Adrenal venous sampling: the learning curve of a single interventionalist with 282 consecutive procedures

PURPOSE:Primary aldosteronism (PA) is a common cause of secondary hypertension. Adrenal venous sampling (AVS) is the gold standard for assessing laterality of PA, which is of paramount importance to decide adequate treatment. AVS is a technically complicated procedure with success rates ranging between 30% and 96%. The aim of this study was to investigate the success rate of AVS over time, performed by a single interventionalist.METHODS:This was a retrospective study based on consecutive AVS procedures performed by a single operator between September 2005 and June 2016. Data on serum concentrations of aldosterone and cortisol from right and left adrenal vein, inferior vena cava, and peripheral vein were collected and selectivity index (SI) calculated. Successful AVS was defined as SI >5.RESULTS:In total, 282 AVS procedures were performed on 269 patients, 168 men (62%) and 101 women (38%), with a mean age of 55±11 years (range, 26–78 years). Out of 282 AVS procedures, 259 were successful, giving an overall success rate of 92%. The most common reason for failure was inability to localize the right adrenal vein (n=16; 76%). The success rates were 63%, 82%, and 94% during the first, second, and third years, respectively. During the last 8 years the success rate was 95%, and on average 27 procedures were performed annually.CONCLUSION:Satisfactory AVS success rate was achieved after approximately 36 procedures and satisfactory success rate was maintained by performing approximately 27 procedures annually. AVS should be limited to few operators that perform sufficiently large number of procedures to achieve, and maintain, satisfactory AVS success rate

Corticotroph Aggressive Pituitary Tumors and Carcinomas Frequently Harbor ATRX Mutations

Context: Aggressive pituitary tumors (APTs) are characterized by unusually rapid growth and lack of response to standard treatment. About 1% to 2% develop metastases being classified as pituitary carcinomas (PCs). For unknown reasons, the corticotroph tumors are overrepresented among APTs and PCs. Mutations in the alpha thalassemia/mental retardation syndrome X-linked (ATRX) gene, regulating chromatin remodeling and telomere maintenance, have been implicated in the development of several cancer types, including neuroendocrine tumors. Objective: To study ATRX protein expression and mutational status of the ATRX gene in APTs and PCs. Design: We investigated ATRX protein expression by using immunohistochemistry in 30 APTs and 18 PCs, mostly of Pit-1 and T-Pit cell lineage. In tumors lacking ATRX immunolabeling, mutational status of the ATRX gene was explored. Results: Nine of the 48 tumors (19%) demonstrated lack of ATRX immunolabelling with a higher proportion in patients with PCs (5/18; 28%) than in those with APTs (4/30;13%). Lack of ATRX was most common in the corticotroph tumors, 7/22 (32%), versus tumors of the Pit-1 lineage, 2/24 (8%). Loss-of-function ATRX mutations were found in all 9 ATRX immunonegative cases: nonsense mutations (n = 4), frameshift deletions (n = 4), and large deletions affecting 22-28 of the 36 exons (n = 3). More than 1 ATRX gene defect was identified in 2 PCs. Conclusion: ATRX mutations occur in a subset of APTs and are more common in corticotroph tumors. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumors.Peer reviewe

Glucocorticoids - outcome in patients with glucocorticoid deficiency and Cushing's syndrome

