Helping others learn more about Cushing’s/Acromegaly

I found this article especially interesting.  This question was asked of a group of endos at an NIH conference a few years ago – if you saw someone on the street who looked like they had symptoms of fill-in-the disease, would you suggest that they see a doctor.  The general answer was no.  No surprise there.

Patients, if you see someone who looks like s/he has Cushing’s, give them a discrete card.

Spread The Word! Cushing’s Pocket Reference

Robin Writes:

This has been a concern of mine for some time. Your post spurred me on to do something I’ve been meaning to do. I’ve designed something you can print that will fit on the business cards you can buy just about anywhere (Wal-mart included). You can also print on stiff paper and cut with a paper cutter or scissors. I’ve done a front and a back.

Cushing's Pocket Reference

Here are the links:

Front: This card is being presented by a person who cares.
Back (The same for everyone)

This Topic on the Message Boards

~~~~~~~~~~~~~~~~~~

And now, the article from http://www.guardian.co.uk/lifeandstyle/2009/nov/03/doctor-diagnosis-stranger:

Are doctors ever really off duty?

Which potentially serious symptoms would prompt them to stop and advise a stranger on a bus?

By Lucy Atkins

Bus

Passengers on a London bus. Photograph: David Levene

A Spanish woman of 55, Montse Ventura, recently met the woman she refers to as her “guardian angel” on a bus in Barcelona. The stranger – an endocrinologist – urged Ventura to have tests for acromegaly, a rare disorder involving an excesss of growth hormone, caused by a pituitary gland tumour. How had the doctor made this unsolicited diagnosis on public transport? Apparently the unusual, spade-like shape of Ventura’s hands was a dead giveaway.

But how many off-duty doctors would feel compelled to alert strangers to symptoms they spot? “If I was sitting next to someone on a bus with a melanoma, I’d say something or I wouldn’t sleep at night,” says GP Mary McCullins. “We all have a different threshold for interfering and you don’t want to terrify people, but this is the one thing I’d urge a total stranger to see a doctor about.” So what other symptoms might prompt a doctor to approach someone on the street?

Moon face

Cushing’s syndrome is another rare hormone disorder which can be caused by a non-cancerous tumour in the pituitary gland. “A puffy, rounded ‘moon face’ is one of the classic signs of Cushing’s,” says Dr Steve Field, chair of the Royal College of GPs. “In a social situation, I wouldn’t just say, ‘You’re dangerously ill’ but I’d try to elicit information and encourage them to see a doctor.”

Different-sized pupils

When one pupil is smaller than the other, perhaps with a drooping eyelid, it could be Horner’s syndrome, a condition caused when a lung tumour begins eating into the nerves in the neck. This can be the first obvious sign of the cancer. “I’d encourage someone to get this checked out,” says Dr Simon Smith, consultant in emergency medicine at the Oxford Radcliffe Hospitals Trust. “People often have an inkling that something’s wrong, and you might spur them to get help sooner.”

Clubbing fingers

Some people are born with club-shaped fingers, but if, over time, they become “drumstick-like”, this could signify serious problems such as lung tumours, chronic lung infections or congenital heart disease. “Because it happens gradually, some people disregard clubbing,” says Smith. “But I’d say something because it can be an important symptom in many serious illnesses.”

Lumpy eyelids

Whitish yellowy lumps around the eyelids can be a sign of high cholesterol, a major factor in heart disease. Sometimes you also get a yellow circle around the iris. “I would suggest they got a cholesterol test with these symptoms,” says Smith. “They can do something about it that could save their life.”

Suntan in unlikely places

A person with Addison’s disease, a rare but chronic condition brought about by the failure of the adrenal glands, may develop what looks like a deep tan, even in non sun-exposed areas such as the palms. Other symptoms (tiredness, dizziness) can be non-specific so the condition is often advanced by the time it is diagnosed. Addison’s is treatable with lifelong steroid replacement therapy. “If someone was saying they hadn’t been in the sun but had developed a tan, alarm bells would ring and I’d probably ask how they were feeling,” says McCullins.

