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.

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.

OBJECTIVE:Insulinoma causes fasting hypoglycaemia due to inappropriate insulin secretion. The diagnosis of insulinoma is based on Whipple's triad during a supervised fasting test. The aim of our study was to evaluate retrospectively the percentage of positive 48-hour fasting tests in a large series of patients with insulinoma.DESIGN, PATIENTS AND METHODS:In a retrospective study, we identified 39 patients (24 females, 15 men; average age 47 years [range 12-78 years]) with insulinoma. Sixteen patients were diagnosed by spontaneous hypoglycaemia. Twenty-three patients with insulinoma were tested with a 48-hour fasting test and compared to 31 healthy controls who had a negative fasting test and were followed up for at least two years.RESULTS:The fast was terminated due to neuroglycopenic symptoms in 4 patients (17.4%) at the 12th hour, in 17 patients (73.9%) at the 24th hour, and in 22 patients (95.7%) at the 48th hour. One patient with insulinoma had no neuroglycopenic symptoms, but was diagnosed by glucose and insulin levels during the 48-hour fast. Healthy controls had significantly higher blood glucose and lower insulin levels, and a lower insulin-glucose ratio than patients with insulinoma at the end of the fast.CONCLUSIONS:In conclusion, the 48-hour fasting test was successful in the diagnosis of insulinoma in 95.7% of patients. In this series we did not observe a need for fasting beyond 48 hours.

BACKGROUND:Multiple-endocrine-neoplasia-type-1 (MEN1) is an autosomal-dominant inherited disorder characterized by the combined occurrence of primary hyperparathyroidism (pHPT), gastroenteropancreatic neuroendocrine tumors (GEP), adenomas of the pituitary gland (APA), adrenal cortical tumors (ADR) and other tumors. As the tumors appear in an unpredictable schedule, uncertainty about screening programs is persisting.OBJECTIVE:To optimize screening and to analyze possible differences in sporadic versus familial cases.METHODS:We analyzed data of 419 individuals including 306 MEN-1 patients (138 isolated and168 familial cases out of 102 unrelated families).RESULTS:A total of 683 tumors occurred consisting of 273 pHPT, 138 APA, 166 GEP, 57 ADR, 24 thymic- and bronchial-carcinoids as well as 25 neoplasms of other tissues. The age-related penetrance was determined as 10%, 35%, 67%, 81% and 100% at 20, 30, 40, 50 and 65 years respectively. Although pHPT being the most frequent first manifestation (41%), also GEP (22%) or APA (21%) were found to be the first presentation. APA occurred significantly more frequent (p<0,05) in isolated (n=138) than in familial (n=168) cases, whereas GEP showed a tendency to occur more often in familial cases. Genotype/phenotype correlation in 140 clinically affected MEN-1 cases showed a tendency for truncating mutations, especially nonsense mutations to be associated to GEP and carcinoids of the lungs and thymus.CONCLUSION:In view of the morbidity and frequency in familial cases an effective screening programme should aim at an early diagnosis of GEP particularly when truncating, especially nonsense mutations are found.

Introduction: Endovascular therapy is being used increasingly also to treat ruptured infrarenal aortic aneurysms. Non-traumatic rupture of non-aneurysmatic infrarenal aorta is an absolute rarity. Methods: The feasibility of endovascular repair of infrarenal aortic rupture is demonstrated with a case history and a literature review. Results: A 58-year-old male developed spontaneous rupture of his infrarenal aorta after successful chemotherapy resulting in regression of a periaortic tumor. The patient suffered from a sepsis for several days before aortic rupture was discovered during computed tomography for focus search. Immediate endovascular stent-graft repair was performed under emergency conditions. There is no recurrence and the patient is doing well with the stent-graft in place without any pathological finding after a follow-up of 24 months. So far only three further cases have been reported of endovascular repair for penetrating atherosclerotic ulcer with rupture of the infrarenal aorta. Discussion: This is the first report of endovascular repair of aortic rupture due to successful chemotherapy of a periaortic mesothelioma. Furthermore, this is the fourth case of successful stent-graft placement to treat non-aneurysmatic rupture of the infrarenal aorta. Minimally invasive endovascular therapy should become a standard treatment option for aortic rupture.

