previously held concept that medical therapy is a lifelong requirement. Complicated situations, such as those encountered in resistance to dopamine agonists, pregnancy, and giant or malignant prolactinomas, may require multimodal therapy involving surgery, radiotherapy, or both. Progress in elucidating the mechanisms underlying the pathogenesis of prolactinomas may enable future development of novel molecular therapies for treatment-resistant cases. This review provides a critical analysis of the efficacy and safety of the various modes of therapy available for the treatment of patients with prolactinomas with an emphasis on challenging situations, a discussion of the data regarding withdrawal of medical therapy, and a foreshadowing of novel approaches to therapy that may become available in the future.

Pendred's syndrome is an autosomal recessive disorder characterized by sensorineural deafness, goiter, and impaired iodide organification. It is caused by mutations in the PDS/SLC26A4 gene that encodes pendrin. Functionally, pendrin is a transporter of chloride and iodide in Xenopus oocytes and heterologous mammalian cells and a chloride/base exchanger in ␤-intercalated cells of the renal cortical collecting duct. The partially impaired thyroidal iodide organification in Pendred's syndrome suggests a possible role of pendrin in iodide transport at the apical membrane of thyroid follicular cells, but experimental evidence for this concept is lacking. The iodide transport properties of pendrin were determined in polarized Madin-Darby canine kidney cells expressing the sodium iodide symporter (NIS), pendrin, or NIS and pendrin using a bicameral system-permitting measurement of iodide content in the basal, intracellular, and apical compartments. Moreover, we determined the functional consequences of two naturally occurring mutations (L676Q and FS306>309X). In polarized Madin-Darby canine kidney cells, NIS mediates uptake at the basolateral membrane. Only minimal amounts of iodide reach the apical compartment in the absence of pendrin. In cells expressing NIS and pendrin, pendrin mediates transport of iodide into the apical chamber. Wild type pendrin also mediates iodide efflux in transiently transfected cells. In contrast, both pendrin mutants lose the ability to promote iodide efflux. These results provide evidence that pendrin mediates apical iodide efflux from polarized mammalian cells loaded with iodide. Consistent with the partial organification defect observed in patients with Pendred's syndrome, naturally occurring mutations of pendrin lead to impaired transport of iodide.

Background:Lymphocytic hypophysitis is a disorder of the pituitary gland that presents as a sellar mass lesion and/or hypopituitarism. It causes pituicyte destruction and hypopituitarism and is speculated to have an autoimmune basis. Diagnosis: Lymphocytic hypophysitis should be considered in the differential diagnosis of pituitary masses and/or hypopituitarism in females who are pregnant or in the early postpartum period, especially in cases associated with other autoimmune diseases or unusual patterns of hormone deficiencies. A definitive diagnosis requires tissue biopsy. A presumptive clinical diagnosis can be made based on a history of gestational or postpartum hypopituitarism, a contrast-enhancing sellar mass with imaging features characteristic of lymphocytic hypophysitis, a pattern of pituitary hormone deficiency with early loss of adrenocorticotrophic hormone and thyroid-stimulating hormone unlike that typically found with macroadenomas, relatively rapid development of hypopituitarism and a degree of pituitary failure disproportionate to the size of the mass.Symptoms resulting from partial or panhypopituitarism occur in approximately 80% of cases and multiple deficiencies are found in approximately 75% of cases. Management:Appropriate management remains controversial. Corticosteroid therapy has been advocated as a means of attenuating inflammation, but given the uncertainty of its efficacy and the known adverse effects, such therapy does not seem justified for most patients. The optimal surgical strategy involves partial resection of the mass to decompress the surrounding structures. All patients with lymphocytic hypophysitis require appropriate replacement therapy for deficient hormones. Long-term follow-up is mandatory to monitor for the development of other hormonal deficits.

Most prolactinomas respond rapidly to low doses of dopamine agonists. Occasionally, stepwise increases in doses of these agents are needed to achieve gradual prolactin (PRL) reductions. Approximately 50% of treated men remain hypogonadal, yet testosterone replacement may stimulate hyperprolactinemia. A 34-yr-old male with a pituitary macroadenoma was found to have a PRL level of 10,362 micro g/liter and testosterone level of 3.5 nmol/liter. Eleven months of dopamine agonist therapy at standard doses lowered PRL levels to 299 micro g/liter. Subsequent stepwise increases in cabergoline (3 mg daily) further lowered PRL levels to 71 micro g/liter, but hypogonadism persisted. Initiation of testosterone replacement resulted in a rise and discontinuation in a fall of PRL levels. Aromatization of exogenous testosterone to estradiol and subsequent estrogen-stimulated PRL release was suspected. Concomitant use of cabergoline with the aromatase inhibitor anastrozole after resuming testosterone replacement resulted in the maintenance of testosterone levels and restoration of normal sexual function, without increasing PRL. Ultimately, further reduction in PRL on this therapy permitted endogenous testosterone production. Thus, novel pharmacological maneuvers may permit successful medical treatment of some patients with invasive macroprolactinomas.

Normal thyroid function is essential for development, growth, and metabolic homeostasis. The prerequisites for an euthyroid metabolic state include a normally developed thyroid gland, a properly functioning system for thyroid hormone synthesis, and sufficient iodine intake. Defects in any of the essential steps in thyroid development or thyroid hormone synthesis may result in morphologic abnormalities and impaired hormonogenesis. These defects can be partial or complete, leading to varying degrees of hypothyroidism. Morphologic alterations associated with congenital hypothyroidism include the absence of detectable thyroid tissue, ectopic tissue, thyroid hypoplasia, or a goitrous thyroid. However, in some patients with hypothyroidism, the thyroid is of normal size. This article focuses on defects in thyroid development. Recent insights into the developmental regulation of the calcitonin-producing C cells will not be discussed, and defects in hormone synthesis are discussed in an accompanying article.