[Prevalence of diabetes in acromegaly and Cushing syndrome]. / Diabetes-Häufigkeit bei Akromegalie und Cushing-Syndrom.

In a retrospective study glucose metabolism was investigated in 206 patients with acromegaly and 131 patients with Cushing's disease. 40.5% of the patients with hypersomatotropism and 32.0% of the patients with hypercortisolism suffered from overt diabetes mellitus. Impaired glucose tolerance was present prior to therapy in 28.2% and 30.6% of the patients, respectively. In acromegaly the incidence of overt diabetes mellitus was higher in women than in men, but no difference existed in the distribution of impaired glucose tolerance between both sexes. No correlation was found between growth hormone levels and occurrence of diabetes. In acromegaly and Cushing's disease overt diabetes increased with advanced age. Diabetes mellitus occurred independently from the etiology of hypercortisolism.

Diagnosis of Cushing's syndrome: re-evaluation of midnight plasma cortisol vs urinary free cortisol and low-dose dexamethasone suppression test in a large patient group.

We studied plasma cortisol levels at 00:00 h and 08:00 h in 103 patients with Cushing's syndrome and 144 patients in whom this diagnosis had been excluded. These patients were hospitalized in our department from 1975 to 1996. Additionally, we measured these parameters in 20 healthy volunteers and in 5 patients with nonendocrine disease. Corresponding data of urinary free cortisol and low-dose dexamethasone suppression testing were included in the evaluation. Values (mean+/-SD) from patients with Cushing's syndrome: 510+/-232 nmol/l (range 165-1488) for plasma cortisol 00:00 h, 574+/-242 nmol/l (range 236-1612) for plasma cortisol 08:00 h, 991+/-885 nmol/24 h (range 154-4866) for urinary free cortisol and 479+/-304 nmol/l (range 34 - 1,393) for plasma cortisol after 1.5 mg dexamethasone. Values from the patients excluded from Cushing's syndrome: 99+/-76 nmol/l (range 5-371) for plasma cortisol 00:00 h, 393+/-136 nmol/l (range 119-812) for plasma cortisol 08:00 h, 126+/-84 nmol/24 h (range 30-485) for urinary free cortisol, and 64+/-82 nmol/l (range 5-395) for plasma cortisol after 1.5 mg dexamethasone. Values of the healthy volunteers respectively patients with non-endocrine disease: 59+/-30 nmol/l (range 25-130) respectively 127+/-80 nmol/l (range 62-265) for plasma cortisol 00:00 h and 388+/-144 nmol/l (range 157-651) respectively 498+/-113 nmol/l (range 302-581) for plasma cortisol 08:00 h. None of the Cushing patients exhibited a 00:00 h plasma cortisol below 140 nmol/l and only one had a urinary free cortisol below 200 nmol/24 h, whereas 4 were complete dexamethasone suppressors. The diagnostic value of these parameters was examined based on various cutoffs. We recommend determination of midnight plasma cortisol as an efficient and simple additional procedure for the diagnosis of Cushing's syndrome. The sensitivity and specificity of this procedure is similar to urinary free cortisol and slightly above the low-dose dexamethasone suppression testing in our hospitalized patients.

[The long-term therapy of hypothalamic-hypophyseal Cushing's syndrome with mitotane (o,p'-DDD)]. / Langzeit-Therapie des hypothalamisch-hypophysären Cushing-Syndroms mit Mitotan (o,p'-DDD).

