Steroid profile in an adrenocortical carcinoma producing aldosterone.

We report a rare case of primary aldosteronism due to an adrenocortical carcinoma. A 61-year-old woman with a history of hypertension and hypokalemia was referred for evaluation of a 4.2 cm measuring adrenal mass without secondary signs of malignancy. Endocrinological testing was consistent with primary aldosteronism. The patient underwent surgical resection of the adrenal mass; histology revealed an adrenocortical carcinoma. Postoperatively blood pressure, serum potassium, and aldosterone returned to normal. Four months after adrenalectomy, the patient presented again with hypokalemic hypertension and was found to have metastatic disease. Endocrinological investigation revealed primary aldosteronism and subclinical autonomous glucocorticoid hypersecretion. Careful hormonal investigation should be obtained in patients with adrenal masses causing excessive aldosterone secretion. In uncertain cases of primary aldosteronism, we would suggest to measure 18-hydroxycortisol levels, as excessive amounts may indicate adrenocortical carcinoma.

Insulin-associated modulation of neuroendocrine counterregulation, hypoglycemia perception, and cerebral function in insulin-dependent diabetes mellitus: evidence for an intrinsic effect of insulin on the central nervous system.

Evidence for an intrinsic effect of insulin on the central nervous system is accumulating. To test the hypothesis that insulin per se may modulate neuroendocrine counterregulation, hypoglycemia perception, and cerebral function in insulin-dependent diabetes mellitus, we examined 27 patients without any sign of classical autonomic neuropathy or evidence of so-called hypoglycemia unawareness. We used the hyperinsulinemic (0.67 vs. 2.00 mU/kg.min), stepped hypoglycemic (5.6/3.5/2.4/2.0 mmol/L) clamp technique to assess the patient's awareness of and response to equivalent hypoglycemic stimuli under different degrees of physiological hyperinsulinemia (approximately 270 vs. approximately 810 pmol/L) after an overnight euglycemic clamp (5.6 mmol/L). Simultaneously, the patient's cerebral function was assessed from his electrophysiological activity and neuropsychological skills. Higher degrees of physiological hyperinsulinemia caused enhanced neuroendocrine response (adrenaline, P < 0.05; noradrenaline, P < 0.03; GH, P < 0.02; beta-endorphin, P < 0.03; ACTH, P = 0.12; cortisol, P = 0.06; PRL, P = 0.08) and symptom awareness (total symptoms, P < 0.04; autonomic symptoms, P < 0.02; neuroglycopenia symptoms, P < 0.05; sweating, P < 0.05; heart pounding, P < 0.02; trembling, P < 0.01; lack of concentration, P < 0.02) to occur. Deteriorations of electrophysiological activity (middle latency auditory-evoked potentials, P < 0.04; Pa peak latencies, P < 0.05; Pa-V interpeak latencies, P = 0.08) and neuropsychological skills (Stroop test, P < 0.05; trail making, P = 0.12) were more pronounced the higher the insulin level, but at similar blood glucose concentrations. We conclude that insulin-associated modulation of neuroendocrine counterregulation, hypoglycemia perception, and cerebral function may occur in insulin-dependent diabetes mellitus, which indicates an intrinsic effect of insulin on the human brain.

Catecholamine secreting glomus tumor detected by iodine-123-MIBG scintigraphy.

We report the case of a 41-yr-old woman who presented with arterial hypertension and tinnitus in the right ear synchronous with pulse. She had previously undergone surgery for suspected pheochromocytoma without positive therapeutic effect. CT and MRI revealed a homogenous tumor with contrast enhancement in the right hypotympanon and foramen jugulare, and [123I]metaiodobenzylguanidine (MIBG) scintigraphy demonstrated strong tracer uptake in the same area. Selective venous sampling of catecholamines in the ipsilateral jugular vein confirmed the tumor to have originated from hormone production.

Case report: Nitazoxanide treatment failure in chronic isosporiasis.

