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Our better understanding of the morphologic spectrum of renal cortical tumors has resulted in a clinically more relevant classification of these tumor types. We now recognize that "granular cell" and "sarcomatoid" renal cell carcinoma are only nonspecific descriptors, and that such features are seen in a variety of types of renal tumors. The authors believe that the recently gained knowledge about molecular-driven antigen expression will play an important role in the characterization, development, and evaluation of targeted therapies in kidney cancer in the coming years.

Two rare cases of pituitary adenoma with neuronal choristoma are described. Both patients were female and presented with features of acromegaly with elevated growth hormone and prolactin levels. Radiologically, both lesions were predominantly intrasellar in location with extension into suprasellar region, but hypothalamus was not involved. Histopathological examination revealed a mixture of chromophobe pituitary adenoma cells and neuronal cells. In both cases, the adenoma component was positive for growth hormone and prolactin. Interestingly, immunopositivity for alpha-subunit, cytokeratin and prolactin was seen in the adenoma and neuronal cells in one case. Our findings support the hypothesis that the neuronal cells possibly arise from adenoma cells as a result of metaplasia.

CASE REPORT We have experienced a case in which surgical removal of a pituitary tumor from a male patient was followed by the occurrence of hyponatremia, which in turn was later associated with central pontine myelinolysis (CPM). A 4 X 3 X 3 cm pituitary tumor with hypothalamic extension was removed via a transsphenoidal approach. The post-operative course was uneventful until severe hyponatremia developed. To avoid drastic correction of electrolyte levels, reestablishment of normal serum levels was spread over 1 week. Following this, however, various neurologic symptoms such as pseudobulbar palsy, quadriplegia, extrapyramidal symptoms, and mental symptoms appeared. The case was diagnosed as CPM and extrapontine myelinolysis (EPM) on the basis of the clinical course and symptoms, and high-dosage steroid therapy was commenced. RESULTS There was consequent gradual improvement in symptoms. One month later, MRI revealed typical demyelination lesions in the central pons and striatum. Abnormal electrolyte conditions easily occur in pituitary tumors associated with hypothalamic extension in an altered hormone environment. It is known that CPM and EPM result from drastic correction of hyponatremia. CONCLUSIONS The frequent measurement of electrolytes and cautious correction of sodium imbalance are important for the prevention of CPM and EPM in the postoperative management of patients who undergo surgery for a pituitary tumor and whose high-dosage steroid therapy are effective.

There are many reports about complications of transphenoidal surgery for pituitary adenomas. We report a patient who suffered severe subarachnoid hemorrhage due to an indirect injury of the intradural internal carotid artery during or immediately after transsphenoidal surgery for pituitary adenoma. An autopsy suggested that a small branch of the intradural internal carotid artery was strongly adherent to the suprasellar portion of the tumor capsule and its avulsion from the internal carotid artery might have been caused as the capsule fell down during the intracapsular removal of the tumor. In a case of pituitary adenoma operated by the transsphenoidal approach the possibility of subarachnoid hemorrhage due to this type of arterial injury, though rare, should be kept in mind.

A 62 year old female died of a chromophobe pituitary adenoma of the sphenoid bone. A normal pituitary gland was present within the sella turcica. She also had a chief cell parathyroid adenoma, a papillary thyroid carcinoma, and an ovarian thecoma (multiple endocrine neoplasia syndrome).

Pituitary prolactin (PRL) secretion was evaluated in 65 galactorrheic individuals with nonfunctioning hypothalamic-pituitary tumors, acromegaly, prolactin-secreting tumors, Chiari-Frommel syndrome, Argonz-del Castillo syndrome, history of phenothiazine or α-methyldopa intake, primary hypothyroidism, use of contraceptive medications, and in patients with idiopathic galactorrhea. Mean serum prolactin concentrations in patients with prolactin-secreting pituitary tumors were significantly higher than those in other groups but over all there was no correlation between the serum prolactin levels and the grade of galactorrhea. Neither a single elevated serum prolactin level nor the degree of suppressibility after L-dopa administration was diagnostic of a pituitary tumor. However, a history of consistently high serum prolactin concentrations was highly indicative of a prolactin-secreting tumor.