BACKGROUND AND OBJECTIVE: Drug treatment of hypothalamic-pituitary Cushing's syndrome is indicated if standard surgical intervention is not possible or has failed. The question arises whether, after unsatisfactory treatment with various adrenostatic drugs, mitotane (o,p'-DDD), used against adrenal cortical cancer, is efficacious and free of significant side effects when used long-term. PATIENTS AND METHODS: The results of long-term administration of mitotane to six patients, including one pregnant woman, were analysed retrospectively. After a moderate initial dosage of 3.0 g daily a maintenance dose of minimally 0.5 g per week was given or the treatment temporarily interrupted. The concentration of urinary free cortisol served as the main criterion of efficaciousness, together with the clinical course. The plasma concentrations of cortisol, aldosterone and ACTH were also determined, as well as routine clinicochemical parameters. RESULTS: Cortisol excretion became normal in all patients between the 2nd and 10th treatment month, falling from 919 +/- 621.3 nmol daily in the six months before treatment to 162 +/- 93.0 nmol daily in the third six-month treatment period (mean +/- standard deviation). Normal cortisol excretion and regression of symptoms was noted, dose-dependent, as long as the 12th year after start of treatment. Adrenocortical insufficiency occurred in one patient and at times required hormone substitution, followed by lasting remission without special treatment. Significant side effects were not observed other than a reversible increase in gamma-glutamyl transpeptidase. CONCLUSION: Mitotane proved to be an efficacious drug which in exceptional cases can be used without significant side effects in low dosage for the long-term treatment of hypothalamic-pituitary Cushing disease.

[Pregnancy in hyperprolactinemic patients]. / Schwangerschaften bei hyperprolaktinmischen Patientinnen.

In a retrospective study we analysed the outcome of 27 pregnancies in 17 hyperprolactinaemic patients. Cranial CT or MRI scans showed a microadenoma in 9, a macroadenoma in 7 and no change in 1 case. In 5 patients macroadenomas were surgically removed but a residual hyperprolactinaemia remained. In 2 patients with selectively removed microadenomas through the transsphenoidal route only in one case normal prolactin levels could be achieved. This patient became two times pregnant. In 24 patients pregnancy was induced by dopaminergic treatment whereas another patient with microadenoma became spontaneously pregnant after surgery and treatment with bromocriptine. The treatment was discontinued as soon as the pregnancy was recognised. 19 pregnancies were finished by spontaneous delivery and 3 by Caesarean section. Termination of pregnancy was artificially induced in 3 patients. One miscarriage was observed. Another patient was suffering from an extrauterine pregnancy. During pregnancy prolactin levels increased in comparison to basal levels. After delivery and lactation the same prolactin level was found compared to basal levels in patients with microprolactinomas. In patients suffering from macroadenomas prolactin levels decreased in comparison to basal levels. CT of MRI scan evaluations performed after delivery revealed a clinical not relevant increase as well as a decrease of tumor size in 2 cases, respectively. During pregnancy there was no complication due to tumor found in treated patients for hyperprolactinaemia. Only about one half of mothers were able to perform regular breast feeding.

[Cushing's syndrome in CRF-producing mediastinal carcinoid]. / Cushing-Syndrom bei CRF-produzierendem mediastinalem Karzinoid.

A 36-year-old patient developed marked pigmentation, marked myopathy and severe hypokalaemic alkalosis which at first pointed towards an ectopic ACTH syndrome. The dexamethasone test at a high dose indicated cortisol suppression. A mediastinal tumour was seen radiologically, but the sella was of normal size. Computed tomography provided indirect signs of a sellar space-occupying lesion which suggested an ectopic production of corticotropin-releasing factor (CRF) as cause of the Cushing's syndrome. CRF concentration in antecubital venous blood was markedly elevated to 280 ng/l. The mediastinal tumour was excised and proved to be a carcinoid histologically. Postoperatively the CRF concentration fell to 70 ng/l. An extract of the carcinoid contained 15.5 ng/g wet-weight of CRF and 254 ng/g wet-weight of beta-endorphin. The patient died 5 weeks postoperatively of sepsis with bilateral pneumonia. At autopsy the hypophysis was of normal size but showed nodular ACTH-cell hyperplasia. This was thus a case of Cushing's syndrome resulting from ectopic CRF production in a mediastinal carcinoid tumour.

A 5 year interdisciplinary control of iodine deficiency in the GDR.

