Progressive Weight Gain Research Articles

12580 Factitious Cushing’s Syndrome Secondary To Indiscriminate Use Of Brazilian Herbal Medicine: Case Report

Abstract Disclosure: L. Warszawski: None. K.F. Seidel: None. C. Padilla: None. V.N. de Souza: None. J.R. Calmon: None. Background: Herbal medicines are obtained exclusively from active plant raw materials, which leads people to believe that these medications are safer and free from side effects. Moreira milk is a Brazilian herbal medicine used mainly for its supposed anti-inflammatory properties. This medication is not regulated by The Brazilian Health Regulatory Agency (Anvisa). Herein we report a case of exogenous Cushing's Syndrome (CS) caused by continuous use of Moreira milk. Case report: A 53-year-old female patient was seen in October 2018 at the endocrinology clinic due to progressive weight gain, mood swings, edema and weakness of the lower limbs, violet streaks on the flanks, easy bruising and dorsocervical fat pad. She brought tests to our specialized consultation that showed low basal cortisol (0.4 mcg/dL - RR 5 to 25 mg/dL) and ACTH ( %lt; 5 pg/ml - RR 10 to 60mg/dL), two HbA1c values above 6.5% and a sella turcica MRI revealing normal-sized pituitary gland with a hypo-enhancing contrast area, possibly corresponding to a microadenoma. New tests were carried out which showed the maintenance of low basal cortisol and ACTH. The patient reported background use of losartan and Moreira milk for 2 years - as a phytotherapy to control joint pain after Chikungunya. She denied use of topical, inhalatory or oral corticoids. Exogenous CS was suspected and the use of Moreira milk was interrupted. We proceeded to use prednisone for weaning, which had to be gradual, but the patient progressed with clinical improvement. Conclusion: There are some cases of hypercortisolism associated with herbal medicines, the majority of which are due to contamination with synthetic glucocorticoids, as is believed to occur with Moreira milk. Despite being widely sold in Brazil, because it is not approved by ANVISA, the production cannot be inspected, therefore, can be contaminated. Those cases of exogenous CS are challenging, and misidentifying Cushing's syndrome can result in a series of improper treatments with severe repercussions. Presentation: 6/1/2024

Monogenic obesity in a familial cluster: insights into laurence-moon-bardet-biedl syndrome and leptin deficiency associated with genetic variants in BBS12 and LEPR genes

Monogenic obesity is a rare but clinically significant condition characterized by excessive weight gain due to genetic mutations that affect appetite regulation and energy balance. This case series explores the clinical presentation and genetic underpinnings of monogenic obesity in a familial cluster, focusing on Laurence-Moon-Bardet-Biedl Syndrome (LMBBS) and leptin deficiency associated with genetic variants in the BBS1 and LEPR genes. The index patient, an 11-year-old female, presented with progressive weight gain since infancy, accompanied by acanthosis nigricans on the neck and axillary region. Genetic testing revealed mutations in both the BBS1 and LEPR genes, confirming a monogenic etiology of obesity. Remarkably, her two siblings and a cousin from the paternal side exhibited similar clinical profiles and shared the same genetic variants. This report shows the significance of genetic testing in diagnosing monogenic obesity disorders and highlights the familial clustering observed in such cases. The findings emphasize the need for heightened awareness and consideration of genetic factors in the evaluation of obesity, particularly in pediatric patients with a family history suggestive of monogenic obesity.

DORA: 48-week weight and metabolic changes in Black women with HIV, in a phase IIIb switch study from dolutegravir- or efavirenz- to doravirine-based first-line antiretroviral therapy.

Treatment-related weight gain and metabolic complications with antiretroviral integrase-based regimens, especially among Black women, suggest the need for alternative options. We conducted a 48-week, open-label, single-arm, single-centre, phase IIIb switch study to evaluate the tolerability, safety and efficacy of switching from stable efavirenz- or dolutegravir-based antiretroviral therapy to doravirine/lamivudine/tenofovir disoproxil fumarate in Black women. The 101 participants enrolled (median age 35 years; interquartile range 31-40) were on efavirenz (n = 46; mean duration on therapy 1.7 years) or dolutegravir-based (n = 55; mean duration 1.5 years) antiretrovirals at screening. Retention at 48 weeks was 92/101 participants, and viral suppression was >90% throughout the study, with a single case of doravirine resistance (106 M, V108I and H221Y mutations). The mean weight percentage change at week 48 was 4.7% (95% confidence interval [CI] 3.0-6.5; p < 0.001), and the adjusted mean change was 2.7 kg (95% CI 1.50-3.98; p < 0.001); for efavirenz, the percentage change was 5.0% (95% CI 2.9-7.1; p < 0.001), and the adjusted weight gain was 3.5 kg (95% CI 1.93-5.13); for dolutegravir, the percentage change was 4.5% (95% CI 1.8-7.3; p < 0.001), and the adjusted weight gain was 2.1 kg (95% CI 0.26-3.90). Statistically significant decreases in lipid panel percent mean to week 48 included: total cholesterol -8.4% (95% CI -11.3 to -5.5; p < 0.001), triglycerides -10.4% (95% CI -16.4 to -4.4; p < 0.001) and high-density lipoprotein -14.8% (95% CI -18.5 to -11.2%; p < 0.001), with minor differences when disaggregating the mean percent change in lipids between previous efavirenz/dolutegravir regimens. Adverse events due to doravirine were few and mild. Our findings suggest that a switch to doravirine from efavirenz or dolutegravir is safe and effective in Black women, with significant improvement in lipid profiles, but does not arrest progressive weight gain.

