Acanthosis Nigricans Research Articles

Acanthosis nigricans - a potentially useful clue to the presence of significant occult disease at autopsy.

A 19-year-old male was found dead in his apartment. At autopsy he was morbidly obese (Body mass index; BMI - 40.5) with multiple areas of velvety pigmented thickening of the skin in folds around the neck, in the axillae, in the inframammary regions, over the anterior waistline and groin regions and over the dorsal aspects of the feet. These had the typical appearance of acanthosis nigricans. Internal examination revealed aspiration of gastric contents into the airways. Vitreous humour biochemistry showed markedly elevated levels of both glucose (62.9mmol/L) and β-hydroxybutyrate (13.54mmol/L). Death was, therefore, due to aspiration pneumonia complicating diabetic ketoacidosis on a background of morbid obesity. The initial indicator of underlying diabetes, in conjunction with obesity had been acanthosis nigricans.

Dermatological manifestations in Costello syndrome: A prospective multicentric study of 31 HRAS-positive variant patients.

Data on dermatological manifestations of Costello syndrome (CS) remain heterogeneous and lack in validated description. To describe the dermatological manifestations of CS; compare them with the literature findings; assess those discriminating CS from other RASopathies, including cardiofaciocutaneous syndrome (CFCS) and the main types of Noonan syndrome (NS); and test for dermatological phenotype-genotype correlations. We performed a 10-year, large, prospective, multicentric, collaborative dermatological and genetic study. Thirty-one patients were enrolled. Hair abnormalities were ubiquitous, including wavy or curly hair and excessive eyebrows, respectively in 68% and 56%. Acral excessive skin (AES), papillomas and keratotic papules (PKP), acanthosis nigricans (AN), palmoplantar hyperkeratosis (PPHK) and 'cobblestone' papillomatous papules of the upper lip (CPPUL), were noted respectively in 84%, 61%, 65%, 55% and 32%. Excessive eyebrows, PKP, AN, CCPUL and AES best differentiated CS from CFCS and NS. Multiple melanocytic naevi (>50) may constitute a new marker of attenuated CS associated with intragenic duplication in HRAS. Oral acitretin may be highly beneficial for therapeutic management of PPHK. No significant dermatological phenotype-genotype correlation was determined between patients with and without HRAS c.34G>A (p.G12S). This validated phenotypic characterization of a large number of patients with CS will allow future researchers to make a positive diagnosis, and to differentiate CS from CFCS and NS.

Acculturation and Health Status in the Children’s Healthy Living Program in the Pacific Region

Acculturation/enculturation has been found to impact childhood health and obesity status. The objective of this study is to use cross-sectional data to examine the association between proxies of adult/caregiver acculturation/enculturation and child health status (Body Mass Index [BMI], waist circumference [WC], and acanthosis nigricans [AN]) in the U.S.-Affiliated Pacific Islands (USAPI), Alaska, and Hawaiʻi. Study participants were from the Children’s Healthy Living (CHL) Program, an environmental intervention trial and obesity prevalence survey. Anthropometric data from 2–8 year olds and parent/caregiver questionnaires were used in this analysis. The results of this study (n = 4121) saw that those parents/caregivers who identified as traditional had children who were protected against overweight/obesity (OWOB) status and WC > 75th percentile (compared to the integrated culture identity) when adjusted for significant variables from the descriptive analysis. AN did not have a significant association with cultural classification. Future interventions in the USAPI, Alaska, and Hawaiʻi may want to focus efforts on parents/caregivers who associated with an integrated cultural group as an opportunity to improve health and reduce child OWOB prevalence.

Terra Firma-Forme Dermatosis: Easy to Diagnose, Easier to Treat!

Terra firma-forme dermatosis is a dermatological condition characterized by the presence of hyperpigmented plaques, which are easily cleared with 70% isopropyl alcohol.CASE 1: A 14-year-old boy, with no relevant past medical history, presented with a brown-colored skin lesion on his chest, which had appeared one year earlier. The lesion was cleared with 70% isopropyl alcohol, proving the diagnosis of terra firma-forme dermatosis.CASE 2: A 12-year-old girl was referred to our consultation. She was obese and had insulin-resistance. On physical examination she had significant hyperpigmentation on her neck and axillae, which was interpreted as acanthosis nigricans. Nonetheless, we performed swabbing of the lesions with 70% isopropyl alcohol, which immediately cleared the skin, confirming the diagnosis of terra firma-forme dermatosis. In conclusion, terra firma-forme dermatosis is a benign and easily solved dermatosis. Nonetheless, its unesthetic appearance is often a cause of great distress to the patient. We aim to increased awareness of this entity.

