Hierarchical perspective on organizational identity : A comparative case study of two IT-companies located in Oslo

This thesis aims to investigate how financial and/or employment growth affects the organizational identity in small and medium sized IT-companies located in the Oslo-region. I also aim to point out how organizational identity is viewed differently depending on the hierarchical position and how what impact hierarchy has on values and roles affecting the organizational identity. This comparative case study of previous entrepreneurial companies, view themself in the perspective of organizational identity. The data was collected from in-depth interviews of multiple layers of the hierarchy of four IT-companies and comparable data from three start-up labs. Literature on Organizational Identity has been used as a background material

High cardiac background activity limits 99mTc-MIBI radioguided surgery in aortopulmonary window parathyroid adenomas

Background: Radioguided surgery using 99m-Technetium-methoxyisobutylisonitrile (99mTc-MIBI) has been recommended for the surgical treatment of mediastinal parathyroid adenomas. However, high myocardial 99mTc-MIBI uptake may limit the feasibility of radioguided surgery in aortopulmonary window parathyroid adenoma. Case presentation: Two female patients aged 72 (#1) and 79 years (#2) with primary hyperparathyroidism caused by parathyroid adenomas in the aortopulmonary window were operated by transsternal radioguided surgery. After intravenous injection of 370 MBq 99mTc-MIBI at start of surgery, the maximum radioactive intensity (as counts per second) was measured over several body regions using a gamma probe before and after removal of the parathyroid adenoma. Relative radioactivity was calculated in relation to the measured ex vivo radioactivity of the adenoma, which was set to 1.0. Both patients were cured by uneventful removal of aortopulmonary window parathyroid adenomas of 4400 (#1) and 985 mg (#2). Biochemical cure was documented by intraoperative measurement of parathyroid hormone as well as follow-up examination. Ex vivo radioactivity over the parathyroid adenomas was 196 (#1) and 855 counts per second (#2). Before parathyroidectomy, relative radioactivity over the aortopulmonary window versus the heart was found at 1.3 versus 2.6 (#1) and 1.8 versus 4.8 (#2). After removal of the adenomas, radioactivity within the aortopulmonary window was only slightly reduced. Conclusion: High myocardial uptake of 99mTc-MIBI limits the feasibility of radioguided surgery in aortopulmonary parathyroid adenoma.publishedVersio

Preclinical cardiac disease in women and men with primary aldosteronism

Purpose We tested the sex-specific associations between primary aldosteronism (PA), left ventricular (LV) hypertrophy and LV systolic myocardial function. Material and methods Conventional and speckle tracking echocardiography was performed in 109 patients with PA and 89 controls with essential hypertension (EH). LV hypertrophy was identified if LV mass index exceeded 47.0 g/m2.7 in women and 50.0 g/m2.7 in men. LV systolic myocardial function was assessed by global longitudinal strain (GLS) and midwall shortening. Results PA patients had higher prevalence of LV hypertrophy (52 vs. 21%, p < 0.001) than EH patients in both sexes, while GLS did not differ by sex or hypertension aetiology. In multivariable analyses, presence of LV hypertrophy was associated with PA and obesity in both sexes, while lower systolic myocardial function, whether measured by GLS or midwall shortening, was not associated with PA, but primarily with higher body mass index and LV mass index, respectively, in both sexes (all p < 0.05). Conclusion Having PA was associated with higher prevalence of LV hypertrophy both in women and men, compared to EH. PA was not associated with LV systolic myocardial function in either sex.publishedVersio

Diagnostic testing of autonomous cortisol secretion in adrenal incidentalomas

Objective: Autonomous cortisol secretion (ACS) is a condition with ACTH-independent cortisol overproduction from adrenal incidentalomas (AI) or adrenal hyperplasia. The hypercortisolism is often mild, and most patients lack typical clinical features of overt Cushing’s syndrome (CS). ACS is not well defined and diagnostic tests lack validation. Methods: Retrospective study of 165 patients with AI evaluated clinically and by assay of morning plasma ACTH, late-night saliva cortisol, serum DHEA sulphate (DHEAS), 24-h urine-free cortisol, and cortisol after dexamethasone suppression. Results: Patients with AI (n = 165) were diagnosed as non-functioning incidentalomas (NFI) (n = 82) or ACS (n = 83) according to current European guidelines. Late-night saliva cortisol discriminated poorly between NFI and ACS, showing a high rate of false-positive (23/63) and false-negative (38/69) results. The conventional low-dose dexamethasone suppression test (LDDST) did not improve the diagnostic specificity, compared with the 1 mg overnight DST. Receiver operating characteristic curve analysis of DHEAS in the two cohorts demonstrated an area under the curve of 0.76 (P < 0.01) with a sensitivity for ACS of 58% and a specificity of 80% using the recommended cutoff at 1.04 µmol/L (40 µg/dL). Conclusion: We here demonstrate in a large retrospective cohort of incidentaloma patients, that neither DHEAS, late-night saliva cortisol nor 24-h urine free cortisol are useful to discriminate between non-functioning adrenal incidentalomas and ACS. The conventional LDDST do not add further information compared with the 1 mg overnight DST. Alternative biomarkers are needed to improve the diagnostic workup of ACS.publishedVersio

