Resumo em Inglês:

Abstract Cushing’sdisease (CD), caused by an adrenocorticotropin-secreting pituitary adenoma, is a rare but severe endocrine disorder associated with high cardiometabolic morbidity and mortality. Diagnosis is challenging as many symptoms are nonspecific, and biochemical or imaging results may be inconclusive, contributing to substantial diagnostic delay. Although the core features of CD are consistent across the lifespan, certain clinical manifestations of chronic hypercortisolism vary from childhood through older age, reflecting differences in growth, puberty, metabolism, and comorbidity burden. In children, impaired growth coupled with weight gain is most prominent, whereas adolescents often present with pubertal disturbances and psychological or academic difficulties. Adults typically exhibit the classic Cushingoid features such as round face, plethora, and central obesity, along with metabolic and reproductive complications. Older individuals typically present with frailty, sarcopenia, fractures, and cognitive decline. Age also influences the interpretation of endocrine tests, the accuracy of pituitary magnetic resonance imaging, the role of inferior petrosal sinus sampling, perioperative risks, and the long-term impact of remission or persistent disease. Given this context, this narrative review used five representative clinical vignettes (pediatric, adolescent, adult female, adult male, and elderly) to illustrate how the presentation, diagnostic evaluation, and management of CD vary across the lifespan. Each case was paired with a structured synthesis of current evidence, highlighting both shared principles and age-specific nuances essential for timely diagnosis, appropriate treatment selection, and effective long-term multidisciplinary care. Understanding age-related differences is crucial to improving outcomes and reducing the substantial morbidity and mortality associated with CD throughout the lifespan.

Resumo em Inglês:

Abstract Hypophosphatemicrickets (HR) represents a heterogeneous group of disorders characterized by renal phosphate wasting, impaired bone mineralization, and skeletal deformities. This narrative review provides an overview of phosphate homeostasis and the molecular mechanisms underlying HR, focusing on the role of Fibroblast Growth Factor 23 (FGF23) in regulating renal phosphate use and vitamin D metabolism. The clinical, biochemical, and genetic features of both FGF23-dependent and -independent forms of HR are discussed, including X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets (ADHR), autosomal recessive hypophosphatemic rickets (ARHR), tumor-induced osteomalacia (TIO), hereditary hypophosphatemic rickets with hypercalciuria (HHRH), and Fanconi syndrome. Advances in understanding these mechanisms have led to the development of targeted therapies, such as burosumab, which are redefining the clinical management of affected individuals.

Resumo em Inglês:

Abstract Pheochromocytomasand paragangliomas (collectively referred as PPGLs) are highly heritable neoplasms arise from chromaffin cells of neural crest tissues; 40% of patients with PPGLs harbour germline pathogenic variants (PV), which up to 45% of patients exhibit somatic mutations in similar susceptibility genes. Endothelial PAS domain-containing protein-1 [also known as hypoxia inducible factor-2α, HIF-2α] is encoded by EPAS1, and along with other hypoxia-inducible factors (HIFs) acts as a key mediator in the cellular response to hypoxia. Gain-of-function mutations in EPAS1 have been linked to the Pacak-Zhuang syndrome, congenital cyanotic heart disease and sickle cell anaemia. Hypoxia due to chronic anaemia and/or associated nephropathy in patients with sickle cell disease (SCD) may increase the expression of genes related to HIFs, thereby increasing susceptibility to the development of PPGLs. We describe a case of young female with a history of sickle cell anaemia and sickle cell nephropathy who was found to have a para-aortic mass. Histology confirmed the diagnosis of a paraganglioma. She did not exhibit somatic mutations of the common predisposition genes but demonstrated a likely pathogenic activating somatic EPAS1 variant mutation. This case illustrates the predisposition of patients with SCD to PPGLs due to somatic EPAS1 mutations, and should increase awareness of such tumours in these patients.

Resumo em Inglês:

Abstract Tirzepatide,a dual GLP-1 and GIP receptor agonist, is increasingly used for weight management in both patients with diabetes and patients without diabetes. While gastrointestinal side effects such as nausea are common, severe metabolic complications like ketoacidosis are rare and often overlooked. We report the case of a 38-year-old woman with congenital heart disease who developed acute ketoacidosis with hyperglycemia following five months of tirzepatide therapy. Laboratory findings confirmed high anion gap metabolic acidosis, elevated ketones, and significant hyperglycemia. With supportive care, including intravenous fluids, insulin infusion, and electrolyte replacement, she recovered fully. This represents a rare case of tirzepatide-induced hyperglycemic ketoacidosis in a patient without diabetes. In contrast, the two previously reported cases by Singh and cols. and Iqbal and cols. involved patients without diabetes who developed euglycemic ketoacidosis with normal glucose levels while on tirzepatide. This case underscores the importance of vigilant monitoring for metabolic complications, including hyperglycemia and ketoacidosis, in patients without diabetes, particularly those with comorbidities.