Trench mouth

Putrid smelling breath – even if the teeth look perfect – can be a sign of acute necrotising periodontitis. “I’d be able to tell when someone walks through the door,” says dentist Laurie Powell. “But people become accustomed to it and don’t notice.” Untreated, the condition damages the bones and connective tissue in the jaw. It can also be a sign of other diseases such as diabetes or Aids.

Prospective Assessment of Mood and Quality of Life in Cushing Syndrome before and after Biochemical Control

Abstract

Context

Cushing syndrome (CS) impairs quality of life (QoL) and mood. Prospective real-life data on post-treatment recovery and predictors of improvement are limited.

Objectives

Evaluate changes in QoL, depression, and anxiety in patients with CS, before and after biochemical control, and identify predictors of clinically meaningful improvement.

Design and Setting

Prospective observational study at a tertiary center.

Patients

67 patients with endogenous CS (60 pituitary, 7 adrenal) were assessed with active disease and again after achieving biochemical control through surgery and/or medication.

Outcomes

Patient-reported outcomes included CushingQoL, Beck Depression Inventory-II (BDI-II), and State-Trait Anxiety Inventory (STAI).

Results

Mean and longest follow-up was 2.3 and 11.5 years, respectively. Treatment led to improvements in mean scores across all domains (QoL: +18.2±20.9, BDI: –6.8±8.6, STAI-State: –9.6±12.5, STAI-Trait: –8.6±12.6; all p < 0.001). However, minimal important difference was achieved in 64.6% for QoL, 67.9% for BDI, 53.2% and 52.8% for STAI subscales. After multivariable analysis, QoL improvements were predicted by lower baseline BMI, pre-treatment symptoms ❤ years, post-operative hydrocortisone replacement >6 months, and normal follow-up late-night salivary cortisol (LNSC). Depression improvements were predicted by symptoms ❤ years, normal follow-up LNSC, and surgical treatment. Anxiety improvements were predicted by younger age and >6 months post-operative hydrocortisone. Depression improved more gradually than QoL and anxiety.

Conclusions

Although effective treatment improves mood and QoL in CS, clinically meaningful recovery is variable and incomplete for some patients. Our findings highlight the need to limit diagnostic delay and provide comprehensive post-treatment care that includes normalization of cortisol circadian rhythm.

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Endogenous Cushing’s Syndrome Market Insights Highlight Expanding Outlook Till 2032

DelveInsight’s “Endogenous Cushing’s Syndrome Market Insights, Epidemiology, and Market Forecast-2032′′ report offers an in-depth understanding of the Endogenous Cushing’s Syndrome, historical and forecasted epidemiology as well as the Endogenous Cushing’s Syndrome market trends in the United States, EU4 (Germany, Spain, Italy, France) the United Kingdom and Japan.

The latest healthcare forecast report provides an in-depth analysis of Endogenous Cushing’s Syndrome, offering comprehensive insights into the Endogenous Cushing’s Syndrome revenue trends, prevalence, and treatment landscape. The report delves into key Endogenous Cushing’s Syndrome statistics, highlighting the current and projected market size, while examining the efficacy and development of emerging Endogenous Cushing’s Syndrome therapies. Additionally, we cover the landscape of Endogenous Cushing’s Syndrome clinical trials, providing an overview of ongoing and upcoming studies that are poised to shape the future of Endogenous Cushing’s Syndrome treatment. This report is an essential resource for understanding the market dynamics and the evolving therapeutic options within the Endogenous Cushing’s Syndrome space.