Comparative analysis of clinical symptoms and biochemical alterations in women with polycystic ovary syndrome: assessing the impact of type 1 diabetes versus non-diabetic controls

BackgroundWomen with type 1 diabetes depend on insulin injections throughout their life. However, the recommendation for strict metabolic control of diabetes requires the administration of supra-physiological doses of insulin, which might result in insulin-mediated stimulation of androgen synthesis. Hyperandrogenism in women with type 1 diabetes may be associated with polycystic ovary syndrome (PCOS). This study was performed to investigate PCOS and its associated clinical symptoms and biochemical alterations in women with type 1 diabetes in the Palestinian Territories. This retrospective cohort study consists of 50 women with type 1 diabetes and 50 apparently healthy non-diabetic controls. Questionnaire interviews were conducted. The diagnosis of PCOS was based on chronic anovulation and biochemical evidence of hyperandrogenism. Serum total testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), and insulin were measured by ELISA.ResultsThe mean waist-to-hip ratio and age at menarche were significantly higher in diabetic women than in non-diabetic controls (81.9 ± 7.9 and 13.9 ± 1.6 years vs. 78.8 ± 5.7 and 13.2 ± 1.2 years, and P = 0.045, P = 0.020, respectively). Oligomenorrhea, acanthosis nigricans, seborrhea, and hirsutism were more frequent in diabetics. The levels of total testosterone and insulin were significantly higher in diabetics (0.58 ± 0.11 ng/ml and 15.8 ± 12.4 mlU/ml vs. 0.44 ± 0.11 ng/ml and 10.8 ± 4.5 mlU/ml, P < 0.001 and P = 0.010, respectively). PCOS was present in 11 (22.0%) of diabetic women compared to 3 (6.0%) in non-diabetics (P = 0.044). Diabetic women with PCOS received higher doses of insulin than non-PCOS women (72.7 ± 23.9 vs. 55.0 ± 19.8 UI.cc/ml/day, P = 0.023). PCOS women showed more frequent oligomenorrhea (100% vs. 15.4%, P < 0.001) and higher levels of total testosterone and insulin (0.64 ± 0.09 and 23.1 ± 13.0 vs. 0.53 ± 0.11 and 14.1 ± 11.8, P = 0.023 and P = 0.041, respectively). PCOS cases were significantly more frequent in diabetic women receiving intensive insulin therapy than their counterparts with non-intensive insulin therapy (40.9% vs. 7.1%, P = 0.012).ConclusionIntensive insulin treatment in type 1 diabetes potentiates the development of PCOS and its related clinical and biochemical features particularly oligomenorrhea, hyperinsulinemia, and hyperandrogenemia.

Speech and Language Development, Hearing, and Feeding in Patients With Genetically Confirmed Crouzon Syndrome With Acanthosis Nigricans: A 36-Year Longitudinal Retrospective Review of Patients at the Oxford Craniofacial Unit.

