Showing papers by "Susan M. Webb published in 2022"

Quality of life impairment after a diagnosis of Cushing’s syndrome

Abstract: Abstract This brief review is devoted mainly to publications in the last 5 years dealing with health-related quality of life (QoL) after a diagnosis of endogenous hypercortisolism, due to pituitary-dependent Cushing’s disease (CD) or any other cause of Cushing syndrome (CS). Despite improvement after treatment, persistent physical morbidity, neurocognitive problems like worse executive capacity and memory as well as stress intolerance, depressive symptoms and more anxiety, lead to long-term impairment of QoL.

CIBERER: Spanish national network for research on rare diseases: A highly productive collaborative initiative

Abstract: CIBER (Center for Biomedical Network Research; Centro de Investigación Biomédica En Red) is a public national consortium created in 2006 under the umbrella of the Spanish National Institute of Health Carlos III (ISCIII). This innovative research structure comprises 11 different specific areas dedicated to the main public health priorities in the National Health System. CIBERER, the thematic area of CIBER focused on rare diseases (RDs) currently consists of 75 research groups belonging to universities, research centers, and hospitals of the entire country. CIBERER's mission is to be a center prioritizing and favoring collaboration and cooperation between biomedical and clinical research groups, with special emphasis on the aspects of genetic, molecular, biochemical, and cellular research of RDs. This research is the basis for providing new tools for the diagnosis and therapy of low‐prevalence diseases, in line with the International Rare Diseases Research Consortium (IRDiRC) objectives, thus favoring translational research between the scientific environment of the laboratory and the clinical setting of health centers. In this article, we intend to review CIBERER's 15‐year journey and summarize the main results obtained in terms of internationalization, scientific production, contributions toward the discovery of new therapies and novel genes associated to diseases, cooperation with patients' associations and many other topics related to RD research.

Patient-reported outcomes in patients with acromegaly treated with pegvisomant in the ACROSTUDY extension: A real-world experience

Abstract: To report the effects of pegvisomant (PEGV) treatment on patient-reported outcomes in acromegaly patients.We conducted an extension study of an open-label, multinational, non-interventional study (ACROSTUDY) evaluating the long-term safety and efficacy of PEGV for acromegaly in routine clinical practice. Enrolled patients were rollover patients from ACROSTUDY, or treatment naïve/semi-naïve (NSN; no PEGV within 6 months of enrollment). Exploratory efficacy endpoints were changes in symptoms with the Patient-Assessed Acromegaly Symptom Questionnaire (PASQ) and quality of life with the Acromegaly Quality of Life questionnaire (AcroQoL) analyzed by controlled or uncontrolled IGF-I levels. Results were analyzed in all patients, in NSN patient subgroup, and by diabetes status.A total of 544 patients with acromegaly were enrolled, including 434 rollover subjects from ACROSTUDY and 110 NSN patients. Mean PEGV treatment duration was 7.8 years (range, 0-19.6 years). Overall, the majority of PASQ scores improved over time, but there was no significant difference between IGF-I controlled or uncontrolled groups. In the NSN subgroup, most PASQ and AcroQoL scores remained similar to baseline up to 1 year, regardless of IGF-I control. Patients with diabetes reported better PASQ scores over time with PEGV treatment, regardless of IGF-I control. IGF-I normalization increased from 10% of patients at baseline to more than 78% at year 10, with a mean daily PEGV dose of 18.7 mg.Overall, patients treated with PEGV had small improvements in PASQ. While IGF-I normalization increased with PEGV treatment, IGF-I control had no effects on PASQ and AcroQoL scores.

Factors associated with therapeutic response in acromegaly diagnosed in the elderly in Spain