We report a 60-year-old immunocompetent patient with chronic biliary isosporiasis who failed to respond to orally administered cotrimoxazole prophylaxis and orally administered treatment with nitazoxanide, a 5-nitrothiazole benzamide compound. Severe malabsorption was regarded as responsible for the subtherapeutic levels of nitazoxanide in plasma and bile, resulting in treatment failure. Intravenously administered cotrimoxazole stopped the shedding of Isospora belli oocysts in bile within 5 days, excluding initially suspected resistance to cotrimoxazole. Patients with malabsorption and cholangitis due to Coccidia such as Isospora belli and Cryptosporidium spp. or due to protozoa that cause microsporidiasis seem to be predisposed to fail to respond to otherwise effective treatment.

Expression and distribution of calcitonin receptor-like receptor in human hairy skin.

Calcitonin gene-related peptide and adrenomedullin exert potent effects in skin but their cellular targets are unknown. This study aimed to identify the cellular location of calcitonin receptor-like receptor (CRLR) which is pharmacologically identical to CGRP receptor-1, a putative molecular target of CGRP and adrenomedullin. RT-PCR analysis of human hairy skin revealed the presence of CRLR mRNA and immunohistochemical analysis, employing a previously characterized polyclonal antibody raised to CRLR, provided novel evidence of the cellular distribution of CRLR. Extensive and specific CRLR-immunostaining was detected in arteriolar smooth muscle and venular endothelium and is consistent with CGRP's putative role in neurogenic inflammation. Novel targets for CGRP and/or adrenomedullin were identified, including capillary endothelium, hair follicles and sweat glands.

Comparison of a mechanized version of the 'König' reaction and a fluorescence polarization immunoassay for the determination of nicotine metabolites in urine.

Smoking can be detected by the determination of cotinine in urine. We compared the performance of an automated modification of the 'König' reaction adapted to a centrifugal analyzer with an automated commercial fluorescence polarization immunoassay (TDX system). In the latter assay, cotinine, as the primary metabolite of nicotine, can be measured with high specificity. In contrast, the 'König' reaction also detects nicotine metabolites other than cotinine by a group colour reaction. Analysis speed of the 'König' reaction was about 66 samples/h with a detection limit 2 S.D. above the mean value of urine samples of non-smokers. Analysis speed of the TDX system was 41 samples/h. The coefficient of variation (C.V.) of both methods in smokers' urine was 8.6% ('König' reaction) vs. 3.4% (TDX system) in the high range and 16.4% vs. 9.5% in the low range. In a controlled, prospective study recruiting 86 cigarette-smoking volunteers, 83.7% were correctly classified as being smokers by both systems, 13.9% were classified as smokers by the 'König' reaction only and 2.4% were misclassified as non-smokers by both systems. Thus, the sensitivity of the 'König' reaction seems to be higher than in the TDX system (97.6% vs. 83.7%). Of 33 non-smoking individuals, 81.8% were correctly classified as non-smokers by both systems, 18.2 were misclassified as smokers by the 'König' reaction and no person was misclassified by the fluorescence polarization immunoassay. Thus, the specificity of the TDX system seems to be higher than that of the 'König' reaction (100% vs. 81.8%). We conclude that both systems are applicable to detect individuals who smoke regularly by simple urine testing. The higher specificity of the TDX system is outweighed by the higher sensitivity of the 'König' reaction at much lower cost.

Different awareness of hypoglycaemia induced by human or purified pork insulin in type I diabetic patients.

Recently, there have been reports on a diminished awareness of hypoglycaemia after a switch from purified pork insulin (PPI) to human insulin (HI) in insulin-dependent diabetes mellitus (IDDM). To clarify this phenomenon we investigated nine IDDM patients without signs of autonomic neuropathy. After an overnight euglycaemic clamp, blood glucose was lowered to hypoglycaemic levels by means of an artificial pancreas (Biostator) on 2 days. Insulin was used in a double-blind, randomized, cross-over fashion, either PPI or HI. The symptomatology and the hormonal counterregulation of developing hypoglycaemia was recorded. Venous concentrations of free insulin, cortisol, glucagon, growth hormone and the prevailing blood glucose were similar under both insulins. Eight out of nine IDDM patients felt more symptoms and at a higher blood glucose concentration under PPI than under HI. The first symptom of developing hypoglycaemia appeared at a mean blood glucose concentration of 61.1 +/- 5.4 mg.dl-1 under PPI and 44.4 +/- 5.3 mg.dl-1 under HI respectively (P less than 0.05). We conclude that HI may cause symptoms of hypoglycaemia to appear later and with a lesser number in comparison to PPI.

