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Some resected adrenal-confined adrenocortical carcinomas metastasize and others not. The present study was designed to evaluate the expression of metallothionein protein (MT) and minichromosome maintenance protein-2 (MCM2) in adrenocortical carcinomas and adrenocortical adenomas, and to test the correlation between this and adrenocortical carcinoma aggressiveness.The study comprised 14 patients operated on for adrenocortical carcinoma, 15 operated on for adrenocortical adenoma and 2 with normal adrenals. Hematoxylin-eosin staining was used for histological evaluation under light microscopy, and sequential sections were used for MCM2 and MT staining.In normal adrenals, positive staining was weak for MT and zero for MCM2. Rates of positive staining for MT and MCM2 were significantly higher in adrenocortical carcinomas than in adrenocortical adenomas (P=0.008 and P0.001, respectively). In adrenocortical carcinomas, a significant positive correlation was found between MCM2 staining and Weiss revisited score (P=0.022) but not for Weiss score, and a significant positive correlation was found between MCM2 and mitotic rate on histology (P=0.033). MCM2 but not MT staining was also shown to correlate significantly with stage IV carcinoma (P=0.008 and P=0.165, respectively).MCM2 and MT are overexpressed in adrenocortical carcinoma, and MCM2 expression correlates significantly with metastatic disease.

Summary Purpose In order to differentiate between Cushing's syndrome (CS) and Pseudo-Cushing's syndrome, it is customary to use a test that is conducted by cortisol suppression with low-dose dexamethasone, followed by the administration of corticotropin releasing hormone (Dex-CRH test). In children with severe obesity, Dex-CRH test has shown a specificity of 55%. The aim of current study was to evaluate the specificity of Dex-CRH test in morbid obese adults. Methods The study included a total of 19 subjects with a body mass index (BMI) equal or higher than 40kg/m 2 . In all subjects Dex-CRH test was performed, and 24h urinary free cortisol was collected prior the test and during the second day of dexamethasone administration (2nd-day-UFC). Results BMI was 45.1±4.6kg/m 2 and 45.7±3.3kg/m 2 in women and men, respectively. 14 subjects underwent bariatric surgery. No subject had surgical or perioperative complications and surgically treated subjects had mean body weight loss of 46.5±16.6kg. All except for 2 subjects had normal Dex-CRH test, as 15-min cortisol falling below 1.4μg/dl. During follow-up, no subject gained additional weight, neither developed signs of CS. 15-min-cortisol concentration of 1.4μg/dl revealed a specificity of 89% and 2nd-day-UFC of 16μg/24h showed a specificity of 100%. Conclusions Morbid obesity in adults seems not to comprise a significant confounder in Dex-CRH test, and 15-min-cortisol concentration of 1.4μg/dl had a higher specificity than previously reported in obese children.

BACKGROUND Earlier research on 1 μg low-dose test (LDT) performed using 20.3 cm plastic IV tubing on healthy volunteers, has shown that afternoon testing was associated with a sevenfold increased likelihood of failing the test. Nevertheless, it has been claimed that subnormal cortisol response using plastic tubes might have resulted from cosyntropin adherence to the tube and, thus, loss of the delivered dosage. Following from our previous study, which showed that using a short (2.5 cm) plastic tube does not alter in-vitro-cosyntropin dosage delivery or healthy-volunteers' morning cortisol responses, we predicted that, when using the same short plastic tube, LDT would show comparable morning and afternoon cortisol stimulation. The current study was designed to investigate this prediction by comparing morning and afternoon cortisol responses in healthy volunteers during LDT, using a short plastic tube. METHODS Thirteen healthy adult volunteers were recruited for the study. Each subject underwent morning and afternoon LDT via 25 mm plastic intravenous line tube. Baseline serum cortisol (SC) in addition to SC and salivary free cortisol (SFC) 30-minute responses were determined. RESULTS Mean baseline morning SC concentration was higher in the morning than in the afternoon (13.63±3.42 and 9.18±2.78 μg/dL, respectively; P