Abstract: Context Some reports suggest that acromegaly in elderly patients has a more benign clinical behavior and could have a better response to first-generation long-acting somatostatin receptor ligands (SRL). However, there is no specific therapeutic protocol for this special subgroup of patients. Objective This study aimed at identifying predictors of response to SRL in elderly patients. Design Multicentric retrospective nationwide study of patients diagnosed with acromegaly at or over the age of 65 years. Results One-hundred and eighteen patients (34 men, 84 women, mean age at diagnosis 71.7 ± 5.4 years old) were included. Basal insulin-like growth factor type 1 (IGF-1) above the upper limit of normal (ULN) and growth hormone (GH) levels (mean ± SD) were 2.7 ± 1.4 and 11.0 ± 11.9 ng/ml, respectively. The mean maximal tumor diameter was 12.3 ± 6.4 mm, and up to 68.6% were macroadenoma. Seventy-two out of 118 patients (61.0%) underwent surgery as primary treatment. One-third of patients required first-line medical treatment due to a rejection of surgical treatment or non-suitability because of high surgical risk. After first-line surgery, 45/72 (63.9%) were in disease remission, and 16/34 (46.7%) of those treated with SRL had controlled disease. Patients with basal GH at diagnosis ≤6 ng/ml had lower IGF-1 levels and had smaller tumors, and more patients in this group reached control with SRL (72.7% vs. 33.3%; p < 0.04) [OR: 21.3, IC: 95% (2.4–91.1)], while male patients had a worse response [OR: 0.09, IC 95% (0.01–0.75)]. The predictive model curve obtained for SRL response showed an AUC of 0.82 CI (0.71–0.94). Conclusions The most frequent phenotype in newly diagnosed acromegaly in the elderly includes small adenomas and moderately high IGF-1 levels. GH at diagnosis ≤6 ng/ml and female gender, but not age per se, were associated with a greater chance of response to SRL.

Patient journey experiences may contribute to improve healthcare for patients with rare endocrine diseases

Abstract: Patient journeys are instruments developed by EURORDIS, The Voice of Rare Disease Patients in Europe, to collect patients’ experiences; they may identify gaps and areas deserving improvement, as well as elements positively considered by affected persons. As with other patient-reported experiences, they can complete the clinical evaluation and management of a specific disease, improving the often long diagnostic delay, therapy, patient education and access to knowledgeable multidisciplinary teams. This review discusses the utility of such patient-reported experience measures and summarises the experiences of patients with acromegaly, Addison’s disease and congenital adrenal hyperplasia from different European countries. Despite rare endocrine diseases being varied and presenting differently, feelings of not having been taken seriously by health professionals, family and friends was a common patient complaint. Empathy and a positive patient-centred environment tend to improve clinical practice by creating a trustworthy and understanding atmosphere, where individual patient needs are considered. Offering access to adequate patient information on their disease, treatments and outcome helps to adapt to living with a chronic disease and what to expect in the future, contemplating the impact of a disease on patients’ everyday life, not only clinical outcome but also social, financial, educational, family and leisure issues is desirable; this facilitates more realistic expectancies for patients and can even lead to a reduction in health costs. Patient empowerment with patient-centred approaches to these complex or chronic diseases should be contemplated more and more, not only for the benefit of those affected but also for the entire health system.

Consequences of Cushing's syndrome: Health versus personal costs.

Abstract: Hypercortisolism due to Cushing syndrome (CS) is bad for health, even years before diagnosis. Despite control after surgery and/or medical therapy, the consequences of prior exposure to cortisol excess are often irreversible, and persistent morbidity requires lifelong follow-up in an expert center, where these specific health problems and possible recurrences are promptly identified and approached (1). In their nationwide longitudinal study on the socio-economic impact of a diagnosis of CS treated with surgery in Denmark over 32 years, Ebbenhoj et al have additionally evidenced the very high cost this entails, both for the affected individuals, and for the health and social welfare system, when compared with a sex- and age-matched reference population (2). In their cohort of 424 patients with CS (225 [53%] of pituitary origin and 199 [47%] due to adrenal causes), they showed how depression was a negative predictor for full-time employment and higher income, as well as other predictors such as being a woman and having a lower educational level (2). Depression can be a reaction to persistent health problems or related to the exposure of the brain—which is rich in glucocorticoid receptors—to elevated cortisol. Neuropsychological issues like stress intolerance, emotional incontinence, less executive capacity, and worse memory compared to their pre-CS status also favor depression. In both genders, this determines worse health perception and quality of life, along with a lower probability of being in a relationship and experiencing parenthood in the previous 2 years (2, 3). Additionally, with information from the national prescription registry and depression-related hospital contacts, they demonstrate that 20% of CS patients were prescribed antidepressants at the time of diagnosis and surgery, explained by a greater risk of depression from 5 years before and until 10 years after surgery. This is in agreement with another recent Swedish nationwide study (4).

