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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.

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.

History and clinical findings A 40-year-old woman complained of weight gain for 10 years. Because of this, she yearly went on a excessive weight reduction diet with weight loss of up to 12 kg. Nevertheless, a total weight gain of 15 kg as well as changing degrees of hypertension, muscular weakness and severe depression were registered during this long period. For 5 years ecchymosis and for 2 years oligomenorrhoea as well as oedema had become evident. Recently large macronodular adrenal glands were found on routine abdominal ultrasound. At the time of clinical investigation early this year she presented with relatively mild Cushing features, such as moon face, central obesity, hirsutism, ecchymosis and hypertension. Investigations Endocrine testing demonstrated suppressed plasma ACTH, low to normal plasma cortisol after overnight fasting and an inverse diurnal rhythm. During 24 hours of fasting plasma cortisol levels and free urinary cortisol excretion were within normal range, but highly elevated under normal food intake. Plasma cortisol levels increased dramatically in response to a lipid-rich meal (5.6-fold), to a protein-rich meal (6.6-fold) and to oral glucose (3.7-fold). Increases in plasma cortisol were closely correlated to increases of gastric inhibitory polypeptide (GIP) concentrations. Subcutaneous injection of octreotide completely inhibited the plasma cortisol and GIP response to oral glucose. Plasma ACTH and cortisol levels did not increase after CRH administration, but fasting plasma cortisol promptly increased after ACTH stimulation. Non-fasting plasma cortisol levels and free urinary cortisol excretion were not suppressed by high doses of dexamethasone. Abdominal computed tomography showed macronodular enlargement of both adrenal glands. Treatment and course The patient underwent bilateral adrenalectomy. Postoperatively, she was treated with replacement doses of hydrocortisone and fludrocortisone. All Cushing features have regressed, a normal menstrual cycle and normal plasma ACTH concentrations have become evident. Conclusion This case report not only presents a very rare cause of Cushing's syndrome--food-dependent or gastric inhibitory peptide (GIP)-dependent hypercortisolism--but it also demonstrates a special course of this disease of relatively long duration. Severe adrenal hyperplasia contrasted with mild clinical symptoms obviously caused by frequent periods of weight reduction diet. Considering this moderate clinical course it might well be that food-dependent hypercortisolism is more frequent than supposed, but not diagnosed owing to relatively mild clinical symptoms.

HISTORY AND CLINICAL FINDINGS A 54-year-old man was admitted to hospital with dyspnoea, giddiness, lack of appetite and burning sensation in the tongue for 3 years. Gastritis was known from his history. Clinical examination showed jaundice, glossitis, systolic murmur and pallhypesthesia of both legs. INVESTIGATIONS Blood and bone marrow investigations revealed pernicious anaemia. At gastroscopy, fundal gastritis was diagnosed and two small polyps of the fundus were removed. Histologically, one of the two polyps turned out to be a gastric carcinoid type 1 (according to [16]). Additional investigations (x-ray, ultrasound of the abdomen, somatostatin-receptor scintigraphy) did not find any metastases. TREATMENT AND COURSE With the diagnosis of a pernicious anaemia the patient was treated with vitamin B12. The original symptoms and the anaemia disappeared. Additional therapy of the gastric carcinoid was not necessary. One year after beginning of the treatment, no signs of the gastric carcinoid were found. CONCLUSION In gastric polyps of patients with pernicious anemia neoplastic transformations will often be found. That is why polypectomy should always be done. The best therapy of the gastric carcinoids type 1, which are the most frequently gastric carcinoids, is endoscopic tumour removal. Surgery is the treatment of choice only for gastric carcinoids type 2 to 4. Concerning quality of life and costs, endoscopic treatment is better for patients with gastric carcinoids type 1 than conventional surgical therapy.