Two Adults with Adrenal Myelolipoma and 21-Hydroxylase Deficiency

We present incidentally discovered adrenal myelolipomas in two adult males with untreated congenital adrenal hyperplasia (CAH). The patients had simple virilizing form of CAH due to mutations in the CYP21 gene coding for 21-hydroxylase; one was heterozygous for the I172N mutation and the other compound heterozygous for the I172N and I2splice mutations. The masses were not removed since myelolipomas are considered benign tumors, and the tumor size did not increase during four- and nine-year observation periods. An adrenal myelolipoma is an important exception to the rule that large tumours should be removed. Untreated CAH with prolonged excessive ACTH stimulation might contribute to the growth of adrenal masses. CAH should be considered as a differential diagnosis of patients with adrenal masses or adrenal myelolipomas

Multisteroid LC-MS/MS assay for glucocorticoids and androgens, and its application in Addison’s disease

Objective: Liquid chromatography–tandem mass spectrometry (LC–MS/MS) offers superior analytical specificity compared with immunoassays, but it is not available in many regions and hospitals due to expensive instrumentation and tedious sample preparation. Thus, we developed an automated, high-throughput LC–MS/MS assay for simultaneous quantification of ten endogenous and synthetic steroids targeting diseases of the hypothalamic–pituitary–adrenal axis and gonads. Methods: Deuterated internal standards were added to 85 μl serum and processed by liquid–liquid extraction. Cortisol, cortisone, prednisolone, prednisone, 11-deoxycortisol, dexamethasone, testosterone, androstenedione and progesterone were resolved by ultra-high-pressure chromatography on a reversed-phase column in 6.1 min and detected by triple-quadrupole mass spectrometry. The method was used to assess steroid profiles in women with Addison's disease (AD, n=156) and blood donors (BDs, n=102). Results: Precisions ranged from 4.5 to 10.1% relative standard deviations (RSD), accuracies from 95 to 108% and extraction recoveries from 60 to 84%. The method was practically free of matrix effects and robust to individual differences in serum composition. Most postmenopausal AD women had extremely low androstenedione concentrations, below 0.14 nmol/l, and median testosterone concentrations of 0.15 nmol/l (interquartile range 0.00–0.41), considerably lower than those of postmenopausal BDs (1.28 nmol/l (0.96–1.64) and 0.65 nmol/l (0.56–1.10) respectively). AD women in fertile years had androstenedione concentrations of 1.18 nmol/l (0.71–1.76) and testosterone concentrations of 0.44 nmol/l (0.22–0.63), approximately half of those found in BDs of corresponding age. Conclusion: This LC–MS/MS assay provides highly sensitive and specific assessments of glucocorticoids and androgens with low sample volumes and is suitable for endocrine laboratories and research. Its utility has been demonstrated in a large cohort of women with AD, and the data suggest that women with AD are particularly androgen deficient after menopause.publishedVersio

Substantial changes in inflammatory and cardiovascular biomarkers in patients with autonomous cortisol secretion

Objective To map inflammatory biomarkers in patients with autonomous cortisol secretion (ACS) and overt Cushing syndrome (CS). Method Observational study including serum from prospectively included patients with ACS (n = 63), adrenal CS (n = 2), pituitary CS (n = 8), and healthy subjects (n = 120). Serum samples were analysed for 92 inflammatory biomarkers using proximity extension assay (OLINK). Results Combined, the ACS and CS patients displayed significant differences in levels of 49/92 inflammatory biomarkers (46 increased/3 decreased) compared with healthy controls. No differences in biomarker levels were found between ACS and overt CS, and none of the biomarkers correlated with the degree of hypercortisolism. Postoperative samples were available for 17 patients, median 24 months (range 6–40) after surgery and biochemical curation. There was no significant normalization of the biomarkers postoperatively. Conclusion There was a systemic rise in inflammatory biomarkers in patients with ACS and CS, not correlated to the degree of hypercortisolism. These biomarkers were not normalized following biochemical cure.publishedVersio

