Acanthosis Nigricans: Pointer of Endocrine Entities
Abstract
:1. Introduction
2. Methods
3. AN and IR
4. AN and DM
5. AN and PCOS
6. Discussions
6.1. AN: The Tip of the Iceberg
6.2. Endocrine Approach of AN and Beyond
6.3. Specific Dermatologic Management of AN
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AN | acanthosis nigricans |
BMI | body mass index |
DM | diabetes mellitus |
EGFR | epidermal growth factor receptor |
eGDR | estimated glucose disposal rate |
FGFR | fibroblast growth factor receptor |
FAN | facial acanthosis nigricans |
GGT | γ-glutamyl transpeptidase |
GH | growth hormone |
HOMA-IR | homeostasis model assessment-insulin resistance |
IGF | insulin-like growth factor |
IRI | insulin resistance index |
IR | insulin resistance |
MS | metabolic syndrome |
MC4R | melanocortin-4 receptor |
MODY | maturity-onset diabetes of the young |
MAN | malignant acanthosis nigricans |
PCOS | polycystic ovary syndrome |
SCANS | scoring for AN severity |
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First Author/ Year of Publication/ Reference No. | Type of Study | Studied Population | Cardio-Metabolic Parameters Addressing AN Assessment |
---|---|---|---|
Philip NE. 2022 [56] | Cross-sectional | N = 60 patients with neck AN N1 = 13 patients without MS (21.7%) (mean age: 27.8 ± 8.2 y) vs. N2 = 47 patients with MS (78.3%) (mean age: 35.8 ± 10.9 y) | BMI: N1 = 26.5 ± 3.8 kg/m2 vs.N2 = 29.5 ± 3.5 kg/m2 (p = 0.01) WC: N1 = 87.6 ± 14.1 cm vs. N2 = 104.5 ± 11.7 cm (p = 0.0003) Total cholesterol: N1 = 192.2 ± 32.3 mg/dL vs. N2 = 210.2 ± 37.8 mg/dL FBG: N1 = 89.9 ± 6.8 mg/dL vs. N2 = 102.4 ± 22.01 mg/dL (p = 0.005) FI: N1 = 9.08 ± 4.3 mIU/mL vs. N2 = 14.09 ± 8.1 mIU/mL HOMA-IR: N1 = 2 ± 0.8 vs. N2 = 3.5 ± 2.2 |
Afify AA. 2022 [71] | Case-control | N1 = 25 patients with obesity with AN N2 = 25 patients with obesity without AN N3 = 25 healthy controls | Chemerin levels: N1 > N3, N2 > N3, N1 > N2 (p < 0.001) 100% of N1 met MS criteria |
Alaqil AI. 2022 [52] | Cross-sectional |
N = 1525 children (age: 9–12 y) Female/male ratio = 856/669 | Cardiorespiratory fitness, AN, HDL-cholesterol, and triglycerides loaded highest on the first component (loadings between 0.42 and 0.57) |
Shah VH. 2022 [76] | Case-control |
N1 = 40 patients with facial AN N2 = 40 healthy controls | N1 > N2: higher HOMA-IR, insulin levels, FBG, triglycerides, and total cholesterol (p < 0.05) |
Daye M. 2021 [80] | Case-control |
N1 =
108 patients with lichen planus N2 = 109 controls (without lichen planus) |
MS: N1 > N2 (50.9 versus 36.7%, p = 0.3) AN incidence: N1 > N2 (p = 0.009) MS: lichen with AN vs. lichen without AN (p < 0.001) |