Insulin action and secretion in healthy, glucose tolerant first degree relatives of patients with type 2 diabetes mellitus. Influence of body weight.

It is a matter of controversy, whether insulin action or secretion - or both - are disturbed in first degree relatives of patients with type 2 diabetes. We intended to assess both the compensatory and the obesity-related part of insulin secretion. In order to dissect out the latter, matching for insulin sensitivity was mandatory to normalize for the compensatory part of hyperinsulinemia. In 154 healthy, glucose tolerant first degree relatives of patients with type 2 diabetes we directly quantified both insulin sensitivity (by euglycemic-glucose-clamp technique) and insulin secretion (oral glucose load; stimulated serum c-peptide). Insulin sensitivity was scattered over a wide range with a considerable overlap of both first degree relatives of patients with type 2 diabetes and 97 controls without a family history of diabetes. Average insulin sensitivity was higher in controls (8.0+/-0.3 vs. 7.1 + 0.2 ml x kg-l x min-1, p < 0.05). Prevalence of insulin resistance (defined as controls, lowest tertile for insulin sensitivity) was 40% in first degree relatives of patients with type 2 diabetes. Insulin secretion after oral glucose was significantly increased in insulin resistant first degree relatives of patients with type 2 diabetes compared to insulin sensitive first degree relatives of patients with type 2 diabetes. Early phase relative insulin secretion (30 min) expressed as x-fold increase above basal was smaller in insulin resistant first degree relatives of patients with type 2 diabetes than in insulin sensitive counterparts (5.3+/-0.4 vs. 7.3+/-0.5; p < 0.01). Body mass index was distributed over the whole range in insulin resistant first degree relatives of patients with type 2 diabetes. In the insulin sensitive subgroup absolute and relative secretion did not differ in obese (Body mass index >25 kg/m2) and insulin sensitivity-matched lean. In obese insulin resistant first degree relatives of patients with type 2 diabetes absolute hyperinsulinemia was combined with reduced and delayed relative early insulin release. In summary, degree and prevalence of insulin resistance is higher in first degree relatives of patients with type 2 diabetes than in controls. However, both groups are of heterogenous metabolic composition and family history as major discriminator should not be overestimated. Our data suggest, that hyperinsulinemia cannot simply be explained as a compensatory event to balance insulin resistance. Hypersecretion is associated with insulin resistance predominantly in combination with obesity. It might be speculated that adipose tissue derived signals to the beta-cell might lead to hypersecretion only in the genetic background that also leads to insulin resistance.

Simple computer-assisted diagnosis of acute myocardial infarction in patients with acute thoracic pain.

In order to minimize the initial diagnostic uncertainty in patients suspected of having acute myocardial infarction, we prospectively extracted predictive variables from previous history, ECG, and clinical chemical parameters of 87 patients, who were admitted for acute thoracic pain. The variables thus extracted were: Thoracic pain in previous history, duration of pain, white blood cell count, blood glucose, creatine-kinase, and S-T elevation in the ECG. These parameters were used for formulating a mathematical model based upon univariate and multivariate statistical methods. The sensitivity of the model in the study population was 95% and the specificity 77%. Correct classification was achieved in 89% of cases. In a second phase, the prognostic index was prospectively evaluated in a second set of 122 consecutive patients. In this test population, the sensitivity was 89% and the specificity 86%. 87% of patients were classified correctly.

[Snakes as pets - consequences of an exotic hobby]. / Schlangen als Haustiere - ein exotisches Hobby und seine Folgen.

