Correction: Sigala et al. A Comprehensive Investigation of Steroidogenic Signaling in Classical and New Experimental Cell Models of Adrenocortical Carcinoma. Cells 2022, 11, 1439.

The authors made the following changes to their paper [...].

COVID-19 in Fabry disease: a reference center prospective study.

BACKGROUND: During the coronavirus disease-19 (COVID-19) pandemic, vulnerable populations must be identified to prevent increased mortality. Fabry disease (FD) is a rare X-linked lysosomal storage disorder leading to chronic kidney disease (CKD), cardiomyopathy, pneumonopathy and premature strokes. Little is known whether SARS-CoV-2 infection bears a particular risk for FD patients. METHODS: During pandemic (02.2020-03.2021) we have regularly followed 104 unvaccinated FD patients. In 61/104, titre of serum antibodies against SARS-CoV-2 were measured and SARS-CoV-2 PCR test was performed in symptomatic patients or in case of positivity of other family members. The symptoms and duration of COVID-19 were reported by the patients or the treating physician. RESULTS: No deaths or intensive care unit hospitalizations occurred. 13/104 (12.5%) were diagnosed with SARS-CoV-2 infection (16.7% (4/24) men 12.2% (6/49) women of classic phenotype, 25% (3/12) of the men and 0% (0/8) of the women of later- onset phenotype). Of those, 2/13 (15.4%) patients-both kidney transplant recipients-developed severe COVID-19, were hospitalized, and required a high-flow oxygen mask. The rest either developed mild COVID-19 manifestations (8/13, 61.5%) or were asymptomatic (3/13, 23.1%). 2/13 (15.4%) of the patients experienced Fabry pain crisis and 3/13 (23.1%) long COVID-19 like symptoms. CONCLUSIONS: Similar to the general population, in FD patients the risk for severe COVID-19 seems to be driven by the immune system rather than by FD itself. Immunosuppression in kidney transplant recipients represented the highest risk in this population.

A Comprehensive Investigation of Steroidogenic Signaling in Classical and New Experimental Cell Models of Adrenocortical Carcinoma.

Adrenocortical carcinoma is a heterogeneous and aggressive cancer that originates from steroidogenic cells within the adrenal cortex. In this study, we have assessed for the preclinical gold standard NCI-H295 in direct comparison with the more recently established MUC-1 and a here newly reported ACC cell line (TVBF-7) the mutational status of important driver genes (TP53, MEN1, PRKAR1A, CTNNB1, APC, ZNRF-3, IGF-2, EGFR, RB1, BRCA1, BRCA2, RET, GNAS and PTEN), Wnt-signaling specificities (CTNNB1 mutation vs. APC mutation vs. wildtype), steroidogenic-(CYP11A1, CYP17A1, HSD3B2, HSD17B4, CYP21A2, CYP11B1, CYP11B2, MC2R, AT1R) and nuclear-receptor-signaling (AR, ER, GCR), varying electrophysiological potentials as well as highly individual hormone secretion profiles (Cortisol, Aldosterone, DHEA, DHEAS, Testosterone, 17-OH Progesterone, among others) which were investigated under basal and stimulated conditions (ACTH, AngII, FSK). Our findings reveal important genetic and pathophysiological characteristics for these three cell lines and reveal the importance of such cell-line panels reflecting differential endocrine functionalities to thereby better reflect clinically well-known ACC patient heterogeneities in preclinical studies.

Can dysglycemia in OGTT be predicted by baseline parameters in patients with PCOS?

