TL;DR: Two different gsp mutations are found in three patients with Cushing's syndrome due to AIMAH, and it is speculated whether they belong to the spectrum of McCune-Albright syndrome or whether these are the first reported cases of AIMah due to gsp mutation.
Abstract: ACTH-independent macronodular adrenal hyperplasia (AIMAH) is an uncommon cause of Cushing’s syndrome characterized by bilateral nodular adrenocortical hyperfunction in the presence of suppressed ACTH levels. We investigated whether activating mutations in the ACTH receptor (MC2-R) or Gsα (GNAS1) genes might be involved in AIMAH genesis. Five women with Cushing’s syndrome due to AIMAH, confirmed by histological studies, and no signs of McCune-Albright syndrome were selected for molecular analysis of these genes. The single exon of the MC2-R gene and exons 8 and 9 of the GNAS1 gene were amplified by PCR in genomic DNA from adrenal nodules and peripheral blood. Direct sequencing revealed only MC2-R wild-type sequences. GNAS1 PCR products at denaturing gradient gel electrophoresis revealed abnormal migration patterns in adrenal tissues of three patients. Automatic sequencing showed two different activating mutations at codon Arg201 of GNAS1, a substitution by histidine in two cases and by serine in one case. ...
TL;DR: Use of the proposed semiquantitative approach associated with both laboratory screening for cortisol production and CTMD measure seems to be able to increase the clinical diagnostic accuracy of PC-CS.
Abstract: The goal of this study was to evaluate the clinical reliability of the 131I-6β-iodomethyl-norcholesterol (131I-NP-59) uptake semiquantitative evaluation method we propose for the characterization of adrenocortical masses in a selected population of patients with disease clinically classified as subclinical (SC) and preclinical (PC) Cushing’s syndrome (CS) according to Reincke’s definition. Methods: Forty-seven consecutive patients with incidentally discovered unilateral adrenal masses were examined by a triple-head SPECT system after intravenous injection of 131I-NP-59. Abdominal SPECT was performed at 24, 48, 72, and, in selected cases, 96 h after tracer injection. Connected with adrenals and liver, a standard elliptic region of interest (ROI) was manually drawn, taking care to avoid the gallbladder region. The adrenal ROI integral count, obtained by summing the 24-, 48-, and 72-h counting values, was normalized by the hepatic integral count. Subsequently, the adrenal percentage of relative uptake (UPT%) was computed. Results: Discriminant analysis was performed on the variables UPT%, adrenocorticotropic hormone (ACTH) serum concentration, and CT mass dimension (CTMD) to determine the variable, or combination thereof, best discriminating between the SC-CS and PC-CS groups. Compared with both ACTH and CTMD variables, univariate analysis confirmed the UPT% variable as the most significant to discriminate between these 2 clinical groups. In fact, UPT% alone correctly classified 8 of 9 patients in the SC-CS group and 20 of 22 patients in the PC-CS group with 95% positive and 80% negative predictive values and with overall accuracy, sensitivity, and specificity equal to 90%, 91%, and 89%, respectively. When all 3 variables were submitted to stepwise discriminant analysis, the derived classification matrix, after cross-validation, correctly classified 9 of 9 patients in the SC-CS group and 18 of 22 patients in the PC-CS group with 100% positive and 69% negative predictive values and with overall accuracy, sensitivity, and specificity equal to 87%, 82%, and 100%, respectively. Conclusion: According to these initial results, use of the proposed semiquantitative approach associated with both laboratory screening for cortisol production and CTMD measure seems to be able to increase the clinical diagnostic accuracy of PC-CS. This approach could be used in the follow-up of adrenal mass function every time hormonal or clinical features are suggestive of adrenocortical hyperfunction.
TL;DR: Data suggest that in dogs with LSA, the UC : Cr ratio frequently is abnormal and may not be a specific test for HAC, or it may be the most sensitive test for increases in cortisol secretion due to chronic illness.