Mindfulness and compassion-based programs on eating behavior of post-bariatric surgery patients: A two phased clinical trial protocol

Introduction: Weight regain after bariatric surgery remains a relevant and worrisome topic, requiring greater understanding and involvement in research into new adjuvant treatments. This study aims to compare the preliminary effectiveness and feasibility of the Mindfulness-Based Health Promotion and Attachment-Based Compassion Therapy programs as opposed to usual treatments (workshops) on the eating behavior of patients with progressive weight gain after bariatric surgery in Brazilian patients at a private clinic. It was hypothesized that both interventions are feasible and that the self-compassion program may be more effective than the mindfulness program. Methods: The study will be divided into two phases: a cross-analytical study of those who underwent bariatric surgery and a randomized controlled trial only with the ones who had weight regain. Interventions will be conducted for eight weeks synchronously with three assessment points (baseline, post intervention, and 6-month follow-up), both online. The primary outcome will be a change in eating behavior. Secondary outcomes will include improved quality of life, enhanced body image satisfaction and reduced distortion (Brazilian Silhouette Scales for adults), better weight management (maintenance or weight reduction), increased frequency of activity and monitoring with the surgery team. Qualitative data will also be collected by online identification of a sub-sample of participants. Results: Improvements are expected in eating behavior, weight, reverse progressive weight gain, classification of self-image, quality of life, and levels of mindfulness, self-compassion, and anxiety. Conclusion: This study seeks to gather preliminary evidence on the effectiveness of mindfulness and compassion training for the adjunctive treatment of progressive weight gain in post-bariatric patients.Clinical Trials.gov Registration ID: NCT04171713.

Impact of Weight Gain on Cardiovascular Outcomes in Patients With Atrial Fibrillation.

The long-term impact of weight gain (WG) on cardiovascular outcomes among patients with atrial fibrillation (AF) is unclear. We studied 62 871 (mean age, 72±12, 43% women) adult patients with AF evaluated at the University of Pittsburgh Medical Center between January 1, 2010, and May 13, 2021. Serial body mass index, risk factors, comorbidities, and subsequent death and hospitalization were ascertained and stratified according to percentage WG (≥0% to <5%, ≥5% to <10%, and ≥10%). Over 4.9±3.19 years of follow-up, 27 114 (43%) patients gained weight (61%, ≥0% to <5%; 23%, ≥5% to <10%; 16%, ≥10%). Patients with progressive WG were incrementally younger (P<0.001) women (40%, 42%, and 47%) with lower median household income (P=0.002) and active smoking (8%, 13% and 13%), and they were less likely to be on a non-vitamin K oral anticoagulant (39%, 37%, and 32%). WG was incrementally associated with a significant increase in risk of hospitalization for AF (≥10% WG; hazard ratio [HR], 1.2 [95% CI, 1.2-1.3]; P<0.0001), heart failure (≥10% WG; HR, 1.44 [95% CI, 1.3-1.6]; P<0.001; ≥5% to <10% WG; HR, 1.17 [95% CI, 1.1-1.2]; P<0.001), myocardial infarction (≥10% WG; HR, 1.2 [95% CI, 1.3-1.6]; P<0.001) and all-cause stroke (4.2%, 4.3%, and 5.6%) despite significantly lower mean CHADS2Vasc score (2.9±1.7, 2.7±1.6, and 2.7±1.7). Patients with more WG were significantly more likely to receive cardiac and electrophysiologic interventions. Among patients with AF, WG is incrementally associated with increased hospitalization for cardiovascular causes, particularly heart failure, stroke, myocardial infarction, and AF.

CMS121: a novel approach to mitigate aging-related obesity and metabolic dysfunction.

