ABSTRACT TheBrazilian Dietary Guidelines provide crucial recommendations for a healthy diet, aiming at promoting health and preventing non-communicable chronic diseases. The core principle is the preference for natural or minimally processed foods and freshly prepared dishes over ultra-processed foods. Despite their growing recognition, healthcare professionals struggle to integrate these guidelines into clinical practice. This article aims to present two innovative strategies for incorporating the Brazilian Dietary Guidelines into healthcare. The Protocols based on the Brazilian Dietary Guidelines for Individual Dietary Advice are standardized clinical tools to support healthcare professionals (nutritionists or not) in giving nutritional advice during individual appointments to various life stages. The Protocols operationalize the assessment of individuals’ dietary patterns using the Food Consumption Markers Questionnaire and support the delivery of personalized and priority recommendations through a stepwise flowchart. Conversely, Brazilian Dietary Guidelines-based Meal Plans consist of personalized dietary prescriptions comprising structured daily menus that, unlike conventional plans primarily focusing on nutrient goals, prioritize overall eating patterns guided by the Brazilian Dietary Guidelines. The proposal encourages, in the first place, the selection of a variety of culinary preparations based on natural or minimally processed foods, emphasizing tasteful, accessible, and culturally appropriate choices as the initial step. In a second step, these plans can be customized to individual energy requirements, and adjustments made based on strategic nutrient needs. This article aims to support the enhancement of healthcare professionals’ skills in promoting healthy eating practices, thereby contributing to improved health and a reduced disease burden among the Brazilian population.

ABSTRACT Objective: To explore the diagnostic value of the TUIAS (SW_TH01/II) computer-aided diagnosis (CAD) software system for the ultrasound Thyroid Imaging Reporting and Data System (TI-RADS) features in thyroid nodules. Materials and methods: This retrospective study enrolled patients with thyroid nodules in Shanghai East Hospital between January 2017 and October 2021. The novel CAD software (SW_TH01/II) and three sonographers performed a qualitative analysis of the ultrasound TI-RADS features in aspect ratio, margin irregularity, margin smoothness, calcification, and echogenicity of the thyroid nodules. Results: A total of 225 patients were enrolled. The accuracy, sensitivity, and specificity of the CAD software in “aspect ratio” were 95.6%, 96.2%, and 95.4%, in “margin irregularity” were 90.7%, 90.5%, and 90.9%, in “margin smoothness” were 85.8%, 88.5%, and 83.0%, in “calcification” were 83.6%, 81.7%, and 82.0%, in “homogeneity” were 88.9%, 90.6%, and 82.2%, in “major echo” were 85.3%, 88.0%, and 85.4%, and in “contains very hypoechoic echo” were 92.0%, 90.0%, and 92.4%. The analysis time of the CAD software was significantly shorter than for the sonographers (2.7 ± 1.6 vs. 29.7 ± 12.7 s, P < 0.001). Conclusion: The CAD system achieved high accuracy in describing thyroid nodule features. It might assist in clinical thyroid nodule analysis.

ABSTRACT FGF21 is a hormone produced primarily by the liver with several metabolic functions, such as induction of heat production, control of glucose homeostasis, and regulation of blood lipid levels. Due to these actions, several laboratories have developed FGF21 analogs to treat patients with metabolic disorders such as obesity and diabetes. Here, we performed a systematic review and meta-analysis of randomized controlled trials that used FGF21 analogs and analyzed metabolic outcomes. Our search yielded 236 articles, and we included eight randomized clinical trials in the meta-analysis. The use of FGF21 analogs exhibited no effect on fasting blood glucose, glycated hemoglobin, HOMA index, blood free fatty acids or systolic blood pressure. However, the treatment significantly reduced fasting insulinemia, body weight and total cholesterolemia. None of the included studies were at high risk of bias. The quality of the evidence ranged from moderate to very low, especially due to imprecision and indirection issues. These results indicate that FGF21 analogs can potentially treat metabolic syndrome. However, more clinical trials are needed to increase the quality of evidence and confirm the effects seen thus far.