Impaired quality of life, but not cognition, is linked to a history of chronic hypercortisolism in patients with Cushing’s disease in remission

Abstract: Context Impaired cognition and altered quality of life (QoL) may persist despite long-term remission of Cushing’s disease (CD). Persistent comorbidities and treatment modalities may account for cognitive impairments. Therefore, the role of hypercortisolism per se on cognitive sequelae remains debatable. Objective To investigate whether memory and QoL are impaired after long-term remission of CD in patients with no confounding comorbidity. Design and Setting Cross-sectional case-control study in two tertiary referral centers Patients 25 patients (44.5 ± 2.4 years) in remission from CD for 102.7 ± 19.3 Mo and 25 well-matched controls, without comorbidity or treatment liable to impair cognition. Main Outcome Measure(s) Hippocampus- and prefrontal cortex-dependent memory, including memory flexibility and working memory, were investigated using multiple tests including sensitive locally-developed computerized tasks. Depression and anxiety were evaluated with the MADRS and HADS questionnaires. QoL was evaluated with the SF-36 and CushingQoL questionnaires. The intensity of CD was assessed using mean urinary free cortisol and a score for clinical symptoms. Results CD patients displayed similar performance to controls in all cognitive tests. In contrast, despite the absence of depression and a minimal residual clinical Cushing score, patients had worse QoL. Most of the SF36 subscales and the CushingQoL score were negatively associated only with the duration of exposure to hypercortisolism (p≤ 0.01 to 0.001). Conclusions Persistent comorbidities can be a primary cause of long-lasting cognitive impairment and should be actively treated. Persistently altered QoL may reflect irreversible effects of hypercortisolism, highlighting the need to reduce its duration. Clinical Trial Registration number https://clinicaltrials.gov, identifier NCT02603653

PRESTO 2: An International Survey to Evaluate Patients’ Injection Experiences with the Latest Devices/Formulations of Long-Acting Somatostatin Analog Therapies for Neuroendocrine Tumors or Acromegaly

Abstract: Real-world data evaluating patients' injection experiences using the latest devices/formulations of the long-acting (LA) somatostatin analogs (SSAs) lanreotide Autogel/Depot (LAN; Somatuline®) and octreotide LA release (OCT; Sandostatin®) are limited.PRESTO 2 was a 2020/2021 e-survey comparing injection experience of adults with neuroendocrine tumors (NETs) or acromegaly treated with LAN prefilled syringe versus OCT syringe for > 3 months in Canada, Ireland, the UK and the USA (planned sample size, 304).the proportion of patients with injection-site pain lasting > 2 days after their most recent injection, analyzed using a multivariate logistic regression model. Secondary endpoints included interference with daily life due to injection-site pain and technical injection problems in patients with current SSA use for ≥ 6 months.There were 304 respondents (acromegaly, n = 85; NETs, n = 219; LAN, n = 168; OCT, n = 136; 69.2% female; mean age, 59.6 years). Fewer patients had injection-site pain lasting > 2 days after the most recent injection with LAN (6.0%) than OCT (22.8%); the odds of pain lasting > 2 days were significantly lower for LAN than OCT, adjusted for disease subgroup and occurrence of injection-site reactions (odds ratio [95% confidence interval]: 0.13 [0.06-0.30]; p < 0.0001). Injection-site pain interfered with daily life "a little bit" or "quite a bit" in 37.2% and 3.8% (LAN) versus 52.5% and 7.5% (OCT) of patients, respectively. Among patients with ≥ 6 months' experience with current SSA (92.4% of patients), technical injection problems never occurred in 76.8% (LAN) and 42.9% (OCT) of patients.Compared with OCT, significantly fewer patients using LAN had injection-site pain lasting > 2 days after their most recent injection. Also, fewer LAN-treated patients experienced technical problems during injection. These findings demonstrate the importance of injection modality for overall LA SSA injection experience for patients with acromegaly or NETs.Patients with neuroendocrine tumors or acromegaly often receive long-term monthly treatment with somatostatin analogs. These injectable drugs stop the body from making an excess of certain hormones. Understanding patients’ experiences of these injections helps to provide better care. The PRESTO 2 online study surveyed 304 patients in Canada, Ireland, the UK and the USA with neuroendocrine tumors or acromegaly who were being treated with a somatostatin analog, either lanreotide Autogel/Depot (LAN) or octreotide long-acting release (OCT). The survey asked about injection experience, including injection-site pain lasting > 2 days and how it affected patients’ lives, anxiety before injections and technical problems during injections (like syringe blockages). The survey showed fewer patients receiving LAN than OCT had injection-site pain that lasted > 2 days, and fewer said that the pain interfered with their daily lives. There were fewer technical injection problems with LAN than with OCT. However, more patients receiving LAN than OCT felt anxious before their injection. In some countries (including Canada, Ireland and the UK, but not the USA), the patient (or family member/friend) can inject LAN if they are on a stable dose, their doctor agrees, and they received training. A nurse/doctor must inject OCT. In PRESTO 2, about 40% of non-US patients who were eligible injected themselves (or were helped by a family member/friend). This may explain why more patients reported anxiety in the LAN group. PRESTO 2 provides important insights into patients’ experiences of receiving somatostatin analogs and helps identify areas for improving patient care.