INTRODUCTION:Endovascular therapy is being used increasingly also to treat ruptured infrarenal aortic aneurysms. Non-traumatic rupture of non-aneurysmatic infrarenal aorta is an absolute rarity.METHODS:The feasibility of endovascular repair of infrarenal aortic rupture is demonstrated with a case history and a literature review.RESULTS:A 58-year-old male developed spontaneous rupture of his infrarenal aorta after successful chemotherapy resulting in regression of a periaortic tumor. The patient suffered from a sepsis for several days before aortic rupture was discovered during computed tomography for focus search. Immediate endovascular stent-graft repair was performed under emergency conditions. There is no recurrence and the patient is doing well with the stent-graft in place without any pathological finding after a follow-up of 24 months. So far only three further cases have been reported of endovascular repair for penetrating atherosclerotic ulcer with rupture of the infrarenal aorta.DISCUSSION:This is the first report of endovascular repair of aortic rupture due to successful chemotherapy of a periaortic mesothelioma. Furthermore, this is the fourth case of successful stent-graft placement to treat non-aneurysmatic rupture of the infrarenal aorta. Minimally invasive endovascular therapy should become a standard treatment option for aortic rupture.

Insulinoma causes fasting hypoglycemia due to inappropriate insulin secretion. The diagnosis of insulinoma is based on Whipple's triad (1. symptoms precipitated by fasting with 2. associated blood sugars of 50mg/dl or less and 3. relief of symptoms by glucose administration) during a supervised 72h fasting test. After introducing reliable assays for measurement of insulin and proinsulin, there is an ongoing debate whether a 48h fasting test is sufficient for diagnosis or a 72h fast is necessary to detect patients with insulinoma. The aim of our study was to evaluate the positive fast within 48h in a large series of patients with insulinoma. In a retrospective study (1970–2004) we identified 39 patients (24 females, 15 men; average age 47 years [range 12–78 years]) with insulinoma. Surgical pathology confirmed the diagnosis in 34 cases: 24 patients had a benign tumor, 4 had malignant insulinoma and 6 patients had multiple endocrine neoplasia type 1. The average body mass index (BMI) was 28.5 (range 17.3–39.1). 16 patients were diagnosed by spontaneous hypoglycaemia. 23 patients were tested with a 48h fasting test. The fast was terminated due to neuroglycopenic symptoms in 4 patients (17.4%) by 12h, in 17 patients (73.9%) by 24h, and in 22 patients (95.7%) by 48h. One patient had no neuroglycopenic symptoms, but was diagnosed by glucose and insulin levels during the 48h fast. In conclusion, the 48h fasting test was successful in the diagnosis of insulinoma in our patient cohort, especially if even subtle signs of neuroglyopenia were recognized by the medical personnel. In this series we did not observe a need for fasting beyond 48h, and we therefore established the 48h fasting test as standard protocol resulting in cost reduction.

Ectopic ACTH production represents a subset of disease entities which lead to hypercortisolism and are due to ectopic ACTH secretion by organs/tumours other than the pituitary gland. Very few of these tumours are of adrenal origin. In rare cases unilateral pheochromocytomas have been observed as a cause of ACTH production. We describe a 53-yr-old female with arterial hypertension who presented with a cushingoid-habitus and serious recurrent hypertensive crisis. Laboratory studies indicated severe hypokalaemia (K 2,28 mmol/l), alkalosis, diabetes (HbA1c 11,8%), and random serum cortisols greater than 1400 nmol/l. ACTH levels were elevated at >62 pmol/l. The endocrinological investigation showed biochemical evidence of ectopic ACTH production (lack of regulation in Dexamethason-/CRH-Test). Unexspecedly urinary catecholamines were markedly elevated (Adr. >300 nmol/l, Noradr. >3500 nmol/l) leading to the diagnosis of a pheochromocytoma.