ABSTRACT Objective: To study associations between polymorphisms in the angiotensin converting enzyme (ACE I/D), actinin 3 (ACTN3 R577X) and paraoxonase 1 (PON1 T(-107)C) genes and chronic diseases (diabetes and hypertension) in women. Materials and methods: Genomic DNA was extracted from saliva samples of 78 women between 18 and 59 years old used for genetic polymorphism screening. Biochemical data were collected from the medical records in Basic Health Units from Southern Brazil. Questionnaires about food consumption, physical activity level and socioeconomic status were applied. Results: The XX genotype of ACTN3 was associated with low HDL levels and high triglycerides, total cholesterol and glucose levels. Additionally, high triglycerides and LDL levels were observed in carriers of the TT genotype of PON1, and lower total cholesterol levels were associated to the CC genotype. As expected, women with diabetes/hypertense had increased body weight, BMI (p = 0.02), waist circumference (p = 0.01), body fat percentage, blood pressure (p = 0.02), cholesterol, triglycerides (p = 0.02), and blood glucose (p = 0.01), when compared to the control group. Conclusion: Both ACTN3 R577X and PON1 T(-107)C polymorphisms are associated with nutritional status and blood glucose and lipid levels in women with diabetes/hypertense. These results contribute to genetic knowledge about predisposition to obesity-related diseases.

ABSTRACT Bisphosphonates (BPs) are medications widely used in clinical practice to treat osteoporosis and reduce fragility fractures. Its beneficial effects on bone tissue have been consolidated in the literature for the last decades. They have a high affinity for bone hydroxyapatite crystals, and most bisphosphonates remain on the bone surface for a long period of time. Benefits of long-term use of BPs: Large and important trials (Fracture Intervention Trial Long-term Extension and Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly-Pivotal Fracture Trial) with extended use of alendronate (up to 10 years) and zoledronate (up to 6 years) evidenced significant gain of bone mineral density (BMD) and vertebral fracture risk reduction. Risks of long-term use of BPs: The extended use of antiresorptive therapy has drawn attention to two extremely rare, although severe, adverse events. That is, atypical femoral fracture and medication-related osteonecrosis of the jaw are more common in patients with high cumulative doses and longer duration of therapy. BPs have demonstrated safety and effectiveness throughout the years and evidenced increased BMD and reduced fracture risks, resulting in reduced morbimortality, and improved quality of life. These benefits overweight the risks of rare adverse events.

ABSTRACT Objective: COVID-19 is a multisystem immunoinflammatory disorder, and the hypothalamo–pituitary-adrenal (HPA) axis may be affected by SARS-CoV-2 as well as by steroid treatment during the illness. Information on the HPA axis after recovering from COVID-19, especially in those treated with steroids, is sparse. Hence, this study was performed to evaluate the hypothalamo-pituitary-adrenal axis during the post-COVID-19 period in patients treated with steroids during the illness. Subject and methods: This prospective study involved 60 patients aged 18-60 years who had recovered from moderate or severe COVID-19 and had received steroid treatment during the illness. The HPA axis was assessed with a low-dose (1 mcg) adrenocorticotropic hormone stimulation test at 3, 6 and 9 months in the post-COVID period. Results: The HPA axis was suppressed in 31.66% of the patients at 3 months and 5% at 6 months; however, all patients recovered at 9 months. Cumulative steroid use during the illness was inversely correlated with stimulated cortisol at 3 months in the post-COVID period. Fatigue was present in 58.33% of the patients at 3 months and was more prevalent in those with HPA axis suppression. Conclusion: Nearly one-third of the patients with moderate to severe COVID-19 who were treated with steroids had suppressed HPA axis at 3 months, with gradual recovery over a period of 9 months. Cumulative steroid equivalent dose, but not disease severity, was predictive of HPA axis suppression at 3 months.

ABSTRACT Objective: Congenital hypopituitarism (CH) is a rare disease characterized by one or more hormone deficiencies of the pituitary gland. To date, many genes have been associated with CH. In this study, we identified the allelic variant spectrum of 11 causative genes in Turkish patients with CH. Materials and methods: This study included 47 patients [21 girls (44.6%) and 26 boys (55.4%)] from 45 families. To identify the genetic etiology, we screened 11 candidate genes associated with CH using next-generation sequencing. To confirm and detect the status of the specific familial variant in relatives, Sanger sequencing was also performed. Results: We identified 12 possible pathogenic variants in GHRHR, GH1, GLI2, PROP-1, POU1F1, and LHX4 in 11 patients (23.4%), of which six were novel variants: two in GHRHR, two in POU1F1, one in GLI2, and one in LHX4. In all patients, these variants were most frequently found in GLI2, followed by PROP-1 and GHRHR. Conclusion: Genetic causes were determined in only 23.4% of all patients with CH and 63% of molecularly diagnosed patients (7/11) from consanguineous families. Despite advances in genetics, we were unable to identify the genetic etiology of most patients with CH, suggesting the effect of unknown genes or environmental factors. More genetic studies are necessary to understand the etiology of CH.

