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Background Transnasal surgery (TNS) is the first choice in the treatment of pediatric Cushing's disease. The question is how can high remission rates be achieved with minimally invasive investigations and TNS whilst avoiding radiotherapy or bilateral adrenalectomy in children. Methods Data from a published series 1 (n=55) of surgeon DKL will be compared with his recent series 2 (n=45) until 2009. All patients were operated by direct transnasal microsurgery. Over time, inferior petrosal sinus sampling (IPSS) was replaced by cavernous sinus sampling (CSS), restricted to unclear cases without increase of salivary cortisol in corticotropin-releasing hormone-test, difficult sellar anatomy or negative magnetic resonance imaging (MRI). Multiple direct intra-operative micro-cytology, micro-doppler and adequate visualization techniques are described. Results In series 1, IPSS was performed in 13 (24%) of whom 46% had false adenoma lateralization. All adenomas could be removed with extensive pituitary exploration. Three patients had early successful re-surgery. In series 2, with more refined MRI and endocrinology, CSS was used in only seven patients (15%) and all micro-adenomas were correctly localized. In three of four patients with persistent cortisol excess, repeat-TNS was necessary and successful. Side effects of TNS were minimal. Recurrence rates were 16% and 11% in series 1 and 2, respectively. Only four of 100 children with invasive adenomas were irradiated, significantly less than in other experienced pediatric centers. Conclusions Thus, 98% remission rate could be achieved with fewer invasive pre-surgical investigations, such as central catheter studies, refined TNS and early repeat-TNS. Repeat-TNS in recurrences minimized the need for irradiation.

The case report describes a teratoma of the sellar region with a gland forming and an immature, relatively clear undifferentiated component without signs of anaplasia. Both components express TTF-1 indicating their presumable origin in the neurohypophysis as part of the circumventricular organs. The differential diagnosis includes pituitary adenoma and spindle cell oncocytoma with inclusion of Rathke's cleft cyst, pituitary blastoma, yolk sac tumor, and other germ cell tumors. The prognosis is the same as in the immature teratomas in the gonads, specifically unclear.

Inflammatory findings in the pituitary glands account for approximately 1 % of operations in the sellar region. Primary inflammation (e.g. lymphocytic and idiopathic granulomatous hypophysitis) have to be differentiated from secondary types (e.g. concomittant inflammation with Rathke's cleft cysts, craniopharyngiomas and germinomas) and involvement of the pituitary in generalized inflammation (IgG4-related disease, sarcoidosis and septicopyemia). Langerhans cell histiocytosis also has to be considered for the differential diagnostics. Lymphocytic hypophysitis shows lymphocytic infiltrations of varying density, predominantly of the T‑cell type. Granulomatous hypophysitis has the features of sarcoidosis and can only be diagnosed by exclusion of generalized sarcoidosis. Secondary hypophysitis has a mixed cell infiltration, especially by histiocytic infiltration and predominantly originates from ruptures or bleeding from Rathke's cleft cysts. The frequently very sparse remnants of cyst epithelium should be confirmed by pankeratin immunostaining.

Radiation therapies of pituitary adenomas induce an increase in fibroses and nuclear pleomorphism. Most growth hormone (GH) secreting pituitary adenomas react to somatostatin analogues by a distinct decrease of GH secretion. In two thirds, levels of IGF-1 can be normalized. Some cases show a shrinkage of adenomas that correlates with fibrosis of the tumor. With these drugs, thyroid stimulating hormone secreting adenomas can also be treated. Prolactin secreting adenomas are mostly treated primarily with dopamine agonists. Up to 90% of cases show a strong decrease in hormone secretion and a distinct shrinkage of the adenomas based on strong decrease in adenoma cell volume. Long-term medication with high doses of glucocorticoids induces Crooke's cells in the anterior pituitary. These are suppressed ACTH cells and characterized by increased numbers of large lysosomes and dense bundles of cytofilaments.