Efficacy of adrenal venous sampling is increased by point of care cortisol analysis

Primary aldosteronism (PA) is a common cause of secondary hypertension and is caused by unilateral or bilateral adrenal disease. Treatment options depend on whether the disease is lateralized or not, which is preferably evaluated with selective adrenal venous sampling (AVS). This procedure is technically challenging, and obtaining representative samples from the adrenal veins can prove difficult. Unsuccessful AVS procedures often require reexamination. Analysis of cortisol during the procedure may enhance the success rate. We invited 21 consecutive patients to participate in a study with intra-procedural point of care cortisol analysis. When this assay showed nonrepresentative sampling, new samples were drawn after redirection of the catheter. The study patients were compared using the 21 previous procedures. The intra-procedural cortisol assay increased the success rate from 10/21 patients in the historical cohort to 17/21 patients in the study group. In four of the 17 successful procedures, repeated samples needed to be drawn. Successful sampling at first attempt improved from the first seven to the last seven study patients. Point of care cortisol analysis during AVS improves success rate and reduces the need for reexaminations, in accordance with previous studies. Successful AVS is crucial when deciding which patients with PA will benefit from surgical treatment.publishedVersio

Systemic Activation of the Kynurenine Pathway in Graves Disease With and Without Ophthalmopathy

Context Graves disease (GD) is one of the most common autoimmune disorders. Recent literature has shown an immune response involving several different inflammatory related proteins in these patients. Objective This work aimed to characterize the kynurenine pathway, activated during interferon-γ (IFN-γ)–mediated inflammation and cellular (T-helper type 1 [Th1] type) immunity, in GD patients with and without thyroid eye disease (TED). Methods We analyzed 34 biomarkers by mass spectrometry in serum samples from 100 patients with GD (36 with TED) and 100 matched healthy controls. The analytes included 10 metabolites and 3 indices from the kynurenine pathway, 6 microbiota-derived metabolites, 10 B-vitamers, and 5 serum proteins reflecting inflammation and kidney function. Results GD patients showed significantly elevated levels of 7 biomarkers compared with healthy controls (omega squared [ω2] > 0.06; P < .01). Of these 7, the 6 biomarkers with the strongest effect size were all components of the kynurenine pathway. Factor analysis showed that biomarkers related to cellular immunity and the Th1 responses (3-hydroxykynurenine, kynurenine, and quinolinic acid with the highest loading) were most strongly associated with GD. Further, a factor mainly reflecting acute phase response (C-reactive protein and serum amyloid A) showed weaker association with GD by factor analysis. There were no differences in biomarker levels between GD patients with and without TED. Conclusion This study supports activation of IFN-γ inflammation and Th1 cellular immunity in GD, but also a contribution of acute-phase reactants. Our finding of no difference in systemic activation of the kynurenine pathway in GD patients with and without TED implies that the local Th1 immune response in the orbit is not reflected systemically.publishedVersio

Outcomes of Patients With Graves Disease 25 Years After Initiating Antithyroid Drug Therapy

Context Graves disease (GD) is a leading cause of hyperthyroidism. Detailed investigations and predictors of long-term outcomes are missing. Objective This work aimed to investigate the outcomes in GD 25 years after initiating antithyroid drug treatment, including disease course, clinical and biochemical predictors of relapse, and quality of life. Methods A retrospective follow-up was conducted of GD patients that participated in a randomized trial from 1997 to 2001. Demographic and clinical data were obtained from medical records and questionnaires. Biobank samples were analyzed for inflammatory biomarkers and compared with age- and sex-matched healthy individuals. Results We included 83% (182/218) of the patients from the original study. At the end of follow-up, normal thyroid function was achieved in 34%. The remaining had either active disease (1%), spontaneous hypothyroidism (13%), or had undergone ablative treatment with radioiodine (40%) or thyroidectomy (13%). Age younger than or equal to 40 years, thyroid eye disease (TED), smoking, and elevated levels of interleukin 6 and tumor necrosis factor receptor superfamily member 9 (TNFRS9) increased the risk of relapsing disease (odds ratio 3.22; 2.26; 2.21; 1.99; 2.36). At the end of treatment, CD40 was lower in patients who maintained normal thyroid function (P = .04). At the end of follow-up, 47% had one or more autoimmune diseases, including vitamin B12 deficiency (26%) and rheumatoid arthritis (5%). GD patients who developed hypothyroidism had reduced quality of life. Conclusion Careful lifelong monitoring is indicated to detect recurrence, hypothyroidism, and other autoimmune diseases. Long-term ATD treatment emerges as a beneficial first-line treatment option, especially in patients with young age at onset or presence of TED.publishedVersio