PMON57 Impact of Injection Modalities on Real-World Injection Experience in Patients with Acromegaly or Neuroendocrine Tumors (NETs) Treated With Somatostatin Analog (SSA) Therapy: Data from the PRESTO 2 Survey

Abstract: Abstract Introduction Long-acting (LA) SSA therapy is a common first-line medical treatment for acromegaly or NETs. Real-world data on patients’ injection experience with the latest LA SSA devices/formulations are limited. Aims PRESTO 2 assessed injection experience among patients treated with lanreotide autogel/depot prefilled syringe (LAN) or octreotide LA release syringe (OCT). Methods Conducted in 2021, PRESTO 2 was an e-survey of adults with acromegaly or NETs in Canada, Ireland, the UK and USA who had received ≥3 months’ treatment with LAN or OCT (planned sample size, 304 [min 76/cohort]; 50: 50 ratio [+/- 10%]). The primary endpoint was the proportion of patients with injection-site pain lasting >2 days after last injection, analyzed using multivariate logistic regression analysis. Secondary endpoints included interference with daily life due to injection-site pain, technical injection problems, and other aspects of injection experience in patients who had used their current SSA for >6 months. Results There were 304 respondents (acromegaly, n=85; NETs, n=219) from the USA (46.1%), Canada (27.3%), Ireland (13.5%) and the UK (13.2%); 55.3% were receiving LAN and 44.7% OCT; 69.2% were female; mean (SD) age was 59.6 (11.1) years. Fewer patients had injection-site pain lasting >2 days after last dose with LAN (6.0%) versus OCT (22.8%); the odds of pain lasting >2 days were significantly lower for LAN versus OCT, adjusted for disease group and occurrence of injection-site reaction (OR 0.13 [95% CI 0.06–0.30]; p<0.0001). Nine patients in the acromegaly subgroup had injection-site pain >2 days after last dose (LAN, 1; OCT, 8). In patients receiving LAN versus OCT, respectively, injection-site pain interfered with daily life 'a little bit' in 37.2% versus 52.5% and 'quite a bit' in 3.8% versus 7.5%. Among patients with >6 months’ experience with current SSA (92.4% of all patients), technical injection problems never occurred in 76.8% with LAN versus 42.9% with OCT. Consequences included replacement of syringe with injection given on the day (LAN, 5.6%; OCT, 23.6%) or not (LAN, 2.8%; OCT, 5.6%), or needle replacement only with injection given that day (LAN, 0.0%; OCT, 50.0%). Pain at injection site occurred with LAN versus OCT 'never' for 13.5% versus 7.1%, 'rarely' for 43.2% versus 37.3%, and 'most of the time' for 27.1% versus 42.9%. Conclusions Fewer patients using LAN had injection-site pain lasting >2 days after last injection compared to OCT; thus the primary endpoint was met. Other advantages of LAN versus OCT were seen and included improvements in occurrence of technical problems. These findings demonstrate the importance of injection modality for overall LA SSA injection experience, and the associated impact on daily life, for patients with acromegaly or NETs. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Real-world injection experience and use of independent injection among patients using lanreotide autogel/depot (LAN) prefilled syringe or octreotide long-acting release (OCT) to treat acromegaly or neuroendocrine tumors (NETs): international PRESTO 2 survey