Modulated by differences in genetic and environmental factors, laboratory mice often show progressive weight gain, eventually leading to obesity and metabolic dyshomeostasis. Since the geroneuroprotector CMS121 has a positive effect on energy metabolism in a mouse model of type 2 diabetes, we investigated the potential of CMS121 to counteract the metabolic changes observed during the ageing process of wild type mice. Control or CMS121-containing diets were supplied ad libitum for 6 months, and mice were sacrificed at the age of 7 months. Blood, adipose tissue, and liver were analyzed for glucose, lipids, and protein markers of energy metabolism. The CMS121 diet induced a 40% decrease in body weight gain and improved both glucose and lipid indexes. Lower levels of hepatic caspase 1, caspase 3, and NOX4 were observed with CMS121 indicating a lower liver inflammatory status. Adipose tissue from CMS121-treated mice showed increased levels of the transcription factors Nrf1 and TFAM, as well as markers of mitochondrial electron transport complexes, levels of GLUT4 and a higher resting metabolic rate. Metabolomic analysis revealed elevated plasma concentrations of short chain acylcarnitines and butyrate metabolites in mice treated with CMS121. The diminished de novo lipogenesis, which is associated with increased acetyl-CoA, acylcarnitine, and butyrate metabolite levels, could contribute to safeguarding not only the peripheral system but also the aging brain. By mimicking the effects of ketogenic diets, CMS121 holds promise for metabolic diseases such as obesity and diabetes, since these diets are hard to follow over the long term.

Prednisolone-Induced Cushing's syndrome: A case report

Objective: Prednisolone, a frequently prescribed corticosteroid, is linked to diverse adverse effects, including Cushing's syndrome. Material and Methods: This report details a case of prednisolone-induced Cushing's syndrome in a 6-year-old girl diagnosed with Acute Disseminated Encephalomyelitis (ADEM). Prednisolone was administered to manage inflammation associated with ADEM. Subsequent to the tapering of prednisolone, the patient exhibited progressive weight gain, facial rounding, fatigue, and muscle weakness. Clinical examination revealed classic manifestations of Cushing's syndrome, including central obesity, moon facies, and proximal muscle weakness. Laboratory analysis confirmed elevated serum cortisol levels and suppressed adrenocorticotropic hormone (ACTH), confirming exogenous Cushing's syndrome induced by prednisolone. The patient's prednisolone dosage was gradually reduced under careful medical supervision. Regular follow-ups were conducted to monitor symptoms, weight fluctuations, and hormonal levels. With the decrease in prednisolone dosage, the patient's symptoms showed gradual improvement. Results and conclusion: Prednisolone-induced Cushing's syndrome arises as a recognized complication of corticosteroid therapy, primarily characterized by the suppression of the hypothalamic-pituitary-adrenal axis. Early awareness of this adverse effect is pivotal for prompt identification and management. This case emphasizes the significance of vigilant monitoring and judicious use of prednisolone to mitigate adverse effects like Cushing's syndrome. Swift recognition, dose adjustments, and a gradual tapering of corticosteroids play a crucial role in effectively managing this condition for optimal patient outcomes.

A 14-year-old male patient with diagnosis of Prader–Willi syndrome in Ethiopia: a case report

BackgroundPrader–Willi syndrome is a complex multisystem disorder due to the absent expression of paternally active genes in the Prader–Willi syndrome-critical region on chromosome 15 (15q11.2-q13). The main clinical features are hyperphagia (which frequently results in early-onset obesity), hypogonadism, developmental delays, typical behaviors (such as obsessive–compulsive tendencies, tantrums, perseveration, insistence on sameness, and rigidity), and distinctive facial features. In infants, the most prominent findings are hypotonia and feeding difficulties.Case presentationThis paper highlights a case of a 14 year old male patient of an Ethiopian ethnicity with diagnosis of Prader–Willi syndrome, which is first report in Ethiopia. He presented with progressive excessive weight gain, insatiable appetite, clinical and laboratory features of hypogonadism, ophthalmological refractory error, and facial features of Prader–Willi syndrome, which was further confirmed by genetic analysis. He is currently on lifestyle intervention, testosterone replacement, and treatment for vitamin D deficiency.ConclusionPrader–Willi syndrome should be considered in a child who presents with progressive weight gain and other typical clinical features such as cognitive impairment, excessive insatiable eating, or hypothalamic hypogonadism. Early lifestyle intervention may help to reduce excessive weight gain. To our knowledge, this is the first case reported in Ethiopia.