To Know in detail about the Endogenous Cushing’s Syndrome market outlook, drug uptake, treatment scenario and epidemiology trends, Click here; Endogenous Cushing’s Syndrome Market Forecast
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Some of the key facts of the Endogenous Cushing’s Syndrome Market Report:
• The Endogenous Cushing’s Syndrome market size is anticipated to grow with a significant CAGR during the study period (2019-2032)
• In December 2024, Corcept Therapeutics, a US-based biotechnology company, has announced positive long-term results from its Phase III trial evaluating relacorilant as a treatment for individuals with endogenous hypercortisolism (Cushing’s syndrome).
• In October 2024, Sparrow Pharmaceuticals, a clinical-stage biopharmaceutical company focused on developing targeted therapies for unmet needs in endocrinology and immunology, announced the completion of its Phase 2 RESCUE trial evaluating clofutriben, a selective HSD-1 inhibitor, for endogenous Cushing’s syndrome. All eligible participants who completed the trial opted to continue treatment in an open-label extension (OLE) protocol. Encouraging results from the trial have accelerated plans for the next phase of development, set to begin next year. Additionally, the FDA has granted Orphan Drug Designation to clofutriben for the treatment of endogenous Cushing’s syndrome.
• Key Endogenous Cushing’s Syndrome Companies: Cortendo AB, RECORDATI GROUP, HRA Pharma, Corcept Therapeutics, and others
• Key Endogenous Cushing’s Syndrome Therapies: Levoketconazole, osilodrostat, metyrapone, CORT125134, and others
• The Endogenous Cushing’s Syndrome market is expected to surge due to the disease’s increasing prevalence and awareness during the forecast period. Furthermore, launching various multiple-stage Endogenous Cushing’s Syndrome pipeline products will significantly revolutionize the Endogenous Cushing’s Syndrome market dynamics.
• Research by Scaroni et al. (2023) indicates that Cushing syndrome occurs at an incidence rate of 1.5 per 1,000,000 individuals annually and has a prevalence of around 60 per 1,000,000 individuals in Europe. In about 80% of cases, Cushing syndrome is caused by adrenocorticotrophic hormone (ACTH) hypersecretion, resulting in ACTH-dependent Cushing syndrome.
• Cushing’s syndrome can be caused by either ACTH-dependent (80% of cases) or ACTH-independent (20% of cases) factors. The latter is primarily attributed to benign adrenal tumors (60%) or malignant tumors (40%). ACTH overproduction can either originate from the pituitary (85% of cases) or result from ectopic tumor secretion (15% of cases). The term “Cushing’s disease” is specifically used to refer to ACTH-secreting pituitary tumors.

Endogenous Cushing’s Syndrome Overview
Endogenous Cushing’s Syndrome is a rare hormonal disorder caused by the body’s overproduction of cortisol, a hormone produced by the adrenal glands. This overproduction can result from tumors or abnormalities in the pituitary gland (Cushing’s disease), adrenal glands, or other parts of the body that cause excessive cortisol secretion. It contrasts with exogenous Cushing’s syndrome, which results from external sources like long-term use of corticosteroid medications.

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Endogenous Cushing’s Syndrome Epidemiology
The epidemiology section provides insights into the historical, current, and forecasted epidemiology trends in the seven major countries (7MM) from 2019 to 2032. It helps to recognize the causes of current and forecasted trends by exploring numerous studies and views of key opinion leaders. The epidemiology section also provides a detailed analysis of the diagnosed patient pool and future trends.

Endogenous Cushing’s Syndrome Epidemiology Segmentation:
The Endogenous Cushing’s Syndrome market report proffers epidemiological analysis for the study period 2019-2032 in the 7MM segmented into:
• Total Prevalence of Endogenous Cushing’s Syndrome
• Prevalent Cases of Endogenous Cushing’s Syndrome by severity
• Gender-specific Prevalence of Endogenous Cushing’s Syndrome
• Diagnosed Cases of Episodic and Chronic Endogenous Cushing’s Syndrome

Download the report to understand which factors are driving Endogenous Cushing’s Syndrome epidemiology trends @ Endogenous Cushing’s Syndrome Epidemiology Forecast
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Endogenous Cushing’s Syndrome Drugs Uptake and Pipeline Development Activities
The drugs uptake section focuses on the rate of uptake of the potential drugs recently launched in the Endogenous Cushing’s Syndrome market or expected to get launched during the study period. The analysis covers Endogenous Cushing’s Syndrome market uptake by drugs, patient uptake by therapies, and sales of each drug.