Background: The aim of this study was to determine the hormones produced in pituitary gland tumours (TM) following fractionated external irradiation in rats. The TM arose in the course of studies on other questions of radiation effects., Methods: The left neck and skull base of sixty female Wistar rats, 3 to 4 months of age at the beginning of the external irradiation, were subjected to roentgen rays exposure, fractionated to 2 Grays daily, either up to 20, 40 or 60 Gy. The midline of the neck and skull was always inside the radiation field. The animals were sacrificed either 6 months or 12 months after completion of the randomly assigned irradiation protocol. Five non-irradiated rats served as controls., Results: No TM developed in the non-irradiated animals. Out of 60 irradiated rats 9 developed a pituitary TM (15%). In remnants of the normal adenohypophysis we revealed immunohistochemical reactivity for growth hormone (GH), adrenocorticotropic hormone (ACTH), prolactin (PRL), thyroid stimulating hormone (TSH), and follicle stimulating hormone (FSH). In the radiation-induced adenomas, 4 TM were immuno-reactive for TSH, 4 for GH, 2 for PRL, and 2 for FSH. The TM did not react with anti-ACTH and anti-LH (luteinizing hormone) anti-sera., Conclusions: Obviously, irradiation accelerates the development of pituitary gland adenomas. In this series the TM were predominantly incidental findings at necropsies after pretermed follow-up intervals with a variety of hormone-producing cells. On the other hand, four of nine TM were null adenomas. Necropsies of the brain should be carried out routinely in irradiation studies of the skull.

The pituitary and adrenal glands are a functional endocrine unit affected by local or organ-limited senile amyloid syndromes. These occur as interstitial (pituitary only) or intracellular (pituitary and adrenal) varieties. The pituitary and right adrenal glands of each of 108 consecutive autopsy cases of individuals aged 85 years and over were investigated for the prevalence, distribution and immunostaining characteristics of local amyloid. Intracellular amyloid was detected in 77 (71%) pituitaries and 73 (68%) adrenals. Interstitial amyloid was found in 86 pituitaries (80%). Immunohistochemical studies, investigating different amyloid fibril proteins, amyloid P component, ubiquitin, intermediate filaments and pituitary hormones, failed to demonstrate any similarities, and a common origin is unlikely. Statistical analyses demonstrated significant correlations between the occurrences of all three local amyloids. The clinical and histopathological significance of local pituitary and adrenal amyloid remains obscure. The results suggested that the pathogenesis of the local senile amyloidoses of the pituitary and adrenals may be influenced by a common, still uncharacterized variable. It is not clear whether this variable also contributes to the pathogenesis of other senile amyloid syndromes, such as those associated with Alzheimers' disease.

The prevalence and immunoreactivity of interstitial amyloid deposits of the pituitary glands of 109 consecutive autopsies of individuals over 84 years of age were studied using Congo red staining and antibodies directed against the major amyloid fibril proteins and pituitary hormones. In addition, the amount of interstitial amyloid formation was evaluated quantitatively and compared with all autopsy-related and clinical diagnoses available. Eighty-seven (80%) of the 109 cases exhibited interstitial amyloid deposits in the anterior lobe. All reacted immunohistochemically with antiamyloid lambda light chain and antiamyloid P-component. Quantitative analysis in 62 cases revealed a mean volume percentage of interstitial amyloid in the anterior lobe of 0.56%. In statistical analysis, only two of the 25 diseases recorded were associated with interstitial amyloid: chronic obstructive pulmonary disease and non-insulin-dependent diabetes mellitus. The prevalence of chronic obstructive pulmonary disease correlated positively with the occurrence (chi 2; P < .02) as well as with the amount of amyloid (Wilcoxon; P < .04) in the pituitary. In addition, non-insulin-dependent diabetes mellitus was accompanied with higher amounts of interstitial amyloid than with all other disorders (Wilcoxon; P < .03). Until now, a correlation was proposed only between non-insulin-dependent diabetes mellitus and islet amyloidosis of the pancreas.