Crouzon syndrome with acanthosis nigricans (CAN) is caused by the specific mutation c.1172C>A (p.Ala391Glu) in the fibroblast growth factor receptor 3 gene, and has an estimated prevalence of 1:1,000,000 births. Most cases occur de novo; however, autosomal dominant inheritance may occur. The clinical presentation typically includes craniosynostosis, midface and maxillary hypoplasia, choanal atresia/stenosis, hydrocephalus, and intracranial hypertension. Patients develop acanthosis nigricans, a hyperkeratotic skin disorder. The authors present the first known study to investigate the speech, language, hearing, and feeding of patients with CAN. A retrospective case-note review of patients with a genetically confirmed diagnosis of CAN attending the Oxford Craniofacial Unit during a 36-year period (1987-2023) was undertaken. Participants were 6 patients with genetically-confirmed CAN (5 females, 1 male), all cases arose de novo. All patients had craniosynostosis (n = 5/6 multisuture synostosis, n = 1/6 left unicoronal synostosis). Hydrocephalus was managed through ventriculoperitoneal shunt in 67% (n = 4/6) of patients, and 67% (n = 4/6) had a Chiari 1 malformation. Patients had a complex, multifactorial feeding history complicated by choanal atresia/stenosis (100%; n = 6/6), and significant midface hypoplasia. All patients required airway management through tracheostomy (83%; n = 5/6); and/or continuous positive airway pressure (67%; n = 4/6). All patients underwent adenotonsillectomy (100%; n = 6/6). Initial failure to thrive, low weight, and/or height were seen in 100% (n = 6/6) patients; 80% (n = 4/5) had reflux; 100% (n = 6/6) had nasogastric, or percutaneous endoscopic gastrostomy based feeding during their treatment journey. All patients had hearing loss (100%; n = 6/6). Early communication difficulties were common: receptive language disorder (50%; n = 3/6); expressive language disorder (50%; n = 3/6); and speech sound disorder in 50% (n = 3/6)-necessitating the use of Makaton in 80% of patients (n = 3/5). Patients with CAN experience significant respiratory, neurological, and structural obstacles to hearing, speech, language, and feeding. The authors present a recommended pathway for management to support patients in these domains.

Dupilumab-induced Acanthosis Nigricans

Dupilumab is a human monoclonal IgG4 antibody to interleukin-4 (IL-4) and IL-13 approved for the treatment of moderate-to-severe atopic dermatitis (AD) in patients six months or older. Several cutaneous adverse reactions to dupilumab have been reported, including facial dermatitis and psoriasis. Herein, we present a unique case of dupilumab-induced acanthosis nigricans (AN) in a patient treated for concomitant AD and contact dermatitis, in the absence of other associated conditions or potential culprit medications. The patient had complete resolution of the lesions with discontinuation of medication, and recurrence upon re-initiation of therapy. This case represents a new cutaneous adverse reaction to dupilumab to which dermatologists should be familiar.

A clinicoepidemiological study of pattern of skin disorders among diabetes mellitus in a tertiary care centre

Diabetes Mellitus (DM), a most common metabolic disorder affects every organ of the body including skin causing increased morbidity and serious impact on quality of life. Aim of this study is to analyse the prevalence and pattern of cutaneous manifestations among type 1 and type 2 DM correlating it with the mean duration of diabetes. This was an observational study conducted on 200 consecutive patients with DM attending dermatology department. Apart from detailed history, thorough clinical examination and relevant investigations were done. Skin biopsy were done in cases with diagnostic ambiguity. Cutaneous infections occurred in majority (70.5%). Among fungal infections (59.5%) candidiasis was the most common (28%). Pruritus and neuropathy were observed in 37% and 33% respectively and was more common in type 1 DM. Leg ulcer was observed in 8.5%. Vitiligo, oral lichen planus, granuloma annulare were seen common among type 1 DM. Psoriasis, acrochordon, acanthosis nigricans, cutaneous amyloidosis, bullous pemphigoid and diabetic bulla were common in Type 2 DM. Mucor mycosis, scleredema diabeticorum, cheiroarthropathy and perforating dermatoses were uniquely observed among prolonged uncontrolled diabetics. Candidiasis was found to be an early manifestation of diabetes. Poor glycemic control and longer duration of diabetes were associated with an increased frequency and number of skin disorders. Skin manifestations are more common among undiagnosed and uncontrolled diabetics..

Analysis of disease characteristics of a large patient cohort with congenital generalized lipodystrophy from the Middle East and North Africa