Moreover, the therapeutics assessment section helps understand the drugs with the most rapid uptake and the reasons behind the maximal use of the drugs. Additionally, it compares the drugs based on market share.
The report also covers the Endogenous Cushing’s Syndrome Pipeline Development Activities. It provides valuable insights about different therapeutic candidates in various stages and the key companies involved in developing targeted therapeutics. It also analyzes recent developments such as collaborations, acquisitions, mergers, licensing patent details, and other information for emerging therapies.

Endogenous Cushing’s Syndrome Therapies and Key Companies
• Levoketconazole: Cortendo AB
• osilodrostat: RECORDATI GROUP
• metyrapone: HRA Pharma
• CORT125134: Corcept Therapeutics

Discover more about therapies set to grab major Endogenous Cushing’s Syndrome market share @ Endogenous Cushing’s Syndrome Treatment Landscape
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Endogenous Cushing’s Syndrome Market Drivers
• Growing Prevalence of Endogenous Cushing’s Syndrome
• Advancements in Diagnostic Techniques
• Emerging Targeted Therapies
• Increasing Investment in Rare Disease Research
• Growing Awareness and Early Diagnosis
• Increased Focus on Orphan Drug Development

Endogenous Cushing’s Syndrome Market Barriers
• High Treatment Costs
• Limited Treatment Options
• Complexity in Diagnosis
• Side Effects of Current Treatments
• Small Patient Population
• Regulatory Challenges

Scope of the Endogenous Cushing’s Syndrome Market Report
• Study Period: 2019-2032
• Coverage: 7MM [The United States, EU5 (Germany, France, Italy, Spain, and the United Kingdom), and Japan]
• Key Endogenous Cushing’s Syndrome Companies: Cortendo AB, RECORDATI GROUP, HRA Pharma, Corcept Therapeutics, and others
• Key Endogenous Cushing’s Syndrome Therapies: Levoketconazole, osilodrostat, metyrapone, CORT125134, and others
• Endogenous Cushing’s Syndrome Therapeutic Assessment: Endogenous Cushing’s Syndrome current marketed and Endogenous Cushing’s Syndrome emerging therapies
• Endogenous Cushing’s Syndrome Market Dynamics: Endogenous Cushing’s Syndrome market drivers and Endogenous Cushing’s Syndrome market barriers
• Competitive Intelligence Analysis: SWOT analysis, PESTLE analysis, Porter’s five forces, BCG Matrix, Market entry strategies
• Endogenous Cushing’s Syndrome Unmet Needs, KOL’s views, Analyst’s views, Endogenous Cushing’s Syndrome Market Access and Reimbursement

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Osilodrostat-associated Adrenal Gland Shrinkage: a Case Series of Patients with ACTH-Dependent Cushing’s Syndrome

The Journal of Clinical Endocrinology & Metabolism, dgaf552, https://doi.org/10.1210/clinem/dgaf552

Abstract

Context

Medical therapy for Cushing’s syndrome (CS) is increasingly used. A potent adrenal steroidogenesis inhibitor, osilodrostat, has been rarely linked to prolonged adrenal insufficiency (AI).

Objective

We hypothesized that osilodrostat-induced adrenal insufficiency could be associated with adrenal gland shrinkage.

Design

Non-interventional, retrospective, longitudinal, IRB-approved study of patients with CS treated at Oregon Health and Science University between January 1, 2000 and July 1, 2025.

Setting

Ambulatory and inpatient, academic, quaternary medical center.