The interdisciplinary iodine prophylaxis in the GDR is a successful measure for control of ID. The iodization of nearly all the salt is planed perhaps with reduction of the iodine concentration. However, next further steps may be done in cooperation of the Interdisciplinary Iodine Commission with the "Arbeitskreis: Jodmangel" in the FRG.

Paradoxical response of plasma beta-endorphin to combined administration of TRH and GnRH in adrenal disorders.

The combined intravenous injection of TRH and GnRH elicited paradoxical responses of plasma beta-endorphin in active and successfully treated pituitary dependent Cushing's disease as well as in ectopic ACTH syndrome and in congenital adrenal hyperplasia. No response was observed in Cushing's syndrome due to adrenal tumours. It is concluded that an abnormal response to inappropriate releasing hormones cannot verify the existence of a pituitary corticotrophic microadenoma.

Interdisciplinary aspects of iodine prophylaxis in German Democratic Republic.

Endemic goiter still occurs in several European countries. Alimentary iodine deficiency could be proved as the main cause of endemic prevalence. Extensive epidemiologic surveys showed the great medical and economical impact of this matter for the GDR. Over 200 million Marks might be spent for diagnosis and treatment of thyroid patients per year. Also in the field of veterinary medicine and animal production iodine deficiency plays an important role. Under the conditions of iodine deficiency the fodder containing nitrate and glucosinolates (e.g. bruised rape extraction) results in additional goitrogenic effects (so-called indirect or relative iodine deficiency). Due to iodine deficiency disorders considerable losses of yields in cattle, pigs and sheep occurred. The content of iodine in animal products used for human nutrition was subsequently low. Considering the ecological implication of these problems an Interdisciplinary Iodine Commission within the Society for Endocrinology and Diseases of Metabolism of the GDR was established. Together with the governement authorities it worked out corresponding recommendations for the prophylaxis and control of its efficiency. In 1986 the iodination of most of the packed salt (32 mg KIO3/kg = = 19 mg I/kg) and the administration of iodinated mineral mixtures for the animal production were started for pigs in the whole territory of GDR and for cattle in the southern counties of the GDR only. These activities have been accompanied by information of TV as well as in the newspapers and medical journals. Thus, an improved supply of iodine to the population through iodinated table salt and animal products can be taken into account. The efficiency of these prophylactic measures is controlled interdisciplinarily.(ABSTRACT TRUNCATED AT 250 WORDS)

[The immunohistochemistry of pituitary adenomas]. / Immunhistochemie der Hypophysenadenome.

A great deal of progress has been achieved in recent years in the field of immunohistochemistry of pituitary adenoma. Continued use of more new antisera and monoclonal antibodies against numerous hormones in the adenohypophysis have resulted in new approaches to classification of pituitary adenoma. However, new problems have been discovered, on the other hand, by large-scale studies in recent years. The great number of multihormonal pituitary adenomas and possible change of the immunohistochemically detectable hormone status in cases of recurrent tumours have particularly re-emphasised the need for new thinking about patterns of classification. It would appear somewhat problematic, in this context, to uncritically accept terms, such as ACTH cellular adenoma or GH cellular adenoma. Reference is also made to the distribution pattern of cell and tissue markers in pituitary adenomas. The paper is based on thorough literature screening as well as on experience obtained by the authors from 450 cases of pituitary adenoma of which 260 had been analysed by immunohistochemistry, 131 by morphometry, and 80 by electron microscopy.

Somatomedin-C in active and successfully treated acromegaly.

Sm-C concentrations in serum were found significantly different in either active acromegaly or following successful treatment with pituitary adenomectomy. Although after normalization of serum GH the Sm-C levels sometimes exceeded the normal range no overlap was found between both groups. Exceptionally two acromegalic patients showed elevated Sm-C levels in spite of normal GH values. Likewise, a high Sm-C concentration was found in one patient suspective of ectopic GH secretion with only moderately elevated serum GH. Sm-C determinations are judged as a good adjunct to usual diagnostic methods which in special cases of acromegaly can be even superior to measurements of serum GH.

