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In a collection of 108 surgically removed, light and electron microscopically studied pituitary tumors, 19 adenomas (17.6%) could be found of which oncocytic tumor cells constituted more than 50%. These showed histologically, in conformity with the criteria of oncocytes, a fairly broad cytoplasm with finely granular or, in part, finely vacuolar structures and distinct cell membranes. The nuclei were predominantly round and moderately rich in chromatin but also in part, pyknotic. In paraffin-embedded sections the tumors could not be distinguished with certainty from chromophobe or moderately granulated acidophil adenomas. In plastic-embedded sections they could be identified by the typical filmy and finely granular feature of the cytoplasm which was distinctly different from conglomerations of secretory granules. Ultrastructurally they were characterized by many densely packed mitochondria. These were, in part, hydropically swollen. Furthermore, 5 tumors exhibited increased hormone-synthesizing organelles, 2 of which induced an acromegaly.

98 biopsies of the paraadenomatous adenohypophysis in acromegaly, galactorrhea combined acromegaly, isolated galactorrhea, hypothalamic-hypophysial Cushing's disease, Nelson's syndrome, and in nonfunctional adenomas were studied by light microscopic methods in order to find evidence for a possible hyperplasiogenic origin of the different types of adenomas. It was hoped that the numerical relations and structures of hypophysial cells might provide significant information. Nodular ACTH cell-hyperplasia was found frequently apart from ACTH cell-tumors in Cushing's disease and Nelson's syndrome and on this basis we suggest that the adenomas in both diseases arise from hyperplasia. During their further development these adenomas seem to become autonomous, since the number of paraadenomatous ACTH cells decreased in bigger tumors.

The gonadotrophic cells of the male rat adenohypophysis were investigated by light and electron microscopy after castration, after administration of the antiandrogen cyproterone, and after treatment with the steroidogenesis inhibitor amino-glutethimide. The numbers of FSH and ICSH gonadotrophs were generally higher in the three test groups than in normal controls and their structures were of the same kind. Examination of the ultrastructure revealed an increase and dilatation of the rough endoplasmic reticulum, enlargement of the ring-shaped Golgi complexes, and a moderate decrease in the content of secretory granules. The dilatation of the ergastoplasm resulted in some cases in signet-ring cells corresponding to the castration cells seen by light microscopy. No qualitative differences in pituitary gonadotrophs were found to result from surgical or so-called chemical castration, but there were quantitative differences. The ultrastructural and histological features after castration were more evident. Many degenerating gonadotrophs were present. FSH cells could be differentiated from ICSH cells in nearly all cases.

Summary The corticotrophic cells of the anterior pituitary glands of male rats were investigated by light and electron microscope after administration of Carbenoxolonesodium, which acts like mineralocorticoids, after treatment with the steroidogenesis-inhibitors Metyrapone and Amino-glutethimide and after injections of Methylprednisolone. Carbenoxolone was administered by stomach tube for 12 weeks, the others were injected intraperitoneally for 3 weeks. After withdrawl of Carbenoxolone, no structural or numerical changes of the corticotrophs could be observed. Metyrapone and Amino-glutethimide caused identical alterations. The corticotrophs were much more numerous and showed a more distinctive stellate form. The rough endoplasmic reticulum increased and contained more ribosomes. The Golgi complexes were ring-shaped and enlarged. The content of secretory granules remained nearly unchanged. The nuclei showed a moderate pleomorphism. These findings indicate an increased synthesis of ACTH. After Methylprednisolone was administered, a considerable reduction of the number of corticotrophic cells and a moderate decrease of the ergastoplasm in the single cell were observed thus a low level of ACTH-production can be supposed.

Summary Cell suspensions of ACTH cell adenomas of 10 patients with Nelson's syndrome were investigated for in-vitro secretion of ACTH. Two incubation systems, one using incubation beakers and the other a superfusion system, were employed. The cells were tested for their reactivity to lysine-vasopressin (LVP), cortisol, and combinations of both.

Summary In 17 primary transnasal operations on Nelson tumours long-term results are assessed measuring ACTH plasma levels and performing regular neuroradiological controls. In small intrasellar adenomas only one recurrent ACTH elevation near to pretreatment levels without symptoms from tumour growth was observed after 10 years. ACTH normalization was rarely achieved in large tumours, but only in one patient was a relapse visible in CT scan after three years. Thus selective tumour removal seems to be advisable at an early stage when sellar enlargement occurs. Interpretation of ACTH plasma levels has to include completeness of adrenalectomy, cystic tumour necrosis, and corticoid replacement which reduces ACTH levels. Elevation of ACTH plasma levels over 5,000 pg/ml has been regularly accompanied by extrasellar tumour extension. In large adenomas with definitely elevated ACTH levels, additional radiation therapy should be considered.