Studies on 1 μg low-dose test showed that among 1 μg cosyntropin samples pushed through long IV plastic tubing, some adrenocorticotropic hormone dosage was not recovered, and in healthy volunteers it provided subnormal cortisol responses. The aim of the current study is to assess whether there is any loss in adrenocorticotropic hormone 1-24 concentration when pushed through a short plastic tube, and to assess serum and salivary cortisol responses in low-dose test among healthy volunteers, using a similar short plastic tube vs. direct intravenous consyntropin injection.We evaluated in vitro if adrenocorticotropic hormone was absorbed in a 2.5 cm plastic tube by measuring adrenocorticotropic hormone 1-24 concentration in a 1 μg/ml adrenocorticotropic hormone aliquot solution before and after being flushed through the plastic tube. For the in vivo study, we recruited 20 healthy adult volunteers. Each subject underwent low-dose test via 2.5 cm plastic tube via plastic tube and via direct intravenous injection by a metal syringe via direct intravenous injection, and cortisol responses were determined.Mean adrenocorticotropic hormone 1-24 concentration did not differ significantly when flushed via plastic tube or measured in the aliquot solution (P = 0.25). In vivo, mean 30-min serum cortisol concentrations were 20.47 ± 2.87 and 21.62 ± 3.89 μg/dl in via plastic tube and in via direct intravenous injection tests, respectively, and did not show a significant difference (P = 0.16).In low-dose test, using a 2.5 cm plastic tube ensures completeness of the intravenous adrenocorticotropic hormone injection dosage and provides equivalent cortisol responses.

Heterophilic antibodies are well described, but poorly appreciated interferents and is often not a recognized problem affecting most immunoassays. We report a patient presented with ectopic Cushing’s syndrome (CS), but repeated plasma adrenocorticotropic hormone (ACTH) concentrations conducted by immunoassay were inappropriately within the reference range and not elevated, most probably as a result of antibody interference. A 36-year-old woman, presented with large gastric neuroendocrine carcinoma and severe ectopic CS, while repeated plasma ACTH concentrations conducted by immunoassay were inappropriately within the reference range. As we expected ACTH concentration to be higher, we performed several tests to evaluate whether there was any assay interference causing falsely lower than expected ACTH results. We measured ACTH using a different immunoassay, assayed the sample in dilution, assayed the sample after being incubated in heterophilic antibody blocking agent tube and performed recovery studies. Tests indicated the presence of interfering compounds, most probably heterophilic antibodies. When clinicians find ACTH concentrations to be lower than expected, we recommend the laboratory investigate antibody interference.

OBJECTIVE: Cushing’s disease during pregnancy is associated with an increased risk for maternal and fetal complications. In recurrent Cushing’s disease following transsphenoidal surgery, and when re-operation is not feasible, medical treatment is usually considered. Cabergoline was found to be effective in reducing hypercortisolism in Cushing’s disease. Evolving data concerning the safety of cabergoline use during pregnancy show no significant increase in the rate of complications during pregnancy or the postnatal period. METHODS: We report a 29-year-old woman, gravida 0, para 0, with recurrent Cushing’s disease, three years after transsphenoidal resection of pituitary ACTH-secreting macroadenoma. Repeated MRI revealed an empty sella with a small gadolinium-enhancing lesion, suspected to be an adenoma remnant on the medial wall of the right cavernous sinus. As the patient was not willing to undergo repeat surgical intervention, treatment with cabergoline was initiated, with a gradual dose titration up to 3.5 mg/week. Clinical improvement ensued, and 4 months later, she conceived spontaneously. After discussing treatment options with the patient, cabergoline treatment at a dose of 2 mg/week was continued throughout pregnancy. RESULTS: The patient showed complete clinical remission during pregnancy. Consecutive tests of 24-h urinary free Cortisol concentration were not found to be elevated. Pregnancy and delivery were uneventful except for mild hypothyroidism observed during the second trimester. At full term the patient delivered a healthy female infant, by an elective cesarean section. CONCLUSION: This case report demonstrates that cabergoline may be an effective and safe therapeutic option for the treatment of Cushing’s disease during pregnancy.