ABSTRACT Objective: To investigate nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH) and hepatic fibrosis in biopsies of people with obesity who underwent bariatric surgery and examine the possible association of different variables with a diagnosis of NAFLD and NASH. Materials and methods: Epidemiological, clinical and laboratory data from 574 individuals with obesity of both genders seen by the same physician between 2003 and 2009 who had a liver biopsy during bariatric surgery were examined. Results: Of the 437 patients included, 39.8% had some degree of liver fibrosis, 95% had a histologic diagnosis of NAFLD, and the risk factors were age ≥ 28 years and Homeostatic Model Assessment (HOMA) ≥ 2.5 (p = 0.001 and p = 0.016, respectively). In the NAFLD group, NASH was present in 26% of patients and the associated factors were aspartate aminotransferase and alanine aminotransferase index (AST/ALT) > 1, high-density lipoprotein cholesterol (HDL-c) < 40 mg/dL, total cholesterol (TC) ≥ 200 mg/dL, gamma-glutamyl transferase (GGT) > 38 U/L and triglycerides (TG) levels > 150 mg/dL. The independent risk factors were low HDL-c, elevated AST/ALT and high TG. Conclusion: The variables associated with a diagnosis of NAFLD were HOMA ≥ 2.5 and age ≥ 28 years. NASH was associated with low HDL-c, high TG and AST/ALT ≤ 1.

ABSTRACT Objective: Nonalcoholic fatty liver disease (NAFLD) is a chronic liver disease and a growing global epidemic. In NAFLD, liver fat surpasses 5% of hepatocytes without the secondary causes of lipid accumulation or excessive alcohol consumption. Given the link between NAFLD and insulin resistance, the possible association between the rs2854744 (−202 G>T) promoter polymorphism of insulin-like growth factor binding protein 3 (IGFBP3) gene and NAFLD was investigated in this study. Materials and methods: In this genetic case-control association study, the IGFBP3 rs2854744 genotypes of 315 unrelated individuals, including 156 patients with biopsy-proven NAFLD and 159 controls, were determined using polymerase chain reaction/restriction fragment length polymorphism analyses. Results: The “GT+TT” genotype of the IGFBP3 rs2854744 polymorphism, compared with the “GG” genotype, was associated with a 2.7-fold increased risk of NAFLD after adjustment for confounding factors (P = 0.009; odds ratio [OR] = 2.71; 95% confidence interval [CI] = 1.19-3.18). Additionally, the IGFBP3 rs2854744 “T” allele, in comparison with the “G” allele, was significantly overrepresented in NAFLD patients than the controls (P = 0.008; OR = 1.85; 95%CI = 1.23-2.94). Conclusion: Our findings first indicated that the IGFBP3 rs2854744 “GT+TT” genotype is a marker of increased NAFLD susceptibility; however, it needs to be supported by further investigations in other populations.