S INCE Dr Edward Ellison’s reign as Chairman of Surgery at the Medical College of Wisconsin from 1958 to 1970, a deep interest has existed at our institution in hyperfunctioning islet cell lesions of the pancreas, Our charge in this report is to discuss the salient features of multiple endocrine neoplasia, Type 1 (MEN I) syndrome, which includes islet cell pancreatic lesions as a major component, and to review the different types of isolated sporadic islet cell pancreatic tumors. Although the MEN I syndrome and isolated pancreatic islet cell tumor are relatively rare, patients with these conditions are being recognized with increasing frequency due to the current general availability of hormone radioimmunoassays. Most radiologists who practice at major hospitals will likely encounter one or more patients with the clinical features of the MEN I syndrome or of a sporadic islet cell tumor. A high index of suspicion is essential to make an accurate diagnosis of the condition, leading to appropriate management of the patient and screening of his family. Since 1960, we have evaluated 66 individuals from among 200 kindred of two families with the MEN I syndrome. Data from the larger of the two families spans five generations.’ Evidence collected to date indicates that 21 individuals in this family have the syndrome (Fig 1). Of these individuals, 12 exhibited biochemical or morphologic evidence, or both, of islet cell neoplasm or hyperplasia. During the past two decades, we have also evaluated 50 isolated patients with sporadic nonfamilial islet cell lesions. Of these, 48 had a functioning neoplasm or hyperplasia while two had a nonfunctioning tumor.

analysis may bias the sample toward higher mortality by including deceased siblings and because of failure to identify the very mild cases. In addition, the sample may have been biased toward lower mortality by omission of those severely affected patients who died prior to diagnosis. Our data are prospective and based on a growing population which is being treated actively. With increased public and professional awareness of the disease, it is possible that our population includes milder cases. However, this same population is known to have progressive neurologic ~~ and renal disease, l~ Sex does not seem to make a significant contribution to prognosis. It remains to be seen if various disease manifestations, such as frequency of vomiting crises, repeated pneumonias, or degree of spinal curvature are factors influencing probability of survival. As familial dysautonomia can no longer be considered only a disease of childhood, greater awareness of the disorder among the general medical community is indicated. Despite physical and emotional developmental lags, intelligence has a normal distributional spread, including some in the superior range) 2, ~3 The ability to achieve at least a basic education and to hold a job should be considered realistic goals. Retarded physical size, easy fatiguability, o r even orthopedic deformity may deter peer and community acceptance. Often a physical handicap is falsely equated with mental deficiency, and appropriate employment opportunities are not always available. It is not enough to prolong life; there is also a responsibility to improve the quality of life. The dysautonomic patient does have the potential of becoming an independen t functioning adult. For more patients to achieve this potential, further strides will have to be made in the care of the child, and the medical community will have to be prepared to receive the adult. In addition, the general expectations of educators and parents, as well as of the patients themselves, will have to be expanded so that sufficient opportunities will be available to nurture social and emotional growth.

The records of the Radiotherapy Division of the Radiology Department of Vanderbilt University Hospital were reviewed for the period 1952–1970. During those 19 years 45 patients with a well-documented diagnosis of Cushing's disease were treated initially by external irradiation of the pituitary. All of the patients were treated with megavoltage equipment using photons. When the results of irradiation are compared against total doses of radiation, it is evident that the control rate is unsatisfactory at doses less than 4000 rad and the maximum benefits of irradiation are evident in the 4500–5000 rad dose range. It is also clear that the complication rate increases as the dose exceeds 4800 rad. If the various treatment regimens of irradiation are converted to “equivalent” doses by the Nominal Standard Dose (NSD) or Time-Dose-Fractionation (TDF) methods, the relationship between “dose” and efficacy of therapy and complications is demonstrated. In order to reduce the possibility of treatment-related morbidity, the use of three or more small (4 × 4 cm) treatment portals or rotational techniques is recommended to a pituitary dose of 4600–5000 rad treating 5 days a week for 5–6 weeks.

Radioimmunoassay (RIA) has provided the tools for wide-reaching investigations that have changed and continue to change many important concepts of thyroid physiology and pathosphysiology. The RIA for human thyrotropin (TSH) was developed in 1965; development of the RIA for triiodothyronine (T 3 ), thyroxine (T 4 ), thyroxine-binding globulin (TBG), and, recently, thyrothropin-releasing hormone (TRH) and thyroglobulin (Tg) followed. The capacity to measure nanogram and picogram concentrations with relative ease and speed has permitted the demonstration of dynamic relationships of the intrathyroidal and circulating thyroid hormones to each other and to the pituitary and hypothalamic regulating hormones. Evidence for the presence of cross-influences between TRH and other hypothalamic regulating hormones on the secretion of pituitary hormones has accumulated. The impact of the new information on clinical practice is now becoming evident. There is new appreciation of the value of assaying serum T 3 and TSH concentrations in the clinical management of patients with disturbed function of the thyroid, pituitary, or hypothalamus. The necessary components for RIA performance can be purchased separately or in kit form from commercial sources. With appropriate quality-control procedures, precise, sensitive, and reliable data can be generated. Awareness of the specific technical problems relating to the RIA of these hormones is absolutely necessary to assure reliable results. The availability of kits or their components permits the performance of these studies in the community hospital and in reliable commercial-service laboratories.