Impact of feed on the yield of Litopenaeus vannamei and Macrobrachium rosenbergii prawn culture from West Godavari district, Andhra Pradesh, India

Aquaculture, a vital sector addressing global food demand, is characterized by its extensive water requirements. Categorized into mariculture, freshwater aquaculture, and brackish water aquaculture, the sector plays a crucial role in food production. This study focuses on prawn cultivation, a significant aspect of aquaculture, emphasizing the influence of feed quality and hydrographic parameters on yield and ecological sustainability. Conducted in Vissakoderu village (Litopenaeus vannamei) and Eduru village (Macrobrachium rosenbergii), the research employed commercial feed, optimizing physicochemical parameters such as temperature, pH, and salinity. Probiotics were integrated into the feed to enhance prawn growth. Results indicated optimal levels of moisture, lipids, protein, fiber, carbohydrates, minerals, and vitamins in the feed. The progressive weight gain of prawns, reaching 30.00 kg for 1000 prawns, was correlated with an increased feeding frequency. Scientifically monitored hydrographic conditions and feed quality contributed to a remarkable average yield of 29 tons for Litopenaeus vannamei and 63.33 tons for Macrobrachium rosenbergii over three years. This underscores the importance of precision in aquaculture practices for both yield enhancement and ecological preservation. The study provides valuable insights into the sensitivity of prawn cultivation, emphasizing the need for meticulous care in managing hydrographical, feed, and disease parameters.

THU012 Incidental Pituitary Adenoma In A Patient With Ectopic ACTH Secreting Cushing Syndrome - A Diagnostic Conundrum

Abstract Disclosure: M.S. Nali: None. R.R. Yatavelli: None. Background: Cushing’s syndrome (CS) is a rare condition with an estimated incidence of 2-3 cases/million. Endogenous CS can be divided into ACTH -dependent (80%) and ACTH Independent (20%) with Ectopic Cushing’s syndrome (ECS) accounting for 10-20% of all cases of ACTH-dependent CS. Herein we present a case with indolent onset ACTH-dependent CS who on initial work-up showed a pituitary microadenoma raising the suspicion for Cushing disease, but the source of excess ACTH was found to be from a pulmonary neuroendocrine tumor. Clinical Case: A 44-yr-old female with history of type 1 DM, Obesity, BMI 43.60, Sleep apnea was evaluated elsewhere for suspected Cushing’s due to increased insulin requirements and progressive weight gain. Outside labs showed cortisol of 4.5 ug/dl on 1 mg DST &amp; 8 mg DST cortisol was 3 ug/dl. MRI of the pituitary showed a 3.5x 2.8x 1.8 mm microadenoma &amp; she was initially presumed to have Cushing’s disease secondary to pituitary microadenoma. The patient was seen by neurosurgery who referred to endocrine for localization of cortisol excess by IPSS. Clinically she had moon facies, hirsutism, dorsocervical fat pad, violaceous striae on abdomen. On further laboratory evaluation her ACTH: 88 (0-46) and random cortisol 14 ug/dl with normal rest of pituitary hormones. Her 24-hour urine free Cortisol was 45ug/d (3.5 - 45) and late-night salivary cortisol: 74 &amp;&amp;lt;50 (Ref. range &amp;lt;100 ng/dl) on couple of nights, respectively. Due to non-suppressed cortisol on high dose DST, a CT chest was obtained which showed a 2cms non calcified nodule in the left lower lobe of lung. Transbronchial biopsy was performed, cytopathology showed well differentiated neuroendocrine tumor, likely carcinoid and stained strongly positive for ACTH confirming ectopic ACTH producing tumor. Gallium-68 Dotatate Scan showed abnormal increased uptake in the known left lung nodule. The patient was recommended for surgical removal of neuroendocrine tumor, but she could not tolerate anesthesia and had to undergo stereotactic body radiation therapy (SBRT) for the lung lesion. Repeat ACTH levels 2 months post SBRT showed the ACTH levels were elevated and lesion was still persistent on imaging, however on discussion with rad oncology, the neuroendocrine tumors tend to take longer to show response on imaging and plan is to repeat imaging and biochemical work up in couple of months. Conclusion: The diagnosis of CS and recognizing the source of hormonal excess poses significant challenges Pituitary adenomas are incidentally discovered in up to 10% of the normal population &amp; IPSS is advised for patients with ACTH-dependent Cushing's syndrome and an adenoma smaller than 6 mm, however in patients with equivocal findings, it is important to look for other sources of ACTH prior to any invasive procedure. The source of ectopic ACTH secretion should be established after diagnosis because the excision of an ACTH-producing tumor can be curative. Presentation: Thursday, June 15, 2023

