Novel Cushing’s Syndrome Drug Improves Hypertension, Hyperglycemia

Posted on July 18, 2025 by MaryO

The investigational selective glucocorticoid receptor modulator relacorilant led to improvements in blood pressure, fasting glucose, and weight for patients with adrenal hypercortisolism, a pair of phase III studies showed.

In pooled data from the GRACE and GRADIENT trials, adults with adrenal hypercortisolism and hypertension on relacorilant had a significant decrease in systolic and diastolic blood pressure measured by 24-hour ambulatory blood pressure monitoring (-10.1 and -6.3 mm Hg, respectively) compared with placebo (1.5 and 2.2 mm Hg, respectively; both P<0.01), according to Corin Badiu, MD, PhD, of the Carol Davila University of Medicine and Pharmacy and National Institute of Endocrinology in Bucharest, Romania.

At week 22, relacorilant patients had an average blood pressure of 128/81 mm Hg compared with 135/84 mm Hg with placebo, Badiu reported at ENDO 2025, the annual meeting of the Endocrine Society.

As for those with hyperglycemia with or without hypertension at baseline, relacorilant significantly improved fasting glucose and glucose area under the curve (-0.7 and -2.4 mmol/L per hour, respectively) compared with placebo (0.4 and 1.3 mmol/L per hour, respectively; both P<0.05).

Relacorilant-treated participants also lost 4.1 kg (9 lb) compared with 1 kg (2.2 lb) in placebo patients (P<0.01).

“We expected a good hypertension control and an improved control of diabetes [with relacorilant],” Badiu told MedPage Today.

Acting as a selective cortisol modulator, relacorilant works by binding to the glucocorticoid receptor but not to other hormone receptors in the body. It was granted orphan drug designation by the FDA.

It works differently than other agents indicated for endogenous hypercortisolism (also known as Cushing’s syndrome) like the nonselective glucocorticoid receptor antagonist mifepristone (Korlym), which can be difficult to use given its drug-drug interactions and side effects like endometrial hypertrophy and vaginal bleeding.

If approved, relacorilant could be a treatment option for patients with mild autonomous hypercortisolism with resistant hypertension or difficult-to-treat diabetes who are avoiding or reluctant to surgery, or have had previous unsuccessful surgery, said Badiu.

Because metabolic issues are so prevalent in endogenous hypercortisolism, Badiu advised healthcare providers to take “an active attitude for screening for endogenous autonomous hypercortisolism in every individual patient with metabolic syndrome.”

After confirmation of an endogenous hypercortisolism diagnosis, providers should present all available treatment options from surgery to medical treatment in a personalized manner, using multidisciplinary management — cardiology, endocrinology, imaging, surgery, rheumatology, psychology, etc. — in order to make appropriate decisions, he recommended.

The GRACE and GRADIENT trials recruited participants ages 18 to 80 with endogenous hypercortisolism along with hypertension, hyperglycemia (defined as impaired glucose tolerance or diabetes), or both.

At baseline, patients given relacorilant had an average weight of 88.6 kg (195.3 lb) and waist circumference was 110.9 cm. Those with hypertension with or without hyperglycemia had average 24-hour systolic and diastolic blood pressures of 139.1 mm Hg and 86.4 mm Hg, respectively. For those with hyperglycemia with or without hypertension, average HbA1c was 6.5%, glucose area under the curve was 23.6 mmol/L per hour, and 2-hour oral glucose tolerance test was 11.8 mmol/L.

Participants on relacorilant had their dose titrated from 100 mg to 400 mg once daily based on tolerability and efficacy.

Treatment was safe and well-tolerated among patients, said Badiu, with no new emerging safety signal. Most adverse events were mild to moderate in severity.

As for adverse events of interest, there were no cases of relacorilant-induced irregular vaginal bleeding with endometrial hypertrophy or adrenal insufficiency, no events of relacorilant-induced QT prolongation, and no increases in cortisol concentrations and relacorilant-induced hypokalemia.

“Lack of hypokalemia as an adverse event was an additional positive finding,” said Badiu. “Some long-term effects on mood, sleep behavior, coagulation profile, bone metabolism, liver steatosis, and body composition are still subject to detailed analysis.”