Yamanaka AB. 2021 [53] | Cross-sectional | N = 4023 children (aged between 2 and 8 years) | 90th percentile cut points for boys aged 2 to 5 years (58.15 cm) and 6 to 8 years (71.63 cm) were slightly higher than for girls in both age groups |
Daye M. 2020 [57] | Cross-sectional | N = 148 obese patients N1 = 59 patients with AN (mean age: 12.29 ± 2.86 y) N2 = 89 patients without AN (mean age: 11.24 ± 2.82 y) | BMI: N1 = 31.9 ± 7.1 kg/m2 vs. N2 = 26.08 ± 4.5 kg/m2 MS: N1 = 13 vs. N2 = 34 WC: N1 = 103.8 ± 15.6 cm vs. N2 = 97.02 ± 18.5 cm FBG: N1 = 93.17 ± 10.63 mg/dL vs. N2 = 92.70 ± 10.00 mg/dL Insulin: N1 = 27.06 ± 18.45 U/L vs. N2 = 25.64 ± 14.62 U/L HbA1c: N1 = 5.24 ± 1.10% vs. N2 = 5.18 ± 1.28% HOMA-IR: N1 = 5.09 ± 2.25 vs. N2 = 3.73 ± 1.40 TG: N1 = 41.8 ± 8.41 mg/dL vs. N2 = 55.58 ± 47.53 mg/dL Cholesterol: N1 = 162.46 ± 47.7 mg/dL vs. N2 = 160.88 ± 33.97 mg/dL |
Özhan B. 2020 [81] | Cross-sectional | N = 40 obese children |
DVISS questionnaire: lower urinary tract dysfunction in 19% of cases. Metabolic lab tests were not correlated with the presence of urinary symptoms, only AN (a risk increase of 1.75-fold, p < 0.05) |
Karadag AS 2020 [43] | Cross-sectional | N1 = 336 patients with AN N2 = 243 healthy controls (AN-free) |
AN–BMI correlation (r = 0.299, p < 0.001) AN–DM not correlated (p = 0.43) Non-DM individuals: AN–WC correlation (r = 0.131, p = 0.24) AN–total cholesterol correlation (r = 0.155, p = 0.04) |
Lopez-Alvarenga JC. 2020. [72] | Cross-sectional | 670 Mexican American children (aged between 6 and 17 years, 49% females) |
AN: 33% AN heritability: 0.75 (p < 0.0001) AN: positive correlation with BMI, HOMA-IR, and CRP (p < 0.05) AN: negative correlation with HDL-cholesterol and physical fitness score |
Rodríguez-Gutiérrez R. 2020 [63] | Retrospective | 628 Mexican children with obesity |
IR: 79.3% MS: 55.4% AN was identified in 94.8% of individuals with IR |
Das RR. 2020 [73] | Cross-sectional | N = 545 children N1 = 119 patients with MS ( mean age: 11.27 ± 0.20 y) N2 = 426 patients without MS (mean age: 9.57 ± 0.12 y) | BMI: N1 = 23.54 ± 0.20 kg/m2 vs. N2 = 20.56 ± 0.11 kg/m2 (p < 0.01) WC: N1 = 79.77 ± 8.23 cm vs. N2 = 70.06 ± 7.81 cm (p < 0.01) FBG: N1 = 99.34 ± 0.54 mg/dL vs. N2 = 83.51 ± 0.30 mg/dL (p < 0.01) TG: N1 = 160.10 ± 1.55 mg/dL vs. N2 = 110.91 ± 1.10 mg/dL (p < 0.01) HDL-cholesterol: N1 = 35.80 ± 0.29 mg/dL vs. N2 = 44.11 ± 0.15 mg/dL (p < 0.01) LDL-cholesterol: N1 = 97.88 ± 0.81 mg/dL vs. N2 = 80.78 ± 0.46 mg/dL (p < 0.01) FI: N1 = 22.06 ± 0.64 mIU/L vs. N2 = 10.47 ± 0.21 mIU/L (p < 0.01) HOMA-IR: N1 = 5.47 ± 0.17 vs. N2 = 2.18 ± 0.04 AN + : N1 = 89.9% vs. N2 = 34.03% |