Patients or Other Participants

Patients with ACTH-dependent CS, treated with osilodrostat for >3 months, and CT imaging before and after osilodrostat available for adrenal volume (AV) measurement.

Intervention(s)

Age, sex, osilodrostat doses and duration, laboratory data and AI were recorded. AV was calculated using manual segmentation on CT images by a board-certified radiologist.

Main Outcome Measure(s)

AV before and after initiation of osilodrostat was expressed as percent reduction.

Results

10 patients (5 ectopic CS, 4 unknown ACTH source, 1 Cushing’s disease) were included. Osilodrostat mean starting, maximum and final doses: 7.7, 13.8 and 5.9 mg/day, respectively, over 23 months. Four patients received block-and-replace regimen, AI developed in 5. Adrenal gland volume decreased by 46.7±22.2% from 25.5±9.9 ml to 12.7±6.4 ml, p<0.001 over a median of 19 months. AV reduction positively correlated with maximum osilodrostat dose, r=0.626, p=0.027.

Conclusions

We found that in selected patients with ACTH-dependent CS, osilodrostat can induce significant adrenal shrinkage, with or without AI. Further confirmation by larger studies of different CS types and monitoring for AI is required for all patients.

The Impact of Adrenalectomy On Metabolic Outcomes of Patients Wwth Mild Autonomous Cortisol Secretion Defined by Low-Dose Dexamethasone Suppression Testing

Abstract

Background

Up to 50% of patients with adrenal incidentalomas have mild autonomous cortisol secretion, which may increase their cardiometabolic morbidity, compared with patients with nonfunctional adrenal tumors. Studies evaluating cardiometabolic outcomes of patients with mild autonomous cortisol secretion defined by 1-mg dexamethasone suppression testing (cortisol 1.8–5 μg/dL) have demonstrated mixed results. The aim of this study was to assess the metabolic outcomes of patients with mild autonomous cortisol secretion, defined by the 1-mg dexamethasone suppression testing criterion, compared with patients with nonfunctional adrenal tumors who underwent adrenalectomy.

Methods

We conducted a single-institution retrospective cohort study comparing adult patients who underwent unilateral adrenalectomy from November 30, 2011, to August 19, 2023, for mild autonomous cortisol secretion (1-mg dexamethasone suppression testing cortisol 1.8–5 μg/dL) or nonfunctional adrenal tumors (1-mg dexamethasone suppression testing cortisol <1.8 μg/dL). Preoperative prevalences and postoperative changes in diabetes mellitus, hypertension, dyslipidemia, and elevated body mass index (≥25) were assessed. Patients were followed from the time of surgery until their last outpatient visit. Multivariable logistic regression was pursued for outcomes that varied between cohorts.

Results

A total of 65 patients (53 mild autonomous cortisol secretion and 12 nonfunctional adrenal tumors) were analyzed. Patients with mild autonomous cortisol secretion were older and more likely to have diabetes mellitus than patients with nonfunctional adrenal tumors (odds ratio: 7.81, 95% confidence interval [0.94, 64.96], P = .04). Patients were followed for a median of 28.1 months [11.1, 55.3 months]. Patients with mild autonomous cortisol secretion were more likely to have postoperative weight improvement (odds ratio: 8.31, [0.97, 71.14], P = .03). After adjusting for clinically relevant variables, the 1-mg dexamethasone suppression testing cortisol was predictive of postoperative weight improvement (odds ratio: 1.88, [1.1, 3.65], P = .04).

Conclusion

Weight loss should be considered as a potential benefit of adrenalectomy in patients with mild autonomous cortisol secretion.