Eleven pituitary adenomas in patients with acromegaly were examined with special reference to their secretory activity. The adenomas with high secretion of growth hormone were histologically characterized by well-developed vascularization, sparsely acidophilic granulation of the cytoplasm, and pleomorphism of the nuclei. Ultrastructural findings were a well-developed rough-surfaced endoplasmatic reticulum, a large, double Golgi-complex, relatively densely packed cytoplasmatic organellas, more immature than mature secretory granules, and only a few products of granule-degradation. Two adenomas showed signs of high activity histologically only but this was not confirmed by ultrastructural examination. The two were recurrent adenomas; therefore we suppose that pleomorphism of the nuclei in association with an increased number of mitoses must be interpreted as sign of increased rate of tumor growth and not of secretory activity. Comparison of the morphological degree of secretory activity with the preoperative plasma level of growth hormone yielded a good degree of correlation in 9 of 10 cases.

5 cases with Cushing's syndrome had typical hormone levels indicating hyperadrenocorticism due to a hypothalamic-hypophyseal disturbance, which was treated by transnasal transsphenoidal hypophysectomy. The anterior pituitary glands of all cases were studied under light and electron microscopes. Compared with normal controls an elevated number of corticotrophic cells were present. Many of them were enlarged and sparsely granulated and large Golgi complexes, elevated amounts of ribosomes, and many immature secretory granules were found in the ultrastructure, indicating a high degree of secretory activity. In 3 cases multiple hyperplasias of corticotrophic cells were found. These consisted of relatively small cells with many secretory granules and pleomorphic and moderately hyperchromatic nuclei which were regarded as signs of proliferation. In one case the transition of hyperplasias into a mucoid cell adenoma was demonstrated. The cells of this adenoma reacted histochemically like normal ACTH cells. The ultrastrncture was characterized by multipolar outlines, large Golgi complexes, many secretory granules, many ribosomes, small accumulations of fine filaments, and pleomorphism of the nuclei with cytoplasmic invaginations. The morphology of this adenoma was almost identical with the structure of corticotrophic adenomas developed after bilateral adrenalectomy (Nelson's adenoma). Moreover in 4 cases cells with Crooke's hyalinization were found. The causes of their presence are discussed.

A collection of 108 surgically removed pituitary adenomas was studied by histologic, immunohistochemical and electron microscopical methods. It included 7 predominantly chromophobe adenomas of patients whose clinical symptoms consisted of a pure galactorrhea. Ultrastructurally, 4 of these adenomas contained little endoplasmic reticulum so that an endocrine activity of the tumors could not be assumed. These cases represented inactive adenomas which probably led to a disturbance of the secretion of prolactin-inhibiting factor by suprasellar extension resulting in stimulation of the non-tumorous adenohypophysis and secondary hyperprolactinemia.

The aim of this study was to investigate the qualitative and quantitative changes of ACTH-cells in the rat after application of a specific and a non-specific stimulus. A CRF-analog (lysin-vasopressin) and a prostaglandin (prostaglandin E1) were used. 40 rats were injected lysin-vasopressin or prostaglandin E1, respectively, for 4 weeks. The pituitary glands were investigated by means of light microscopy, electron microscopy and morphometry. Activation of the ACTH-cells could be observed after use of both substances, the effect of lysin-vasopressin being more intense than that of prostaglandin E1. Enlargement of the nucleus, the cytoplasm and the organelles involved in hormone-production and -transport were found and verified by morphometry. Additionally an increase in number of the cells could be demonstrated. Prostaglandin influenced not only ACTH-cells, but also other cells of the anterior pituitary.

Male Wistar rats were partially hypophysectomized and sacrificed at intervals of from 2 days to 1 year following the operation. The resected material was examined under the light microscope and the residual pituitary under the light and electron microscope. Neither regeneration nor an anatomical restoration of the adenohypophysis occurred even one year after partial hypophysectomy. An increased number of small chromophobe stem cells and juvenile chromophil cells were found in the residual pituitary. The amount of mitoses were not significantly increased.

A 54 year old woman suffered from acromegaly due to a pancreatic islet cell tumour producing GHRH. The tumour was demonstrated on CT scan. The diagnosis was established from elevated plasma levels of GHRH, GH and prolactin, and by the lack of signs of a pituitary adenoma in trans-sphenoidal surgery. Acromegaly was cured by tumour removal. Light microscopically, the tumour showed a medullary and microlobular pattern. The cells were large and often cuspidal. Small granules were found in semi-thin sections. Small aggregations of amyloid fibres were seen, mostly around capillaries. Immunocytochemistry revealed GHRH, NSE, neurotensin, serotonin, VIP and PP. S 100 was positive only in nerve fibres. Staining for GH, ACTH, calcitonin, a-HCG,ß-HCG, insulin, glucagon, gastrin, substance P, bombesin and somatostatin was negative. Ultrastructure showed oval partly lobulated nuclei with small nucleoli, moderate amounts of rough endoplasmic reticulum, many free ribosomes, some large Golgi fields and small numbers of secretory granules measuring 150 nm or, in a few cells, 650 nm.

