OBJECTIVE: To present a case series of Cushing\'s syndrome (CS) during pregnancy caused by adrenocortical adenomas, highlighting clinical features, hormonal assessments and outcomes.
METHODS: We describe five pregnant women with CS, detailing clinical presentations and laboratory findings.
RESULTS: Common clinical features included a full moon face, buffalo back and severe hypertension. Elevated blood cortisol levels with circadian rhythm disruption and suppressed adrenocorticotrophic hormone (ACTH) levels were observed. Imaging revealed unilateral adrenal tumours. Two cases underwent laparoscopic adrenalectomies during the second trimester, while three had postpartum surgery. All required hormone replacement therapy, with postoperative pathological confirmation of adrenocortical adenomas.
CONCLUSIONS: Diagnosis of CS during pregnancy is challenging due to overlapping features with normal pregnancy: elevated blood cortisol levels and abnormal diurnal rhythm of blood cortisol, suppressed aid diagnosis. Treatment should be individualised due to a lack of explicit optimum therapeutic approaches. Laparoscopic adrenalectomy may be an optimal choice, along with multidisciplinary management including hormone replacement therapy.

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. Thirty-one studies reported HRQoL using validated patient reported outcome (PRO) measures in pre- or post-surgery, radiotherapy and pharmacotherapy patients. Overall, this SLR found that patients with CS have worse outcomes relative to healthy populations across specific dimensions, such as depression, despite an improvement in HRQoL post-treatment. These findings reveal that CS symptoms are not fully resolved by the existing care paradigm. Few studies report on the economic burden of CS and currently available data indicate a high direct healthcare system cost burden.
CONCLUSIONS: Patients with CS experience a significant, complex and multifactorial HRQoL burden. Symptom-specific burden studies are sparse in the literature and the understanding of long-term CS symptomatic burden and economic burden is limited. This review intends to provide an updated reference for clinicians, payers and other stakeholders on the burden of CS as reported in published literature and to encourage further research in this area.

Gastrointestinal perforation is a well-addressed complication of exogenous hypercortisolism; however, patients with endogenous Cushing\'s syndrome (CS) do not usually experience this condition in clinical practice. The literature on this subject is limited and consists solely of clinical case reports/series with only 23 instances of gastrointestinal perforation occurring in individuals with endogenous Cushing\'s syndrome. This is mainly attributed to the rarity of Cushing\'s syndrome itself and the low chance of occurrence of such complications. We report a case of a recently diagnosed adrenocorticotropic hormone (ACTH)-dependent Cushing\'s syndrome in a 30-years-old female who presented initially with a three-month history of progressive weight gain, generalized weakness, acne, menstrual irregularity, and severe hypokalemia, and then developed a gastric ulcer perforation only one month after her ACTH-dependent Cushing\'s syndrome diagnosis and was managed through emergent surgery.

Primary bilateral macronodular adrenal hyperplasia (PBMAH) accounts for <2% of cases of Cushing\'s syndrome. The majority of patients present with no obvious steroid excess it means with autonomous cortisol secretion (ACS). The classic treatment for patients with overt Cushing\'s syndrome is bilateral adrenalectomy, but unilateral resection of the larger adrenal gland can result in clinical and/or biochemical remission in >90% of cases, especially in cases of ACS. In this article, a series of 32 cases with PBMAH is described. Most of the cases of PBMAH had ACS, except for one case with overt Cushing\'s syndrome. A study of aberrant receptors was performed in six patients, being negative in three cases, positive in the metoclopramide test in two cases and positive in the metoclopramide test and in the mixed meal test in another patient. The patient with overt Cushing\'s syndrome was treated with adrenostatic therapy achieving biochemical control, while two patients with ACS underwent unilateral adrenalectomy with resection of the largest adrenal gland, demonstrating hypercortisolism remission and improvement of cardiovascular risk factors after surgery. This article describes a series of 32 cases of PBMAH and offers a comprehensive review of PBMAH.