A patient with multiple cutaneous hemangiomas and skeletal dyschondroplasia (the Maffucci syndrome) was found to have a pituitary chromophobe adenoma, a parathyroid adenoma and two other neoplasms. The presence of two endocrine tumors suggested the syndrome of multiple endocrine adenomatosis, and raised the issue of an etiologic relationship between this disease and the Maffucci syndrome. Dyschondroplasia, however, has no known influence on the secretion of parathyroid hormone or any of the pituitary hormones. The Maffucci syndrome is associated with a high incidence of malignancy, but it involves primarily mesodermal derivatives, whereas multiple endocrine adenomatosis affects tissues of ectodermal origin. The association of the two in our patient is probably fortuitous.

A 37-year-old woman presented with a proven case of malignant fibrous histiocytoma of the skull. This is thought to be a rare complication of post-radiation to a chromophobe adenoma which was treated by radiotherapy nine years previously. The radiation dose given to the sella region after the removal of the chromophobe adenoma was 4500 cGy.

In the present paper the microsurgical, fronto-temporal technique for the surgical treatment of chromophobe pituitary adenomas with extra-sellar extension is described in detail. The complete treatment of expansive chromophobe adenomas includes 4000 rad of external irradiation by the rotation technique and hormonal replacement therapy. The results of this treatment in 36 consecutive patients from 1971 through 1975 are given. There is no mortality nor recurrence of tumor in the follow-up period. The postoperative morbidity is low, especially in the group operated by the microsurgical fronto-temporal approach. The visual acuity improved or normalized in 86%, for the visual fields this percentage was 90%. These results are compared to those of our own series of 65 patients, treated from 1945 through 1959, and to some other data from the literature. Finally, some arguments in favour of the intracranial approach versus the transsphenoidal approach are presented.

The records of the Radiotherapy Division of the Radiology Department of Vanderbilt University Hospital were reviewed for the years 1952-71. During that period of time, 122 patients with diagnosis of pituitary adenomas were treated by external irradiation. A variety of techniques (2 or 3 stationary fields, 180° rotational fields), equipment ( 60 Co, 6 MeV Linac) and fractionation schedules (treating 4, 5 or 6 days per week, doses ranging between 150 and 280 rad per fraction), were used. Five patients developed severe complications: 1 with brain necrosis and 4 with blindness related radiation damage to optic pathways. From analysis of time-dose factors (TDF), it is evident that the risk of complications increases from 0% to 25% as the dose exceeds a TDF of 80. Although a significant increase in success rate has resulted from doses in excess of 3500 rad, there is little support for believing that doses in excess of 5000 rad (TDF 80) achieve improved results.

The patient presented with poor vision (particularly OS) which had declined progressively over ten years. He had had bifrontal headaches over the past two years. Examination and visual field testing showed optic atrophy and a bitemporal hemianopia. Procedures leading to the diagnosis of pituitary adenoma are discussed, as are treatment modalities and association of pituitary adenomas with other entities.

The unopposed continuous administration of biologically active estrogenic materials produces a wide variety of cancers in experimental animals. Most of these cancers occur in the target tissues for estrogenic activity and appear to be characteristic of the animal rather than the estrogens. In mice and rats the most commonly induced tumor is breast cancer, followed by pituitary chromophobe adenoma, bladder cancer, tumors of the lymphatic system, adrenal tumors, etc. The characteristic tumor occurring in the hamster under these circumstances is clear cell cancer of the kidney. The dog appears to be an exception in that the continuous administration of estrogenic materials does not lead to such tumors but the administration of certain progestogens leads to the production of mammary tumors. Cancers of the cervix occur largely in mice while cancers of the uterine corpus are seen in rabbits. Laboratory primates appear to be remarkably resistant to the carcinogenic effect of steroids, either individually or in combination. In man, there is the suggestion that androgens given for long periods to stimulate erythropoiesis or oral contraceptives in combination with estrogen may be capable of producing benign hepatomas. In man there is also the suggestion that continuous administration of estrogen may produce adenocarcinoma of the corpus uteri and that women who are exposed to very high doses of synthetic estrogen during their intrauterine development have subsequently developed both benign adenosis and clear cell cancer of the vagina.