The morphological structure and immunohistochemical reactions of 100 pituitaries from cases of SIDS children (58 males and 42 females, average age 5.34 +/- 3.12 months) were studied. Controls consisted of 19 pituitaries from children (14 males and 5 females, average age 5.63 +/- 2.52 months) with a clearly identifiable cause of death e.g. drowing or strangulation. The microscopical and immunohistochemical studies for identifying pituitary cell types revealed normally developed organs. Unspecific necroses and haemorrhages were observed in 2 cases of SIDS but in none of the controls. Hyperaemia was detected in 51 (30 male/21 female) cases of SIDS. No significant differences were found in the distribution of microfollicles (54%), cysts of the intermediate zone (14%), persistency of the Rathke's pouch (44%), Erdheim's squamous epithelium (8%) or heterotopic salivary glands (3%). The semiquantitative immunohistochemical evaluations of the different cell types showed no significant variations from the control group. The pattern of distribution of the intracytoplasmic vacuolisations of the ACTH and gonadotropic cells showed no significant differences. Folliculo-stellate cells were either not demonstrable--commensurate with age--or showed a normal distribution. The results for both study groups may be defined as consequences of terminal agony, but failed to reveal the cause of the sudden infant death.

Various drugs and hormones influence the light microscopic and especially the electron microscopic structure of the anterior pituitary and its tumors. Many structural effects are known only from animal experiments since specimens from human pituitaries are mostly not available. The structure of growth hormone (GH) cells is relatively stable. A massive GH cell hyperplasia is known only in rare cases with growth hormone releasing factor (GRF) excess from tumors. Prolactin cells can be stimulated by drugs, neurotransmitters, and hormones which decrease the dopamine inhibition. Adrenocorticotropic hormone (ACTH) cells are stimulated by stress, some hormones, loss of adrenals, and drugs which activate the alpha 1- and beta-receptors or inhibit the alpha 2-receptors. They are suppressed and changed into Crooke's cells by treatment with glucocorticoids. Thyroid-stimulating hormone (TSH) cells increase in number and size in states for overstimulation especially by thyrotropin releasing hormone (TRH). A decrease results from hyperthyroidism and possibly from somatostatin, L-dopa, and dopamine. Gonadotroph cells transform into castration cells in strongly hyperactive states (gonadectomy, antiandrogens, gonadotropin releasing hormone [Gn-RH]agonists, aminoglutethimide). Special types of pituitary adenomas can be treated with drugs which suppress hormone production and proliferation. Dopamine agonists and somatostatin reduce the tumor size of varying proportions of GH secreting adenomas in acromegaly. Ultrastructurally, a decrease of cytoplasmic and nuclear volume and an increase of lysosomes are found. Bromocriptine and other dopamine agonists are established in the treatment of prolactin secreting adenomas. They induce a shrinkage in many cases. Ultrastructurally, a reduction of cellular and nuclear size, an increase in number of secretory granules and of lysosomes, and a reduction of rough endoplasmic reticulum can be demonstrated.

The frequency and the significance of the 3 main features of pituitary in Cushing's disease (ACTH secreting adenomas, ACTH cell hyperplasia, and Crooke's cells) are reported and discussed. In our most recent surgical series (1989-1990) the rate of demonstration of adenoma increased up to 96%. The frequency of paraadenomatous ACTH cell hyperplasia depends on the amount of resected tumor-free tissue. The significance of such peritumorous hyperplasia seems to be low. Crooke's cells as suppressed and transformed ACTH cells were present in each case and are a reliable indicator of a hypercortisolism.

The first study was undertaken for detecting hormone-receptors for estrogen and progesteron with immunohistochemical methods in frozen sections of 58 pituitary adenomas of different types. In all cases the result was negative. In the second study we tested the binding pattern for the lectins Peanut lectin (PNA), Ulex europaeus agglutinin (UEA-1) and the Concanavalin agglutinin (Con-A) in 144 pituitary adenomas of different types and in 20 post-mortem pituitaries using the two-layer indirect technique. All normal pituitaries reacted positive for all three lectins, elsewhere the binding feature for pituitary adenomas was different. Via statistical analysis, correlating lectin-bindings with clinical hyperfunction and immunohistochemical hormone content, we found an association of acromegaly and PNA and ConA and of Cushing's disease and PNA and UEA-1; furthermore of GH and UEA-1 and Con-A, of TSH and UEA-1 and of ACTH and PNA and UEA-1. Using serial sections (AB-method for demonstrating hormones and two layer indirect technique for lectin-binding) and the double-staining technique (labelled Streptavidin-Biotin-method for demonstration of hormones and the two-layer indirect technique for lectins) we found Con-A reacting with GH and PRL cells and with a part of FSH-cells, UEA-1 reacting with most of the ACTH-cells and PNA reacting with FSH-cells.