Glucocorticoids (GCs) are steroid hormones that have a major impact on human metabolism and are essential for life. Chronic GC overexposure, called Cushing’s syndrome, is characterized by central obesity, muscle atrophy, osteoporosis, hypertension, impaired glucose tolerance and neurocognitive impairment. Cushing’s syndrome can be caused by increased endogenous GC production or arise due to pharmacological GC treatment. This thesis is based on four studies, including four different patient populations, aimed at investigating outcomes in patients with Cushing’s syndrome and patients receiving current standard GC replacement therapy for adrenal insufficiency. In a large study of patients with hypopituitarism it was demonstrated that GC replacement therapy was independently associated with reduced bone mineral density in women with adrenal insufficiency receiving an average daily hydrocortisone dose of approximately 20 mg. In another study of adult patients, treated for Cushing’s disease during childhood, final adult height was compromised in the majority of the patients and the prevalence of hypertension was high. In a study of patients in long-term remission after successful treatment for Cushing’s syndrome, numerous domains of cognitive function were impaired at long-term follow-up in comparison to healthy individuals. Finally it was demonstrated that short-term treatment with growth hormone and testosterone increases skeletal muscle mass in men on chronic low dose GC treatment. In conclusion, this thesis demonstrates that long-term GC exposure has various long-term adverse health related consequences for patients receiving GC replacement therapy and in patients in long-term remission from Cushing’s syndrome. Furthermore, anabolic treatment with growth hormone and testosterone has the potential to improve GC induced muscle wasting

Successful Treatment with Selpercatinib for Ectopic Cushing’s Syndrome Due to Medullary Thyroid Cancer

Selpercatinib, a RET kinase inhibitor, is an effective treatment for patients with medullary thyroid cancer with RET mutations. In this paper, we present the case of a 62-year-old man with ectopic Cushing’s syndrome due to medullary thyroid cancer who received treatment with selpercatinib. Six months later, all the cushingoid features had resolved, and s-calcitonin had decreased from 580 pmol/L to 3.5 pmol/L (normal < 3). After further 6 months, s-calcitonin had normalized (1.5 pmol/L), and radiological evaluation showed a profound tumour volume reduction. We are aware of two other cases where treatment with selpercatinib has also been successful. Thus, selpercatinib may be a promising treatment alternative in patients with ectopic Cushing’s syndrome due to medullary thyroid cancer, especially when other treatment options are ineffective or not tolerated

Mental Fatigue and Executive Dysfunction in Patients with Cushing’s Syndrome in Remission

Patients with Cushing’s syndrome (CS) in remission often suffer from impaired quality of life and cognitive dysfunction. The primary aim was to investigate the occurrence of mental fatigue, characterized by mental exhaustion and long recovery time following mentally strenuous tasks, in patients with CS in remission. The secondary aim was to examine whether the newly developed parts C and D of the trail making test (TMT) are more sensitive, compared to the conventional parts A and B, to evaluate attention and executive function. This was a cross-sectional study including 51 patients with CS in remission and 51 controls. All subjects completed the self-administrated mental fatigue scale (MFS) and performed all four parts of the TMT. The patients had worse outcome on all components of the MFS except for sensitivity to noise. After adjustment for mental fatigue, depression, and anxiety, the patients performed worse only on part D of the TMT (P<0.05). Mental fatigue is common in patients with CS in remission and can be captured by using the MFS. The most demanding part of the TMT, part D, is more useful to capture cognitive deficits in patients with CS in remission compared to the conventional parts A and B

Pituitary dysfunction in granulomatosis with polyangiitis

Purpose: Granulomatosis with polyangiitis (GPA) is a multisystem disease, characterized by necrotizing small-vessel vasculitis, which mainly affects the respiratory tract and the kidneys. Pituitary involvement in GPA is rare, present in about 1% of all cases of GPA. To date, only case reports or small case series have been published. Herein we report clinical features, imaging findings, treatment and outcomes in three patients with GPA-related pituitary dysfunction (PD). Methods: A retrospective analysis of three cases of GPA-related PD was conducted, followed by systematic review of the English medical literature using PubMed. Results: The three cases include three women aged between 32 and 37 years. PD was the presenting feature in one and two developed PD in the course of the disease. All patients had a pituitary lesion on MRI. Conventional treatment with high doses of glucocorticoids and cyclophosphamide led to resolution or improvement of the MRI abnormalities, whereas it was not effective in restoring PD. A systematic review identified 51 additional patients, showing that GPA can lead to partial or global PD, either at onset or, during the course of the disease. Secondary hypogonadism is the predominant manifestation, followed by diabetes insipidus (DI). Sellar mass with central cystic lesion is the most frequent radiological finding. Conclusion: GPA should be carefully considered in patients with a sellar mass and unusual clinical presentation with DI and systemic disease. Although conventional induction-remission treatment improves systemic symptoms and radiological pituitary abnormalities, hormonal deficiencies persist in most of the patients. Therefore, follow-up should include both imaging and pituitary function assessment