BackgroundCongenital generalized lipodystrophy (CGL) is a rare inherited disease characterized by a near-total absence of adipose tissue and is associated with organ system abnormalities and severe metabolic complications. Here, we have analyzed the disease characteristics of the largest CGL cohort from the Middle East and North Africa (MENA) who have not received lipodystrophy-specific treatment.MethodsCGL was diagnosed clinically by treating physicians through physical assessment and supported by genetic analysis, fat loss patterns, family history, and the presence of parental consanguinity. Data were obtained at the time of patient diagnosis and during leptin-replacement naïve follow-up visits as permitted by available medical records.ResultsData from 43 patients with CGL (37 females, 86%) were collected from centers located in eight countries. The mean (median, range) age at diagnosis was 5.1 (1.0, at birth–37) years. Genetic analysis of the overall cohort showed that CGL1 (n = 14, 33%) and CGL2 (n = 18, 42%) were the predominant CGL subtypes followed by CGL4 (n = 10, 23%); a genetic diagnosis was unavailable for one patient (2%). There was a high prevalence of parental consanguinity (93%) and family history (67%) of lipodystrophy, with 64% (n = 25/39) and 51% (n = 20/39) of patients presenting with acromegaloid features and acanthosis nigricans, respectively. Eighty-one percent (n = 35/43) of patients had at least one organ abnormality; the most frequently affected organs were the liver (70%, n = 30/43), the cardiovascular system (37%, n = 16/43) and the spleen (33%, n = 14/43). Thirteen out of 28 (46%) patients had HbA1c > 5.7% and 20/33 (61%) had triglyceride levels > 2.26 mmol/L (200 mg/dl). Generally, patients diagnosed in adolescence or later had a greater severity of metabolic disease versus those diagnosed during childhood; however, metabolic and organ system abnormalities were observed in a subset of patients diagnosed before or at 1 year of age.ConclusionsThis analysis suggests that in addition to the early onset of fat loss, family history and high consanguinity enable the identification of young patients with CGL in the MENA region. In patients with CGL who have not received lipodystrophy-specific treatment, severe metabolic disease and organ abnormalities can develop by late childhood and worsen with age.

Case report: Glycaemic management and pregnancy outcomes in a woman with an insulin receptor mutation, p.Met1180Lys

BackgroundHeterozygous insulin receptor mutations (INSR) are associated with insulin resistance, hyperglycaemia and hyperinsulinaemic hypoglycaemia in addition to hyperandrogenism and oligomenorrhoea in women. Numerous autosomal dominant heterozygous mutations involving the INSR β-subunit tyrosine kinase domain resulting in type A insulin resistance have been previously described. We describe the phenotype, obstetric management and neonatal outcomes in a woman with type A insulin resistance caused by a mutation in the β-subunit of the INSR.Case presentationWe describe a woman with a p.Met1180Lys mutation who presents with hirsutism, oligomenorrhoea and diabetes at age 20. She has autoimmune thyroid disease, Coeliac disease and positive GAD antibodies. She is overweight with no features of acanthosis nigricans and is treated with metformin. She had 11 pregnancies treated with insulin monotherapy (n = 2) or combined metformin and insulin therapy (n = 9). The maximum insulin dose requirement was 134 units/day or 1.68 units/kg/day late in the second pregnancy. Mean birthweight was on the 37th centile in INSR positive offspring (n = 3) and the 94th centile in INSR negative offspring (n = 1).ConclusionThe p.Met1180Lys mutation results in a phenotype of diabetes, hirsutism and oligomenorrhoea. This woman had co-existent autoimmune disease. Her insulin dose requirements during pregnancy were similar to doses observed in women with type 2 diabetes. Metformin may be used to improve insulin sensitivity in women with this mutation. Offspring inheriting the mutation tended to be smaller for gestational age.

Obesity and Acanthosis Nigricans as the Clinical Markers of Insulin Resistance and Type-2 Diabetes Mellitus in Young Patients; A Case Report of Two Cases

Two young girls, aged 11 and 12 years, presented with obesity and Acanthosis Nigricans. They were found to have severe insulin resistance and type-2 diabetes mellitus. Anti-glutamic acid decarboxylase and anti-islet cell antibodies were negative. Tests for hypothyroidism and Cushing’s syndrome were negative. They were managed with lifestyle modification and metformin.