Introduction

Mild autonomous cortisol secretion (MACS) is the most common hormonal abnormality diagnosed in patients with adrenal incidentalomas, impacting 20%–50% of patients.1 Patients with MACS have biochemical evidence of adrenocorticotropic hormone (ACTH)-independent hypercortisolism but lack clinical stigmata commonly associated with overt hypercortisolism, such as facial plethora, abdominal adiposity, extremity weakness and wasting, and/or violaceous striae.2 Overt hypercortisolism is well recognized to cause cardiovascular, musculoskeletal, and metabolic disorders, which have variable resolution even after diagnosis and treatment.3 There is a growing body of evidence that patients with MACS also have increased cardiometabolic morbidity and mortality compared with patients with nonfunctional adrenal tumors,4 but this evidence is challenging to interpret given wide variability in diagnostic criteria that have historically been used.5, 6, 7
Recent guidelines have suggested that a diagnosis of MACS be applied to all patients with a morning (AM) serum cortisol of >1.8 μg/dL after low-dose (1-mg) dexamethasone suppression testing (DST) who lack overt features of hypercortisolism.8,9 However, prior studies comparing cardiometabolic outcomes between patients with MACS and nonfunctional adrenal tumors as well as between patients who underwent operative and nonoperative management have used a 1-mg DST AM serum cortisol of 1.8–5.0 μg/dL as a definition of mild (“subclinical”) hypercortisolism.10, 11, 12, 13, 14, 15, 16 Given that these studies have demonstrated mixed results,4 the primary aim of this study was to assess the metabolic outcomes of patients with MACS, as defined by a 1-mg DST AM cortisol of 1.8–5.0 μg/dL, compared with patients with nonfunctional adrenal tumors who underwent adrenalectomy.

Section snippets

Methods

This was a single-institution retrospective cohort study of patients aged ≥18 years who underwent initial unilateral adrenalectomy from November 30, 2011, to August 19, 2023. Patients were identified through a prospectively maintained database of all patients who underwent adrenalectomy at the study institution. Patients were excluded if they had a 1-mg DST AM serum cortisol of >5 μg/dL, ACTH-dependent hypercortisolism, primary aldosteronism, pheochromocytoma, primary bilateral macronodular

Results

Of the 460 patients who underwent adrenalectomy during the study period, 53 patients met criteria for MACS and 12 patients for nonfunctional adrenal tumors, yielding a cohort of 65 patients. Patients with MACS were older than those with nonfunctional adrenal tumors (MACS, median 60 years [IQR: 54, 68 years] vs nonfunctional adrenal tumors, 49 years [37, 57 years], P = .02) but were similar by sex, race, ethnicity, BMI, nodule size, laterality, and surgical approach (Table II). Among patients

Discussion

MACS is the most common hormonal abnormality diagnosed in patients with adrenal incidentalomas. Despite lacking clinical stigmata of overt hypercortisolism, patients with MACS appear to have increased cardiometabolic morbidity and mortality similar to patients with overt hypercortisolism. The optimal management of MACS is debated, and prior studies using a 1-mg DST AM serum cortisol of 1.8–5.0 μg/dL as a definition of mild hypercortisolism have demonstrated mixed results. Hence, this study

Funding/Support

This project is funded in part by the Advancing a Healthier Wisconsin Endowment at the Medical College of Wisconsin. This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational SciencesNational Institutes of Health (NIH), through grant number UL1TR001436. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. The grant supports the creation and maintenance of

CRediT authorship contribution statement

Alexa Lisevick Kumar: Writing – original draft, Visualization, Methodology, Formal analysis, Data curation, Conceptualization. Sophie Dream: Writing – review & editing, Validation, Supervision, Methodology, Investigation. Tahseen Shaik: Resources, Project administration, Investigation, Data curation. Kara Doffek: Resources, Project administration, Investigation, Data curation. Ryan Conrardy: Writing – review & editing, Methodology, Formal analysis. James W. Findling: Writing – review & editing,

Conflict of Interest/Disclosure

Dr Findling reports consulting for Corcept, Diurnal, Crinetics and serving as an investigator for Recordati. The rest of the authors reported no biomedical financial interests or potential conflicts of interest.

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