The diagnostic value of salivary cortisol and salivary cortisone in patients with suspected hypercortisolism

Background: Diagnosing endogenous hypercortisolism remains a challenge, partly due to a lack of biochemical tests with good diagnostic accuracy. Objectives: To evaluate the diagnostic value of salivary cortisol and cortisone in patients with suspected hypercortisolism. Methods: Retrospective study including 155 patients with adrenal incidentaloma, and 54 patients with suspected Cushing's syndrome (CS). Salivary samples were collected at home, at 11 p.m., and at 8 a.m. following an over-night dexamethasone suppression test (DST). Salivary cortisol and cortisone were measured with liquid chromatography-tandem mass spectrometry. Results: Ten of 155 patients with adrenal incidentaloma were considered to have autonomous cortisol secretion (ACS). Using previously established cut-offs, all patients with ACS had elevated plasma-cortisol (&gt;50 nmol/L) following DST, 9/10 had elevated late-night salivary cortisone (&gt;15 nmol/L) whereas only 4/10 had elevated late-night salivary cortisol (LNSC; &gt;3 nmol/L) compared to 35%, 9% and 8%, respectively, of the 145 patients with non-functioning adrenal incidentaloma. Six (60%) patents with ACS had elevated salivary cortisol and cortisone at 8 a.m. following DST compared to 9% and 8%, respectively, of patients with non-functioning adrenal incidentaloma. One of 6 patients with overt CS had a normal LNSC and one had normal late-night salivary cortisone, while all had increased salivary cortisol and cortisone following DST. Conclusion: LNSC is not sufficiently sensitive or specific to be used for screening patients with suspected hypercortisolism. Instead, late-night salivary cortisone seems to be a promising alternative in patients with adrenal incidentaloma and salivary cortisone at 8 a.m. following DST in patients with suspected CS. Larger studies are needed to confirm these findings

The importance of personal documentation for patients living with long‐term illness symptoms after pituitary surgery: A Constructivist Grounded Theory study

Abstract Introduction Despite surgical treatment, pituitary adenomas often cause long‐term illness symptoms, that profoundly impact patients' quality of life physically, psychologically and socially. Healthcare professionals often fail to recognize and discuss the ensuing problems. Personal documentation, such as symptom monitoring, reflective writing or even posts on social media, may help this patient group to manage their daily life and support communication of their care needs. Documentation strategies and the role of documentation for people with long‐term symptoms after pituitary adenoma surgery are currently unknown. Aim To examine the effects and strategies of documenting symptoms, activities and physical and emotional well‐being among people living with long‐term pituitary adenoma. Methods In this Constructivist Grounded Theory study, 12 individuals living with long‐term illness symptoms after pituitary adenoma surgery described their documentation strategies in in‐depth interviews using teleconferencing and photo‐elicitation between August and October 2020. Results Strategies for documentation included analogue and digital media. One core category (Exercising autonomy) and three categories describing processes (Gaining insight, Striving for control and Sharing) emerged from the analysis. These three interrelated processes become an expression of autonomy to manage life and make sense of chronic illness. Personal documentation is a flexible tool that is used more extensively in times of ill health and less in times of relative well‐being. Sharing documentation with healthcare professionals facilitated care planning and sharing with friends and family fostered emotional well‐being. Conclusion Personal documentation is a valuable resource for managing life after pituitary adenoma surgery. The current findings may be relevant to other chronic illnesses. Further research exploring potential tools for personal documentation is needed. Patient or Public Contribution We deliberately chose a Constructivist Grounded Theory approach for this interview study. Using Constructivist Grounded Theory, we gave people living with long‐term symptoms a voice, allowing them to freely speak about managing their illness in connection with personal documentation. The theoretical sampling approach enabled us to invite participants that could provide a broad overview of the landscape of personal documentation