Developer Corcept Therapeutics submitted a new drug application for relacorilant to the FDA late last year; a decision on approval is expected by the end of 2025. The drug is also currently being studied for ovarian, adrenal, and prostate cancers.

From https://www.medpagetoday.com/meetingcoverage/endo/116508

 

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Adrenal Gland Volume Measurement Could Assist Surgery Option in Patients With Primary Pigmented Nodular Adrenocortical Disease

Posted on July 16, 2025 by MaryO

Abstract

Background

Primary pigmented nodular adrenocortical disease is a rare form of adrenocorticotropic hormone–independent Cushing syndrome originating from bilateral adrenal lesions. Current guidelines do not specify a recommended strategy for determining the optimal surgery. This study evaluates the concordance between bilateral adrenal gland volume and adrenal venous sampling results and the predictive value of adrenal gland volume for postoperative outcomes in patients with primary pigmented nodular adrenocortical disease.

Method

This is a retrospective study conducted at a single center. The study cohort included 10 hospitalized patients with primary pigmented nodular adrenocortical disease from 2011 to 2023. Patients underwent thin-slice adrenal computed tomography scan. An nnU-NET–based automatic segmentation model segmented the adrenal region of interest, and adrenal gland volume were computed. The ratio of left to right adrenal gland volume were also determined. All patients underwent either unilateral or bilateral adrenalectomy and received postoperative follow-up.

Results

Adrenal gland volume enlargement was asymmetrical between the 2 sides. Larger adrenal gland volumes typically corresponded to the side of dominant cortisol production as indicated by adrenal venous sampling. Clinical and biochemical remission was achieved with left adrenalectomy when left to right adrenal gland volume exceeded 1.2, and with right adrenalectomy when left to right adrenal gland volume was below 0.9. When the left to right adrenal gland volume was approximately 1, unilateral adrenalectomy proved less effective, often necessitating bilateral adrenalectomy, either simultaneously or sequentially.

Conclusion

Measuring adrenal gland volume can aid in formulating the optimal surgical approach for patients with primary pigmented nodular adrenocortical disease.

Introduction

Primary pigmented nodular adrenocortical disease (PPNAD) is an uncommon cause of adrenocorticotropic hormone (ACTH)-independent Cushing syndrome (ACS).1 Frequently, PPNAD is associated with the Carney complex (CNC), a rare multiple endocrine neoplasia syndrome characterized by distinctive pigmented lesions on skin and mucous membranes, cardiac and extracardiac myxomas, and multiple endocrine tumors.2 Approximately 45–68.6% of patients with CNC develop PPNAD. CNC is most commonly linked to mutations in the PRKAR1A gene, which follows an autosomal-dominant inheritance pattern, although approximately 25% of cases emerge sporadically from de novo mutations.1,2
The adrenal morphology in PPNAD typically includes multiple small nodules forming a “string of beads” appearance1; however, some patients exhibit atypical features such as a normal adrenal contour, unilateral large nodules, or adenomas.3, 4, 5 In cases lacking other CNC components, these atypical features increase the risk of diagnostic errors.
To date, no universally endorsed surgical strategies exist for PPNAD. Although bilateral adrenalectomy was once the standard treatment to eliminate autonomous cortisol secretion, it leads to lifelong adrenal insufficiency, necessitating continuous glucocorticoid and mineralocorticoid replacement, and poses an ongoing risk of adrenal crisis.1 Accumulating evidence suggests that unilateral adrenalectomy can diminish cortisol levels and ameliorate metabolic disturbances associated with glucocorticoid excess, with some patients experiencing temporary adrenal insufficiency.1,6 This suggests that cortisol production may not be synchronously increased in bilateral adrenals in patients with PPNAD. Selecting the dominant cortisol-producing adrenal for resection could control the metabolic effects of autonomous cortisol production while avoiding the need for lifelong hormone replacement and the risk of an adrenal crisis.
Bilateral adrenal venous sampling (AVS), typically used to identify the dominant aldosterone-secreting side in primary aldosteronism,7 also has been employed to determine the dominant cortisol-secreting side in PPNAD, thus guiding surgical decisions.8,9 However, AVS is technically demanding, involves radiation exposure, has a notable failure rate, and is costly. Moreover, there are no standardized criteria for successful AVS or for determining the dominant side in patients with PPNAD. Therefore, exploring simpler, cost-effective, and reliable criteria for surgical decision-making is crucial.
In this study, we included previously diagnosed patients with PPNAD to apply machine-learning algorithms for segmenting adrenal region of interest (ROI) and analyze the relationship between adrenal morphologic changes and clinical outcomes, thereby providing guidance for surgical planning.

