CO-OCCURRENCE OF ADRENOCORTICAL CARCINOMA AND GASTROINTESTINAL STROMAL TUMOR IN A PATIENT WITH NEUROFIBROMATOSIS TYPE 1 AND A HISTORY OF ENDOMETRIAL CANCER.

Neurofibromatosis type 1 (NF-1) is an autosomal dominant inherited syndrome affecting 1 per 3000-4000 individuals. Patients with the neurofibromin gene mutation are more likely to develop malignancies. We report the case of a 57-year-old female with NF-1 who presented during her lifetime three neoplasms: endometrial cancer, adrenocortical carcinoma (ACC) and gastrointestinal stromal tumor (GIST). We describe the clinical, radiological and histopathological features of this rare condition. There have been reported only 10 cases of ACC together with NF-1 and 18 cases of ACC with other tumors. To the best of our knowledge it is the first reported case of NF-1 diagnosed with three cancers. Our report indicates the importance of careful and all-embracing care of patients with NF-1 in order to make a thorough investigation of any symptoms that might be a manifestation of a malignant disease.

"La Toilette". When a doctor becomes a painter: Frederic Bazille.

PURPOSE: To find endocrinological disturbances in impressionism. PATIENTS AND METHODS: Analysis of "La Toilette" painting of Frederice Bazille. RESULTS: We present a masterpiece work of Frederic Bazille "La Toilette" where a large goiter is visible. Short description of Bazille's life and painting is included. CONCLUSION: Despite of unique painting technique, thyroid disorders are visible even in impressionism.

Hageman factor C46T promoter gene polymorphism in patients with hypercortisolism.

Glucocorticoids are a group of hormones with a particularly significant effect on hemostasis. In hypercortisolemic patients increased concentrations of II, VIII, and von Willebrand factors were reported. Considerably fewer studies were concerned with factor XII (FXII). There are reports of decreased FXII concentrations in both venous and arterial thrombosis patients. Also, it was determined that FXII C46T promoter gene polymorphism leads to changes of its concentration. The aim of the study was to determine the C46T polymorphism of FXII promoter gene in hypercortisolemic patients. Thirty hypercortisolemic patients were enrolled in the study. Twenty-nine healthy individuals served as controls. Genomic DNA was isolated from peripheral blood leukocytes. To analyse the polymorphism, PCR products were digested by Hga I at 37°C for 23 h, subjected to 2% agarose gel, and stained with ethidium bromide. In all subjects FXII activity was determined using a clot-based method. All statistical calculations were performed using STATA 12.0 software. A p-value lower than 0.05 was considered statistically significant. Prevalence of FXII C46T polymorphism did not differ significantly between hypercortisolemic patients and controls. No correlation was found between FXII activity and its gene promoter polymorphism in the hypercortisolemic group; however, a clear trend was recorded toward higher FXII activities in 46C homozygotes, and lower in 46T homozygotes. Mean FXII activities did not differ significantly between hypercortisolemic patients and the control group. It seems that in hypercortisolemic patients no significant disorders are present concerning FXII concentrations due to the C46T polymorphism of its gene promoter.

Factors Affecting Dexamethasone Suppression Test Results.

Dexamethasone suppression tests are basic tools in diagnostics of hypercortisolemia. Low-dose tests play major role in screening and initial assessment. High-dose tests are aimed at more elaborate diagnostics, however their clinical value is questionable. Dexamethasone is a highly potent, synthetic steroid. It is metabolized by cytochrome P450 3A4 (CYP3A4), and so are various other xenobiotics. Due to wide spectrum of substances processed by CYP3A4, interferences and interactions are not uncommon. Physicians should be familiar with drugs modifying dexamethasone metabolism, and therefore the results of dynamic tests. Other important concerns are: drugs enhancing cortisol-binding globulin production, organ dysfunction, pseudo-Cushing states, pregnancy and other physiological conditions leading to elevated blood cortisol, cyclic Cushing disease. To properly assess and assist patients, it is crucial for health professionals to understand and be able to overcome such clinical dilemmas.

The role of immunohistochemistry in histopathological diagnostics of clinically "silent" incidentally detected adrenal masses.