Singh SK. 2020 [61] | Cross-sectional | N = 70 patients with AN (mean age: 36.48 ± 10.70 y) N1 = 70 controls (mean age: 34.61 ± 11.53 y) | BMI: N = 27.36 ± 3.79 kg/m2 vs. N1 = 25.27 ± 3.55 kg/m2 (p = 0.001) WC: N = 96.48 ± 7.09 cm vs. N1 = 94.17 ± 6.79 cm HbA1c: N = 5.78 ± 0.71% vs. N1 = 5.55 ± 0.32% FG: N = 97.47 ± 23.76 mg/dL vs. N1 = 87.20 ± 9.41 mg/dL (p = 0.001) FI: N = 15.97 ± 10.10 μIU/mL vs. N1 = 10.38 ± 3.18μIU/mL (p = 0.013) HOMA-IR: N = 4.32 ± 4.44 vs. N1 = 2.27 ± 0.90 (p = 0.012) |
Rodríguez-Gutiérrez R. 2019 [62] | Retrospective | N1 = 178 infants with obesity without AN (mean age: 16.4 ± 4.8 months) N2 = 49 infants with obesity and AN (mean age: 16.1 ± 4.6 months) N = 227 infants (mean age: 16.4 ± 4.7 months) (control) | BMI: N = 16.47 ± 2.24 kg/m2 vs. N1 = 16.22 ± 1.74 kg/m2, respective vs. N2 = 17.38 ± 3.39 kg/m2 (p < 0.001) Family history of diabetes: N = 57.3% vs. N1 = 59%, respective vs. N2 = 51% FI: N1 = 2.42 ± 1.45 μU/mL vs. N2 = 3.67 ± 2.56 μU/mL (p= 0.005) FBG: N1 = 77 ± 9.9 mg/dL vs. N1 = 84.2 ± 12.6 mg/dL (p < 0.001) HOMA-IR: N1 = 0.46 ± 0.28 vs. N2 = 0.77 ± 0.54 (p = 0.001) |
Liimatta J. 2019 [68] | Longitudinal | N1 = 30 patients with premature adrenarche N2 = healthy controls |
Similar MS prevalence N1 vs. N2 IR: N1 > N2 (p = 0.014) AN: N1 > N2 (p = 0.01) |
das Merces MC. 2019 [55] | Multi-centric, population–based, cross-sectional | N = 1125 primary health care nurses |
MS prevalence: 24.4% Most frequent element of MS: low HDL-cholesterol MS-AN correlation (PR = 3.23, 95% CI between 2.65 and 3.92) |
Videira-Silva A. 2019 [59] | Cross-sectional | N = 139 overweight patients N1 = 67 patients with AN (mean age: 179 ± 19 months) N2 = 72 patients without AN (mean age: 170 ± 22 months) | BMI z-score: N1 = 2.51 ± 1.34 vs. N2 = 2.49 ± 0.87 WC: N1 = 102.4 ± 14.2 cm vs. N2 = 99.4 ± 12.8 cm FBG: N1 = 84.6 ± 8.2 mg/dL vs. N2 = 84.1 ± 6.5 mg/dL FI: N1 = 26.4 ± 16.3 μIU/mL vs. N2 = 19.0 ± 10.3 μIU/mL (p= 0.003) HOMA-IR: N1 = 5.59 ± 3.51 vs. N2 = 4.00 ± 2.29 (p= 0.003) Cholesterol: N1 = 159.5 ± 27.7 mg/dL vs. N2 = 152.8 ± 28.0 mg/dL TG: N1 = 94.5 ± 55.1 mg/dL vs. N2 = 79.0 ± 39.3 mg/dL Hyperinsulinemia: N1 = 70.2% vs. N2 = 47.2% IR: N1 = 62.7% vs. N2 = 38.9% |
Ribeiro FA. 2019 [69] | Longitudinal | N = 34 females with premature adrenarche |
At the age of final height: obesity (11.8%) High blood pressure (8.8%) Hyperinsulinemia (29.4%) Abnormal HOMA-IR (38.2%) AN (14.7%) |
Nithun TM. 2019 [74] | Cross-sectional | N = 60 with AN (aged between 2 and 24 y) | AN correlates with IR in normal weighted patients (p = 0.045) |