A review of a series of 1,550 pneumoencephalograms showed that the ventricles failed to fill in 48 patients (3.1%), in whom a tumour or obstructive lesion was present in 18 (37.5%). Possible causes for the non-filling of the ventricular system are discussed. Emphasis is placed upon filling of the pericallosal cisterns, as their position accurately indicates the size of the lateral ventricles.

The serum growth-hormone response to insulin-induced hypoglycemia has been measured in control subjects and patients with dwarfism of various causes. The normal response has been defined and applied to the assessment of growth-hormone function in patients with growth retardation. Definitive evaluation of growth-hormone responsiveness was possible in 58 of 59 patients with dwarfism.

The author discusses some of the problems of tumour diagnosis and localisation within the skull. Nine case histories and their radiological investigation are presented in order to illustrate these problems and to indicate how radiology may help to solve them.

The author reviews the historical aspects of the radiotherapy of pituitary tumours and then analyses the results of treatment at Sheffield between 1940 and 1963. One hundred and sixty eight pituitary tumours were treated. The Chromophobe adenomas and the Acidophil adenomas are analysed in detail. In the first group, surgery alone achieved a 30% 4 year recurrence free rate, radiotherapy alone a 75% 4 year recurrence free rate and a combination of surgery and post-operative radiotherapy produced a 93% 4 year recurrence free rate. Patients with Eosinophil adenomas can be relieved of their symptoms but their life expectancy is not improved.

The pattern of hormone secretion of human pituitary adenomas in culture has been compared with hormone production by cultures of normal human pituitaries. Normal pituitaries and pituitary adenomas were placed in primary explant culture and dispersed cell subcultures and maintained for periods up to one year. Five normal pituitaries initially produced large amounts of immuno-reactive growth hormone (GH), luteinizing hormone (LH), and thyrotropin (TSH), but production of these hormones fell rapidly and was undetectable after 125 days in vitro. In contrast, cultures of adenomas from four acromegalic patients produced GH for up to one year. Cultures of adenoma tissue from five patients with hypopituitarism produced LH and/or TSH.

Thyroid-function studies were performed in 12 patients with active acromegaly. 1 patient had thyrotoxicosis, the rest were considered euthyroid although 3 of them had abnormal thyroid scans. All patients had a normal serum thyroid-stimulating-hormone (T.S.H.) level. The euthyroid group had renal and thyroid iodide clearances significantly greater than normal (P

1. 1. One hundred and two electroencephalograms from 59 patients with a pituitary chromophobe adenoma and 32 EEG's from 17 patients with a Rathke pouch cyst have been reviewed. 2. 2. The records of those with a pituitary chromophobe adenoma could be divided as follows: the bulk of the records showed a clear theta rhythm (4–7 c/sec.) which was often asymmetrical. Of the remainder, 10 were normal or borderline normal; 9 were of low voltage; and 3 showed generalized delta waves. 3. 3. Although similar features occurred among some of the patients with a Rathke pouch cyst, recordings in the presence of a Rathke pouch cyst frequently showed bilaterally synchronous rhythmic delta bursts (1.5–2.5 c/sec.) such as were only once observed with a pituitary chromophobe adenoma. 4. 4. Serial EEG's have been obtained in many of these patients, and it has usually been possible to demonstrate recession of the abnormal activity with hormone replacement therapy (cortisone, thyroid and sometimes testosterone). It is known that symmetrical theta activity may occur as a manifestation of suprarenal failure and that it can be dispersed by treatment with cortisone. 5. 5. It is our belief that many of the EEG abnormalities commonly ascribed to pituitary tumour are in fact caused by associated endocrine deficiencies. However, it seems possible that the asymmetries of the record in these patients are associated with asymmetrical pressure upon structures at the base of the brain. 6. 6. The possible value of the EEG in the diagnosis and management of these patients is discussed.

These radioimmunoassay studies were designed to test three hypotheses: (1) prolactin plays a major role in regulation of mammary function; (2) in the normal woman, prolactin is not a major obligatory factor in gonadal and menstrual cycle regulation; and (3) assessment of alterations in circulating prolactin concentration in response to stimulatory agents is useful in the evaluation of the hypothalamic-pituitary axis. (1) During pregnancy, serum prolactin increased progressively to term. Suckling resulted in a prompt increase in prolactin concentrations. (2) Daily prolactin determinations during the menstrual cycle revealed no cyclic pattern and no significant daily variation. (3) Increase in prolactin response to TRF in nine patients with idiopathic galactorrhea, eight of whom had amenorrhea, was similar to that observed in normal control subjects. Administration of l -dopa resulted in a decrease in prolactin in normal women, women with idiopathic galactorrhea, women following hypophysectomy, a patient with primary hypothyroidism, and in a patient with a chromophobe adenoma. These data support the validity of the first two hypotheses and suggest that further studies on the response to administration of hypothalamic-releasing factors may be useful clinical tools to distinguish neoplastic from nonneoplastic states.