Abstract: Many dogs with chronic illness have serum biochemical abnormalities consistent with hyperadrenocorticism (HAC). Lymphoma (LSA) is a chronic disease of dogs. The purpose of this study was to evaluate adrenocortical screening test results in dogs with LSA to evaluate their specificity. Criteria for inclusion in the study included a diagnosis of LSA, an expected survival time of 16-56 weeks, no glucocorticoid treatment beyond 4 weeks after the initiation of chemotherapy, no evidence of HAC, and owner consent. Post-ACTH stimulation plasma cortisol concentrations (PACs), urine cortisol : creatinine (UC : Cr) ratios, and maximal left adrenal width measurements were performed at the time of LSA diagnosis before the initiation of chemotherapy and at 16, 24, 32, 40, and 52 weeks or until the loss of remission or the development of another disease. Ten dogs met the criteria for inclusion. Forty-two PACs were performed; 1 abnormal, 2 borderline, and 39 normal values were detected. Thirty-five maximal left adrenal width measurements were obtained; 0 abnormal, 5 borderline, and 30 normal measurements were detected. Thirty-six UC : Cr ratios were obtained, with 26 abnormal, 4 borderline, and 6 normal values detected and 9 of 10 dogs having at least 1 abnormal value. These data suggest that in dogs with LSA, the UC : Cr ratio frequently is abnormal and may not be a specific test for HAC, or it may be the most sensitive test for increases in cortisol secretion due to chronic illness. Maximal left adrenal width measurements and PACs were almost always normal and may be more specific for HAC or less sensitive for demonstrating chronic increases in cortisol secretion.
TL;DR: CT-guided percutaneous acetic acid injection might be a simple, cost-effective, and far less invasive treatment for small functioning adrenocortical adenomas in patients with primary aldosteronism and Cushing's syndrome.
Abstract: We reported the outcomes of computed tomography (CT)-guided percutaneous acetic acid injection therapy for functioning adrenocortical adenomas. With the patient in a prone position, the puncture needle was inserted vertically downward into the adenoma with frequent CT scanning. After confirmation by pilot injection with contrast medium, a small aliquot of 40-50% acetic acid was injected and repeated. Between 1997 and 2002, 18 sessions of CT-guided injection therapy, including one session of ethanol injection, were performed on 10 patients (five patients with primary aldosteronism and five patients with Cushing's or subclinical Cushing's syndrome) without any complications except transient upper abdominal pain during the acetic acid injection. The follow-up period ranged from 5-69 months. The treatment resulted in almost an extirpation of the adrenocortical hyperfunction in seven patients after one or two sessions. CT-guided percutaneous acetic acid injection might be a simple, cost-effective, and far less invasive treatment for small functioning adrenocortical adenomas.
TL;DR: The findings of the examinations performed indicate that increased incidence of arteriosclerotic processes is present in patients with the florid Cushing's syndrome as well as in those who have suffered from Cushing’s syndrome before.
Abstract: UNLABELLED: Hypercortisolism is associated with a high risk of sickness rate and death rate particularly in view of facilitated arteriosclerotic processes. It is most frequently induced by drug therapy, but endogenous hypercortisolism (Cushing's syndrome) may serve as a suitable model of the effect of hypercortisolism on vascular wall. Our cohort included the following groups of patients and control individuals: 1. a group of patients with florid so far untreated Cushing's syndrome--14 patients, 2. a control group to these patients--16 individuals, 3. a group recently operated on and healed-up patients with Cushing's syndrome--8 patients, 4. a group of previous of previous cured-up patients with Cushing's syndrome--27 subjects, 5. a control group to those patients of group 4--17 persons. The following differences were found between the respective groups: 1. the ultrasonographic examination of carotid arteries demonstrated sclerotic plates or carotid stenosis in 21.3% of patients with florid Cushing's syndrome and 41.4% in patients with corticolism having been cured-up against 11.7% in the relevant control group; 2. the examination of skin microcirculation by the laser-doppler method revealed a lower velocity of perfusion increase during examination of postocclusion hyperemia in patients with florid Cushing's syndrome and hypercortisolism having been cured-up against a control group (CUSH., P < 0.04; previous cured-up, P < 0.02) as well as thermally-induced hyperemia (CUSH., P < 0.03; formerly cured-up, P < 0.04); 3. the laboratory examination of patients with florid Cushing's syndrome revealed higher values of LDL-cholesterol (P < 0.05) and total cholesterol (P < 0.001), malonyldialdehyde as an indicator of increased formation of oxygen radicals (P < 0.05) and oromucoid, the protein of acute phase, signaling a chronic inflammation (P < 0.05); 4. in patients who previously suffered from hypercortisolism increased levels of fibrinogen (P < 0.03) and the cytoadhesive molecule ICAM-1 (P < 0.05) were accompanied by decreased levels of the growth factor of vascular endothelia (VEGF) (P < 0.05) against patients with florid Cushing's syndrome. CONCLUSION: The findings of the examinations performed indicate that increased incidence of arteriosclerotic processes is present in patients with the florid Cushing's syndrome as well as in those who have suffered from Cushing's syndrome before.