SAT673 Novel Mutation Of TBX3 Associated With Morbid Obesity In Human

Abstract Disclosure: H.R. Alkaissi: None. B. Ji: None. S. McFarlane: None. Background: TBX3 is a transcription involved in the development of the heart conduction system, apocrine and mammary glands, limbs, and lung development and maturation, with variable oncogenic roles. Recently, the role of TBX3 and body weight control has been demonstrated in animal models, showing an essential role for TBX3 in hypothalamic arcuate neuronal maturation, function, and identity [1]. Case: 26-year-old woman referred for the management of morbid obesity and menstrual irregularities. The patient weighed 330 lbs, with a BMI of 55 kg/m2, with hypertension T2DM. The patient had a normal development until age five, after which she experienced regression in milestones and lost the ability to communicate, and was diagnosed with autism. She had a history of food-seeking behavior, leading to progressive weight gain, which was managed by blocking access to food, such as locking the fridge. The patient's weight fluctuated from 290 lbs to 330 lbs. Family history of T2DM in her maternal relatives. She was diagnosed with T2DM at the age of 18, with HbA1c level of 9.4%. Autoantibody testing was negative for glutamic acid decarboxylase (GAD), islet cell antibody (ICA), and zinc transporter 8 (ZnT8). The fasting C-peptide level was detectable at 1.87 ng/mL. T2DM was well controlled with an HbA1C range of 6.0-6.7% with the use of short and long-acting insulin regimen. However, with improved glycemic control, short-acting insulin was stopped and she was started on liraglutide. Syndromic obesity was suspected due to early-onset of the disease and the developmental regression. Testing for Prader-Willi syndrome was negative, based on a normal chromosome 15 methylation study. Leptin levels were elevated at 66 ng/mL, prompting further testing for obesity-related genetic mutations. Next-generation sequencing and targeted Sanger sequencing for 79 genes associated with obesity in human and animal models was performed. A novel mutation was identified in TBX3 activation domain, c. C1513T (p.P505S). UniProt peptide sequence alignment analyzed for sequence conservation. ClinVar, HGMD and GWAS Catalogue databases screened for similar variants. Discussion: We present the first case in human, where novel TBX3 mutation results in hypothalamic dysfunction, leptin resistance manifesting as morbid obesity, hyperphagia, and menstrual irregularities. The reported mutation in the activation domain (A) of TBX3. In silico analysis showed high evolutionary conservation of the mutated domain (across vertebrate species), indicating the mutation is likely pathogenic.

FRI249 New Onset Heart Failure In A Patient With Rapidly Progressive Adrenocortical Carcinoma

Abstract Disclosure: J. Peeples: None. S. Shu: None. K.G. Romo: None. J. Tereul: None. B.B. Grissett: None. Background: Adrenocortical carcinomas (ACC) are rare, relatively large (&amp;gt;4cm), lipid-rich, and often aggressive tumors. They may be functional, which typically presents as Cushing’s syndrome and/or virilization, or non-functional, which typically presents as an abdominal mass or incidental finding. They occur in two peak incidences: at the first decade of life and between 40-50 years of age. Over half of adult patients with ACC present with an advanced tumor stage. This case describes a young man with new onset heart failure and adrenal mass with metastases who was found to have biopsy-confirmed ACC. Clinical Case: A 20-year-old man with a history of cigarette smoking and marijuana use, but otherwise in prior good health, presented as a transfer for new onset heart failure in the setting of hypertensive emergency (SBP 260s), and CT findings of left adrenal mass, with multiple lung and liver masses. He noted 2 months of rapidly progressive weight gain, easy fatigability, dyspnea on exertion, and leg swelling. Exam revealed central adiposity with abdominal striae, bilateral clavicular and cervical fat pad, and bilateral lower extremity swelling. Investigations revealed hypercortisolism and ventricular ejection fraction 20-25%. Liver mass biopsy revealed metastatic ACC. Family history was significant for multiple members with early onset hypertension and congestive heart failure, including the death of maternal grandmother at age 40. The patient was initially managed in the ICU with an etomidate drip for adrenal suppression. Cortisol levels appropriately decreased to goal. Additionally, he started IV dexamethasone while inpatient. He was discharged once euvolemic on PO furosemide and follow-up was scheduled with cardiology, oncology, and endocrinology. At discharge, he transitioned to PO hydrocortisone (HC) and was placed on trimethoprim/sulfamethoxazole for PJP prophylaxis, doxazosin, and ketoconazole. He also started mitotane for his cancer treatment, with HC to prevent adrenal insufficiency while on mitotane. Subsequently, he started and failed carboplatin plus etoposide palliative chemotherapy with a continued increase in adrenal mass size. Now, he is on second line pembrolizumab with an ECOG score of 2. Conclusion: ACC is a rare and often aggressive tumor that should be considered in the setting of hypercortisolism and cushingoid features. This is particularly important for patients with a relatively unremarkable history and new onset heart failure with dyspnea on exertion. In these cases, mitotane can be used for hypercortisolism associated with ACC. Unfortunately, these tumors are usually diagnosed when they have already progressed to a late stage, and the prognosis for ACC is poor. Presentation: Friday, June 16, 2023

Use of chin sling for conservative treatment of mandibular fracture in a guinea pig (Cavia porcellus).