BACKGROUND: The detectability of adrenal incidentalomas (incidentally found adrenal tumours) in the whole population is estimated at 0.1%; 0.42% in non-endocrine patients and at 4.3% in oncologically diagnosed ones. Even up to 16% of incidentalomas of adrenal glands can be malignant lesions. The issue of crucial importance is the histopathological differentiation between benign lesions and malignant tumours of the adrenal cortex and medulla. OBJECTIVES: To evaluate whether the immunohistochemical analysis of the expression of p53, p21, PCNA and Ki67 in the tumour's tissue can be useful in the histopathological diagnostics of adrenal incidentalomas and whether it is important for prognosis. MATERIAL AND METHODS: Our series consisted of 74 tumour samples from 164 patients operated for incidentalomas. There were 43 cortical adenomas, 11 cortical adrenocarcinomas and 20 PHEOs (including 5 malignant lesions). Using monoclonal antibodies, the expression of p53, p21, PCNA and Ki67 was evaluated. RESULTS: We found a statistically significant correlation between the expression of p53, p21, Ki67 and the differential diagnosis of adrenal cortical adenoma and adrenocortical carcinoma (for proteins: p53 p=0.010, for p21 p=0.010, for Ki67 p<0.001). The statistical significant correlation between PCNA protein and diagnosis of adrenal cortical adenoma and adrenocortical carcinoma was not found. The statistically significant correlation between p21, PCNA proteins and the diagnosis of benign and malignant PHEOs was not estimated. There was no expression of Ki67 or p53 protein above the assumed level in benign and malignant pheochromocytomas. The statistically significant correlation between p53, p21, PCNA or Ki67 and the occurrence of metastases in adrenocarcinoma and malignant PHEOs was not found.

Nesidioblastosis--a rare cause of hypoglycaemia in adults.

A case of suspected clinically hormonally active insulinoma in a 48-year-old woman is presented. Despite the lack of features, which might correspond to the insulinoma in radiological examinations, the patient was qualified for a distal subtotal pancreatectomy and then, due to persistent hyperinsulinism, for total pancreatectomy. The insulinoma was found neither in a palpable examination of the pancreas nor in the intraoperative ultrasonic examination. In a histopathological examination supplemented with immunohistochemical tests, nesidioblastosis - a rare cause of hypoglycaemia in adults - was diagnosed.

Vitamin D in thyroid disorders.

Vitamin D's canonical role are its effects exerted on the musculoskeletal system. In the last decades the importance of this hormone has been studied in the context of extraskeletal health. Hypovitaminosis D and several polymorphic variants of genes coding proteins crucial in the transport, metabolism and effects of vitamin D have been associated with negative health outcomes.In this review the current state of knowledge on the role of vitamin D in thyroid disorders is presented. The review is based on a literature search of the PubMed database performed in December 2014. The following search terms were used in conjunction with 'vitamin D': thyroid cancer, Graves', Hashimoto, thyroiditis, autoimmune thyroid, AITD, nodules, hyperthyroidism, and hypothyroidism.Currently, similarly to other extraskeletal health outcomes, a clear role of vitamin D has not been demonstrated in thyroid disorders. Further research is necessary to fully elucidate the importance of vitamin D in case of thyroid disease.

Hemostatic Disorders in Hormonally Active Pituitary Tumors.

Endocrinopathies encompass heterogeneous diseases that can lead to hemostasis disorders at various stages over their clinical course. Normal hemostasis requires an equilibrium between the processes of coagulation and fibrinolysis, which depend on multiple activators and inhibitors. To date, the influence of various hormonal disorders on the hemostatic system has been assessed many times. The aim of this review was to analyze hemostasis abnormalities that occur in patients with hormonally active pituitary tumors: corticotropinoma, somatotropinoma, prolactinoma, gonadotropinoma and thyrotropinoma. Authors discuss studies that examined coagulation and hemostasis parameters among patients with these tumors, as well as analyze antithrombotic prophylaxis approach for endogenous hypercortisolemia subjects in particular.

One hundred and ten consecutive uncomplicated retroperitoneal videoscopic adrenalectomies--Polish multicentre study.

AIM: The authors evaluate the effectiveness of videoscopic adrenalectomy (VA) for a variety of endocrine disorders. METHODS: One hundred and ten consecutive videoscopic adrenalectomies performed from October 1995 till December 2000 were reviewed and followed up for adequacy of surgical treatment in 2 surgical departments. There were 79 females and 31 males included in the study. The mean age was 48.0 years (range 23-71 years). Indications for the operations were: phaeochromocytomas (n=5), aldosterone-producing adenomas (n=19), cortisol-producing adenomas (n=10), Cushing's disease (n=3) and non-secreting tumours (n=72). RESULTS: There was no mortality and no morbidity both intraoperatively and in the postoperative course. In 8 cases conversion to open surgery was instituted - in 4 cases due to an unintended lesion of pertioneum without damage to the intraperitoneal organs. Mean operative time was 156 min (range 52-280 min), and estimated blood loss was 73 ml (range 20-300 ml). The average length of hospital stay was 2.9 days (range 2-7 days). None of the patients revealed either recurrence of hormonal hypersecretion or tumour mass in imaging studies during the follow-up period (range 1-34 months). CONCLUSION: 1. VA is recommended in patients with hormonally active tumours and in patients with benign adrenal masses of a diameter up to 6 cm. 2. VA is a safe and feasible procedure if performed by a team experienced in endocrine and endoscopic surgery. 3. VA is a procedure better than open adrenalectomy in management of small, non-malignant tumours because of the reduction of operative trauma.

