Bilateral testicular tumors resulting in recurrent Cushing's syndrome after bilateral adrenalectomy

Contains fulltext : 170123.pdf (publisher's version ) (Closed access)Context: Recurrence of hypercortisolism in patients after bilateral adrenalectomy for Cushing disease is extremely rare. Patient: We present a 27-year-old man who previously underwent bilateral adrenalectomy for Cushing disease with complete clinical resolution. Cushingoid features recurred 12 years later, with bilateral testicular enlargement. Hormonal tests confirmed adrenocorticotropic hormone (ACTH)-dependent Cushing disease. Surgical resection of the testicular tumors led to clinical and biochemical remission. Design and Results: Gene expression analysis of the tumor tissue by quantitative polymerase chain reaction showed high expression of all key steroidogenic enzymes. Adrenocortical-specific genes were 5.1 x 105 (CYP11B1), 1.8 x 102 (CYP11B2), and 6.3 x 104 (MC2R) times higher than nonsteroidogenic fibroblast control. This correlated with urine steroid metabolome profiling showing 2 fivefold increases in the excretion of the metabolites of 11-deoxycortisol, 21-deoxycortisol, and total glucocorticoids. Leydig-specific genes were 4.3 x 101 (LHCGR) and 9.3 x 100 (HSD17B3) times higher than control, and urinary steroid profiling showed twofold increased excretion of the major androgen metabolites androsterone and etiocholanolone. These distinctly increased steroid metabolites were suppressed by dexamethasone but unresponsive to human chorionic gonadotropin stimulation, supporting the role of ACTH, but not luteinizing hormone, in regulating tumor-specific steroid excess. Conclusion: We report bilateral testicular tumors occurring in a patient with recurrent Cushing disease 12 years after bilateral adrenalectomy. Using mRNA expression analysis and steroid metabolome profiling, the tumors demonstrated both adrenocortical and gonadal steroidogenic properties, similar to testicular adrenal rest tumors found in patients with congenital adrenal hyperplasia, suggesting the presence of pluripotent cells even in patients without congenital adrenal hyperplasia

Guideline on urothelial carcinoma of the bladder

Urothelial carcinoma of the bladder is diagnosed predominantly in people over 60 years of age. The most common symptom is haematuria. Smoking is an important risk factor (relative risk 2.5 to 3). Cystoscopy is performed whenever bladder carcinoma is suspected. The recurrence rate of a non-muscle invasive urothelial carcinoma is high (31-78% within 5 years). A single intravesical instillation with a chemotherapeutic agent within 24 hours of transurethral resection (TUR) reduces the risk of recurrence. Carcinoma in situ (CIS) should be treated as high-grade urothelial carcinoma. Standard treatment for patients with non-metastasized muscle-invasive urothelial carcinoma is cystectomy in combination with extensive lymph node dissection. There are several possibilities for urinary diversion following cystectomy, none of which are any better than the others. Bladder-sparing brachytherapy may be used in patients with solitary T1 - T2 urothelial carcinoma &lt; 5 cm. Neoadjuvant cisplatin-containing chemotherapy prior to cystectomy in muscle-invasive carcinoma only slightly improves survival. Cisplatin-containing combination chemotherapy is the standard treatment for metastasized urothelial carcinoma.</p

Diagnosis of alpha-1-antitrypsin deficiency in bleeding disorder-related neonatal death

Alpha-1-antitrypsin (AAT) deficiency is a rare genetic disorder characterized by hepatitis in neonates, childhood and adulthood (protease inhibitor (PI)*ZZ) and emphysema with or without hepatitis (PI*ZZ)/(PI*SS,SZ or null) in adulthood. We report the case of a female neonate born at 40 weeks of gestation who presented with vitamin K deficiency-related intracranial bleeding and cholestasis of which she died at 28 days of age. At autopsy, the infant was found to have intracranial bleeding, hepatomegaly, and cholestasis with paucity of bile ducts in the liver. Small periodic acid-Schiff diastase positive intrahepatic granules and positive staining with antibodies against AAT protein suggested an AAT deficiency. AAT is a glycoprotein that has a protease inhibitor function. Its deficiency can be the result of various point mutations in Serpin 1 located on chromosome 14. The diagnosis AAT deficiency was confirmed by mutation analysis showing the PI*ZZ genotype in the neonate. In conclusion, AAT deficiency is a rare genetic disorder that can lead to a serious bleeding disorder in the neonatal period if not recognised on time. Pathological diagnosis together with verifying molecular analysis can be used to identify index patients

GATA transcription factors in testicular adrenal rest tumours

Testicular adrenal rest tumours (TARTs) are benign adrenal-like testicular tumours that frequently occur in male patients with congenital adrenal hyperplasia. Recently, GATA transcription factors have been linked to the development of TARTs in mice. The aim of our study was to determine GATA expression in human TARTs and other steroidogenic tissues. We determined GATA expression in TARTs (n = 16), Leydig cell tumours (LCTs; n = 7), adrenal (foetal (n = 6) + adult (n = 10)) and testis (foetal (n = 13) + adult (n = 8)). We found testis-like GATA4, and adrenal-like GATA3 and GATA6 gene expressions by qPCR in human TARTs, indicating mixed testicular and adrenal characteristics of TARTs. Currently, no marker is available to discriminate TARTs from LCTs, leading to misdiagnosis and incorrect treatment. GATA3 and GATA6 mRNAs exhibited excellent discriminative power (area under the curve of 0.908 and 0.816, respectively), while immunohistochemistry did not. GATA genes contain several CREB-binding sites and incubation with 0.1 mM dibutyryl cAMP for 4 h stimulated GATA3, GATA4 and GATA6 expressions in a human foetal testis cell line (hs181.tes). Incubation of adrenocortical cells (H295RA) with ACTH, however, did not induce GATA expression in vitro Although ACTH did not dysregulate GATA expression in the only human ACTH-sensitive in vitro model available, our results do suggest that aberrant expression of GATA transcription factors in human TARTs might be involved in TART formation

The influence of thermo-chemotherapy on bladder tumours: an immunohistochemical analysis

To study the influence of microwave induced thermo-chemotherapy on high-grade urothelial cell carcinomas. Five groups of each three patients were formed of whom initial biopsies and cystectomy samples were collected. Patients were treated 2 days prior to cystectomy with mitomycin-C (group 1), hyperthermia (group 2) or thermo-chemotherapy (group 3). Group 4 patients had been treated with a cycle of six thermo-chemotherapy treatments prior to cystectomy and group 5 patients served as control (no treatment). Tumour samples were stained with Haematoxylin and Eosin, monoclonal antibody Ki-67 and the monoclonal antibody p53. In six out of the nine patients treated with hyperthermia a decrease in proliferation activity in the tumour was found. Seven out of nine patients treated with hyperthermia showed a decrease in p53 activity. A decrease in proliferation activity and p53 activity illustrate the potential role of thermo-chemotherapy as a promising intravesical treatment