Background: Polycystic ovary syndrome (PCOS) is considered a risk factor for the development of type 2 diabetes mellitus (T2DM). However, which is the most appropriate way to evaluate dysglycemia in women with PCOS and who are at increased risk are as yet unclear. Aim of the study: To determine the prevalence of T2DM, impaired glucose tolerance (IGT), and impaired fasting glucose (IFG) in PCOS women and potential factors to identify those at risk. Subjects and methods: The oral glucose tolerance test (OGTT), biochemical/hormonal profile, and ovarian ultrasound data from 1614 Caucasian women with PCOS and 362 controls were analyzed in this cross-sectional multicenter study. The data were categorized according to age and BMI. Results: Dysglycemia (T2DM, IGT, and IFG according to World Health Organization criteria) was more frequent in the PCOS group compared to controls: 2.2% vs 0.8%, P = 0.04; 9.5% vs 7.4%, P = 0.038; 14.2% vs 9.1%, P = 0.002, respectively. OGTT was essential for T2DM diagnosis, since in 88% of them basal glucose values were inconclusive for diagnosis. The presence of either T2DM or IFG was irrespective of age (P = 0.54) and BMI (P = 0.32), although the latter was associated with IGT (P = 0.021). There was no impact of age and BMI status on the prevalence of T2DM or IFG. Regression analysis revealed a role for age, BMI, fat deposition, androgens, and insulin resistance for dysglycemia. However, none of the factors prevailed as a useful marker employed in clinical practice. Conclusions: One-third of our cohort of PCOS women with either T2DM or IGT displayed normal fasting glucose values but without confirming any specific predictor for dysglycemic condition. Hence, the evaluation of glycemic status using OGTT in all women with PCOS is strongly supported.

Endocrine disorders in patients with Fabry disease: insights from a reference centre prospective study.

CONTEXT: Fabry Disease (FD) is a rare X-linked storage disease characterised by a-galactosidase A deficiency and diffuse organ accumulation of glycosphingolipids. Enzyme replacement and chaperone therapies are only partially effective. It remains unclear if FD-related endocrine disorders contribute to the observed morbidity. OBJECTIVE: To investigate the function of the endocrine system in patients with FD. DESIGN: We conducted an observational prospective study from 2017 to 2020. SETTING AND PATIENTS: We included 77 patients with genetically confirmed FD (27 men, 20/27 Classic, 7/26 Late Onset phenotype, 50 women, 41/50 and 9/50 respectively), who are systematically followed by our reference centre. RESULTS: 36/77 (46.8%) patients had VitD deficiency (25(0H)VitD <20 µg/L) despite the fact that 19/36 (52.8%) were substituted with cholecalciferol. Only 21/77 (27.3%) patients had normal VitD levels without VitD substitution. 11/77 (14.3%) had significant hypophosphatemia (p < 0.80 mmol/L). Three new cases (3.9%) of subclinical, two (2.6%) of overt and six (7.8%) of known hypothyroidism were identified. Of note, men had significantly higher renin levels than women [61.4 (26.1-219.6) vs.25.4 (10.9-48.0) mU/L, p = 0.003]. There were no major abnormalities in adrenal, growth and sex-hormone axes. Patients of Classic phenotype had significantly higher High-Density Lipoprotein Cholesterol (HDL-C) levels (p = 0.002) and in men those levels were positively correlated with globotriaosylsphingosin (Lyso-Gb3) values. 10/77 (13%) of the patients were underweight. CONCLUSIONS: VitD supplementation should be considered for all patients with FD. Thyroid screening should be routinely performed. Malnutrition should be prevented or treated, particularly in Classic phenotype patients. Overall, our data suggest that FD specialists should actively seek and diagnose endocrine disorders in their patients.

Treatment of alopecia totalis/universalis/focalis with vitamin D and analogs: Three case reports and a literature review.