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Patients and diagnoses

From December 2011 to August 2024, 321 patients with ACS were diagnosed and treated in the Department of Endocrinology and Metabolism at West China Hospital of Sichuan University. Among them, 12 patients with PPNAD were identified, and 10 of them with preoperative adrenal computed tomography (CT) imaging, comprising 2 male and 8 female patients, were included in this study. Among them, 8 patients were found to carry PRKAR1A gene mutations, as identified by next-generation sequencing of DNA

Patient clinical characteristics

The study analyzed data from 10 patients, comprising 8 women and 2 men, with a mean age of 30.5 years (range, 15–55 years). Eight patients were diagnosed with arterial hypertension, 4 exhibited impaired glucose regulation, and 2 had normal glucose levels and arterial blood pressure. Nine patients displayed typical features of Cushing syndrome, with the exception of 1 individual who presented solely with hypertension and central obesity. In addition, all female participants experienced menstrual

Discussion

This retrospective study examined the relationships among AGV, AVS, and surgical outcomes in 10 patients diagnosed with PPNAD. We observed that AGVs in patients with PPNAD were not uniformly enlarged. Variability in enlargement was noted, with some patients developing larger left adrenal lesions, others larger right adrenal lesions, and some exhibiting equivalently sized bilateral adrenal lesions. Generally, larger AGVs correlated with the dominant side of cortisol production as indicated by

Funding/Support

The study was supported by a grant from the Science &Technology Department of Sichuan Province (2023YFS0262) and a grant from the Ministry of Science and Technology of the People’s Republic of China (2022YFC2505303).

CRediT authorship contribution statement

Tao Chen: Writing – review & editing, Writing – original draft, Visualization, Validation, Software, Resources, Project administration, Methodology, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Sikui Shen: Resources, Project administration, Investigation. Yeyi Tang: Resources. Wei Xie: Resources. Huaiqiang Sun: Software, Methodology, Data curation. Yuchun Zhu: Resources. Mingxi Zou: Resources. Ying Chen: Resources. Haoming Tian: Supervision. Xiaomu Li:

Conflict of Interest/Disclosure

The authors have no relevant financial disclosures.

References (18)

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    Cushing syndrome in a young woman due to primary pigmented nodular adrenal disease

    Endocr Pract

    (2010)
  • G. Luo et al.

    An optimized two-stage cascaded deep neural network for adrenal segmentation on CT images

    Comput Biol Med

    (2021)
  • A.C. Powell et al.

    Operative management of Cushing syndrome secondary to micronodular adrenal hyperplasia

    Surgery

    (2008)
  • L. Bouys et al.

    Bilateral adrenocortical nodular disease and Cushing’s syndrome

    J Clin Endocrinol Metab

    (2024)
  • L. Bouys et al.

    Management of endocrine disease: carney complex: clinical and genetic update 20 years after the identification of the CNC1 (PRKAR1A) gene

    Eur J Endocrinol

    (2021)
  • L. Groussin et al.

    Mutations of the PRKAR1A gene in Cushing’s syndrome due to sporadic primary pigmented nodular adrenocortical disease

    J Clin Endocrinol Metab

    (2002)
  • K.M. Lowe et al.

    Cushing syndrome in carney complex: clinical, pathologic, and molecular genetic findings in the 17 affected mayo clinic patients

    Am J Surg Pathol

    (2017)
  • D. Vezzosi et al.

    Hormonal, radiological, NP-59 scintigraphy, and pathological correlations in patients with Cushing’s syndrome due to primary pigmented nodular adrenocortical disease (PPNAD)

    J Clin Endocrinol Metab

    (2015)
  • Y. Zhu et al.