To describe a treatment for a mandibular fracture in a guinea pig (Cavia porcellus). A 6-month-old sexually intact male guinea pig referred for a 24-hour history of hyporexia. Physical examination showed lateral displacement of the incisors and inflammation and crepitation during mandible lateralization. Imaging tests revealed a minimally displaced complete oblique fracture of the left mandible with fracture of the left mandibular first premolar tooth and incisor tooth. Conservative treatment was established by placing a chin sling (CS) to immobilize the jaw and a nasogastric tube for nutritional support. Imaging tests repeated 3 weeks later showed initial callus formation, and the conservative treatment was discontinued. Follow-up examinations showed appetite and progressive weight gain. Five months later, the clinical crown of the left mandibular incisor was absent and a resorptive lesion on the left mandibular first premolar tooth was detected. Complete ossification of the fracture without premolar and moler teeth elongation was observed on control imaging tests. Ten months after initial examination, the patient was reportedly healthy with no signs of pain or dental disease. Jaw fracture treatments in guinea pigs are poorly described in the literature. Surgical treatment can be challenging in this species due to its skull and dental anatomy. Although CS was originally employed to increase the congruency of premolar and molar teeth after coronal reduction, this device yielded satisfactory results as a noninvasive, inexpensive treatment of a mandibular fracture in this guinea pig. Alopecia on the back of the head was the only undesired adverse effect associated with the CS.

Carbohydrate-insulin model: does the conventional view of obesity reverse cause and effect?

Conventional obesity treatment, based on the First Law of Thermodynamics, assumes that excess body fat gain is driven by overeating, and that all calories are metabolically alike in this regard. Hence, to lose weight one must ultimately eat less and move more. However, this prescription rarely succeeds over the long term, in part because calorie restriction elicits predictable biological responses that oppose ongoing weight loss. The carbohydrate-insulin model posits the opposite causal direction: overeating doesn't drive body fat increase; instead, the process of storing excess fat drives overeating. A diet high in rapidly digestible carbohydrates raises the insulin-to-glucagon ratio, shifting energy partitioning towards storage in adipose, leaving fewer calories for metabolically active and fuel sensing tissues. Consequently, hunger increases, and metabolic rate slows in the body's attempt to conserve energy. A small shift in substrate partitioning though this mechanism could account for the slow but progressive weight gain characteristic of common forms of obesity. From this perspective, the conventional calorie-restricted, low-fat diet amounts to symptomatic treatment, failing to target the underlying predisposition towards excess fat deposition. A dietary strategy to lower insulin secretion may increase the effectiveness of long-term weight management and chronic disease prevention. This article is part of a discussion meeting issue 'Causes of obesity: theories, conjectures and evidence (Part II)'.

Dietary supplement using cockroach meal: impact on growth indices and biochemical responses in hybrid catfish

Globally the need to substitute fishmeal with other animal protein sources in the fish diet has gained more attention; which is occasioned by the increasing cost of fish. A 12-week trial was conducted to ascertain the growth indices and biochemical response of hybrid catfish (Clarias gariepinus(♀) and Heterobranchus bidorsalis (♂)) fed cockroach meal supplement. A total of 800 hybrid catfish were randomly distributed into four dietary treatments (Diet A- control feed), Diet B (50 % cockroach and 50 % fishmeal), Diet C (100 % cockroach meal) and Diet D (100 % fishmeal). Each treatment was replicated with 35 fish per experimental pond in a completely randomized design. Progressive weight gain was determined bi-weekly. At the end of the study period, fishes were randomly sacrificed for proximate compositions and plasma biochemical analyses (glucose, triglyceride, cholesterol, total protein, albumin) using standard protocols. The study revealed that growth parameters (Weight gain, Average weight gain, Protein efficiency ratio, Feed Conversion rate, Specific growth rate and Survival rate (SR) were influenced by the dietary treatments (p&gt;0.05). The highest weight gain was recorded in Diet 1 (8847.73±292.65 g) &gt; Diet 2 (7816.33±121.71 g)&gt;Diet 3 (7811.67±566.08 g) &gt;Diet 4 (7022.00±44.193 g). Similarly, the best feed conversion ratio was found in fish fed Diet A (10.12±0.01),&gt;Diet B, C and D had the same values of 0.11 g respectively. There was no significant (p&gt;0.05) difference in plasma biochemical indicators measured when compared to the control (Diet A). Thus, indicating that all the fish were healthy and had normal physiological activities. Cockroach meal can therefore, be used as a feed supplement without having any adverse effect on the growth and well-being of hybrid catfish fingerlings

Glucagon-like peptide-1 analog therapy in rare genetic diseases: monogenic obesity, monogenic diabetes, and spinal muscular atrophy.