Mosimah CI. 2019 [54] | Cross-sectional | CARDIAC project: examination of 52,545 5th grade students in West Virginia to detect AN | AN prevalence: 4.5% of cases 79% of subjects with AN |
Palhares HMDC. 2018 [64] | Cross-sectional | N1 = 83 patients with AN (mean age: 11.7 ± 2.9 y) N2 = 78 patients without AN (mean age: 10.8 ± 3.1 y) | BMI: N1 = 27.4 ± 3.4 kg/m2 vs. N2 = 23.4 ± 3.6 kg/m2 HDL-cholesterol: N1 = 43.0 ± 10.7 mg/dL vs. N2 = 48.1 ± 10.8 mg/dL LDL-cholesterol: N1 = 102.8 ± 28.4 mg/dL vs. N2 = 99.4 ± 32.5 mg/dL TG: N1 = 86.0 mg/dL (41.0–286.0 mg/dL) vs. N2 = 83.0 mg/dL (31.0–445.0 mg/dL) FBG: N1 = 89.2 ± 10.5 mg/dL vs. N2 = 84.1 ± 12.5 mg/dL FI: N1 = 15.1 μUI/mL (4.6–117.2 μUI/mL) vs. N2 = 11.3 μUI/mL (1.4–35.7 μUI/mL) (p < 0.0001) HOMA-IR: N1 = 3.2 (0.8–28.7) vs. N2 = 2.3 (0.3–7.1) (p < 0.0001) |
González-Saldivar G. 2018 [58] | Cross-sectional | N = 294 patients (mean age: 20.2 ± 1.4 y) N1 = 145 patients without AN (mean age: 20.2 ± 1.4 y) N2 = 149 patients with AN (mean age: 20.3 ± 1.4 y) | BMI: N = 24.7 ± 4.7 kg/m2 vs. N1 = 23.4 ± 3.7 kg/m2 vs. N2 = 26.1 ± 5.2 kg/m2 (p < 0.001) WC: N = 81.7 ± 13.3 cm vs. N1 = 77.4 ± 11.6 cm, vs. N2 = 85.9 ± 13.6 cm (p < 0.001) FI: N1 = 8.6 ± 3.6 μU/mL vs. N2 = 13.5 ± 7.8 μU/mL HOMA-IR: N1 = 1.8 ± 0.8 vs. N2 = 2.9 ± 1.7 |
Margolis-Gil M. 2018 [65] | Longitudinal | N = 230 obese patients (with a BMI above 95th percentile), aged between 6 and 17.6 y | 20.9% met the criteria of MHU MHU patients had a higher IR, as defined by AN + higher HOMA-IR AN at baseline predicted MHU (follow-up for 1 y) (OR = 2.35, p = 0.35) |
Assunção SNF. 2018 [67] | Cross-sectional | N = 90 patients with AN N1 = 27 patients with obesity and AN(mean age: 11.4 ± 2.3 y) vs. N2 = 63 patients severely obese with AN (mean age: 12.2 ± 2.9 y) | BMI: N1 = 28.25 ± 3.5 kg/m2 vs. N2 = 33.57 ± 6.5 kg/m2 (p < 0.001) WC: N1 = 87.7 ± 9.1 cm vs. N2 = 98.3 ± 13.8 cm (p < 0.001) HbA1c high risk for DM: N1 = 33.3% vs. N2 = 66.7% |
First Author/ Year of Publication/ Reference No. | Type of Study | Studied Population | Cardio-Metabolic Correlations with AN |
---|---|---|---|
Calcaterra V. 2021 [101] | Retrospective | N = 138 patients with T1DM N1 = 7 patients with T1DM and AN N2 = 131 patients with T1DM without AN | BMI: N1 = 23.86 ± 4.95 kg/m2 vs. N2 = 20.56 ± 4.21 kg/m2 (p = 0.047) WC: N1 = 72.79 ± 18.92 cm vs. N2 = 69.80 ± 13.53 cm eGDR: N1 = 9.26 ± 2.01 mg kg−1 min−1 vs. N2 = 10.55 ± 1.52 mg kg−1 min−1 (p = 0.033) Total cholesterol: N1 = 165.64 ± 33.63 mg/dL vs. N2 = 185.00 ± 26.39 mg/dL |
Lin V. 2021 [105] | Transversal | N = 151 patients (aged between 10 and 14 y) (T2DM screening) | Patients with ≥ 95% percentile BMI and AN were more likely to have high GGT |