BACKGROUND:Estimation of body cell mass (BCM) has been regarded valuable for the assessment of malnutrition.AIM:To investigate the value of segmental bioelectrical impedance analysis (BIA) for BCM estimation in malnourished subjects and acromegaly.METHODS:Nineteen controls and 63 patients with either reduced (liver cirrhosis without and with ascites, Cushing's disease) or increased BCM (acromegaly) were included. Whole-body and segmental BIA (separately measuring arm, trunk, leg) at 50 kHz was compared with BCM measured by total-body potassium. Multiple regression analysis was used to develop specific equations for BCM in each subgroup.RESULTS:Compared to whole-body BIA equations, the inclusion of arm resistance improved the specific equation in cirrhotic patients without ascites and in Cushing's disease resulting in excellent prediction of BCM (R(2) = 0.93 and 0.92, respectively; both P<0.001). In acromegaly, inclusion of resistance and reactance of the trunk best described BCM (R(2) = 0.94, P<0.001). In controls and in cirrhotic patients with ascites, segmental impedance parameters did not improve BCM prediction (best values obtained by whole-body measurements: R(2)=0.88 and 0.60; P<0.001 and <0.003, respectively).CONCLUSION:Segmental BIA improves the assessment of BCM in malnourished patients and acromegaly, but not in patients with severe fluid overload.

Clinical EndocrinologyVolume 59, Issue 3 p. 404-405 PET scan in occult ectopic ACTH syndrome: a useful tool? H. Biering, Corresponding Author H. Biering Clinic for Internal Medicine, Gastroenterology, Hepatology and Endocrinology and Dr med. Henrik Biering, Universitätsklinikum Charité, Medizinische Klinik mit Schwerpunkt Gastroenterologie, Hepatologie und Endokrinologie, Schumannstr. 20/21, 10117 Berlin, Germany. Tel: +49-30-450-514032; Fax: +49-30-450-514901. E-mail: [email protected]Search for more papers by this authorM. Pirlich, M. Pirlich Clinic for Internal Medicine, Gastroenterology, Hepatology and Endocrinology andSearch for more papers by this authorJ. Bauditz, J. Bauditz Clinic for Internal Medicine, Gastroenterology, Hepatology and Endocrinology andSearch for more papers by this authorD. Sandrock, D. Sandrock Clinic for Nuclear Medicine, University Hospital Charité, Humboldt University, Berlin, GermanySearch for more papers by this author H. Lochs, H. Lochs Clinic for Internal Medicine, Gastroenterology, Hepatology and Endocrinology andSearch for more papers by this authorH. Gerl, H. Gerl Clinic for Internal Medicine, Gastroenterology, Hepatology and Endocrinology andSearch for more papers by this author H. Biering, Corresponding Author H. Biering Clinic for Internal Medicine, Gastroenterology, Hepatology and Endocrinology and Dr med. Henrik Biering, Universitätsklinikum Charité, Medizinische Klinik mit Schwerpunkt Gastroenterologie, Hepatologie und Endokrinologie, Schumannstr. 20/21, 10117 Berlin, Germany. Tel: +49-30-450-514032; Fax: +49-30-450-514901. E-mail: [email protected]Search for more papers by this authorM. Pirlich, M. Pirlich Clinic for Internal Medicine, Gastroenterology, Hepatology and Endocrinology andSearch for more papers by this authorJ. Bauditz, J. Bauditz Clinic for Internal Medicine, Gastroenterology, Hepatology and Endocrinology andSearch for more papers by this authorD. Sandrock, D. Sandrock Clinic for Nuclear Medicine, University Hospital Charité, Humboldt University, Berlin, GermanySearch for more papers by this author H. Lochs, H. Lochs Clinic for Internal Medicine, Gastroenterology, Hepatology and Endocrinology andSearch for more papers by this authorH. Gerl, H. Gerl Clinic for Internal Medicine, Gastroenterology, Hepatology and Endocrinology andSearch for more papers by this author First published: 14 August 2003 https://doi.org/10.1046/j.1365-2265.2003.01853.xCitations: 16Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume59, Issue3September 2003Pages 404-405 RelatedInformation

