Sleep disruption in patients with active and treated endogenous Cushing's syndrome.

Context: The hypothalamic-pituitary-adrenal axis is a critical regulator of circadian rhythm in humans. Impaired sleep adversely affects metabolic, emotional, and cognitive health.

Objective: To characterize sleep disturbances in patients with active and treated Cushing's syndrome (CS), and identify factors associated with impaired sleep in treated patients.

Genome-wide loss of heterozygosity predicts aggressive, treatment-refractory behavior in pituitary neuroendocrine tumors.

Pituitary neuroendocrine tumors (PitNETs) exhibiting aggressive, treatment-refractory behavior are the rare subset that progress after surgery, conventional medical therapies, and an initial course of radiation and are characterized by unrelenting growth and/or metastatic dissemination. Two groups of patients with PitNETs were sequenced: a prospective group of patients (n = 66) who consented to sequencing prior to surgery and a retrospective group (n = 26) comprised of aggressive/higher risk PitNETs. A higher mutational burden and fraction of loss of heterozygosity (LOH) was found in the aggressive, treatment-refractory PitNETs compared to the benign tumors (p = 1.

Long-term Pegvisomant Therapy of Acromegaly: Effects on Bone Density, Turnover and Microstructure Using HRpQCT.

Context: Fracture rate is increased in patients with active acromegaly and those in remission. Abnormalities of bone microstructure are present in patients with active disease and persist despite biochemical control after surgery. Effects of treatment with the GH receptor antagonist pegvisomant on bone microstructure were unknown.

Different patient versus provider perspectives on living with Cushing's disease.

Context: Patients with Cushing's disease (CD) face challenges living with and receiving appropriate care for this rare, chronic condition. Even with successful treatment, many patients experience ongoing symptoms and impaired quality of life (QoL). Different perspectives and expectations between patients and healthcare providers (HCPs) may also impair well-being.

A medical chart audit to assess endocrinologist perceptions of the burden of endogenous Cushing's syndrome.

Purpose: This study was undertaken to assess the unmet needs within the endogenous Cushing's syndrome (CS) care paradigm from the endocrinologist's perspective, including data abstracted from patient charts. The study evaluated endocrinologists' perceptions on burden of illness and treatment rationale along with the long-term clinical burden of CS, tolerability of CS treatments, and healthcare resource utilization for CS.

Methods: Retrospective medical chart data from treated patients with a confirmed diagnosis of CS was abstracted using a cross-sectional survey to collect data from qualified endocrinologists.

Holistic burden of illness in patients with endogenous Cushing's syndrome: A systematic literature review.

Objective: The objective of this systematic literature review (SLR) was to summarize the latest studies evaluating the burden of illness in endogenous Cushing's syndrome (CS), including the impact of CS on overall and domain-specific health-related quality of life (HRQoL) and the economic burden of CS to provide a holistic understanding of disease and treatment burden.

Methods: An SLR was conducted in PubMed, MEDLINE and Embase using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist to identify peer-reviewed manuscripts and conference abstracts published in English from 2015 to December 4, 2020.

Results: Forty-five publications were eligible for inclusion; data were extracted from 37 primary studies while 8 SLRs were included for reference only.

Dabrafenib as a diagnostic and therapeutic strategy for the non-surgical management of papillary craniopharyngioma.

Purpose: Papillary craniopharyngiomas can cause considerable morbidity due to mass effect and potential surgical complications. These tumors are known to harbor BRAF V600 mutations, which make them exquisitely sensitive to BRAF inhibitors.

Methods: The patient is a 59 year old man with a progressive suprasellar lesion that was radiographically consistent with a papillary craniopharyngioma.

The treatment of aggressive prolactinomas with everolimus.

Introduction: Aggressive prolactinomas are life-limiting tumors without a standard of care treatment option after the oral alkylator, temozolomide, fails to provide tumor control.

Methods: We reviewed an institutional database of pituitary tumors for patients with aggressive prolactinomas who progressed following treatment with a dopamine receptor agonist, radiotherapy and temozolomide. Within this cohort, we identified four patients who were treated with everolimus and we report their response to this therapy.

Medical therapy for refractory pituitary adenomas.

Introduction: Refractory pituitary adenomas are those that have progressed following standard of care treatments. Medical therapy options for these challenging tumors are limited.

Purpose: To review the landscape of tumor directed medical therapies and off-label investigational approaches for refractory pituitary adenomas.

Evaluating the burden of endogenous Cushing's syndrome using a web-based questionnaire and validated patient-reported outcome measures.

Introduction: Endogenous Cushing's syndrome (CS) is a rare endocrine condition caused by chronic oversecretion of cortisol, resulting in a diverse constellation of symptoms. This study examined the ongoing burden of illness (BOI), from the first appearance of symptoms through treatment, which is currently not well evaluated.

Methods: A quantitative, cross-sectional, web-enabled survey including 5 validated patient reported outcomes (PRO) measures was conducted in patients with CS who had been diagnosed ≥ 6 months prior and who had received ≥ 1 treatment for their endogenous CS at the time of the survey.

Levoketoconazole treatment in endogenous Cushing's syndrome: extended evaluation of clinical, biochemical, and radiologic outcomes.

Objective: This extended evaluation (EE) of the SONICS study assessed the effects of levoketoconazole for an additional 6 months following open-label, 6-month maintenance treatment in endogenous Cushing's syndrome.