    Primary pigmented nodular adrenocortical disease: report of 5 cases

    Chin Med J (Engl)

    (2006)
There are more references available in the full text version of this article.

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Ectopic Adrenocorticotropic Hormone Syndrome Due To Olfactory Neuroblastoma: A Case Report And Literature Review

Posted on July 14, 2025 by MaryO

Abstract

Ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS) is a cause of Cushing’s syndrome usually associated with neuroendocrine tumors. Olfactory neuroblastoma (ONB) is a rare malignant neoplasm of the olfactory epithelium. This is the case of a 56-year-old woman with an ONB presenting with EAS. After initiating metyrapone, she developed a  Pneumocystis jirovecii  pneumonia. Following successful treatment of the infection, she underwent surgical tumor excision and radiotherapy, which has been in remission for the past 3 years. The authors provide a literature review of the 30 previously published cases of ONB presenting with EAS. Most were reported in middle-aged men, with a recurrence rate of 15.6% (3 patients eventually died). A total of 9.5% of all reported had an infection after starting corticosteroid-blocking therapy. ONB is a very rare cause of EAS with poor prognosis and a relapsing course. In the presence of severe hypercortisolism, chemoprophylaxis for common opportunistic agents must be considered.

Summary

Ectopic adrenocorticotropic hormone secretion syndrome (ACES) is a cause of Cushing’s syndrome commonly associated with neuroendocrine tumors. Olfactory neuroblastoma (ON) is a rare malignant tumor of the olfactory epithelium. We describe the case of a 56-year-old woman with ACES secondary to ON. After starting metyrapone, the patient developed  Pneumocystis jirovecii pneumonia . The infection was treated, the tumor was surgically removed, and she received radiotherapy. The patient has maintained remission for the past 3 years. We review the 30 previously reported cases of ACEs secondary to ON. Most occurred in middle-aged men, with a recurrence rate of 15.6% (3 patients died). Ninety-five percent of these cases had an infection after starting control of hypercortisolism. ON is a rare cause of ACEs with a poor prognosis and high recurrence rate. In the presence of hypercortisolism, chemoprophylaxis for common opportunistic agents should be considered.

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Case description

Production of adrenocorticotropic hormone (ACTH) from nonpituitary tumors – known as ectopic ACTH syndrome (EAS) – is the cause of ACTH-dependent hypercortisolism in up to 18% of all cases of Cushing’s syndrome. 1  EAS is more commonly associated with neuroendocrine tumors located in the chest, namely small-cell lung carcinoma, bronchial carcinoids and thymic neuroendocrine tumors. 2  These are followed less frequently by breast, colon, gastric, pancreatic and prostate cancers.2, 3, 4, 5, 6

Management and evidence

We consider our case particularly interesting for two reasons: the rarity of an ONB as a cause of the EAS (there are only 30 other cases reported worldwide) (Table 1) 30, 31, 32, 33, 34, 35, 36, 37, 38 and clinical progression with an opportunistic infection after starting corticosteroid-blocking therapy. To identify the 30 cases referenced we performed a literature review across PubMed, until August 2024, using the

Areas of uncertainty

Although there is some doubt about the elevated infectious risk of these patients, not only due to hypercortisolism but also after starting steroid-blocking therapy, diagnosis of these complications is frequently delayed. Additionally, infectious chemoprophylaxis is not routinely instituted in these patients. Our case highlights these areas of discussion.
Once ACTH secretion is detected, steroid-blocking therapy is often initiated to control symptoms related to Cushing’s syndrome. Metyrapone and

Guidelines

Due to the rarity of ONB presenting with ACTH secretion, there are no specific and well-established guidelines that delineate the management of these conditions presenting simultaneously, but there are recommendations for the treatment of each of them separately.2, 13, 45, 46
Regarding ONB management, surgery must be considered whenever it is feasible, and adjuvant radiotherapy is recommended in every case.13, 46 Adjuvant and neoadjuvant chemotherapy can be considered, depending on the initial

Conclusions and recommendations

EAS secretion is a cause of Cushing’s syndrome and should be suspected in the presence of signs and symptoms of severe hypercortisolism, even without the typical Cushing’s syndrome stigmata. Although ONB is a very rare cause of the ACTH syndrome, it should not be missed considering its poor outcome when left untreated. Hypercortisolism should be controlled until it is possible to treat the underlying tumor, bearing in mind that normalizing cortisol levels can precipitate opportunistic

Funding

None declared.