HISTORY AND ADMISSION FINDINGS: We report on a young man who presented at our emergency unit with pain and swelling of his left hand, after he had been bitten into his left middle finger by a sidewinder rattlesnake one hour ago. INVESTIGATIONS: Local findings were a swollen left middle finger, a red-livid discoloration along his nail rim with paleness of the surrounding skin. Vital signs were stable, ECG showed sinus rhythm, laboratory parameters were normal, without signs of liver or kidney damage and without coagulopathy. DIAGNOSIS, TREATMENT AND COURSE: Diagnosis was local tissue reaction due to a snake bite of a sidewinder rattlesnake without evidence of systemic toxic effect. Due to the absence of systemic toxic effects the patient received monitoring of his vital signs and we controlled local tissue reaction constantly and laboratory parameters every 6 hours, as recommended by the "Giftnotrufzentrale" (poison emergency advisory service). The patient left hospital on his own will against medical advice in the night after first laboratory control, which showed no signs of organ damage and we recommended reasessment the following morning. At that time the swelling had extended to the whole arm, furthermore large hematoma reaching up to the axilla had developed over night. Again we contacted the "Giftnotrufzentrale" and decided to begin the administration of an antivenom, after allergic testing. The administration was without complications, the swelling decreased constantly and since laboratory controll still showed no signs of systemic toxin effect, we could discharge the patient on day 3. Follow-up visit 6 months later showed complete and natural healing. CONCLUSION: Snake bites are altogether rare among our patients, nevertheless since possible toxin effects and its dynamics are unpredictable and can vary highly, they demand monitoring at close intervals of vitals signs, local swelling and laboratory parameters. As early as possible an advisory service, such as "Giftnotrufzentrale" should be contacted to acquire information on possible toxin effects and availability of antivenoms. Contact to other medical disciplines (e.g. dermatology, intensive care unit, surgery, neurology, dialysis…) should be sought, depending on the further course of toxin effects. Possible comorbidities as well as allergisation due to previous bites strongly influence the course of the disease and should be evaluated. We recommend to keep precise records on the ocurrence of systemic toxin effects, as well as on local findings (e.g. fotodocumentation, marking of erythema, measurement of swelling). Manipulation of the wound is usually ineffective and therefore not recommended, also in respect of self-endangerment. After stabilization of the patient a vaccination against tetanus, if necessary, should not be forgotten.

Adrenocortical carcinoma producing 11-deoxycorticosterone: a rare cause of mineralocorticoid hypertension.

A 37-yr-old man presented with the classic signs of mineralocorticoid excess hypertension and hypokalemia. The cause was not aldosterone excess, but elevation of plasma 11-deoxycorticosterone (DOC). Computed tomography (CT) scans showed a large right adrenal mass without signs of metastatic disease. The tumor was removed by open laparotomy, and histology revealed an adrenocortical carcinoma. Two yr after diagnosis, the patient is in good general condition and there is no sign of recurrence or metastatic disease, despite the large tumor size. DOC producing adrenocortical carcinomas causing mineralocorticoid hypertension are very rare, so far only 10 cases have been described in the literature.

[Large vessel vasculitis as cause of fever of unknown origin (FUO) or systemic inflammation. Diagnosis using 18-F-fluor-2-deoxy-D-glucose positron emission tomography ((18)F-FDG-PET)]. / Vaskulitiden der grossen Gefässe als Ursache eines Fiebers unklarer Genese (FUO) oder unklarer Entzündungskonstellationen Diagnostik mittels 18-F-Fluor-2-deoxy-D-Glukose Positronen-Emissionstomographie (18F-FDG-PET).

BACKGROUND: Diagnosis and treatment of FUO or systemic inflammation with unknown reason are still a great challenge for the treating physician. We used (18)F-FDG-PET for further diagnostic work in patients in whom a diagnosis could not be established despite intensive diagnostic efforts. METHODS/RESULTS: We studied nine patients with (18)F-FDG-PET. Two female patients with known Takayasu's arteritis but undefined disease activity, and seven patients with the clinical suspicion of an underlying large vessel vasculitis. The diagnosis of active vasculitis could be confirmed by the PET-results in eight patients. Active vasculitis could be nearly ruled out in one. The diagnoses could be confirmed by follow-up visits. CONCLUSION: (18)F-FDG-PET is a useful diagnostic tool in patients with unclear systemic inflammation and FUO. Especially when large vessel vasculitis is suspected, further diagnostic work by PET seems to be of benefit. Furthermore, it offers the opportunity to evaluate disease activity and to check which vessels are involved.