Background: Medullary thyroid cancer (MTC) is a neuroendocrine tumor arising from parafollicular C-cells of the thyroid gland that, in rare cases, can cause a paraneoplastic ectopic Cushing\'s syndrome (ECS). The development of Cushing\'s syndrome (CS) in MTC patients is generally associated with advanced disease and poor prognosis. Summary: We described a case of severe CS due to MTC in a young male. We performed a systematic review to identify cases of ECS due to MTC. We searched PubMed, Scopus, and Web of Science for publications between database inception and February 2022 and we collected the patient characteristics, disease presentation, employed treatment strategies, and disease outcomes. In addition to our patient, we identified 96 cases of ECS due to MTC reported in literature. Mean age at diagnosis was 44.4 years (range 10-84), and there was a male predominance (male:female [M:F] = 1.8:1). Most patients (51%) presented with metastatic disease at diagnosis and showed severe hypercortisolism. Seventeen patients developed distant metastasis and hypercortisolism during follow-up. Interestingly, in 48% of patients, the diagnosis of CS followed the diagnosis of MTC with a median time of 48 months but, among patients in whom the diagnosis was concomitant (38%), symptoms due to hypercortisolism were frequently the reason for seeking medical advice. Pathology results showed evidence of adrenocorticotropic hormone (ACTH) or corticotropin releasing hormone (CRH) positive cells in 76% of patients in whom they were tested. The management of hypercortisolism was challenging in most patients with 48% requiring, eventually, definitive treatment with bilateral adrenalectomy (BLA). Recently, some limited evidence has emerged regarding tyrosine kinase inhibitors (TKIs) treatment for hypercortisolism in patients with ECS due to MTC. Despite limited information on survival, prognosis was generally poor and the main causes of death were either complications of CS or disease progression. Conclusions: Despite its rarity, MTC should be considered in the differential diagnosis of ECS. Management of hypercortisolism is a key factor to improve the patient\'s symptoms but it is often challenging and BLA is frequently required. Further studies are needed for investigating the role of TKIs in patients with MTC with ECS.

Background: Endogenous Cushing\'s syndrome (CS), also called hypercortisolism, leads to a significant increase in mortality due to excessive cortisol production, which is mainly due to cardiovascular disease. CS complicated with cardiomyopathies, which is a rare and severe condition, has rarely been reported in the literature. Objective: To investigate the clinical characteristics of CS complicated with cardiomyopathies, we retrospectively reviewed the clinical manifestations, laboratory results, cardiac imaging results and prognosis to further understand the diagnosis, treatment, and management of these cases. Methods: The clinical data of patients diagnosed with CS complicated with cardiomyopathies obtained from discharge sheets from Peking Union Medical College Hospital from January 1986 to August 2021 were collected. Case reports of CS complicated with cardiomyopathies were retrieved from PubMed. In addition, Cushing\'s disease (CD) patients without cardiomyopathies were collected as controls to compare the clinical features. Results: A total of 19 cases of CS complicated with cardiomyopathies and cases of CD without cardiomyopathies (n = 242) were collected. The causes of CS included pituitary adenoma (n = 8, 42.11%), adrenal adenoma (n = 7, 36.84%), ectopic adrenocorticotropic hormone (ACTH) tumor (n = 2, 10.53%) and unclear causes (n = 2, 10.53%) in the CS complicated with cardiomyopathies group. The types of cardiomyopathies were dilated cardiomyopathies (n = 15, 78.94%) and hypertrophic cardiomyopathies (n = 4, 21.05%). The serum sodium concentration was significantly higher [145.50 (140.50-148.00) mmol/L vs. 141.00 (140.00-143.00) mmol/L], while the serum potassium concentration was significantly lower [2.70 (2.40-3.60) mmol/L] vs. 3.90 (3.50-4.20 mmol/L)] in the CS complicated with cardiomyopathies group compared to the CD patients without cardiomyopathies. There were no significant differences between the CS complicated with cardiomyopathies group and the CD patients without cardiomyopathies in the serum cortisol concentration and 24-h urine free cortisol, but a significant difference in the adrenocorticotropic hormone level [109.00 (91.78-170.30) pg/ml vs. 68.60 (47.85-110.00) pg/ml]. Twelve/16 (75.0%) patients showed significant improvement or even a complete healing of the heart structure and function after remission of hypercortisolemia after treatment with CS. Conclusions: CS complicated with cardiomyopathies is a very rare clinical entity, in which cortisol plays an important role and it can be greatly improved after remission of hypercortisolemia.