Conflicts of interest

None declared.

References (46)

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Cushing’s Syndrome Study for Patients and Caregivers

Posted on July 9, 2025 by MaryO

We have an opportunity for you to take part in a Cushing’s Syndrome Study for patients and caregivers. Our project number for this study is SJO_11379.

Project Details:

  • Web-assisted telephone interview (you must be by a computer with high-speed internet access while on the phone during the time of the interview) – WEBCAM REQUIRED
  • Interview is 60-minutes long, plus optional 30-40 minute homework assignment
  • up to 195 Dollar Reward (120 Dollar Reward for Interview, 75 Dollar Reward for completion of optional homework assignment)

Things to Note:

  • Provide detailed and thoughtful responses. Rushed responses may be rejected by the client.
  • Using AI may be flagged, and your reward forfeited.
  • Using a VPN may cause you to disqualify from the study
  • Study is open to patients and caregivers
  • Please do not share study links
  • Please use a laptop/computer ONLY. No smartphones or tablets – Preliminary questions are mobile friendly!
  • Save this email to reference if you have any questions about the study!
  • If you have any problems, email jennifer.harscheid@rarepatientvoice.com and reference the project number.  

If you are interested in this study, please click the link below to answer a few questions to see if you qualify.

Study link: Start Here

OR if the study hyperlink is not clickable above, please copy/paste this URL below.
https://panel.rarepatientvoice.com/newdesign/site/rarepatientvoice/surveystart.php?surveyID=b9bk3vluq338&panelMemberID=trfnbc7mvduh1gseff1h&invite=email

Thanks as always for your participation! Please be aware that by entering this information you are not guaranteed that you will be selected to participate. As always, we do not share any of your contact information without your permission.

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Reconstructive Liposuction for Residual Lipodystrophy After Remission of Cushing’s Disease

Posted on July 3, 2025 by MaryO

​Abstract

Cushing’s syndrome (CS) is often presented due to an adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma, characterized by high chronic cortisol levels. Surgical resection of the pituitary adenoma is the primary treatment, but long-term metabolic and physical sequelae can persist, affecting psychological well-being and social functioning. Glucocorticoids are directly involved in alterations of fat metabolism, favoring centripetal adiposity. Even after hormonal normalization, patients may experience residual lipodystrophy. Impairment of body image may cause psychological distress and social isolation. The objective is to illustrate the potential therapeutic value of reconstructive liposuction in restoring body image and psychological well-being in a patient with persistent lipodystrophy after Cushing’s disease remission.

We report a case of a 16-year-old female with recurrent Cushing’s disease secondary to a pituitary microadenoma, confirmed by elevated urinary free cortisol and magnetic resonance imaging (MRI). It was initially treated with transsphenoidal resection in 2019; disease recurrence was confirmed and again treated in 2024. Despite intervention, the prolonged hypercortisolism developed into secondary lipodystrophy, leading to severe body image dissatisfaction and social withdrawal. Thyroid function remained euthyroid, ruling out metabolic contributors. Because of the psychological distress caused by persistent fat redistribution, the patient underwent elective liposuction in 2025. Postoperative follow-up revealed reduced psychological distress and improved well-being and self-esteem. Reconstructive liposuction can play a key role in the treatment and management of persistent post-CS lipodystrophy, contributing significantly to psychological recovery. Prospective studies evaluating surgical criteria and long-term psychosocial outcomes are needed to define eligibility criteria and assess outcomes, leading to the development of clinical guidelines for aesthetic interventions in post-CS recovery.

Introduction

Corticotroph pituitary adenomas (corticotropinomas) are pituitary tumors that secrete excess adrenocorticotropic hormone (ACTH), causing endogenous Cushing’s syndrome (CS). Most of these adenomas are sporadic and monoclonal, although in some rare cases, they are associated with germline mutations (e.g., in USP8) or genetic syndromes [1,2]. Clinically, excess ACTH causes a classic presentation with centripetal obesity, purple striae, muscle asthenia, hypertension, and emotional disturbances such as depression or anxiety [3-5]. Chronically elevated cortisol levels promote fat deposition in central body regions – face, neck, torso, and abdomen – at the expense of relative thinning of the limbs [3], leading to lipodystrophy that can seriously affect the patient’s quality of life.