98 biopsies of the paraadenomatous adenohypophysis in acromegaly, galactorrhea combined acromegaly, isolated galactorrhea, hypothalamic-hypopphysial 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. Some of the cases with isolated galactorrhea showed hyperplasia of acidophil and chromophobe cells in the paraadenomatous adenohypophysis. It can thus be assumed that porlactin cell-tumors also develop from prolactin cell-hyperplasia. Both the adenomas and the nonfunctional tumors in acromegaly seem to grow autonomously from the beginning, since paraadenomatous hyperplasia is seldom seen.

Pituitaries of 137 cases with Cushing's disease were microscopically and immunohistologically studied. Many alterations and parameters (sex, age, anamnesis, cortisol plasma levels, tumor size, invasiveness, localization, differentiation of adenomas, immunohistological hormone content, capillarity, recurrences, peritumorous ACTH cell hyperplasia, and Crooke's cells) were analyzed and compared. Whereas most parameters were not correlated, we found some important statistically significant correlations: Undifferentiated adenomas are more frequently invasive than differentiated ones. Invasive adenomas recur more frequently than non-invasive adenomas. Extremely laterally localized adenomas are more often invasive. Larger adenomas are more frequently invasive than micro-adenomas. ACTH cell hyperplasia are more often demonstrable in specimens from total hypophysectomies (confined to our earlier series) than from partial hypophysectomies and adenomectomies. Recurrences of adenomas are more frequent in pituitaries with periadenomous ACTH cell hyperplasia. Very rarely ACTH cell hyperplasia are the only source of ACTH hyperfunction. The more Crooke's cells are demonstrable, the longer the post-operative replacement dose of Cortisol is required. Adenomas in Cushing's disease and adenomas in Nelson's syndrome differ significantly in the following points: Adenomas in Nelson's syndrome are larger and contain more plurinuclear cells. In the ultrastructure, adenomas in Cushing's disease show more cytofilaments. Paraadenomous Crooke's cells are lacking in Nelson's syndrome.

A marker for T-lymphocytes (UCHL 1) was immunohistologically found in many folliculo-stellate cells of the normal human anterior pituitary. Another antibody for T-lymphocytes (MT 1) and a marker for B-cells were negative. The results must be critically discussed.

Chronic stimulation of the ACTH-cells in rats was undertaken by adrenalectomy, chemical adrenostasis, by application of a CRF-analog and by non-specific means. The ultrastructural findings of the ACTH-cells were compared to those of the human pituitary gland in Cushing's disease. The pituitaries of 12 patients with the hypothalamic-hypophyseal form of Cushing's syndrome were studied by electron microscopy. A good correlation of the experimental observations to those in human pathology could be seen in the first steps of reaction. There was an enlargement of the ACTH-cells with well developed organelles and there was a simple hyperplasia. The following forms of reaction, nodular hyperplasia and adenomas, were only observed in the human pituitary glands. Chronic suppression by steroids leads to a diminution of the single ACTH-cell and their organelles and a reduction. The appearance of Crooke's cells is specific for the human pituitary and is not reproduced in animal experiments.

The pituitary and adrenal glands are a functional endocrine unit affected by local or organ-limited senile amyloid syndromes. These occur as interstitial (pituitary only) or intracellular (pituitary and adrenal) varieties. The pituitary and right adrenal glands of each of 108 consecutive autopsy cases of individuals aged 85 years and over were investigated for the prevalence, distribution and immunostaining characteristics of local amyloid. Intracellular amyloid was detected in 77 (71%) pituitaries and 73 (68%) adrenals. Interstitial amyloid was found in 86 pituitaries (80%). Immunohistochemical studies, investigating different amyloid fibril proteins, amyloid P component, ubiquitin, intermediate filaments and pituitary hormones, failed to demonstrate any similarities, and a common origin is unlikely. Statistical analyses demonstrated significant correlations between the occurrences of all three local amyloids. The clinical and histopathological significance of local pituitary and adrenal amyloid remains obscure. The results suggested that the pathogenesis of the local senile amyloidoses of the pituitary and adrenals may be influenced by a common, still uncharacterized variable. It is not clear whether this variable also contributes to the pathogenesis of other senile amyloid syndromes, such as those associated with Alzheimers' disease. [ABSTRACT FROM AUTHOR]