BACKGROUND: Alopecia areata (AA) is an inflammatory disease with autoimmune, environmental, and inherited components directed at the hair follicle, either limited to patchy hair loss over the scalp (Focalis, AF), total loss of scalp hair (Totalis, AT), or total loss of both scalp and body hair (Universalis, AU). Despite multiple treatment modalities, no therapy exists. Vitamin D deficiency in patients with AA/AT/AF influences disease severity and duration, inversely correlating with inflammation histologically. CASE SUMMARY: Three girls presented with AT (P1), AU (P2), and AF (P3) at the ages of 1, 5, and 5 years, respectively. For P1-P2, all available treatments implemented for 2 years had failed. We started an initial 6-mo repletion with oral cholecalciferol 2000/4000 IU/d, with no apparent effect. Then we attempted immunomodulation using oral calcitriol and its analog paricalcitol. On calcitriol, 0.5 mcg/d P1 regrew hair within 6 mo. After 4 years, a relapse with loss of eyebrow hair was resolved after doubling the calcitriol dose to 0.5 mcg × 2/d; the results have been maintained for 6 years to date. On calcitriol, 0.25 mcg × 3/d P2 led to the development of asymptomatic hypercalcemia-hypercalciuria, which was immediately resolved by switching to paricalcitol 2 mcg × 3/d; mild tolerable hypercalciuria was maintained. Hair regrowth was observed at 6 mo, stabilizing only as fur at 12 mo. AF in P3 was resolved completely within 3 mo on a daily high dose (8000 IU) of cholecalciferol. CONCLUSION: Vitamin D may have immunomodulating therapeutic impact on AT/AU/AF, which needs to be explored with further pilot clinical trials.

Novel Insights into the Molecular Regulation of Ribonucleotide Reductase in Adrenocortical Carcinoma Treatment.

Current systemic treatment options for patients with adrenocortical carcinomas (ACCs) are far from being satisfactory. DNA damage/repair mechanisms, which involve, e.g., ataxia-telangiectasia-mutated (ATM) and ataxia-telangiectasia/Rad3-related (ATR) protein signaling or ribonucleotide reductase subunits M1/M2 (RRM1/RRM2)-encoded ribonucleotide reductase (RNR) activation, commonly contribute to drug resistance. Moreover, the regulation of RRM2b, the p53-induced alternative to RRM2, is of unclear importance for ACC. Upon extensive drug screening, including a large panel of chemotherapies and molecular targeted inhibitors, we provide strong evidence for the anti-tumoral efficacy of combined gemcitabine (G) and cisplatin (C) treatment against the adrenocortical cell lines NCI-H295R and MUC-1. However, accompanying induction of RRM1, RRM2, and RRM2b expression also indicated developing G resistance, a frequent side effect in clinical patient care. Interestingly, this effect was partially reversed upon addition of C. We confirmed our findings for RRM2 protein, RNR-dependent dATP levels, and modulations of related ATM/ATR signaling. Finally, we screened for complementing inhibitors of the DNA damage/repair system targeting RNR, Wee1, CHK1/2, ATR, and ATM. Notably, the combination of G, C, and the dual RRM1/RRM2 inhibitor COH29 resulted in previously unreached total cell killing. In summary, we provide evidence that RNR-modulating therapies might represent a new therapeutic option for ACC.

Risk of type 2 diabetes mellitus in polycystic ovary syndrome is associated with obesity: a meta-analysis of observational studies.

PURPOSE: The exact risk of type 2 diabetes mellitus (T2DM) in women with polycystic ovary syndrome (PCOS) is unknown. It is also unclear if obesity independently increases T2DM risk in this population. The aim of this study was to systematically review and synthesize the best available evidence regarding the association between PCOS and T2DM, stratified according to obesity status. METHODS: A comprehensive search was conducted in PubMed, CENTRAL and Scopus databases up to October 31, 2020. Data are expressed as relative risk (RR) with 95% confidence interval (CI). The I2 index was employed for heterogeneity. RESULTS: The eligibility criteria were fulfilled by 23 studies (319,780 participants; 60,336 PCOS and 8847 type 2 diabetes cases). Women with PCOS demonstrated a higher risk of T2DM than those without PCOS (RR 3.45, 95% CI, 2.95-4.05, p < 0.001; I2 81.6%). This risk remained significant both in studies matched or unmatched for participants' age. With regard to body mass index (BMI), the RR for developing T2DM in obese and non-obese PCOS women compared with their non-PCOS counterparts was 3.24 (95% CI 2.25-4.65; p < 0.001; I2 30.9%) and 1.62 (95% CI 0.14-18.50; p = 0.70; I2 89.9%), respectively. The RR for developing T2DM was 3.85 (95% CI 1.99-7.43; p < 0.001; I2 46.2%) in obese compared with non-obese women with PCOS. This was also the case for overweight compared with lean women with PCOS. CONCLUSIONS: Women with PCOS present an increased risk of T2DM compared with non-PCOS women only if they are obese/overweight.