At the molecular level, glucocorticoids stimulate the differentiation of preadipocytes into mature adipocytes and enhance lipoprotein lipase activity in peripheral fat tissues [6], thereby increasing the uptake of circulating fatty acids and the storage of triglycerides. At the same time, they increase hepatic lipogenesis and modulate cortisol receptor homeostasis (e.g., 11β-HSD1 in adipose tissue), favoring visceral fat distribution [6]. Although glucocorticoids can induce acute lipolysis, they exert chronic lipogenic effects – especially in subcutaneous adipose tissue – which promotes fat accumulation in the face, neck, and trunk [6]. This central adiposity, characteristic of CS, is further enhanced by increased hepatic lipogenesis and the overexpression of 11β-HSD1 in adipose tissue, which amplifies the local action of cortisol [6].

Case Presentation

In 2019, a 16-year-old female patient was initially diagnosed with a 4 × 3 mm pituitary microadenoma (Figure 1), following clinical suspicion of Cushing’s disease. The diagnosis was confirmed through imaging studies and endocrinological testing, which revealed consistently elevated urinary free cortisol levels ranging from 459 to 740.07 µg/24 hours (normal range: <50 µg/24 hours), indicative of endogenous hypercortisolism. No dynamic load tests (such as dexamethasone suppression or ACTH stimulation) were performed, as the diagnosis was supported by the clinical context and laboratory findings. Moreover, no clinical or biochemical evidence of adrenal insufficiency was observed during follow-up.

T1-weighted-sagittal-MRI-scan-showing-a-corticotroph-pituitary-microadenoma-(4-×-3-mm)-circled-in-red
Figure 1: T1-weighted sagittal MRI scan showing a corticotroph pituitary microadenoma (4 × 3 mm) circled in red

The lesion is localized within the anterior pituitary gland, consistent with an ACTH-secreting adenoma causing Cushing’s disease in the patient.

MRI, magnetic resonance imaging; ACTH, adrenocorticotropic hormone

The patient underwent transsphenoidal endonasal resection of the pituitary tumor in 2019. Although initially successful, disease recurrence was confirmed, and a second endonasal transsphenoidal surgery was performed in 2024. Despite these interventions, the prolonged hypercortisolism led to the development of secondary lipodystrophy, manifesting as centripetal fat accumulation, a dorsal fat pad, and disproportionate truncal adiposity (Figure 2). These physical alterations had a significant psychosocial impact, as reported by the patient during follow-up visits, resulting in body image dissatisfaction, low self-esteem, and social withdrawal. No formal psychometric scales were administered.

Preoperative-and-intraoperative-images-of-the-patient
Figure 2: Preoperative and intraoperative images of the patient

A and B panels show the anterior and posterior views prior to liposuction, demonstrating centripetal adipose accumulation characteristic of Cushing’s syndrome. The C panel shows the intraoperative stage following abdominal and flank liposuction, with placement of drainage tubes, and visible reduction in subcutaneous fat volume.

A thyroid function panel revealed a slightly elevated thyroid-stimulating hormone (TSH) level (4.280 μUI/mL; reference range: 0.270-4.200), with total and free T3 and T4 values within normal limits, ruling out clinically significant hypothyroidism as a confounding factor for her phenotype. The biochemical profile suggested a euthyroid state, despite borderline TSH elevation, which was interpreted as a subclinical or adaptive response to chronic cortisol excess (Table 1).

Parameter Normal Range Patient’s Value
Cortisol (µg/24 hour) 58.0 – 403.0 459.5 – 740.07
TSH (µUI/mL) 0.270 – 4.200 4.280
Total T3 (ng/mL) 0.80 – 2.00 1.02
Free T3 (pg/mL) 2.00 – 4.40 3.33
Total T4 (µg/dL) 4.50 – 12.00 8.63
Free T4 (ng/dL) 0.92 – 1.68 1.36
Table 1: Comparison between the patient’s hormone levels and standard reference ranges

A persistently elevated 24-hour urinary cortisol range is observed, consistent with endogenous hypercortisolism. The thyroid profile remains within normal limits, with a mildly elevated TSH in the absence of overt thyroid dysfunction. These findings support the functional and metabolic profile characteristic of Cushing’s syndrome.