Summary DNA analysis was performed by flow cytometry (FCM) in 59 cases of different types of pituitary adenomas who underwent microsurgery and were actively followed over a period of 3–6 years. Aneuploid DNA patterns were detected in 12 (20%) cases. Frequency of aneuploidy was highest in prolactin-secreting (36%) as compared to 17% in GH- and 7% in non-secreting adenomas. Some adenoma parameters valid for tumour growth, such as rate of recurrences and mitotic index, were correlated with aneuploidy of the tumour. FCM studies are, therefore, recommended to gain further parameters for the estimation of proliferative activity of pituitary adenomas.

Four faculty members in removable prosthodontics participated in a three‐phase rater training program. Nine complete dentures were given an overall rating by three outside experts to obtain an accuracy measure. A three‐point rating scale was used: R (cannot be appreciably improved), S (clinically acceptable), and T (clinically unacceptable). During the pretraining phase, the average interrater reliability was .57 as estimated by intraclass correlation, and the mean accuracy correlation was .76. The rater training phase consisted of a four‐hour session including presentations and discussions of rating terminology and formats, observer accuracy, and related issues. In the post‐training phase, the same nine complete dentures were rated by the four faculty members, using the same three‐point rating scale and a five‐point scale. The average post‐training interrater reliabilities were .56 and .76 on the three‐ and five‐point scales, respectively. The mean accuracy correlation was .78.

Summary After partial hypophysectomy in rats, fibrin foam was implanted in the wound cavity. The fate of the implant was followed over a period of time up to three months by light and electron microscopy. First of all granulocytes appeared, whose granules obviously participated in the fragmentation of the fibrin network. Two days after operation and then in rapidly increasing numbers histiocytes could be found which surrounded the fibrin fibres with pseudopodia and absorbed them. They were broken down intracellularly by the lysosomes. In the wound cavity the gradually increasing number of fibroblasts formed collagen that often lay close to the fibrin fibres. The disintegration of the Fibrospum corresponded largely to that of natural native fibrin even though some could be identified three months after operation. The isolated appearance of foreign giant cells argued in favour of a moderate tuberculin type allergic reaction by the rat.

Summary The aim of this study of 101 pre- and postoperatively controlled hypersecreting pituitary adenomas (80 acromegalies, 15 Cushing's diseases, 6 Nelson's syndromes) was to establish in what cases a selective adenoma extirpation by the transnasal route is possible and advisable.

Summary Specimens of the anterior pituitary lobe were investigated histologically in 28 craniopharyngioma patients operated on transsphenoidally. The pituitary glands in 3 patients revealed lymphocytic invasion giving a histological appearance typical of lymphocytic hypophysitis (incidence: 11%). At follow-up examination all three patients with associated lymphocytic hypophysitis had complete pituitary insufficiency, whereas only 36% of the craniopharyngioma patients without associated lymphocytic hypophysitis were in this poor postoperative endocrine state.

85 surgically removed pituitary adenomas were studied by light and electron microscopical and in part immunohistochemical methods. The tumors were histologically classified and reexamined by the ultrastructure.

Four pituitary tumors of patients adrenalectomized for bilateral adrenal hyperplasia with Cushing's syndrome 4–12 years before, were classified histologically as mucoid cell adenomas. Histochemically the tumor cells reacted like normal ACTH cells. The ultrastructure showed cells with multipolar outlines tending to surround other cells, large Golgi complexes, many immature secretory granules, a lot of mature granules with perigranular membranes and 200–600mµ in diameter, scattered particles of endoplasmic reticulum, a great abundance of ribosomes, pleomorphic mitochondria, a few small accumulations of fine filaments, and moderate pleomorphism of the nuclei with distinct nucleoli and sporadically cytoplasmic invaginations. It can be assumed that these adenomas developed from hyperplasias of ACTH cells. In all cases elevated levels of ACTH had been found in the plasma.

The atrophic adrenal cortex associated with corticosteroid-producing tumours was investigated by electron microscopy in 5 cases. The well-preserved zona glomerulosa was easily distinguished from lipid-rich glomerular cell complexes of the outer zona fasciculata in epoxy sections. Little difference from normal ultrastructure was observed in the cells of the zona glomerulosa. The zona fasciculata-reticularis, however, showed marked changes in the ultrastructure. The mitochondria are diminished, with reduced internal structures. Almost no agranular endoplasmic reticulum is evident. The fasciculata cells contain huge membranebound lipid vacuoles. Comparable ultrastructural changes in animals have been described after hypophysectomy or after treatment with glucocorticoid hormones. The electron microscope findings are considered to be the result of the suppression of ACTH secretion and probably of a direct inhibition of protein synthesis in adrenocortical cells by the elevated steroid hormone levels produced by the adrenal tumours.