Resumo em Inglês:

Abstract Objective: Exercise interventions can improve parameters in offspring predisposed to metabolic issues. In this study, we investigate whether acute aerobic exercise in offspring can improve metabolism via miRNA modulation in mice programmed by maternal obesity. Materials and methods: Female Swiss mice fed either a standard chow (C) or a high-fat diet (HF) during gestation and lactation were mated with C male mice. Offspring fed the C diet underwent swimming exercise protocols, consisting of water adaptation (14 days), a lactate minimum test, and an aerobic intensity exercise session or no exercise at 84 days of age. Results: Offspring of obese dams (OHF) exhibited increased hepatic glycogen and triglyceride compared to offspring of control dams (OC). However, in offspring of obese dams subjected to an individualized aerobic session (OHF-E), these parameters did not differed from the other groups. Hepatic gene expression analysis showed that miR-122 was upregulated in OHF-E, inversely to Agpat levels. Additionally, OHF exhibited higher miR-370 and lower Cpt1a levels; exercise restored miR-370 and elevated Cpt1a levels in OHF-E. Regarding muscle tissue, exercise reduced Ptp1b expression in OHF-E and increased Hif1a and Pparg, despite no changes observed in miR-206 levels. Conclusion: A single session of exercise significantly affected miRNA and transcript levels related to hepatic lipid and muscle glucose metabolism, suggesting that even one bout of exercise can benefit offspring in the context of maternal metabolic programming. This highlights tissue responsiveness and adaptive capacity, warranting further investigation into its potential as a long-term, non-pharmacological intervention.

Resumo em Inglês:

Abstract Objective: MOTS-c is a mitochondria-derived peptide associated with reduced insulin resistance and obesity. The m.1382A>C polymorphism of the MOTS-c gene is linked to an increased risk of type 2 diabetes in men. However, no studies have explored the relationship between this polymorphism and MOTS-c levels in adolescents with polycystic ovary syndrome (PCOS). This study aimed to investigate the differences in MOTS-c levels between adolescents diagnosed with PCOS and those without PCOS, as well as the associations with metabolic parameters. The association between the MOTS-c gene polymorphism and serum MOTS-c levels in adolescents with PCOS was also evaluated. Subjects and methods: Adolescents aged 12-18 diagnosed with PCOS were recruited based on irregular menstrual cycles and clinical/biochemical hyperandrogenism, excluding other conditions. The control group consisted of adolescents with regular menstruation. Serum MOTS-c levels were measured using ELISA, and the m.1382A>C polymorphism was analyzed by sequencing. Results: The study included 121 adolescents with PCOS and 125 healthy controls. The mean serum MOTS-c levels in the PCOS group were higher than in the control group; however, this difference did not reach statistical significance (p = 0.059). There was no significant association between MOTS-c levels and anthropometric or metabolic parameters within the PCOS group (p > 0.05). All participants had the wild-type (A/A) genotype for the m.1382A>C polymorphism. Conclusion: Results indicate that the MOTS-c gene (m.1382A>C) polymorphism shows no significant association with PCOS, and serum MOTS-c levels are comparable between individuals with PCOS and healthy controls, suggesting that MOTS-c may have a minor involvement in the pathophysiology of PCOS.

Resumo em Inglês:

Abstract Objective: Early diagnosis of overt diabetes has not been extensively explored. We compared pregnancy outcomes of women diagnosed with overt diabetes in the first trimester (up to the 13 completed weeks) to those with a later diagnosis. Subjects and methods: We evaluated women with overt diabetes and a type 2 diabetes phenotype. Pregnancy evolution (gestational weight gain, HbA1c, inpatient glycemic control) and outcomes (preeclampsia, neonatal hypoglycemia, and admission to the neonatal intensive care unit) were compared using multivariable analyses (linear regression or Poisson regression with robust variances). All models computed the early diagnosis and other specific clinically relevant outcome-related variables. Results are b (linear coefficient) or adjusted relative risk (RR) with 95% CI. Results: Of the 217 study participants, 127 (58.5%) were diagnosed in the first trimester (early diagnosis group); those with a late diagnosis presented a higher 3rd-trimester HbA1c (n = 169; b = 1.29; 0.04; 0.55, p = 0.026). Maternal inpatient care was associated with later diagnosis (n = 195; RR 1.29; 1.02; 1.63, p = 0.033) and higher initial HbA1c (n = 195; RR 1.25; 1.16; 1.35, p < 0.001). Aside from a better maternal metabolic control, early diagnosis of overt diabetes did not impact any other pregnancy outcome. Conclusions: In the present cohort of women with overt diabetes, diagnosis before the 14 gestational week modestly improved a few maternal metabolic aspects that did not translate into better pregnancy outcomes.

Resumo em Inglês:

Abstract Objective: Postoperative weight regain remains a challenge after bariatric surgery and affects long-term outcomes. This study aimed to develop a clinical model to predict weight regain within 12 months, prior to surgery by using preoperative inflammatory, metabolic, and ferritin as biomarkers. Subjects and methods: This retrospective observational study included 394 patients with obesity who underwent bariatric surgery (2020-2023), including laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB). Patients were divided into a training set (70%, n = 276) and a validation set (30%, n = 118) using a random number table. Weight regain was defined as a ≥ 10% increase from the postoperative nadir (median time to regain: 8.2 months). Key variables included peripheral blood inflammatory markers [systemic immune-inflammation index (SII, calculated as platelet count × neutrophil count/lymphocyte count), neutrophil-to-lymphocyte ratio (NLR)], glycolipid metabolism indicators [low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C)], and ferritin levels. Multivariate logistic regression was used to identify independent predictive variables, and the nomogram model was validated via calibration, area under the receiver operating characteristic curve (AUC), and decision curve analysis (DCA). Results: The weight regain rate was 19.9% (55/276) in the training set. Independent predictive variables included elevated SII (OR=1.004; 95% CI = 1.000-1.007), LDL-C (OR = 1.873; 95% CI = 1.054-3.329), ferritin (OR = 1.005; 95% CI = 1.003-1.008), and reduced HDL-C (OR = 0.103; 95% CI = 0.013-0.844) (all P < 0.05). The model showed strong discrimination (training AUC = 0.852, 95% CI = 0.795-0.910; validation AUC = 0.812, 95% CI = 0.709-0.915) and good calibration (Hosmer-Lemeshow P > 0.05). DCA confirmed the model’s clinical utility across threshold probabilities. Conclusion: Preoperative SII, LDL-C, ferritin, and HDL-C levels effectively predict postoperative weight regain. Early monitoring of these biomarkers may guide personalized interventions to improve long-term outcomes.

Resumo em Inglês:

Abstract Objective: To evaluate the association between specific/all-cause mortality and the individual’s age at death. Materials and methods: This was a retrospective study that employed STROBE guidelines to its development. Medical records of 1,367 individuals diagnosed with diabetes mellitus (DM) who died between 1981 and 2021, in Bauru, São Paulo state, Brazil, were evaluated. Demographic, clinical, and obituary data were collected from medical records and death certificates, serving as adjustment variables in the analysis. Statistics were developed by using Cox-regression models. Results: The final model, adjusted by male sex and T2DM, revealed Hazard Ratios of 0.74 (95% CI: 0.59-0.92; p < 0.01) for infectious causes and 1.92 (95% CI: 1.12-3.37; p < 0.01) for gastrointestinal conditions. These findings suggest that infectious causes were associated with later ages at death, while gastrointestinal conditions were related to younger ages at death. The other evaluated variables and groups of death causes did not show statistical significance. Conclusion: Our study demonstrates that sex and DM type significantly influenced age at death. These findings emphasize the importance of considering demographic and clinical factors when assessing mortality patterns in DM, contributing to improved risk stratification and clinical management strategies.