Diabetes mellitus and its skin manifestations - dermatology for diabetologists

Introduction: Diabetes Mellitus (DM) one of the most common chronic disease in Europe, can affect every part of the body including the skin. Metabolic changes during the progress of diabetes mellitus , influence the occurence of various dermatoses such as Acanthosis nigricans, Necrobiosis lipoidica diabeticorum, bullosis diabeticorum, eruptive xanthomatosis and diabetic dermopathy.  On the other hand, there are allergic skin reactions as a consequence of insulin infusion, diabetic pills treatment and using diabetic devices like insulin pumps and glucose monitors that can improve patiens glycemic control and their quality of life.    Aim of the study: The aim of our study is to present skin manifestations associated with diabetes mellitus patients. The importance of early detection skin changes and its significance are also analysed.    Material and methods: We searched electronic databases, using keywords such as „Diabetes Mellitus” , „ Skin dermatoses assosiated with diabetes mellitus „ and „Acanthosis Nigricans”    Conclusions: Human skin is a reflection of the processes that take place in the body. The characteristc dermatoses that appear on it, can be a clue for the doctor and help him in the diagnostic process and proper control of diabetes. Technological progress has led to the develompent of specialized devices to control the glycemia of patients, however, this is often associated with the deterioration in the well-being of patients and the benefits of treatment ,by reverse allergic skin reactions to contact with the equipment.

Maturational hyperpigmentation: An update

Maturational hyperpigmentation is a form of acquired idiopathic facial melanosis, which is a relatively recently described entity, mainly seen in middle-aged individuals. Apart from its disturbing nature due to significant psychosocial impact and cosmetic concern, it is also believed to be associated with a metabolic syndrome similar to facial acanthosis nigricans. While both these disorders are close differentials of each other and could represent the same spectrum, there are significant differences between both. It is therefore important to raise awareness among dermatologists so as not to miss this relatively new, under-recognized, and frequently misdiagnosed entity.

Comparison of efficacy and safety of tretinoin 0.05% and glycolic acid peeling 70% in axillary and neck lesions of acanthosis nigricans: A single-blinded, randomized trial.

Acanthosis nigricans is a non-inflammatory skin pigmentary disorder characterized by a dark, velvety appearance, primarily observed in the neck and axillary areas. It is commonly associated with obesity, diabetes, and insulin resistance. Although the primary treatment is correcting the underlying disorders, many aesthetic modalities have been established to improve appearance owing to cosmetic concerns. We aimed to compare and investigate the effectiveness and side effects of tretinoin 0.05% and glycolic acid 70% in treating acanthosis nigricans lesions of the axillary and neck area. This single-blinded, randomized trial recruited patients with neck or axillary involvement. Each patient was randomized to use cream tretinoin 0.05% every other night on one side, while the other side was treated with glycolic acid 70%, which was applied every 2 weeks at the clinic for four consecutive sessions. The study duration was 8 weeks, and patients were evaluated every 2 weeks based on their response to treatment, satisfaction, and side effects. Thirty patients, including 14 with neck lesions and 16 with axillary lesions, were included. Tretinoin was significantly more effective for axillary lesions in terms of treatment response and patient satisfaction (p = 0.02 and p = 0.008, respectively). It was also shown that as the severity of the lesions increased, the response to treatment and patient satisfaction decreased, specifically when treating axillary lesions with glycolic acid (p = 0.02 and p = 0.03, respectively). Neither method was significantly effective for neck lesions. However, tretinoin 0.05% was shown to be more efficacious in treating axillary lesions of acanthosis nigricans, despite causing minimal side effects.

Grading Acanthosis Nigricans Using a Smartphone and Color Analysis: A Novel Noninvasive Method to Screen for Impaired Glucose Tolerance and Type 2 Diabetes

Objective The objective of this study was to develop ANcam, a novel method for identifying acanthosis nigricans (AN) using a smartphone camera and computer-aided color analysis for noninvasive screening of people with impaired glucose tolerance (IGT). Research Design and Methods Adult and juvenile participants with or without diagnosed type 2 diabetes were recruited in Trinidad and Tobago. After obtaining informed consent, participants’ history, demographics, anthropometrics, and A1C were collected and recorded. Three subject-matter experts independently graded pictures of the posterior neck and upper back using the ANcam smartphone application and Burke methods. A correlation matrix investigated 25 color channels for association with hyperpigmentation, and the diagnostic thresholds were determined with a receiver operating characteristic curve analysis. Results For the 227 participants with captured images and A1C values, the cyan/magenta/yellow/black (CMYK) model color channel CMYK_K was best correlated with IGT at an A1C cut-off of 5.7% [39 mmol/mol] (R = 0.45, P &amp;lt;0.001). With high predictive accuracy (area under the curve = 0.854), the cut-off of 7.67 CMYK_K units was chosen, with a sensitivity of 81.1% and a specificity of 70.3%. ANcam had low interrater variance (F = 1.99, P = 0.137) compared with Burke grading (F = 105.71, P &amp;lt;0.001). ANcam detected hyperpigmentation on the neck at double the self-reported frequency. Elevated BMI was 2.9 (95% CI 1.9–4.3) times more likely, elevated blood pressure was 1.7 (95% CI 1.2–2.4) times more likely, and greater waist-to-hip ratio was 2.3 (95% CI 1.4–3.6) times more likely with AN present. Conclusion ANcam offers a sensitive, reproducible, and user-friendly IGT screening tool to any smartphone user that performs well with most skin tones and lighting conditions.