Barros BSV. 2021 [102] | Transversal | N = 1640 (Brazilian population with type 1 DM | MS: 29.8% MS-AN: OR = 5.93, p < 0.001 (self-reported color-race model) OR = 6.12, p < 0.001 (self-reported European genomic ancestry model) |
Álvarez-Villalobos NA. 202 [106] | Transversal | N = 320 patients (mean age of 49.3 y; 59.4% women) N1 = 80 with normal glucose profile N2 = 240 with hyperglycemia (pre-DM or DM) | AN: 43.6% (36.3% in N1, 49.6% in N2, p = 0.04) AN specificity to predict IR of 0.85 and 0.9, respectively AN positive predictive value of 0.86 and 0.96, respectively |
Trihan JE. 2020 [107] | Transversal | N = 213 p DM+ (mean age: 67.3 ± 11.9y) N1 = 77 patients with cutaneous signs (mean age: 66.2 ± 12.64y) N2 = 136 patients without cutaneous signs (mean age: 67.9 ± 11.35y) | AN+: N = 5 patients HbA1c: N = 7.16 ± 0.96% vs. N1 = 7.34 ± 0.93% vs. N2 = 7.05 ± 0.95% (p = 0.03) Macrovascular disease AN+: N = 5 patients (2.3%) (p = 0.024) |
Lascar N. 2019 [93] | Retrospective | N = 95 patients with T2DM | AN+: 11 patients (12.4%) BMI: 35.05 ± 9.54 kg/m2 WC: 112.5 ± 19.3 cm DM duration: 7.7 ± 3.8 y |
Ozlu E. 2018 [108] | Prospective | N = 600 patients N1 = 450 DM+ (mean age: 37.25 ± 11.37y) N2 = 150 controls (mean age: 35.67 ± 11.24y) | AN+: N1 = 213 (47.3%) vs. N2 = 5 (3.3%) (p < 0.001) BMI: N1 = 37.22 ± 6.07 kg/m2 vs. N2 = 22.23 ± 2.19 kg/m2 (p < 0.001) WC: N1 = 119.72 ± 12.98 cm vs. N2 = 82.37 ± 9.21 cm (p < 0.001) |
First Author/ Year of Publication/ Reference No. | Type of Study | Cardio-Metabolic Parameters | Hormonal Parameters |
---|---|---|---|
Abusailik MA. 2021 Cross-sectional study [129] | N = 146 females with PCOS N1 = 46 AN+ (31.5%) (mean age: 27.0 ± 4.3 y) N2 = 100 AN– (mean age: 26.0 ± 4.7 y) | BMI ≥ 25 kg/m2: N1 = 46 vs. BMI ≤ 24.9 kg/m2: N1 = 0 (p < 0.001) | High LH: N1 = 18 (39.1%) vs. N2 = 16 (16%) (p = 0.003) (n = 2.4–12.6 IU/L) High FSH: N1 = 1 (2.2%) vs. N2 = 3 (3.0%) (NR = 3.5–12.5 IU/L) High LH/FSH: N1 = 27 (58.7%) vs. N2 = 38 (38.0%) (p = 0.021) (NR < 2) High PRL: N1 = 3 (6.5%) vs. N2 = 5 (5.0%) (NR = 8.4–23.3 ng/mL) High TT: N1 = 12 (26.1%) vs. N2 = 16 (16.0%) (NR = 8.4–48.1 ng/dL) High FT: N1 = 3 (6.5%) vs. N2 = 1 (1.0%) (NR = 0.3–2 ρg/mL) |
Kamrul Hasan A. 2021 Cross-sectional study [119] | N = 175 women with PCOS (mean age: 16.8 ± 1.7 y) N1 = 136 (77.7%) AN+ vs. N2 = 39 (22.2%) AN– | BMI: N = 26.3 ± 5.6 kg/m2 WC: N = 85.6 ± 12.4 cm FG: N = 4.9 ± 0.8 mmol/L 2h OGTT G: N = 6.5 ± 1.6 mmol/L TG: N = 136.5 ± 47.6 mg/dL TC: N = 164.9 ± 31.4 mg/dL LDL-C: N = 99.4 ± 25.6 mg/dL HDL-C: N = 37.7 ± 7.5 mg/dL | Testosterone: N = 0.91 ng/mL (NR: 0.51–1.60 ng/mL) PRL: N = 14.97 ng/mL (9.63–22.43 ng/mL) |