TSH antibody 222 Apparent cortisone reductase deficiency

Hypokalaemic periodic paralysis is a fairly common complication of hyperthyroidism in Asian populations, but a rare event in Caucasians. In the present work we describe 2 male Caucasian patients with thyrotoxic periodic paralysis (TPP) as initial clinical manifestation of Graves’ disease. Further diagnostic procedures demonstrated unilateral adrenal adenoma and hyperandrogenaemia in both patients. To date, only few data are available concerning the hormonal status of Caucasian patients with TPP. The constellation of TPP and adrenal adenomas with increased levels of androgens has not been described previously. Since androgens are capable of inducing sodium-potassium ATPase, which is thought to be centrally involved in the pathogenesis of TPP, hyperandrogenaemia may have triggered the manifestation of paralytic attacks in our patients. It may be of interest to focus not only on thyroid dysbalances in patients with TTP but also to investigate other hormonal disturbances.

The vast majority of Caucasian patients presenting with hereditary hemochromatosis demonstrate a single homozygous missense mutation in the HFE gene (C282Y). The underlying genetic defects in hemochromatosis patients of non-Caucasian origin are largely unknown. A 48-year-old man of Vietnamese origin presented with insulin-dependent diabetes mellitus, tertiary adrenocortical insufficiency, and laboratory results highly indicative of hereditary hemochromatosis. Because the patient was negative for the known HFE gene mutations C282Y, H63D, and S65C HFE, the entire coding region and intron/exon boundaries of the HFE gene was investigated. Sequencing studies identified a homozygous G-to-A transition at position +1 of intron 5 (IVS5+1 G/A). This newly described mutation alters the invariant G at position +1 of the 5' splice site causing altered mRNA splicing and exon skipping with exon 4 being spliced to exon 6. Both heterozygously affected children (age 19 and 20 years) had moderately increased ferritin levels with normal serum iron concentration and transferrin saturation. The newly described mutation was not detected in a control group consisting of 220 Caucasian individuals as verified by allele-specific polymerase chain reaction. We describe for the first time a homozygous HFE splice site mutation (IVS5+1 G/A) in a non-Caucasian patient with hereditary hemochromatosis. Although the absence of this novel HFE gene mutation in Caucasian subjects suggests that the mutation is exclusive to this family, mutation screening in populations of different ethnic background is recommended to precisely define its contribution to hereditary hemochromatosis in non-Caucasian patients.

Cushing's syndrome (CS) is associated with low fat-free mass, but it is unclear whether hypercortisolism causes a loss of whole body protein. Body composition was studied prospectively in 15 patients with untreated CS (n = 14 pituitary adenoma; n = 1 adrenal adenoma), in 15 nonobese healthy controls, and in 15 weight-matched obese controls by 3 different methods: total body potassium counting (TBP), bioelectrical impedance analysis (BIA), and anthropometry. In 6 patients, body composition was studied before and within 6 months after pituitary surgery. In CS patients and weight-matched controls, body weight and total body fat were significantly higher than in nonobese controls. In CS patients, TBP was 18.4% lower than predicted, whereas in weight-matched controls TBP was 7.1% higher than predicted. As compared with nonobese and weight-matched controls, in CS patients TBP indicated a significant loss of body cell mass (BCM) of -20.2 and -21.1%, respectively. A significantly reduced arm muscle area of -21.3% compared with weight-matched controls also indicated a loss of whole body protein. In CS, however, BIA overestimated BCM when compared with TBP by +18% and agreement between BIA and TBP in the individual patient was poor (limits of agreement plus minus 27.6%), indicating the invalidity of standard BIA equations in this population. Measurements performed before and 6 months after successful pituitary surgery demonstrated a significant loss of body weight (-11%) and body fat (-33%), but BCM and muscle mass remained on a constant low level. In conclusion, this study shows that, in patients with CS, a significantly reduced BCM indicates a true protein loss. The second interesting finding is that in the early recovery after successful treatment of hypercortisolism patients lose body fat without gaining BCM or muscle mass.

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.