TSH, thyroid-stimulating hormone

The procedure targeted lipodystrophic regions identified through clinical examination and patient concerns, rather than formal imaging or anthropometric measurements. It aimed to restore body contour, alleviate somatic distress, and improve her overall self-perception and quality of life. Postoperative follow-up revealed patient-reported improvements in body image and psychological well-being. While these outcomes were not evaluated with formal instruments, the clinical improvement was evident and significant from the patient’s perspective, highlighting the role of plastic surgery not only as a reconstructive tool, but also as a therapeutic strategy for restoring dignity and social functioning in patients recovering from CS.

Discussion

After successful treatment of the pituitary adenoma, many metabolic parameters improve; however, fat distribution usually only partially reverses. Longitudinal studies show that, in the medium term, weight and abdominal circumference decrease, and there is some redistribution of fat toward the limbs following cortisol remission [3].

For example, Bavaresco et al. (2024) observed that, after hormone levels normalized, total fat was reduced and part of it shifted from the visceral area to the legs [3]. Nevertheless, their review highlights that a significant proportion of patients continue to present with residual visceral adiposity and moderate obesity (body mass index, or BMI >25), despite hormonal control [7]. In our case, truncal adiposity persisted based on clinical assessment, though no formal anthropometric measurements were performed.

Although liposuction is not traditionally considered first-line therapy for cortisol-induced lipodystrophy secondary to Cushing’s disease, increasing evidence from related lipodystrophic syndromes supports its clinical utility. For instance, in human immunodeficiency virus (HIV)-associated cervicodorsal lipodystrophy, Barton et al. (2021) conducted a 15-year retrospective analysis comparing liposuction and excisional lipectomy, finding that 80% of patients undergoing liposuction alone experienced recurrence, while none of the patients treated with excisional lipectomy showed recurrence – albeit with a higher risk of postoperative seroma formation [7]. These findings underscore that, while liposuction may be less durable than excision, it remains a viable option for selected cases, especially when used for contouring or as an adjunct [7]. Similarly, the Endocrine Society guidelines on lipodystrophy management emphasize the importance of personalized approaches, particularly when localized adipose accumulation contributes to persistent metabolic dysfunction or psychological distress [8]. Akinci et al. (2024) also highlight that, even in partial or atypical lipodystrophy syndromes, patients often report substantial impairment in quality of life due to disfiguring fat redistribution [9]. In this context, liposuction should not be dismissed as merely cosmetic but considered part of a functional and psychosocial rehabilitation strategy. The present case exemplifies this rationale, as the patient – despite biochemical remission of Cushing’s disease – continued to experience debilitating body image disturbances and emotional distress, which were ameliorated following targeted liposuction. This supports the integration of body-contouring procedures into multidisciplinary care protocols for endocrine-related lipodystrophies, especially when residual physical stigma persists after hormonal normalization [7-9].

Body image disorders, such as those secondary to CS or lipodystrophy, significantly impact self-perception, self-esteem, and social functioning. For example, a study by Alcalar et al. (2013) reported that patients with active Cushing’s disease had significantly lower SF-36 scores – particularly in emotional role functioning and mental health domains – compared to controls [10]. Similarly, Akinci et al. (2024) described that patients with partial lipodystrophy demonstrated marked reductions in EQ-5D index values and visual analog scale (VAS) scores, indicating impaired health-related quality of life [9]. These findings underscore that fat redistribution disorders can substantially compromise psychosocial well-being, even after endocrine remission.