ABSTRACT Objectives To evaluate the accuracy of routinely available parameters in screening for GCK maturity-onset diabetes of the young (MODY), leveraging data from two large cohorts – one of patients with GCK-MODY and the other of patients with type 1 diabetes (T1D). Materials and methods The study included 2,687 patients with T1D, 202 patients with clinical features of MODY but without associated genetic variants (NoVar), and 100 patients with GCK-MODY (GCK). Area under the receiver-operating characteristic curve (ROC-AUC) analyses were used to assess the performance of each parameter – both alone and incorporated into regression models – in discriminating between groups. Results The best parameter discriminating between GCK-MODY and T1D was a multivariable model comprising glycated hemoglobin (HbA1c), fasting plasma glucose, age at diagnosis, hypertension, microvascular complications, previous diabetic ketoacidosis, and family history of diabetes. This model had a ROC-AUC value of 0.980 (95% confidence interval [CI] 0.974-0.985) and positive (PPV) and negative (NPV) predictive values of 43.74% and 100%, respectively. The best model discriminating between GCK and NoVar included HbA1c, age at diagnosis, hypertension, and triglycerides and had a ROC-AUC value of 0.850 (95% CI 0.783-0.916), PPV of 88.36%, and NPV of 97.7%; however, this model was not significantly different from the others. A novel GCK variant was also described in one individual with MODY (7-44192948-T-C, p.Ser54Gly), which showed evidence of pathogenicity on in silico prediction tools. Conclusions This study identified a highly accurate (98%) composite model for differentiating GCK-MODY and T1D. This model may help clinicians select patients for genetic evaluation of monogenic diabetes, enabling them to implement correct treatment without overusing limited resources. maturityonset maturity onset MODY, , (MODY) GCKMODY TD . T D (T1D) 2687 2 687 2,68 20 NoVar, (NoVar) 10 GCK. (GCK) receiveroperating receiver operating ROCAUC ROC AUC (ROC-AUC groups HbA1c HbAc HbA c (HbA1c) glucose diagnosis hypertension complications ketoacidosis 0980 0 980 0.98 95% 95 (95 [CI 0.9740.985 09740985 0.974 0.985 974 985 0.974-0.985 (PPV (NPV 4374 43 74 43.74 100% respectively 0850 850 0.85 0.7830.916, 07830916 0.783 0.916 783 916 0.783-0.916) 8836 88 36 88.36% 97.7% 977 97 7 however others 744192948TC, 744192948TC TC 44192948 C, C (7-44192948-T-C p.Ser54Gly, pSer54Gly pSerGly p.Ser54Gly p Ser54Gly Ser Gly p.Ser54Gly) tools 98% 98 (98% resources (MODY (T1D 268 68 2,6 (NoVar (GCK (HbA1c 098 0.9 9 (9 9740 0.9740.98 0974098 0974 0.97 0985 0.974-0.98 437 4 43.7 085 85 0.8 7830 0.7830.916 0783091 0783 0.78 0916 0.91 78 91 0.783-0.916 883 8 3 88.36 97.7 4419294 pSer SerGly (98 26 6 2, 09 0. ( 0.9740.9 097409 097 0.974-0.9 43. 08 0.7830.91 078309 078 0.7 091 0.783-0.91 88.3 97. 441929 0.9740. 09740 0.974-0. 0.7830.9 07830 07 0.783-0.9 88. 44192 0.9740 0.974-0 0.7830. 0.783-0. 4419 0.974- 0.7830 0.783-0 441 0.783- 44

ABSTRACT Objective Subcentimeter papillary thyroid carcinoma (sPTC), also known as papillary thyroid microcarcinoma, is associated with a good prognosis and low mortality risk. However, some sPTCs exhibit biologically aggressive characteristics. The aim of this study was to identify factors affecting the prognosis and aggressiveness of sPTC by considering the demographic characteristics of patients with sPTC and the pathologic characteristics of the tumors. Subjects and methods The study included 255 patients aged ≥ 18 years who were operated on at Ondokuz Mayis University, Faculty of Medicine (Samsun, Turkey) between June 2008 and December 2021. All patients had histopathologic confirmation of sPTC (≤10 mm) and underwent regular follow-up for at least 36 months. Results The tumors had a mean size of 5 mm (0.1-10 mm) and were multifocal in 53.7% of patients. Capsular invasion was observed in 9% of patients. Vascular invasion, lymphatic invasion, and extrathyroidal invasion were present in 2%, 5.5%, and 0.8% of patients, respectively. Metastatic cervical lymph nodes were observed in 9.4% of patients. On multivariate logistic regression analysis, tumor size (odds ratio [OR] 1.380, 95% confidence interval [CI] 1.106-1.722, p = 0.004) and sex (OR 4.233, 95% CI 1.355-13.226, p = 0.013) were the main predictive factors influencing lymph node metastasis. Tumors > 5 mm, compared with tumors ≤ 5 mm, had higher rates of multifocality (p = 0.009), parenchymal invasion (p = 0.008), calcifications (p = 0.001), microscopic lymphatic invasion (p = 0.002), and presence of metastatic lymph nodes (p < 0.001). Conclusion The findings of this study highlight important factors to consider in making decisions about prophylactic central compartment neck dissection in patients with sPTCs, particularly those with clinically node-negative tumors. sPTC, , (sPTC) microcarcinoma risk However 25 1 University Samsun, Samsun (Samsun Turkey 200 2021 ≤10 10 (≤1 followup follow up 3 months 0.110 0110 0.1 0 (0.1-1 537 53 7 53.7 9 2 2% 55 5.5% 08 8 0.8 respectively 94 4 9.4 analysis odds OR [OR 1380 380 1.380 95 [CI 1.1061.722, 11061722 1.106 1.722, 106 722 1.106-1.722 0.004 0004 004 4233 233 4.233 1.35513.226, 135513226 1.355 13.226, 355 13 226 1.355-13.226 0.013 0013 013 metastasis 0.009, 0009 0.009 009 0.009) 0.008, 0008 0.008 008 0.008) 0.001, 0001 0.001 001 0.001) 0.002, 0002 0.002 002 0.002) 0.001. . nodenegative negative (sPTC 20 202 ≤1 (≤ 110 0.11 011 01 0. (0.1- 53. 5.5 9. 138 38 1.38 1061 1.1061.722 1106172 1106 1.10 1722 1.722 72 1.106-1.72 0.00 000 00 423 23 4.23 35513 1.35513.226 13551322 1355 1.35 13226 13.226 35 22 1.355-13.22 0.01 ( 11 (0.1 5. 1.3 1.1061.72 110617 1.1 172 1.72 1.106-1.7 0.0 42 4.2 3551 1.35513.22 1355132 135 1322 13.22 1.355-13.2 (0. 1. 1.1061.7 11061 17 1.7 1.106-1. 4. 1.35513.2 135513 132 13.2 1.355-13. (0 1.1061. 1.106-1 1.35513. 13551 13. 1.355-13 1.1061 1.106- 1.35513 1.355-1 1.3551 1.355-