Production of polyclonal antibodies in ascitic fluid of mice: technique and applications.

Balb/c mice immunised intraperitoneally with insulin developed significantly higher antibody concentrations in their serum than mice immunised subcutaneously. The antibody response was dose related, 50 ug amounts being more effective than either 20 ug or 5 ug amounts. In contrast, the antibody titres in the ascitic fluid of mice immunised with growth hormone were significantly higher after 5 ug when compared to 25 and 100 ug amounts. Repeated intraperitoneal injections of an emulsion of sheep IgG or human growth hormone in complete Freund's adjuvant, together with a single intraperitoneal injection of Pristane, induced ascites formation in most mice within 5 weeks. Up to 90 mL could be obtained from a single mouse by abdominal tapping, and the antibodies derived from the ascitic fluid proved suitable for application in a radioimmunoassay.

Successful monochemotherapy of extensive gastrointestinal Kaposi's sarcoma with bowel obstruction in acquired immunodeficiency syndrome.

We report the case history of a 28-year-old homosexual man of Caucasian origin whose diagnosis of acquired immunodeficiency syndrome was established one year before admission on the basis of a positive human immunodeficiency virus serology and cutaneous Kaposi's sarcoma. Severe postprandial vomiting pointed to bowel obstruction in an emaciated, poor risk patient. Endoscopy revealed multifocal, violaceous tumours throughout the upper gastrointestinal tract which, eventually, obstructed the duodenum. Histology confirmed the putative diagnosis of gastrointestinal Kaposi's sarcoma, which responded well to monochemotherapy with vincristine. Significant clinical improvement and repeat endoscopy indicated tumour regression and resolution of bowel obstruction.

Features of malignancy in a benign pheochromocytoma.

Pheochromocytomas are rare conditions with a prevalence of 1-2/100,000 in the general population and 1/1,000 hypertensive subjects [1]. 10% of pheochromocytomas are malignant and various attempts have been made to find useful prognostic indicators of malignancy. In general, increased plasma or urine dopamine concentrations or increased homovanillic acid excretion and lack of 131-methyliodo-benzylguanidine uptake have been associated with malignancy [2]. However, to date no specific metabolic, radiologic or histopathologic features of either benign or malignant pheochromocytomas allowing the safe diagnosis of one or the other have been identified. The diagnosis of malignant pheochromocytoma can be made only in the presence of local tissue invasion or distant metastases. We present a benign pheochromocytoma exhibiting several features suggestive of malignant disease.

Systemic vasculitis positive for circulating anti-neutrophil cytoplasmic antibodies and with predominantly neurological presentation.

A 57-year-old male patient suffering from dramatically deteriorating diffuse and focal central nervous system symptoms was admitted to hospital after a short prodromal period in a somnolent state. He was diagnosed as having systemic vasculitis positive for circulating anti-neutrophil cytoplasmic antibodies, primarily involving the brain, but also most other organ systems. Circulating anti-neutrophil cytoplasmic antibodies are highly specific for Wegener granulomatosis, though they have been detected in rare cases of other vasculitic syndromes. Central nervous system lesions as presenting signs in Wegener granulomatosis have to be regarded as rare. This case nonetheless suggests that Wegener granulomatosis has to be considered in patients with a predominantly cerebral manifestation of a vasculitic syndrome.

Selected ion monitoring gas chromatography/mass spectrometry using uniformly labelled (13C)glucose for determination of glucose turnover in man.

An optimized method is described for the mass fragmentographic determination of uniformly labelled (13C)glucose in human plasma using a butylboronic acid acetate derivative, and capillary gas chromatography. The advantages of the method are the ease and speed of the derivatization procedure, the small sample size, high precision (interassay coefficient of variation 5.7%), and applicability of a relatively low-cost mass spectrometer. This method allows glucose tracer experiments to be performed in man using the bolus injection technique, necessitating analysis of many samples. The results on glucose turnover obtained in a clinical experiment were in full agreement with previously published data.