Resumo em Inglês:

Abstract Objective: Diabetes mellitus (DM) is currently one of the main public health challenges, not only because of its physical complications, but also because of the emotional impact associated with its chronic management. Diabetes distress (DD) is defined as the emotional response that results from living with DM and the consequent self-care required to manage it. The Diabetes Distress Scale (DDS-17) is an instrument used to assess DD. The aim of this study was to translate and culturally adapt the DDS-17 into European Portuguese, assessing its psychometric properties. Subjects and methods: Cross-sectional study divided into three phases: translation and back-translation; cultural adaptation with pre-testing in 30 patients; and psychometric validation (descriptive analysis of the items, exploratory factor analysis and reliability analysis) with 170 patients with type 2 DM from three Primary Care Units of the Braga Local Health Unit. Results: The European Portuguese version of the DDS-17 replicated the four original factors. Internal consistency was high (total Cronbach’s alpha = 0.89), with all subscales scoring above 0.70. The overall DD was considered low (M = 1.68), but the “emotional burden related to DM” subscale showed values suggestive of moderate DD (M = 2.07). Conclusion: The European Portuguese version of the DDS-17 showed adequate validity and reliability and could be used in clinical and research contexts to better understand and manage DD in patients with type 2 DM in Portugal.

Resumo em Inglês:

Abstract Objective: This study aimed to evaluate body composition, quality of life, and depression risk in women with polycystic ovary syndrome (PCOS) compared to women without PCOS. Subjects and methods: This prospective, cross-sectional study assessed quality of life (QoL) and depressive symptoms in women with polycystic ovary syndrome (PCOS) compared with controls with and without overweight or obesity. Assessments included body composition, QoL, health-related quality of life (HRQoL), and depressive symptoms. Participants without PCOS were divided into two groups according to BMI: < 25 kg/m2 [median age 30 years (27-33)] and ≥ 25 kg/m2 [median age 32 years (29-35)]. Results: The study included 47 women with polycystic ovary syndrome (PCOS) phenotypes A and B. The median age was 29 years (25-35), and the median body mass index (BMI) was 32.08 kg/m2 (28.48-36.40). Women with PCOS showed a higher risk of depression (24% with moderate to severe risk) compared with women without PCOS, both with and without overweight or obesity (5% and 3%, respectively). Additionally, women with PCOS consistently reported lower QoL and HRQoL scores, particularly in the physical, environmental, and overall QoL domains, as well as in functional capacity, pain, general health status, vitality, emotional well-being, and mental health domains of HRQoL. Conclusion: Based on these findings, we concluded that body composition does not appear to be a determining factor for increased risk of depressive symptoms or poorer perceptions of QoL and HRQoL in women with PCOS.

Resumo em Inglês:

Abstract Objective: Previous studies suggest a bidirectional relationship between thyroid dysfunction and sleep disorders. However, prospective evidence regarding the impact of sleep characteristics on subclinical hypothyroidism remains limited. This study aimed to evaluate the association between insomnia symptoms, sleep duration, and sleep debt and the incidence of subclinical hypothyroidism. Subjects and methods: We conducted a prospective cohort analysis of 7,983 euthyroid participants from the second wave (2012-2014) of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) who were not taking thyroid-related or psychiatric medications. Insomnia symptoms (initial, middle, and terminal), sleep duration, sleep debt, sociodemographic characteristics, and health behaviors were assessed via questionnaires. Subclinical hypothyroidism was defined as thyrotropin >4.0 μIU/mL and normal free thyroxine in the third wave (2016-2018). Crude and adjusted log-binomial regression models estimated relative risks (RR) and 95% confidence intervals (95% CI). Results: The incidence of subclinical hypothyroidism was 6.6% for both sexes. In women, middle insomnia was associated with a 35% reduced risk of subclinical hypothyroidism (RR: 0.65; 95% CI: 0.44-0.92). Among men, sleep debt was linked to a 30% increased incidence (RR: 1.30; 95% CI: 1.01-1.66), and in the continuous model, each additional hour of sleep debt raised the risk by 9% (RR: 1.09; 95% CI: 1.02-1.14). Conclusion: Of the sleep characteristics assessed, middle insomnia due to nocturnal awakenings appeared to be protective against subclinical hypothyroidism among women, while sleep debt increased the risk among men.