SUMMARY Maturity-onset diabetes of the young (MODY) is a clinically heterogeneous group of monogenic diabetes characterized by onset at a young age and an autosomal dominant mode of inheritance. Notably, MODY accounts for 2%-5% of all diabetes cases, and its distinction from types 1 (T1DM) and 2 (T2DM) diabetes mellitus is often challenging. We report herein the cases of two girls and a boy who presented initially with diabetic ketoacidosis. In view of the strong family history of diabetes in all three of them, the diagnosis of MODY was considered and confirmed by molecular testing. The patient in Case 1 (a 10-year-old girl) had a variation in the HNF1A gene (MODY 3). The patient in Case 2 (a 13-year-old girl) had a variation in the HNF1B gene (MODY 5) and was also clinically diagnosed with HNF1B MODY due to short stature, abnormal renal function, renal cysts, unicornuate uterus, and diabetic ketoacidosis at presentation. The patient in Case 3 (a 14-year-old boy) had a variation in the KCNJ11 gene (MODY 13) and presented with diabetic ketoacidosis; after initially being treated as having T1DM, he developed progressive weight gain, acanthosis nigricans, and decreased requirement of insulin. The patients in Cases 1 and 3 were subsequently treated with oral sulfonylureas and insulin was gradually tapered and interrupted, resulting in drastic improvement in glucose control. The patient in Case 2 remained on insulin, as this is the appropriate management for MODY 5. This case series demonstrates that atypical cases of MODY with ketoacidosis do occur, underscoring the potential for this complication within the phenotypic spectrum of MODY. In patients with atypical presentations, a thorough family history taking may reveal the diagnosis of MODY. Maturityonset Maturity inheritance Notably 2%5% 25 2% 5% 5 2%-5 T1DM TDM T DM (T1DM T2DM (T2DM challenging them testing 10yearold yearold 10 year old girl HNFA HNF A 3. . 3) 13yearold 13 HNFB B stature function cysts uterus presentation 14yearold 14 KCNJ KCNJ1 gain nigricans interrupted control occur presentations 2%5 2%-