[Development and effectiveness of struma prevention in East Germany]. / Zur Entwicklung und Effektivität der Strumaprophylaxe in der DDR.

For the control of iodine deficiency disorders in man and animal since 1985/1986 measures have been introduced which were interdisciplinary attuned: 84% of the paketed salt are iodized (32 mg KIO3/kg) and iodized mixtures of mineral substances are used in the animal production of agricultural useful animals. The effectiveness of the iodine prevention becomes visible by an increase of the renal iodine excretion, regression of the frequency of connatal goitre and iodine deficiency disorders in the animal production. Increased manifestations of cases of hyperthyroidism as sequelae are of transient importance.

[Status of goiter prevention in East Germany from an interdisciplinary viewpoint]. / Zum Stand der Strumaprophylaxe in der DDR aus interdisziplinärer Sicht.

The endemic goiter occurs still in many countries of Europe. Alimentary iodine deficiency could be proved as essential cause of the increased prevalence. Comprehensive epidemiological investigations refer to the medical importance of this appearance for the GDR. 200 million marks might have to be spent annually for diagnostics and therapy. Also in the production of animals sequelae of iodine deficiency play a great part. Nitrate containing and glucosinolate containing feeding stuffs (e. g. rape extraction groats) here under the conditions of the iodine deficiency additionally develop goitrogenous effects (so-called indirect or relative iodine deficiency), which lead to decrease in vitality and clinical symptoms in the agricultural useful animals cattle, pig and sheep. The iodine content of animal products was frequently low. In view of the ecological connection of these problems an interdisciplinary iodine commission was founded which in accordance with the responsible state organs elaborates adequate recommendations for the prophylaxis and control of efficiency. From 1986 was begun with the iodisation of the largest part of packet salt (32 mg KJO3/kg) und the delivery of iodized mineral mixtures for the production of animals. Thus is to be reckoned with an improved direct supply of iodine for the population by iodized table salt or an indirect one over animal product. The iodisation of the entire common salt with modified iodine concentration is striven for. Measures for the control of efficiency are introduced.

[Current aspects of therapy of ovarian cancer. Surgical therapy of epithelial ovarian cancer at the Göttingen University Gynecologic Clinic. A retrospective analysis of 82 patients 1981-1984]. / Aktuelle Aspekte der Therapie des Ovarialkarzinoms. Die operative Therapie des epithelialen Ovarialkarzinoms an der Universitäts-Frauenklinik Göttingen. Eine retrospektive Analyse bei 82 Patientinnen der Jahre 1981-1984.

The most important step in the treatment of epithelial ovarian carcinoma is radical surgery which should be as radical as possible, since this can exercise a decisive influence on the effectiveness of subsequent chemotherapy or radiotherapy. During 1981-1984 98 patients with an ovarian carcinoma were operated upon. 82 of these patients had epithelial tumours that will be discussed in the article. The mean age was 59.9 years. 88% of the patients were additionally at risk by one or several risk factors. Surgical approach was standardised: longitudinal incision, hysterectomy, adenectomy, resection of omentum and, if necessary, maximum possible removal of the peritoneum of the pelvis. In 28 cases additional surgery became necessary at the intestine. 77% of the patients (n = 63) were in the advanced stages FIGO III and IV. In 50 patients the operation lasted for up to 4 hours, in 24 up to 6 hours and in 8 for more than 6 hours. Intraoperative complications occurred in 37% (twice lesion of the ureter, in 5 cases intestinal lesion, in 23 cases anaesthesiological problems due to preexisting risks). In stages I and II reduction of tumour size below 2 cm was achieved in 100% of the cases, in stage III in 87.5%, in stage IV in 45%. Two patients died postoperatively. The postoperative complication rate was 48%. Almost 30% of these were represented by cardiopulmonary disturbances. Although the percentage appears high, most of the problems were well manageable, so that the patients could be transferred to follow-up therapy within 2-3 weeks. For type of follow-up therapy, tumour response.(ABSTRACT TRUNCATED AT 250 WORDS)

[Postoperative therapy of epithelial ovarian cancer at the Göttingen University Gynecologic Clinic. A retrospective analysis of 82 patients 1981-1984]. / Die postoperative Therapie des epithelialen Ovarialkarzinoms an der Universitäts-Frauenklinik Göttingen. Eine retrospektive Analyse bei 82 Patientinnen der Jahre 1981-1984.