Resumo em Inglês:

Abstract Objective: To analyze temporal trends in radioiodine (RAI) prescription patterns for differentiated thyroid carcinoma (DTC) in Brazil from 2000 to 2024, assessing adherence to evolving clinical guidelines and identifying opportunities for practice optimization. Materials and methods: This retrospective study utilized data from the Brazilian Unified Health System (Datasus) to evaluate RAI prescriptions, categorized by activity: low (30 and 50 mCi), high (100 and 150 mCi), and very high (200 and 250 mCi). Population-adjusted rates, procedure-adjusted ratios (RAI/oncologic thyroidectomies and RAI/new cases), and activity-level trends were analyzed. Results: Three distinct phases emerged: (1) 2000-2007, marked by increasing very high-activity RAI use (≥ 200 mCi); (2) 2008-2015, peak utilization with initial diversification (introduction of 30/50 mCi in 2014); and (3) 2016-2024, significant de-escalation, with high/very high-activity prescriptions declining by 34.2% and low-activity use increasing by 163%. By 2024, RAI distribution comprised 15.3% very high-, 67.1% high-, and 17.6% low-activity prescriptions. The RAI/new cases ratio fell sharply from 0.63 (2010) to 0.25 (2024), and RAI/oncologic thyroidectomies dropped from 1.22 (2013) to 0.70 (2024), reflecting more selective prescription. Conclusion: Brazilian medical practice has increasingly aligned with international DTC guidelines, showing a decline in RAI use and a shift toward low-to-high RAI activities. This suggests broader adoption of risk-adapted strategies. Notwithstanding, high-dose RAI still predominates, pointing that dissemination of standardized treatment protocols could further enhance DTC care within the Brazilian health system.

Resumo em Inglês:

Abstract Objective: This study aimed to analyze preoperative, intraoperative, and postoperative factors that affect the surgical prognosis of non-functioning pituitary adenomas (NFPA) and to determine postoperative complication rates. Materials and methods: We conducted a retrospective cohort study of patients with NFPA who underwent surgery between 1995 and 2024 at a tertiary public hospital in Brazil. Variables analyzed included tumor size, cavernous sinus invasion (Knosp classification), endocrinological status, preoperative clinical features, surgical complications, and outcomes. Statistical significance was set at p ≤ 0.05. Results: Seventy-three patients were included, with a mean age of 53 years and a slight predominance of females. Tumors were classified as macroadenomas (59%) and giant adenomas (41%). The transsphenoidal approach was used in 81% of cases. Partial resection was achieved in 56%, subtotal in 16%, and total in 27%. Immediate postoperative complications included diabetes insipidus (30%), bleeding (11%), hydrocephalus (10%), ischemia (10%), meningitis (6%), and cerebrospinal fluid fistula (11%). Mortality was 9.6%, significantly associated with postoperative hydrocephalus, ischemia, and larger tumor size. Giant tumors were correlated with higher rates of preoperative neurological deficits and postoperative complications. Transcranial surgery was more frequently performed in cases of giant adenomas and was associated with increased rates of ischemia and neurological deficits. Tumor recurrence was observed in 33% of patients over a mean follow-up of 48 months. Tumor size and postoperative complications such as hydrocephalus and ischemia were associated with increased morbidity and mortality. Conclusion: Postoperative hydrocephalus, ischemia, and tumor size are key determinants of mortality in NFPA surgical treatment. Implementing preventive and management strategies targeting these complications could improve patient outcomes, albeit rigorous long-term follow-up is essential due to the high rates of recurrence and reoperation.

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Abstract Objective: This study aimed to compare body composition measurements between patients with nonfunctional adrenal incidentalomas (NFAI) and mild autonomous cortisol secretion (MACS) using bioelectrical impedance analysis (BIA) and anthropometric methods. Subjects and methods: This cross-sectional study included patients diagnosed with MACS or NFAI. Body composition was assessed using BIA, anthropometric measurements, and the Durnin and Womersley (DW) method. Correlation and Bland-Altman analyses were performed to assess the relationship and agreement between the DW method and BIA. Results: Fifty-seven patients (32 with MACS and 25 with NFAI) were included; those with MACS were older (p = 0.004). Post-dexamethasone suppression test cortisol levels (p < 0.001) and the incidence of bilateral tumors (p = 0.017) were higher in MACS patients. No significant differences in body composition parameters were observed between the MACS and NFAI groups. A strong correlation was observed between BIA- and DW-derived fat mass in MACS patients (r = 0.890, p < 0.001). Bland-Altman analysis revealed a slight mean bias for body fat mass of -0.4 kg (limits of agreement: -9.14-8.34 kg) and for body fat percentage of -0.83% (limits of agreement: -11.32-9.66%) between methods. Conclusion: A robust correlation and acceptable agreement was demonstrated between the DW method and BIA for estimating body fat. The DW equation may provide a practical and low-cost alternative for assessing body composition in MACS and NFAI cohorts. Limitations include the lack of a healthy control group and the inability to validate BIA and anthropometric estimates against gold-standard imaging techniques, potentially introducing accuracy bias.