ABSTRACT Objective Sulfonylureas have been used to improve performance in strength sports. However, this hypothetical effect has not been proven. We examined the ergogenic acute effect of gliclazide on resistance training performance and muscle recovery. Subjects and methods We conducted a double-blind, randomized, crossover pilot study with 10 healthy resistance-trained adults (29.3 ± 4.4 years), nonusers of anabolic steroids. The participants were randomized to two exercise sessions. In the first session, five participants received placebo and the other five received gliclazide modified release, both administered 8 hours before the session. Session two was performed in a crossover fashion a week later. The volume load was calculated as the maximum number of repetitions of four sets multiplied by load (65% 1-RM). Blood samples were collected before and after exercise, as well as 24 hours and 48 hours after exercise for measurement of creatine kinase (CK-MM) and lactate dehydrogenase (LDH) activity. Blood glucose was measured with a glucometer before, during, and after the exercise sessions. Results Gliclazide did not enhance volume load for bench press (placebo: 2,698.0 ± 923.0 kg; gliclazide: 2,675.0 ± 1,088.0 kg; p = 0.073) or leg press (placebo: 10,866.0 ± 2,671.0 kg; gliclazide: 10,817.0 ± 2,888.0 kg; p = 0.135). However, CK-MM (-27.7%; p = 0.034) and LDH (-21.1%; p = 0.021) activities were decreased with gliclazide 48 hours after exercise. There was also a decrease in blood glucose in the gliclazide compared with the placebo session (p = 0.018). Conclusion Gliclazide did not enhance performance in a single resistance training session, but promoted faster muscle recovery. The decrease in blood glucose post-exercise with gliclazide was an undesirable effect that could lead to long-term glucose metabolism disorders. Registered in ClinicalTrials.gov under number NCT04443777. sports However proven recovery doubleblind, doubleblind double blind, blind double-blind 1 resistancetrained trained 29.3 293 29 3 (29. 44 4 4. years, years , years) steroids sessions release later 65% 65 (65 1RM. 1RM RM . 1-RM) 2 CKMM CK MM (CK-MM (LDH activity during (placebo 26980 698 0 2,698. 9230 923 923. kg 26750 675 2,675. 10880 088 1,088. 0.073 0073 073 108660 866 10,866. 26710 671 2,671. 108170 817 10,817. 28880 888 2,888. 0.135. 0135 0.135 135 0.135) 27.7% 277 27 7 (-27.7% 0.034 0034 034 21.1% 211 21 (-21.1% 0.021 0021 021 0.018. 0018 0.018 018 0.018) postexercise post longterm long term disorders ClinicalTrialsgov ClinicalTrials gov NCT04443777 NCT 29. (29 6 (6 1-RM 2698 69 2,698 92 2675 67 2,675 1088 08 1,088 0.07 007 07 10866 86 10,866 2671 2,671 10817 81 10,817 2888 88 2,888 013 0.13 13 27.7 (-27.7 0.03 003 03 21.1 (-21.1 0.02 002 02 001 0.01 01 NCT0444377 (2 ( 269 2,69 9 267 2,67 108 1,08 0.0 00 1086 10,86 1081 10,81 288 2,88 0.1 27. (-27. 21. (-21. NCT044437 26 2,6 1,0 0. 10,8 28 2,8 (-27 (-21 NCT04443 2, 1, 10, (-2 NCT0444 (- NCT044 NCT04 NCT0

ABSTRACT Objective The aim of this study was to estimate the budget impact of adding cabergoline to the Brazilian Unified Health System (SUS) formulary for the treatment of patients with Cushing’s disease (CD) who do not achieve disease control after transsphenoidal surgery. Materials and methods We conducted a budget impact analysis (BIA) from the perspective of the Brazilian SUS over a 5-year time horizon. We compared two scenarios: ketoconazole (Scenario 1) versus including cabergoline as a treatment option (Scenario 2). All analyses were conducted using Microsoft Excel. Uncertainty was explored in univariate sensitivity analyses. Results The total costs were BRL $25,596,729 for Scenario 1 and BRL $32,469,169 for Scenario 2. The budget impact of adding cabergoline to the formulary for CD treatment within the SUS would be BRL $6,091,036 over 5 years. On univariate analyses, variations in the rates of surgical failure and CD recurrence had the greatest potential to affect the final costs associated with cabergoline. Conclusions The estimated budget impact of adding cabergoline to the formulary for CD treatment within the Brazilian SUS would be about BRL $6 million. While cost savings cannot be expected, the budget impact of adding cabergoline would be lower than that of adding other treatment options for CD. (SUS Cushings Cushing s (CD surgery BIA (BIA 5year year horizon scenarios 2 . 2) Excel 25596729 25 596 729 $25,596,72 32469169 32 469 169 $32,469,16 6091036 6 091 036 $6,091,03 years $ million expected 2559672 59 72 $25,596,7 3246916 3 46 16 $32,469,1 609103 09 03 $6,091,0 255967 7 $25,596, 324691 4 $32,469, 60910 0 $6,091, 25596 $25,596 32469 $32,469 6091 $6,091 2559 $25,59 3246 $32,46 609 $6,09 255 $25,5 324 $32,4 60 $6,0 $25, $32, $6, $25 $32 $2 $3