A patient is presented in whom global dementia was the initial clinical manifestation of pituitary adenoma in the absence of visual or endocrine symptoms or signs of increased intracranial pressure. The tumor had partially obstructed the flow of cerebrospinal fluid (CSF) resulting in low-pressure hydrocephalus, manifesting as dementia, urinary incontinence and a characteristic motor disorder found on clinical examination. This is the first reported instance, to our knowledge, of pituitary adenoma causing low-pressure hydrocephalus. It is postulated that transventricular absorption of CSF accounted for the normalization of the patient's intraventricular pressure. Clinical and experimental evidence in support of this contention is briefly reviewed.

The authors describe 100 consecutive patients who were eventually diagnosed as suffering from a variety of space occupying lesions in and around the sella. Their radiological examinations have been analysed by being broken down into a variety of individual signs, and the significance of some of these individual signs has been assessed. Tables have been constructed to demonstrate the frequency of these radiological signs in the different lesions. As a result a few generalisations are made about the clinical and radiological management of such cases. More comprehensive analysis is being attempted by computer methods.

During necropsy the pituitary stalk is usually deliberately divided and the median eminence is separated from the posterior pituitary. In a series of 133 necropsies the brain was removed in a manner that preserved the integrity of the neurohypophysis and allowed histological examination of the entire neurohypophysis and the juxtaposed adenohypophysis. Neurosecretory bodies were found within the neurohypophysis in 2 patients,and in both microadenomas were found within the adenohypophysis. 2 other patients had larger tumours within the adenohypophysis but had no abnormalities within the neurohypophysis.

Both in vivo and in vitro responses of prolactin and growth hormone to stimuli were studied in an acromegalic, amenorrheic woman with a chromophobe adenoma of the pituitary gland. Preoperative testing revealed a prolactin rise after thyrotropin-releasing hormone and chlorpromazine and a decline after l -dopa and bromocriptine administration. During 3.5-hour incubations, cultured tumor cells produced significant increases of growth hormone and prolactin after dibutyryl adenosine 3',5'-cyclic monophosphate stimulation, while bromocriptine inhibited both hormones.

Bromocriptine therapy may cause regression of prolactinomas, but its effect on nonsecretory pituitary tumors is uncertain. Conventional treatment for such "functionless" tumors is surgery and/or radiotherapy, but recurrences pose a therapeutic dilemma. We describe a patient with such a tumor treated by surgery and radiotherapy who presented with recurrent disease 14 years later. On treatment with bromocriptine, 20 mg daily for 25 months, the intrasellar tumor recurrence had diminished in size and a suprasellar extension had almost disappeared. Bromocriptine therapy may therefore benefit some patients with nonsecretory pituitary tumors considered unsuitable for surgery or radiotherapy.

Thioridazine was found to increase the serum prolactin level as well as the tumor size of a prolactin--secreting pituitary chromophobe adenoma in a schizophrenic man. He was then successfully treated with clonidine, an antinoradrenergic compound without antidopaminergic properties, which had no effect on serum prolactin or tumor growth. This case report highlights the importance of careful neuroleptic usage in patients in whom elevated prolactin levels are of concern and discusses alternative methods of treating psychosis when antidopaminergic medications are contraindicated.

Of the 11 patients with pituitary or suprasellar tumours seen at Muhimbili Medical Centre, Dar es Salaam, from January, 1980, until July, 1982, 6 (54·5%) were totally blind, 3 (27·3%) were blind in one eye and had severe visual impairment in the other, and 2 (18·2%) had marked visual field abnormalities but normal visual acuity in one eye. Blindness in most of these patients highlights the absence of neurosurgical services in many developing countries. In addition there is little prospect of countries like Tanzania establishing neurosurgical services in the foreseeable future. The only help for patients with neurosurgical problems is from referral overseas. This, however, is possible for only a limited number because of costs, unless neurosurgical units in developed countries offer their services at nominal cost. Such an offer would not only benefit patients who would otherwise die but would also help to further the interests of neurosurgery in the helper country.