Exploring the association of ESR1 and ESR2 gene SNPs with polycystic ovary syndrome in human females: a comprehensive association study

BackgroundPolycystic Ovary Syndrome (PCOS) affects a significant proportion of human females worldwide and is characterized by hormonal, metabolic, and reproductive dysfunctions, including infertility, irregular menstrual cycles, acanthosis nigricans, and hirsutism. Mutations in the estrogen receptor genes ESR1 and ESR2, involved in normal follicular development and ovulation, can contribute to development of the PCOS. The present study focuses on investigating the potential correlation between single nucleotide polymorphisms (SNPs) of ESR1 and ESR2 genes and the incidence of this syndrome.MethodsFor this study, SNPs in ESR1 and ESR2 genes were retrieved from the ENSEMBL database and analyzed for their effect on mutated proteins using different bioinformatics tools including SIFT, PolyPhen, CADD, REVEL, MetaLR, I-Mutant, CELLO2GO, ProtParam, SOPMA, SWISS-MODEL and HDDOCK.ResultsAll the SNPs documented in the present study were deleterious. All the SNPs except rs1583384537, rs1450198518, and rs78255744 decreased protein stability. Two variants rs1463893698 and rs766843910 in the ESR2 gene altered the localization of mutated proteins i.e. in addition to the nucleus, proteins were also found in mitochondria and extracellular, respectively. SNPs rs104893956 in ESR1 and rs140630557, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene significantly changed the secondary structure of proteins (2D). SNPs that markedly changed 3D configuration included rs1554259481, rs188957694 and rs755667747 in ESR1 gene and rs1463893698, rs140630557, rs1596423459, rs766843910, rs1596405923, rs762454979 and rs1384121511 in ESR2 gene. Variants rs1467954450 (ESR1) and rs140630557 (ESR2) were identified to reduce the binding tendency of ESRα and β receptors with estradiol as reflected by the docking scores i.e. -164.97 and -173.23, respectively.ConclusionDue to the significant impact on the encoded proteins, these variants might be proposed as biomarkers to predict the likelihood of developing PCOS in the future and for diagnostic purposes.

Comparison of the Outcome of Treatment of 15% Trichloroacetic Acid versus Topical 0.05% Tretinoin in the Treatment of Acanthosis Nigricans at Tertiary Care Hospital, Karachi

Background: Acanthosis Nigricans (AN) is a dermatological condition characterized by hyperpigmented, velvety plaques, commonly linked with insulin resistance, obesity, and hormonal disorders. The treatment of AN primarily focuses on managing skin changes, with topical agents like trichloroacetic acid (TCA) and tretinoin being explored for their efficacy. Objective: The study aimed to compare the effectiveness of 15% trichloroacetic acid and topical 0.05% tretinoin in the treatment of Acanthosis Nigricans, focusing on improvements in hyperpigmentation and patient satisfaction. Methods: This randomized control trial was conducted at Jinnah Postgraduate Medical Centre, Karachi, from August 2022 to June 2023. A total of 90 participants with diagnosed AN were recruited and randomly assigned into two groups: Group A (n=45) received 15% TCA peels every two weeks, and Group B (n=45) applied topical 0.05% tretinoin daily, both for a duration of 8 weeks. The efficacy was assessed using serial photographs and a grading system for improvement. Data analysis was performed using SPSS Version 25.0, with the Chi-square test employed for comparing efficacy. Results: The mean age in Group A was 35.11 ± 7.05 years and in Group B was 37.20 ± 6.37 years. Group A showed a higher success rate with 42 participants (93.3%) demonstrating improvement, compared to 35 participants (77.8%) in Group B (P-value: 0.034, Odds Ratio: 4.000). Grades of improvement indicated that 26 participants (57.8%) in Group A and 14 (31.1%) in Group B experienced good improvement (51%-75%). Adverse effects such as erythema and post-inflammatory hyperpigmentation were more common in Group A. Conclusion: The study suggests that 15% trichloroacetic acid may offer greater improvement in hyperpigmentation in Acanthosis Nigricans compared to topical 0.05% tretinoin. However, the treatment choice should consider individual patient factors, and further research is needed to confirm these findings.