Implementing genetic analyses have unraveled rare alterations causing early-onset obesity and complications, in whom treatment is challenging. We aimed to report on the effects of adjuvant off-label therapy with liraglutide, glucagon-like peptide-1 analogue (GLP-1a), in rare genetic diagnoses. Case scenarios and review of the literature. Case 1: Nine-year-old boy with early-onset severe obesity and nonalcoholic fatty liver disease (NAFLD) due to a homozygous mutation in the MC4R gene deteriorated under lifestyle change and metformin therapy [at 10.5 years: body mass index (BMI) 51.2kg/m2, 226% of the 95th percentile, fat percentage (FP) 65% and muscle-to-fat ratio (MFR) z-score of -2.41]. One year of liraglutide treatment halted progressive weight gain [BMI 50.3kg/m2, 212% of the 95th percentile, 63.7% FP and MFR z-score of -2.34], with biochemical improvement. Case 2: Twelve-year-old boy with obesity presented with diabetes and progressive NAFLD. Exome analysis revealed two heterozygous mutations compatible with monogenic diabetes (HNF1A) and familial hypercholesterolemia (LDLR). Lifestyle modifications resulted in clinical and laboratory improvement (BMI 87th percentile, 32.8% FP, MFR z-score of -1.63, HbA1c 5.5%) without the expected recovery in liver transaminases. Liraglutide treatment augmented the improvement in weight status (BMI 68th percentile, 22.6% FP, MFR z-score of -1.13) with normalization of liver transaminases. Case 3: Nineteen-year-old male with spinal muscular atrophy type 3 presented with sarcopenic obesity and comorbidities. Treatment strategy included dietary counseling and multiple drug therapies (metformin, anti-hypertensive and statins). Liraglutide therapy led to a gradual recovery of metabolic complications allowing tapering-down other medications. Considering the pleiotropic effects of GLP1-a beyond BMI reduction, this treatment modality may serve as a game changer in challenging cases.

Primary bilateral macronodular adrenocortical hyperplasia (PBMAH) patient with ARMC5 mutations

BackgroundPrimary bilateral macronodular adrenocortical hyperplasia (PBMAH) is a highly heterogeneous disease with divergent manifestations ranging from asymptomatic subclinical Cushing syndrome (CS) to overt Cushing syndrome with severe complications. ARMC5 mutations occur in 20 to 55% PBMAH patients usually with more severe phenotypes. Different ARMC5 mutations might be associated with diverse phenotypes of PBMAH.Case presentationA 39-year-old man was admitted to our hospital with progressive weight gain and severe hypertension. He presented typical CS and its classical metabolic and bone complications like hypertension and osteoporosis. The laboratory results showed high levels of cortisol and low levels of ACTH. Low- and high-dosed dexamethasone suppression tests were negative. Contrast-enhanced computed tomography (CT) revealed multiple bilateral irregular macronodular adrenal masses. Adrenal venous sampling (AVS) confirmed that the right adrenal gland with larger nodules secreted more hormone that the left side did. Right adrenalectomy and subsequent contralateral subtotal resection were conducted. His blood pressure and CS symptoms as well as comorbidities including backache and muscle weakness improved. Whole exome sequencing identified one ARMC5 germline mutation (c.1855C > T, p. R619*), five ARMC5 somatic mutations (four novel mutations) in his right and left adrenal nodules.ConclusionsThis PBMAH patient was identified with one ARMC5 germline mutation and five different somatic ARMC5 mutations (four novel mutations) in the different nodules of the bilateral adrenal masses. AVS combined with CT imagine could be helpful to determine the dominant side for adrenalectomy. Genetic testing is important for the diagnosis and management of the patient with PBMAH.

Cushing’s disease and bipolar disorder: study of medicopsychiatric intricacies from a clinical vignette