BACKGROUND: There are significant drug-drug interactions between human immunodeficiency virus antiretroviral therapy and intranasal steroids, leading to high serum concentrations of iatrogenic steroids and subsequently Cushing\'s syndrome.
METHODS: All articles in the literature on cases of intranasal steroid and antiretroviral therapy interactions were reviewed. Full-length manuscripts were analysed and the relevant data were extracted.
RESULTS: A literature search and further cross-referencing yielded a total of seven reports on drug-drug interactions of intranasal corticosteroids and human immunodeficiency virus protease inhibitors, published between 1999 and 2019.
CONCLUSIONS: The use of potent steroids metabolised via CYP3A4, such as fluticasone and budesonide, are not recommended for patients taking ritonavir or cobicistat. Mometasone should be used cautiously with ritonavir because of pharmacokinetic similarities to fluticasone. There was a delayed onset of symptoms in many cases, most likely due to the relatively lower systemic bioavailability of intranasal fluticasone.

Independent Cushing\'s adrenocorticotropic hormone (ACTH) syndrome can have several causes, including adrenal carcinoma or simple adrenal hyperplasia. Although the distinction between malignant and benign can be effectively made through imaging investigations, in the situation where there are bilateral formations, their hormonal activity is impossible to appreciate via non-invasive techniques. The present study includes the presentation of a clinical case on the basis of which a literature review was made. The clinical case pertains to a 32-year-old patient with ACTH-independent Cushing\'s syndrome and bilateral adrenal tumor formations leading to the utility of adrenal venous sampling to avoid bilateral adrenalectomy. A literature review was subsequently conducted focusing on articles pertaining to the PICO criteria in order to describe: The diagnosis of adrenal tumor masses, the decision on the type of surgery and most importantly, the impact of adrenal venous sampling in avoiding surgical resection. These interventions severely limit the patients\' quality of life.

BACKGROUND: Cushing\'s syndrome (CS) is a rare and severe disease. Acute pancreatitis is the leading cause of hospitalization. The association of the two disease is rare and uncommon. We report the case of a 37-year-old woman admitted in our service for acute pancreatitis and whose Cushing syndrome was diagnosed during hospiatilisation. The aim of this work is to try to understand the influence of de Cushing in acute pancreatitis and to establish a causative relationship between the two diseases.
METHODS: It is a 37-year-old woman with a history of corticosteroid intake for six months, stopped three months ago who consulted for epigastralgia and vomiting. The physical exam found epigastric sensitivity with Cushing syndrome symptoms. A CT scan revealed acute edematous-interstitial pancreatitis stage E of Balthazar classification. 24 h free cortisol of 95 μg/24 h and cortisolemia of 3.4 μg/dl. The patient was treated symptomatically and referred after to endocrinology service for further treatment.
CONCLUSIONS: The association with acute pancreatitis and CS is rare and uncommon. Although detailed studies and evidence are lacking, it can therefore be inferred that CS is one of the risk factors for the onset of acute pancreatitis. The medical treatment and management of acute pancreatitis in those patients do not differ from other pancreatitis of any etiologies.

Adrenal cortical carcinoma (ACC) is a rare aggressive endocrine tumor with poor prognosis. About 60% of ACC are functional tumors. Bilateral ACC is extremely rare, roughly 2%-10% of cases. Diagnosis and staging of ACC by imaging modalities are crucial for preoperative planning and prognostication. Detection of hyperfunctional bilateral adrenocortical carcinoma by 18F-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F- FDG PET/CT) has never been reported. Herein, we report a male patient who presented with Cushing\'s syndrome, type II diabetes mellitus due to Cushing\'s syndrome, and hypogonadism with biopsy confirmed left ACC. He underwent 18F-FDG PET/CT to evaluate the contralateral adrenal mass and to plan for laparoscopic adrenalectomy, which subsequently confirmed bilateral ACC. Furthermore, 18F-FDG PET/CT was useful in staging, which revealed paraaortic lymph node and lung metastasis.