Phenotype and predictors of insulin independence in adults presenting with diabetic ketoacidosis: a prospective cohort study

Aims/hypothesisThe aim of this work was to describe the phenotype of adults presenting with a first episode of diabetic ketoacidosis (DKA) in Cape Town, South Africa, and identify predictors of insulin independence at 12 and 60 months after presentation.MethodsA prospective, descriptive cohort study of all individuals, 18 years or older, presenting for the first time with DKA to four public-sector hospitals of the Groote Schuur Academic Health Complex was performed. Clinical, biochemical and laboratory data including GAD antibody and C-peptide status were collected at baseline. Insulin was systematically weaned and stopped in individuals who achieved normoglycaemia within the months after DKA. Individuals were followed for 12 months and then annually until 5 years after initial presentation with ketoacidosis.ResultsEighty-eight individuals newly diagnosed with diabetes when presenting with DKA were included and followed for 5 years. The mean ± SD age was 35±10 years and the median (IQR) BMI at diagnosis was 28.5 (23.3–33.4) kg/m2. Overall, 46% were insulin independent 12 months after diagnosis and 26% remained insulin independent 5 years after presentation. Forty-one participants (47%) tested negative for anti-GAD and anti-IA-2 antibodies and had C-peptide levels >0.3 nmol/l; in this group, 68% were insulin independent at 12 months and 37% at 5 years after diagnosis. The presence of acanthosis nigricans was strongly associated with insulin independence (OR 27.1 [95% CI 7.2, 102.2]; p<0.001); a positive antibody status was associated with a lower likelihood of insulin independence at 12 months (OR 0.10 [95% CI 0.03, 0.36]; p<0.001). On multivariable analysis only acanthosis (OR 11.5 [95% CI 2.5, 53.2]; p=0.004) was predictive of insulin independence 5 years after diagnosis.Conclusions/interpretationThe predominant phenotype of adults presenting with a first episode of DKA in Cape Town, South Africa, was that of ketosis-prone type 2 diabetes. These individuals presented with obesity, acanthosis nigricans, negative antibodies and normal C-peptide and could potentially be weaned off insulin at follow-up. Classic type 1 diabetes (lower weight, antibody positivity, low or unrecordable C-peptide levels and long-term insulin dependence) was less common. The simple clinical sign of acanthosis nigricans is a strong predictor of insulin independence at 12 months and 5 years after initial presentation.Graphical

