The pituitary gland is an organ that has fascinated scientists and clinicians for centuries. The ancient Greeks believed that the pituitary drained waste products from the brain and secreted them as nasal mucus from the nose. There was remarkably little advance from this notion until the revolutionary discovery in the early 1930s of the neurosecretion of vasopressin and oxytocin from the posterior pituitary gland, and the demonstration of the primary importance of the anterior gland in the regulation of reproduction. It was a decade later that Geoffrey Harris and John Green suggested that nerve fibers in the hypothalamus secreted substances into the portal capillaries whence they were carried to the pituitary gland to excite or inhibit the activity of specialized secreting cells. After centuries of belief that it was a secretory organ, the pituitary became the "conductor of the endocrine orchestra" and subsequently, and more accurately, an amplifier for messages sent by the real conductor, the hypothalamus.
The first hypothalamic-releasing factor, thyrotropin-releasing hormone, was finally characterized by Roger Guillemin and Andrew Schally in 1971, rapidly followed by the other releasing factors. In 1977, the Nobel Prize for Medicine was awarded to them in recognition of this work. Since then, the identification of many other hypothalamic-releasing and -inhibitory factors has continued and to date almost 30 neuropeptides have been localized in the endocrine hypothalamus with neuroendocrine or neurotransmitter effects on hypothalamohypophyseal regulation. The CIBA Foundation has recently published an up-to-date review on this field, which we would recommend (Functional anatomy of the neuroendocrine hypothalamus, CIBA Foundations symposium 168, 1992, John Wiley).
Harvey Cushing stands as a giant in the history of pituitary disease. The founder of modern neurosurgery (in his surgical work, pioneering one of the transsphenoidal routes to the pituitary fossa) and a brilliant neurophysiologist, he made full and detailed descriptions of acromegaly and, of course, demonstrated the connection between the disease that bears his name and pituitary adenomas. Less well known, he also suggested that the patient with postpartum amenorrhea and persistent lactation might be secreting a lactogenic hormone, which has now been identified as prolactin.
Since Cushing's day, pituitary management has benefited significantly from a number of technological advances in three main fields. First, endocrinology, through radioimmunoassay, has led to the early diagnosis of disease caused by microadenomas and allowed us to assess the therapeutic value of the different treatments of the disease. Second, advances in computer imaging, initially with transmission computed tomography and now magnetic resonance imaging, have allowed anatomical diagnosis of microadenomas at a very early stage. Finally, the operating microscope and microinstruments have allowed surgeons to make enormous improvements in surgical technique.
In the UK, the interest in transsphenoidal surgery was rekindled after the World War II and hypophysectomy was used as endocrine control of the spread of hormone-sensitive secondary cancers, such as breast and prostate. As neurosurgery was developing in other directions at that time, otolaryngologists such as Angel-James in Bristol, Richards in Cardiff, and Williams in London developed the transethmoidal technique, gaining enormous experience at a time when endocrinologists were able to measure accurately and to a certain extent control pituitary diseases medically. It was only on the continent and in Canada, through the legacy of Cushing's trainees (Norman Dott, who taught Guiot in Paris, who taught Jules Hardy in Montreal), that transsphenoidal surgery remained in the neurosurgical domain.
The interest in radiation treatment of pituitary gland began after Carl Beck (1905) described positive treatment results with the use of Roentgen rays in "Basedow's syndrome." Two French physicians working separately, Gramagnea and Beclere, extended this work to the management of acromegaly associated with the "acidophil" pituitary tumor in 1909. During the succeeding 20 years, several reports confirmed the value of radiotherapy in the management of pituitary tumors. With the major advances in megavoltage equipment and other developments in medical physics, the superiority of high-energy X-rays and particle radiation compared with the lower-energy orthovoltage modalities, which were used in the early part of the century, have produced significant advances in the field of radiotherapy to the pituitary gland.
Successful medical management of pituitary tumors is a much more recent therapeutic advance. The use of dopamine agonists in the 1970s and more recently the development of somatostatin analogs have opened new noninvasive approaches to the treatment of pituitary tumors. This is clearly only the vanguard of new pharmacological approaches to pituitary disease.
Michael P. Powell, mb, bs, frcs
Stafford L. Lightman, mb, bchir, phd, frcp, fmedsci
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