Clinical and histopathological evaluation of the adrenal incidentaloma.

Clinically silent adrenal masses (incidentaloma) are incidentally discovered lesions, when noninvasive imaging methods (USG, CT, MRI) are performed for reasons other than known or suspected adrenal disease. Most studies report on a prevalence of adrenal incidentaloma range between 1% and 10% in radiological series. Between 1994 and 1999 we observed in our Department 57 patients with incidentalomas of adrenal glands. After endocrinological evaluation silent Cushing's syndrome was found in 2 cases (3.5%). Fifty two patients were qualified for surgery. Adrenocortical adenoma was diagnosed in 73.1%; adrenocortical carcinoma in 7.7%; pheochromocytoma in 7.7% and less frequent adrenal lesions in 11.5%. All adrenal carcinomas and malignant pheochromocytomas (11.5%) were found in tumors with diameter over 4 cm.

[Carcinoid: unusual clinical course]. / Rakowiak--nietypowe przebiegi kliniczne.

Carcinoid is a slowly developing neuroendocrine tumour. It appears with frequency of 1.5/100,000 persons. Usually it is localized in appendix, small intestine, rectum and bronchi. Clinical sings. of carcinoid syndrome develop in only 10% cases of tumour. We present three cases of carcinoid: the first one with evidences of heart insufficiency, the second one with evidences of colon cancer, the third one coexisting with Graves-Basedow disease.

[Laparoscopic adrenalectomy from the lateral retroperitoneal approach]. / Adrenalektomia laparoskopowa z dostepu pozaotrzewnowego.

From April to November 1998 eleven patients (8 female and 3 male, mean age 48.5; range 23-69) with adrenal gland tumor underwent laparoscopic adrenalectomy from the lateral retroperitoneal approach. Authors report their primary experience; introduce their own material and describe the operative technique of laparoscopic adrenalectomy from lateral retroperitoneal approach. Besides one case of Conn syndrome, all tumors were hormonally non-active. In 10 patients the adrenal masses were incidentally discovered during such imaging examination as abdominal ultrasonography and computed tomography. All tumors were benign in postoperative histopathological examination. The localization was unilateral and suprarenal in all cases (7 right, 4 left). Both operation and postoperative course in all patients were uncomplicated. One conversion to "open" procedure had been performed due to laparoscopic equipment damage.

[Primary hyperparathyroidism--advances in diagnosis and treatment]. / Pierwotna nadczynnos'c' przytarczyc--poste,py w rozpoznawaniu i leczeniu.

The primary hyperparathyroidism (PHP) is a complex of nosological symptoms associated with disturbances of calcium-phosphate equilibrium and bone metabolism, caused by excessive secretion of parathyroid hormone. In the past regarded as rare entity, today it is arousing great interest due to ever more frequent diagnosis of it in the stage of subtle psychoneurological changes or in the asymptomatic period. Untreated PHP leads to the development of a number of organ complications, and even to a life-threatening state, that is hypercalcemic crisis. Surgical operation is the treatment of choice.

[Depression syndrome in a patient with primary hyperparathyroidism. Differential diagnostic difficulties]. / Zespól depresyjny u chorej z pierwotna nadczynnoscia przytarczyc. Trudnosci rozpoznawcze i rónicowe.

A case is presented of a 62-year-old female patient treated for 18 months for depression syndrome. Occurrence of hypercalcaemic crisis enabled the diagnosis of primary hyperparathyroidism. Differential diagnostic difficulties are discussed.

[Carcinoid--advances in diagnosis and treatment]. / Rakowiak--postepy w rozpoznawaniu i leczeniu.

Carcinoid is one of the most frequently diagnosed neuroendocrine tumours. It develops slowly but grows by infiltration and has the ability to give metastases in distant organs. The clinical picture is very diverse and in 10% of cases the signs called carcinoid syndrome develop. Not infrequently it produces also peptide hormones. In the present paper the most modern diagnostic methods, possibilities of surgical and pharmacological treatment of this extremely interesting neoplasm are discussed.

[A case of Kearns-Sayre syndrome]. / Przypadek zespolu Kaerns-Sayre.