An epithelial ovarial carcinoma was diagnosed and treated during 1981 to 1984 in 82 patients of the Department of Gynaecology of the University of Göttingen. The diagnostic approach and therapy are described in the paper by Grospietsch et al. [Geburtsh. u. Frauenheilk. 46 (1986), 588]. The present paper deals with the results of postoperative treatment, with particular emphasis on those factors presently considered to be prognostically relevant, such as postoperative tumour residue, age of the patient and stage of tumour spread. The results are classified according to rate of response, progression-free interval and survival time or survival rate. Analysis of the results shows that on the one hand an improvement of long-term results (survival time) has been very unsatisfactory with present-day methods--and moreover, that partly such long-term results are obtained only on the basis of an accurate diagnosis--whereas on the other hand the short-term results (tumour-free interval) together with a clear improvement of the quantity and quality of life do justify the considerable effort required by the treatment concept. Improvement of the overall result is more likely to be achieved by clinical and preclinical research towards consolidation of the primary therapy effect than by employing "trial-and-error" methods within the framework of primary therapy.

Iodine deficiency disease in the GDR.

In the last decade several epidemiologic surveys were carried out in the GDR. The findings of all studies indicate consistently that the goiter is existing in the whole country increasing from the north to the south. Inhabitants of all ages are involved. The main cause appears to be an iodine deficiency of grade II. In the south of the GDR more than 90% of the groups examined are subjected to it. The introduction of iodinated salt prophylaxis is going on. An Interdisciplinary Iodine Commission has been established to control and coordinate these measures.

[New aspects of the pathogenesis of acromegaly-somatoliberinomas]. / Neue Aspekte in der Pathogenese der Akromegalie--Somatoliberinome.

According to modern knowledge, acromegaly can develop in at least three ways. A pituitary adenoma with growth hormone overproduction is the most frequent. Much rarer is ectopic growth hormone secretion by extra-hypophyseal tumors. A further possibility is the production of growth hormone releasing factor (GRF) by hypothalamic or ectopic tumors. This involves the secretion of a substance which selectively stimulates the GH producing cells of the pituitary. Special features of the clinical and morphological picture of this condition are described, based on the authors own observations. Two patients developed acromegaly: one had a retroperitoneal paraganglioma and the other a bronchial carcinoid. Ectopic GRF secretion could be confirmed radioimmunologically and immunohistologically in both cases. As a result of the on-going, tumor related GRF stimulation the patients developed nodular or diffuse GH-cell hyperplasia in the adenohypophysis. Since ectopic GH secretion does not cause hyperplasia of the adenohypophyseal cells, morphologic examination of the hypophysis can contribute to the differential diagnosis in such cases.

[Unusual abdominal apudomas. I. Cushing syndrome in association with Zollinger-Ellison syndrome in an endocrine pancreas tumor]. / Ungewöhnliche abdominelle Apudome. I. Mitteilung: Cushing-Syndrom in Kombination mit Zollinger-Ellison-Syndrom bei endokrinem Pankreastumor.

Ectopic production of ACTH is observed in 6% of patients with Cushing syndrome. Ten percent of these cases are related to endocrine pancreatic tumors. In a few cases a multiplicity of hormones are produced. The combination with a Zollinger-Ellison syndrome is very infrequent. In the present case, a female patient aged 54, there was an interval between the onset of Zollinger-Ellison and Cushing syndrome. The combination of bilaterally enlarged adrenals in the absence of an adrenal adenoma and the presence of Crooke-cells in the adenohypophysis in a patient with Cushing syndrome are of diagnostic significance. This trias should always alert the physician to the possibility of extrahypophyseal ACTH production.