Design/methods: SONICS included dose-titration (150-600 mg BID), 6-month maintenance, and 6-month EE phases. Exploratory efficacy assessments were performed at months 9 and 12 (relative to the start of maintenance).

Evaluating Patient-Reported Outcomes in Cushing's Syndrome.

The importance of the patient's perspective on disease has increasingly gained traction among clinical investigators and clinicians. Patient-reported outcomes (PROs) are those which pertain to a patient's health, quality of life, or functional status (associated with health care or treatment) that are reported directly by the patient, without interpretation by a clinician. In this article, we will review PROs as they relate to the signs, symptoms, health-related quality of life, and comorbidities of active Cushing's syndrome (CS), and CS after treatment with surgery, radiotherapy, and medical therapy.

Patients with hypercortisolemic Cushing disease possess a distinct class of hematopoietic progenitor cells leading to erythrocytosis.

Although human cell cultures stimulated with dexamethasone suggest that the glucocorticoid receptor (GR) activates stress erythropoiesis, the effects of GR activation on erythropoiesis in vivo remain poorly understood. We characterized the phenotype of a large cohort of patients with Cushing disease, a rare condition associated with elevated cortisol levels. Results from hypercortisolemic patients with active Cushing disease were compared with those obtained from eucortisolemic patients after remission and from volunteers without the disease.

Virtual education programming for patients with acromegaly: a pilot study.

Objectives: To assess the impact of virtual education programming for patients with acromegaly.

Design: We conducted a mixed methods study to evaluate patient attitudes, examine if patient-centered educational forums change these attitudes, and determine the role of virtual education as a means to learn about patients' unmet needs, self-reported outcomes, and educational priorities.

Methods: The study included 653 total virtual program registrants.

Consensus on diagnosis and management of Cushing's disease: a guideline update.

Cushing's disease requires accurate diagnosis, careful treatment selection, and long-term management to optimise patient outcomes. The Pituitary Society convened a consensus workshop comprising more than 50 academic researchers and clinical experts to discuss the application of recent evidence to clinical practice. In advance of the virtual meeting, data from 2015 to present about screening and diagnosis; surgery, medical, and radiation therapy; and disease-related and treatment-related complications of Cushing's disease summarised in recorded lectures were reviewed by all participants.

Synergism of Checkpoint Inhibitors and Peptide Receptor Radionuclide Therapy in the Treatment of Pituitary Carcinoma.

Context: Aggressive pituitary tumors that have progressed following temozolomide have limited treatment options. Peptide receptor radionuclide therapy and immunotherapy may have a complementary role in the management of these tumors.

Methods: We provide follow-up data on a previously reported patient with a hypermutated recurrent tumor.

Levoketoconazole in the Treatment of Patients With Cushing's Syndrome and Diabetes Mellitus: Results From the SONICS Phase 3 Study.

Background: Cushing's syndrome (CS) is associated with numerous comorbidities, including diabetes mellitus (DM). Levoketoconazole, an orally administered ketoconazole stereoisomer, is in clinical trials for the treatment of CS.

Methods: SONICS, a prospective, open-label, phase 3 study in adults with confirmed CS and mean 24-h urinary free cortisol (mUFC) ≥1.

USP8 and TP53 Drivers are Associated with CNV in a Corticotroph Adenoma Cohort Enriched for Aggressive Tumors.

Context: Pituitary corticotroph adenomas are rare tumors that can be associated with excess adrenocorticotropin (ACTH) and adrenal cortisol production, resulting in the clinically debilitating endocrine condition Cushing disease. A subset of corticotroph tumors behave aggressively, and genomic drivers behind the development of these tumors are largely unknown.

Objective: To investigate genomic drivers of corticotroph tumors at risk for aggressive behavior.

Levoketoconazole improves clinical signs and symptoms and patient-reported outcomes in patients with Cushing's syndrome.

Purpose: The efficacy of levoketoconazole in treating hypercortisolism was demonstrated in an open-label phase 3 study (SONICS) of adults with endogenous Cushing's syndrome (CS) and baseline mean urinary free cortisol (mUFC) ≥  1.5× ULN. Clinical signs and symptoms and patient-reported outcomes from the SONICS trial were evaluated in the current manuscript.

Approach to the Treatment of a Patient with an Aggressive Pituitary Tumor.

A small subset of pituitary adenomas grows despite maximal treatment with standard therapies; namely, surgery and radiotherapy. These aggressive tumors demonstrate 2 patterns of growth: they may be locally aggressive or metastasize distantly, either hematogenously or through the spinal fluid. Further surgery and radiotherapy may be helpful for palliation of symptoms, but they are rarely definitive in the management of these malignant tumors.

Patient reported outcome data from acromegaly patients treated with injectable somatostatin receptor ligands (SRLs) in routine clinical practice.

Background: Acromegaly patients managed on Somatostatin receptor ligands (SRLs), the most common first-line pharmacotherapy for acromegaly, may still experience acromegaly symptoms such as headache, sweating, fatigue, soft tissue swelling, and joint pain, even those with normal IGF-1. Additionally, treatment with SRLs may cause injection site reactions and other side effects such as gastro-intestinal (GI) symptoms. This study utilized patient-reported outcome measures to examine the burden associated with acromegaly and its treatment for patients receiving a stable dose of long-acting SRLs in routine clinical practice.