O-07 Lipodystrophy: A disease to be considered in diabetes clinics

Abstract Introduction Lipodystrophy syndromes are disorders with no adipose tissue. Lipodystrophy is classified based on the degree of adipose tissue deficiency, distinguishing between partial and generalized forms, and considering if it is inherited or acquired. The condition is characterized by ectopic steatosis, severe dyslipidemia, insulin resistance, and severe comorbidities including uncontrolled diabetes mellitus (DM), acute pancreatitis, hepatic cirrhosis, proteinuria, renal failure, and premature cardiovascular disease. Congenital Generalized Lipodystrophy (CGL, Berardinelli-Seip Syndrome) is inherited autosomal recessively. Four genetic mutations linked to CGL have been identified: AGPAT2, BSCL2, CAV1, and PTRF. This report describes a case of a patient with uncontrolled diabetes and other health conditions. The patient was diagnosed with CGL2 as an adult after admission to our facility. Clinical Case This case involves a 43-year-old female patient seeking help for glycemic control and menstrual cycle irregularities. She was diagnosed with DM at 24 and received care at multiple hospitals. Her mother, older brother, and three sisters were diagnosed with DM before the age of 40. Her BMI was 23.4 kg/m2. The physical examination revealed muscularly prominent lipoatrophy in the upper and lower limbs and acanthosis nigricans in the axilla. Additionally, the person had facial features resembling acromegaly, with enlarged extremities and swelling of soft tissues. Blood pressure was regulated with ramipril, hydrochlorothiazide, and amlodipine. She had used various insulin and OAD regimens in the past. Despite this, euglycemia was challenging to achieve, and she frequently needed to be hospitalized for diabetic ketoacidosis. Anti-glutamic acid decarboxylase, anti-insulin, and islet antibodies were negative. HbA1c level was 13.3% and C-peptide level was 2.5 ng/ml. Moreover, grade 3 hepatosteatosis and hypertriglyceridemia were present. Polyneuropathy and diabetic nephropathy were also identified. Acromegaly and cushing syndrome were excluded. After excluding acquired lipodystrophy syndromes, she was consulted to the genetics department for CGL. Next-gen sequencing found a homozygous missense mutation (c.666G&amp;gt;C; p.Met222Ile) in exon 5 of the BSCL2 gene. Following this result, the patient was diagnosed as CGL2. Caloric and fat restricted dietary was recommended. Fat intake was below 20-30% of total energy. The patient was treated with insulin aspart, glargine U300/mL, metformin, alpha lipoic acid, and fenofibrate. The patient's blood glucose was more regulated, did not apply to the emergency department. Family members were also given genetic counseling. Conclusion Lipodystrophy is rare however medical professionals must exercise caution and consider lipodystrophy as a possible diagnosis for non-obese individuals who have difficulty maintaining euglycemia, fatty liver disease, and elevated triglyceride levels. The physical examination is crucial for diagnosis.

O-10 Lymph node ACTH washout determined the source of ACTH secretion in a patient with Cushing's Syndrome due to medullary thyroid cancer

Abstract Introduction Ectopic ACTH syndrome constitutes 18% of Cushing's syndrome cases, and in rare cases, ACTH secretion from medullary thyroid cancer cells is the source of ectopic ACTH production. Here we report a catastrophic Cushing's syndrome case owing to medullary thyroid cancer in which the source of ACTH production was demonstrated by lymph node ACTH washout. Clinical Case A 23 year-old male was admitted to other clinics with complaints of inability to lose weight despite diet and exercise, and weight gain of approximately 40 kg, which had been going on for the last two years. At his application, his weight was 160 kg and his body mass index was 42.51 kg/m2. On physical examination, clinical stigmata suggesting Cushing's syndrome such as moon face, buffalo hump, supraclavicular fat deposition, acanthosis nigricans, centripedal obesity, purple striae on the abdomen were noted. The biochemical and hormonal evaluation confirmed ACTH-dependent Cushing's syndrome (Table 1). To establish the source of excess ACTH, first, a pituitary MRI was performed which revealed a 4×2 mm adenoma on the left side of the gland. In PET-CT, a 24×20 mm hypoechoic nodule in the inferior of the right thyroid lobe, and several pathological lymph nodes at the right side of the neck were detected. Serum calcitonin levels were high (6528 ng/L) and fine-needle aspiration biopsy from the thyroid nodule documented medullary thyroid cancer. The patient underwent bilateral total thyroidectomy and right cervical lymph node dissection. The pathology report was compatible with metastatic medullary thyroid cancer. After surgery, the remission of hypercortisolemia was not achieved and the patient was started on metyrapone treatment before the permanent treatment plan. Postoperative Gallium-68 DOTA PET-CT indicated residual disease and increased uptake in retropharyngeal, bilateral cervical level 2-4, right level 3, bilateral central, and bilateral lower cervical lymph nodes. The persistence of hypercortisolemia after surgery was most likely attributed to residual disease, however, it was considered that pituitary adenoma may also be the cause of ACTH secretion. Therefore, to confirm the source of ACTH secretion, ACTH washout samples were taken from the cervical lymph nodes and were found to be high as 958 ng/L. Reoperation was performed for recurrent mass and lymph node metastases. Conclusion Medullary thyroid cancer should definitely be considered in cases of ectopic ACTH syndrome. ACTH washing from the suspected lymph node may be an option for diagnostic purposes. In addition to the patient's primary tumor, hypercortisolism should also be treated.Table 1.Cushing's assessment tests