IntroductionCushing’s syndrome is a relatively rare condition that results from chronic hypercortisolism. This syndrome is characterized by the presence of various psychiatric manifestations that can accompany it at all its stages of evolution. They can either inaugurate the clinical picture, or appear during the course of the disease, as they can persist even after the resolution of the syndrome. of Cushing. Through a clinical vignette, we report a case of Cushing’s syndrome in a 52-year-old patient who presented with a picture of melancholic depression as part of a bipolar disorder and who had preceded the discovery of Cushing’s disease.Objectivesestablish the relationship between Cushing’s syndrome and bipolar disorder and identify the main pillars of care.MethodsIt was proposed to present the clinical case of a 52-year-old patient in whom psychiatric manifestations of the psychotic and thymic types preceded the discovery of Cushing’s disease, to recall the main psychiatric symptoms that can be encountered during such endocrine disorders and their possible entanglement with psychiatric pathologies.ResultsMrs. F. is 52 years old. married and mother of 3 children, without social security coverage for medullary carcinoma of the thyroid, having benefited from thyroidectomy with radiotherapy, admitted for treatment of paraneoplastic Cushing’s syndrome. The beginning of his troubles goes back to 6 months before his consultation with psychiatry. The initial symptoms were typical of a progressive weight gain noticed by the entourage. There was the installation of thymic symptoms such as an elation of mood, self-esteem, multiple projects. One month before admission to the internal medicine department, the patient presented with a depressed mood, anhedonia , a disgust for life, and dark thoughts. She had stopped all drug treatment.Cushing’s disease is the most common cause of endogenous hypercortisolism (&gt;85%). Corticotropic micro-adenomas , are the most frequently observed, i.e., in 90% of cases, and are sometimes not visible on magnetic resonance imaging . Its first-line treatment is neurosurgical with trans-sphenoidal excision. In its second intention, it uses drugs whose targets are pituitary or adrenal, as well as radiotherapy.Conclusionswe present the case of a patient with a picture of bipolar mood disorder and Cushing’s disease. Thymic and psychotic psychiatric symptoms preceded the discovery of endocrine disease whose symptoms were not apparent at first. The hypotheses of comorbidity or rather of the inauguration of the endocrine disease by a psychiatric picture, in particular bipolar mood disorder, remain advanced and the limits betweenDisclosure of InterestNone Declared

Prolonged Adrenal Insufficiency after Unilateral Adrenalectomy for Cortisolic Adenoma

Background: The suppression of the hypothalamic-pituitary-adrenal axis by cortisol-secreting adrenocortical tumors is well recognized and requires peri- and postoperative hydrocortisone substitution. Case Presentation: A 48-year-old female patient with hypertension and progressive weight gain, the clinical signs of hypercorticism motivated a hormonal workup revealing an independent ACTH Cushing’s syndrome: with urinary free cortisol (UFC) at 649 nmol/24h (4× normal), adrenocorticotropin hormone (ACTH) at 1.5 ng/l. The rest of the hormonal workup was not performed due to a lack of financial means. An Adrenal CT scan showed a 4 cm right adrenal adenoma. The patient underwent a right adrenalectomy with an adrenal adenoma on pathological examination. The contralateral side was normal. The patient was treated with hydrocortisone 30 mg/d for 6 weeks then 15 mg/d, during the monitoring we noted a persistence of the adrenal insufficiency for now 4 years. Basal cortisol levels during follow-up were very low (synacthen stimulation tests. Conclusion: Adrenal cortisol tumors are recognized by suppression, the duration of hypothalamic-pituitary-adrenal axis suppression is variable from 11 to 60 months depending on the series, which depends on the duration, severity of hypercortisolism, tumor size and other unknown factors. A longer follow-up of these patients is necessary to look for recovery of the contralateral adrenal gland.

Novel Fat Taste Receptor Agonists Curtail Progressive Weight Gain in Obese Male Mice

The spontaneous preference for dietary lipids is principally regulated by 2 lingual fat taste receptors, CD36 and GPR120. Obese animals and most of human subjects exhibit low orosensory perception of dietary fat because of malfunctioning of these taste receptors. Our aim was to target the 2 fat taste receptors by newly synthesized high affinity fatty acid agonists to decrease fat-rich food intake and obesity. We synthesized 2 fat taste receptor agonists (FTA), NKS-3 (CD36 agonist) and NKS-5 (CD36 and GPR120 agonist). We determined their molecular dynamic interactions with fat taste receptors and the effect on Ca2+ signaling in mouse and human taste bud cells (TBC). In C57Bl/6 male mice, we assessed their gustatory perception and effects of their lingual application on activation of tongue-gut loop. We elucidated their effects on obesity and its related parameters in male mice fed a high-fat diet. The two FTA, NKS-3 and NKS-5, triggered higher Ca2+ signaling than a dietary long-chain fatty acid in human and mouse TBC. Mice exhibited a gustatory attraction for these compounds. In conscious mice, the application of FTA onto the tongue papillae induced activation of tongue-gut loop, marked by the release of pancreato-bile juice into collecting duct and cholecystokinin and peptide YY into blood stream. Daily intake of NKS-3 or NKS-5 via feeding bottles decreased food intake and progressive weight gain in obese mice but not in control mice. Our results show that targeting fat sensors in the tongue by novel chemical fat taste agonists might represent a new strategy to reduce obesity.