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Abstract Objective: To evaluate the impact of a structured tele-education program on hospital hyperglycemia and diabetes, focusing on residents’ medical knowledge and inpatient care. Subjects and methods: This open-label, multicenter, randomized clinical trial enrolled internal medicine residents from four university hospitals in southern Brazil. Teams were block-randomized to an intervention group that received an online lecture plus 30 days of tele-education via WhatsApp, or to a control group with no intervention. The primary outcome was medical knowledge, assessed with a validated 10-item questionnaire. Secondary outcomes included quality of insulin prescriptions, hypoglycemia and hyperglycemia rates, and hospital length of stay (LOS). Analyses were performed using SPSS v29 (5% significance). Results: Fifty residents completed the study. The intervention group achieved higher post-intervention knowledge scores than the control group (median 8 vs. 6 correct answers; p = 0.005) and showed significant improvement from preto post-test (6 to 8; p < 0.001), with consistent gains across centers. Clinical data from 149 hospitalized patients were analyzed (mean age 67.8 years; 55% female); 56% had diabetes, and 44% had hospital-related hyperglycemia. There was a nonsignificant trend toward more appropriate NPH (p = 0.107) and regular insulin (p = 0.203) prescriptions in the intervention group. Median LOS was longer in the intervention group (19 vs. 13 days; p = 0.009). Conclusion: The tele-education program improved residents’ knowledge of inpatient hyperglycemia. Larger studies are needed to confirm clinical effects and long-term outcomes of tele-education in hospital glycemic management.

Resumo em Inglês:

Abstract Objective: The objective of this study was to assess the outcomes of various treatment strategies in patients with relapsed Graves’ disease (GD) after standard antithyroid drug therapy (ATD). The three treatment strategies evaluated were radioiodine therapy (RAI), continuous low-dose methimazole (MMI), and a second course of MMI. Subjects and methods: This was a retrospective cohort study of 330 patients with GD who received initial MMI therapy for 12 to 24 months, of whom 159 subsequently relapsed. The cohort was categorized into three groups: 39 patients received RAI therapy plus levothyroxine, 46 patients received continuous low-dose MMI, and 74 patients received a second course of MMI. The analysis included thyroid function monitoring, progression of thyroid eye disease (TED), quality-of-life measures, and changes in body weight during follow-up. Results: The group receiving continuous low-dose MMI had a longer period of euthyroidism compared with the other groups. The TED outcomes and body weight changes were similar across all groups. Quality of life did not differ significantly across groups. Notably, 45% of patients in the group receiving a second MMI course relapsed when MMI was discontinued after a mean treatment duration of approximately 42 months. Conclusion: The administration of continuous low-dose MMI is an alternative for managing patients with relapsed GD, particularly for those who prefer to avoid definitive treatments.

Resumo em Inglês:

Abstract Objective: Cushing’s syndrome, characterized by chronic hypercortisolism, is associated with various health risks, including psychiatric symptoms and cognitive impairments. This systematic review of case studies aimed to map and categorize these symptoms. Materials and methods: We hypothesized that a broader range of psychiatric and cognitive manifestations would be observed beyond anxiety, depression, and memory impairment. The review followed PRISMA guidelines and was preregistered in PROSPERO (CRD42024433186). We conducted searches in PsycINFO, Embase, PubMed, and Scopus, identifying 273 potentially relevant studies. After screening, 66 studies were included, comprising 74 cases (81% female; mean age 35.7 years, range 13-81). Results: Results revealed that 93% of cases presented psychiatric complaints, including depression (39.2%), psychosis/schizophrenic symptoms (35.1%), suicidal ideation/attempts (20.3%), anxiety (17.5%), panic attacks (2.7%), and post-traumatic stress disorder (1.4%). Cognitive complaints were reported in 32% of cases, primarily as general cognitive complaints (18.9%), memory impairment (9.5%), and attentional deficits (5.4%). An overlap of psychiatric and cognitive symptoms was observed in 26% of cases. Conclusion: This review underscores the clinical relevance of symptoms such as mania, psychosis, and suicidal behavior in Cushing’s syndrome, which are often underreported. Individualized clinical assessment informed by these case studies is crucial for comprehensive management that extends beyond the typical focus on depression and memory. Moreover, greater awareness of the full spectrum of neuropsychiatric manifestations in hypercortisolism is needed.