Kazemi M. 2019 Cross-sectional study [118] | N = 279 women N1 = 237 PCOS+ N2 = 42 controls AN+ : N1 = 123 (51.9%) vs. N2 = 3 (7.1%) (p < 0.001) | BMI: N1 = 32.2 kg/m2 (31.1–33.3 kg/m2) vs. N2 = 23.6 kg/m2 (22.4–24.8 kg/m2) (p < 0.001) TG: N1 = 1.3 mmol/L (1.2–1.4 mmol/L) vs. N2 = 0.8 mmol/L (0.7–0.9 mmol/L) (p = 0.001) HDL-C: N1 = 1.3 mmol/L (1.3–1.3 mmol/L) vs. N2 = 1.6 mmol/L (1.5–1.7 mmol/L) (p < 0.001) FG: N1 = 5.0 mmol/L (4.9–5.1 mmol/L) vs. N2 = 4.8 mmol/L (4.8–4.9 mmol/L) (p = 0.05) FI: N1 = 14.3 μIU/mL (12.7–16.0 μIU/mL) vs. N2 = 5.0 μIU/mL (4.2–5.8 μIU/mL) (p < 0.001) 2hOGTT I: N1 = 79.6 μIU/mL (70.2–89.0 μIU/mL) vs. N2 = 35.8 μIU/mL (29.8–41.7 μIU/mL) (p < 0.001) 2hOGTT G: N1 = 6.2 mmol/L (5.9–6.5 mmol/L) vs. N2 = 4.8 mmol/L (4.5–5.1 mmol/L) (p < 0.001) HOMA-IR: N1 = 2.4 (2.1–2.7) vs. N2 = 0.8 (0.7–0.9) (p < 0.001) | LH/FSH: N1 = 2.2 (2.0–2.4) vs. N2 = 1.2 (0.9–1.4) (p < 0.001) (days 1–5 of MC) TT: N1 = 2.0 nmol/L (1.8–2.1 nmol/L) vs. N2 = 1.6 nmol/L (1.1–2.1 nmol/L) (p = 0.04) (days 1–5 of CM) SHBG: N1 = 38.7 nmol/L (35.5–41.9 nmol/L) vs. N2 = 61.3 nmol/L (53.1–69.4 nmol/L) (p < 0.001) (days 1–5 of MC) |
Zhang D. 2019 Randomized study [133] | N = 1000 women with PCOS undergoing ovulation induction | AN correlates with FI and HOMA-IR | LH/FSH did not correlate with FI or HOMA-IR |
Keen MA. 2017 Cross-sectional study [132] | N = 100 women with PCOS (mean age: 25.18 ± 3.61y) AN+ = 30% | BMI: N = 26.95 ± 4.50 kg/m2 | LH: N = 7.61 ± 5.34 IU/L (NR:1.9–12.5 IU/L) FSH: N = 4.29 ± 1.61 IU/L (NR:2.5–10.2 IU/L) LH/FSH: N = 1.88 ± 1.16 Testosterone: N = 58.59 ± 24.19 ng/dL (NR: 14–76 ng/dL) DHEAS: N = 124.34 ± 39.47 μg/dL (NR: 61.2–493.6 μg/dL) PRL: N = 15.21 ± 7.26 IU/L (NR: 2.8–29.2 IU/L) |
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Radu, A.-M.; Carsote, M.; Dumitrascu, M.C.; Sandru, F. Acanthosis Nigricans: Pointer of Endocrine Entities. Diagnostics 2022, 12, 2519. https://doi.org/10.3390/diagnostics12102519
Radu A-M, Carsote M, Dumitrascu MC, Sandru F. Acanthosis Nigricans: Pointer of Endocrine Entities. Diagnostics. 2022; 12(10):2519. https://doi.org/10.3390/diagnostics12102519
Chicago/Turabian StyleRadu, Andreea-Maria, Mara Carsote, Mihai Cristian Dumitrascu, and Florica Sandru. 2022. "Acanthosis Nigricans: Pointer of Endocrine Entities" Diagnostics 12, no. 10: 2519. https://doi.org/10.3390/diagnostics12102519
APA StyleRadu, A. -M., Carsote, M., Dumitrascu, M. C., & Sandru, F. (2022). Acanthosis Nigricans: Pointer of Endocrine Entities. Diagnostics, 12(10), 2519. https://doi.org/10.3390/diagnostics12102519