Abstract: Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

11-Deoxycorticosterone Producing Adrenal Hyperplasia as a Very Unusual Cause of Endocrine Hypertension: Case Report and Systematic Review of the Literature

Abstract: Background and Objectives 11-deoxycorticosterone overproduction due to an adrenal tumor or hyperplasia is a very rare cause of mineralocorticoid-induced hypertension. The objective is to provide the most relevant clinical features that clinicians dealing with patients presenting with the hallmarks of hypertension due to 11-deoxycorticosterone-producing adrenal lesions should be aware of. Design and Methods We report the case of a patient with an 11-deoxycorticosterone-producing adrenal lesion and provide a systematic review of all published cases (PubMed, Web of Science and EMBASE) between 1965 and 2021. Results We identified 46 cases (including ours). Most cases (31, 67%) affected women with a mean age of 42.9 ± 15.2 years and presented with high blood pressure and hypokalemia (average of 2.68 ± 0.62 mmol/L). Median (interquartile range) time from onset of first suggestive symptoms to diagnosis was 24 (55) months. Aldosterone levels were low or in the reference range in 98% of the cases when available. 11-deoxycorticosterone levels were a median of 12.5 (18.9) times above the upper limit of the normal reference range reported in each article and overproduction of more than one hormone was seen in 31 (67%). Carcinoma was the most common histological type (21, 45.7%). Median tumor size was 61.5 (60) mm. Malignant lesions were larger, had higher 11-deoxycorticosterone levels and shorter time of evolution at diagnosis compared to benign lesions. Conclusions 11-deoxycorticosterone-producing adrenal lesions are very rare, affecting mostly middle-aged women with a primary aldosteronism-like clinical presentation and carcinoma is the most frequent histological diagnosis. Measuring 11-deoxycorticosterone levels, when low aldosterone levels or in the lower limit of the reference range are present in hypertensive patients, is advisable. Systematic Review Registration Open Science Framework, 10.17605/OSF.IO/NR7UV.

Corticotroph tumor progression after bilateral adrenalectomy: data from ERCUSYN.

Abstract: Corticotroph tumor progression after bilateral adrenalectomy/Nelson's syndrome (CTP-BADX/NS) is a severe complication of bilateral adrenalectomy (BADX). The aim of our study was to investigate prevalence, presentation and outcome of CTP-BADX/NS in patients with Cushing's disease (CD) included in the European Registry on Cushing's Syndrome (ERCUSYN). We examined data on 1045 CD patients and identified 85 (8%) who underwent BADX. Of these, 73 (86%) had follow-up data available. Median duration of follow-up since BADX to last visit/death was 7 years (IQR 2-9 years). Thirty-three patients (45%) experienced CTP-BADX/NS after three years (1.5-6) since BADX. Cumulative progression-free survival was 73% at three years, 66% at 5 years and 46% at 10 years. CTP-BADX/NS patients more frequently had a visible tumor at diagnosis of CD than patients without CTP-BADX/NS (p<0.05). Twenty-seven CTP-BADX/NS patients underwent surgery, 48% radiotherapy, and 27% received medical therapy. Median time since diagnosis of CTP-BADX/NS to last follow-up visit was 2 years (IQR, 1-5). Control of tumor progression was not achieved in 16 of 33 (48%) patients, of whom 8 (50%) died after a mean of 4 years. Maximum adenoma size at diagnosis of CD was associated with further tumor growth in CTP-BADX/NS despite treatment (p=0.033). Diagnosis of CTP-BADX/NS, older age, greater UFC levels at diagnosis of CD and initial treatment predicted mortality. In conclusion, CTP-BADX/NS was reported in 45% of the ERCUSYN patients who underwent BADX, and control of tumor growth was reached in half of them. Future studies are needed to establish effective strategies of prevention and treatment.

The effect of mindfulness therapy in acromegaly, a pilot study

Abstract: Patients with acromegaly have often several comorbidities, including decreased quality of life, mood alterations and chronic pain. Mindfulness is effective at improving mood, quality of life and pain management; however, there is no data available on its effect in patients with acromegaly.