In the literature there are only 3 cases of women with Kaerns-Sayre Syndrome (KSS) who delivered a healthy child. Our case is the fourth. The purpose of the report is to describe a 30-year old woman presenting typical clinical features of KSS, namely progressive external ophthalmoplegia, pigmentary retinal degeneration and onset of the disease before the age of 20. It was also associated with cardiac conduction defects, neurological symptoms and variety of endocrine and metabolic disorders. On muscle biopsy (m. biceps brachii) mitochondrial abnormalities on electron microscopy were seen. KSS is a form of mitochondrial myopathy with specific clinical features. Recognition of mtDNA deletion as the genetic basis of KSS confirmed the validity of clinical criteria.

[Scintigraphically detected "hot" thyroid nodules in the specimens from patients of the Thyroid Disease Clinic in Gda'nsk--clinico- histopathological analysis]. / Guzki scyntygraficznie gorace w materiale chorych poradni chorób tarczycy w Gdansku--analiza kliniczno-histopatologiczna.

A group of 153 patients with scintigraphically detected autonomic "hot" nodules of the thyroid has been subjected to clinical and histopathological analysis. Substantial part of these patients (30.1%) had hyperthyroidism, partly (in 19.9% of cases) in the form of the thyrocardiac syndrome. A most frequent histopathological lesion found within "hot" nodules was follicular adenoma. The occurrence of malignancy in the form of highly differentiated thyroid carcinoma was observed in 2.6% of cases. The incidence of thyroid carcinoma within "hot" nodules was in our material only two and half times smaller than in a previously analyzed group of patients with "cold" nodules of the thyroid.

Influence of receptor activator of nuclear factor kappa B ligand, osteoprotegerin and interleukin-33 on bone metabolism in patients with long-standing ulcerative colitis.

BACKGROUND: Ulcerative colitis (UC) is a chronic disease with periods of remission and recurrences. Dysfunction of the local immune response leads to chronic inflammation within the large intestine which triggers morphological changes in the intestinal wall as well as induces the synthesis of numerous factors that have an adverse impact on the bone metabolism. The aim of the study was to determine the expression of RANKL, OPG and IL-33 in mucosal biopsies of UC patients with long disease duration as well as serum level of these cytokines in the context of bone density and bone metabolism. MATERIALS AND METHODS: The UC group consisted of 56 patients with average disease duration of 16y. The control group comprised 37 healthy individuals. Local expression of cytokines was assessed in the biopsies of colonic mucosa by the real-time PCR and immunohistochemistry (IHC), and their serum concentration was measured by ELISA. RESULTS: The increased bone resorption observed in patients with UC was reflected by low bone density and high serum level of C-terminal telopeptide (CTX). Mucosal RANKL expression and serum concentration were similar in UC group and healthy subjects, however, UC patients had higher local expression of OPG and serum OPG concentration. Increased IL-33 gene expression was observed only in UC at the mRNA level. We propose that bone resorption in UC patients despite OPG up-regulation could be caused by IL-33-induced mucosal synthesis of a potent proinflammatory cytokine, such as TNF-α, known as a possible inducer of osteoclastogenesis in the way independent of RANKL.

Disorders of hemostasis in overt and subclinical hypercortisolism.

Glucocorticoids are a group of hormones of a particular impact on hemostasis. Epidemiological studies show an approximately severalfold greater incidence of thromboembolic events in hypercortisolemic patients compared to those without hormonal disorders. The prothrombotic action of this steroid class is caused by both the direct impact of hypercortisolism on the activation of coagulation and the inhibition of fibrinolysis, as well as, the pathology of hemostasis due to metabolic disorders, which occur in this endocrinopathy. The aim of this study was to discuss the hemostasis abnormalities that occur in patients with overt and subclinical hypercortisolism with a particular emphasis on plasmatic coagulation, endogenous anticoagulation system, homocysteine and proinflammatory cytokines.

Giving radioiodine? Think about airport security alarms.

An increased sensitivity of airport detectors, a growing number of isotopic tests, and globalization of the society have raised a number of false positive radioactive alarms at airports and public places. This paper presents two new cases of patients who triggered airport security alarms after receiving 740MBq of (131)I for non-toxic goitre and attempts to compare surprisingly limited literature concerning this problem. A 57-year-old man triggered a security alarm at three different airports on the 17th, 28th, and 31st day after radioiodine exposure. Interestingly enough, in the meantime, on the 18th and 22nd day, no radiation was detected in him at the airport where he was twice detained as a source of radiation later on. The second case presents a 45-year-old woman who activated security alarm detectors while crossing a border on her coach trip 28 days after radioiodine administration.