This is especially relevant in women, where sociocultural stereotypes surrounding female physical appearance reinforce thinness, symmetry, and youthfulness as standards of personal value and social acceptance [1]. This societal context amplifies body dissatisfaction when visible physical changes occur, even after the clinical remission of endocrine diseases, often leading to social withdrawal, anxiety, or depression [3,10]. Within this framework, plastic surgery – such as reconstructive liposuction – has proven to be a valuable therapeutic tool, offering physical restoration that can enhance self-confidence and promote social reintegration [4]. Postoperative follow-up in our case revealed patient-reported improvements in body image and psychological well-being. While these outcomes were not assessed using formal psychometric tools, the clinical benefit was evident from the patient’s perspective. This aligns with prior findings demonstrating the psychosocial value of reconstructive surgery, which can enhance self-esteem and social reintegration after physical disfigurement [11,12]. These observations underscore the role of plastic surgery not only as a reconstructive intervention, but also as a therapeutic strategy for restoring dignity and quality of life in patients recovering from CS.

Although validated psychometric instruments such as the Body Image Quality of Life Inventory (BIQLI) and the Dysmorphic Concern Questionnaire (DCQ) are available to assess body image disturbances, these were not applied in our case. Nonetheless, they represent useful tools for evaluating subjective impact in both clinical practice and research settings. The BIQLI evaluates the effect of body image on various aspects of life – social interactions, self-worth, sexuality, and emotional well-being – using a Likert scale ranging from -3 (very negative impact) to +3 (very positive impact), providing a quantifiable assessment of its influence on quality of life [5]. The DCQ, on the other hand, identifies dysfunctional concerns about perceived physical flaws by assessing behaviors such as avoidance, mirror checking, and concealment; higher scores are associated with suspected body dysmorphic disorder (BDD) [6]. These tools are useful for initial diagnosis, surgical candidate selection, and postoperative follow-up, as they objectively measure subjective changes related to body image. Their advantages include ease of use, clinical validity, and applicability in research settings. However, they also have limitations: they do not replace comprehensive psychological evaluation, may be influenced by cultural context, and do not detect deeper psychiatric comorbidities. Therefore, a multidisciplinary and ethically grounded approach – integrating plastic surgery, endocrinology, and psychology – is essential to ensure safe and patient-centered treatment planning.

Aesthetic liposuction is associated with significant improvements in perceived body image and patient quality of life [11]. For example, Papadopulos et al. (2019) observed statistically significant increases in perception of one’s own body appearance and high satisfaction with postoperative results [12]. These aesthetic gains were accompanied by psychological improvements: the same study documented an increase in emotional stability and a reduction in postoperative anxiety [12]. Similarly, Kamundi (2023) found that nearly all assessed dimensions of quality of life improved after liposuction (p < 0.05 in most of them). Altogether, these findings suggest that liposuction not only corrects physical alterations typical of CS, but also strengthens self-esteem and psychological well-being by substantially improving satisfaction with one’s body image [11].

Moreover, self-esteem influences adherence to medical treatments and lifestyle changes. By improving self-image through reconstructive surgery, it is plausible that the patient feels more motivated to maintain healthy habits, such as diet and regular exercise, that prevent metabolic relapse [12,13].

Nonetheless, it is important to emphasize that liposuction, in this context, should be viewed as a reconstructive complement, not a primary treatment. There are no established protocols or formal guidelines that explicitly include plastic surgery in the care of cured CS; the decision is personalized, based on the residual functional and psychological impact.

Conclusions

Reconstructive plastic surgery, though not a primary therapeutic approach for CS, plays a key role in enhancing patients’ quality of life following remission. Liposuction, in particular, offers a safe and effective solution for persistent lipodystrophy, providing aesthetic benefits with minimal scarring, rapid recovery, and low complication rates in properly selected patients.

This case underscores the importance of addressing both physical and psychosocial sequelae after endocrine stabilization. A multidisciplinary approach – encompassing endocrinology, neurosurgery, and plastic surgery – not only restores physical appearance but also contributes to emotional recovery, self-esteem, and overall patient satisfaction.

References

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  13. Saariniemi KM, Salmi AM, Peltoniemi HH, Charpentier P, Kuokkanen HOM: Does liposuction improve body image and symptoms of eating disorders?. Plast Reconstr Surg Glob Open. 2015, 3:461. 10.1097/GOX.0000000000000440

From https://www.cureus.com/articles/376886-reconstructive-liposuction-for-residual-lipodystrophy-after-remission-of-cushings-disease-a-case-report#!/

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