Premature Adrenarche and its Association with Cardiovascular Risk in Females.

Early activation of the adrenal zona reticularis, leading to adrenal androgen secretion, mainly dehydroepiandrosterone sulfate (DHEAS), is called premature adrenarche (PA). The fact that adrenal hyperandrogenism in females has been linked to a cluster of cardiovascular (CV) risk factors, even in prepubertal children, warrants investigation. Controversial results have been obtained in this field, probably due to genetic, constitutional, and environmental factors or differences in the characteristics of participants. In an attempt to understand, in depth, the impact of PA as a potential activator of CV risk, we critically present available data stratified according to pubertal status. It seems that prepubertally, CV risk is increased in these girls, but is somewhat attenuated during their second decade of life. Furthermore, different entities associated with PA, such as polycystic ovary syndrome, non-classical congenital adrenal hyperplasia, heterozygosity of CYP21A2 mutations, and the impact of DHEAS on CV risk, are reviewed. At present, firm and definitive conclusions cannot be drawn. However, it may be speculated that girls with a history of PA display a hyperandrogenic hormonal milieu that may lead to increased CV risk. Accordingly, appropriate long-term follow-up and early intervention employing a patient-oriented approach are recommended.

Anemia and Systemic Inflammation Rather than Arterial Circulatory Dysfunction Predict Decompensation of Liver Cirrhosis.

BACKGROUND: While systemic inflammation is recognized as playing a central role in the pathogenesis of organ failures in patients with liver cirrhosis, less is known about its relevance in the development of classical hepatic decompensation. AIM: To characterize the relationship between systemic inflammation, hemodynamics, and anemia with decompensation of liver cirrhosis. METHODS: This is a post-hoc analysis of a cohort study of outpatients with advanced liver fibrosis or cirrhosis. RESULTS: Analysis included 338 patients of whom 51 patients (15%) were hospitalized due to decompensation of liver cirrhosis during a median follow-up time of six months. In univariate analysis, active alcoholism (p = 0.002), model of end-stage liver disease (MELD) score (p = 0.00002), serum IL-6 concentration (p = 0.006), heart rate (p = 0.03), low arterial blood pressure (p < 0.05), maximal portal venous flow (p = 0.008), and low hemoglobin concentration (p < 0.00001) were associated with hospitalization during follow-up. Multivariate analysis revealed an independent association of low hemoglobin (OR = 0.62, 95% CI = 0.51-0.78, p = 0.001) and serum IL-6 concentration (OR = 1.02, 95% CI = 1.01-1.04, p = 0.03)-but not of hemodynamic parameters-with hepatic decompensation. An inverse correlation between hemoglobin concentration and portal venous flow (R = -0.362, p < 0.0001) was detected for the non-hospitalized patients. Accuracy of baseline hemoglobin levels for predicting hospitalization (AUC = 0.84, p < 0.000001) was high. CONCLUSION: Anemia and systemic inflammation, rather than arterial circulatory dysfunction, are strong and independent predictors of hepatic decompensation in outpatients with liver cirrhosis.

Current Management and Outcome of Pregnancies in Women With Adrenal Insufficiency: Experience from a Multicenter Survey.

CONTEXT: Appropriate management of adrenal insufficiency (AI) in pregnancy can be challenging due to the rarity of the disease and lack of evidence-based recommendations to guide glucocorticoid and mineralocorticoid dosage adjustment. OBJECTIVE: Multicenter survey on current clinical approaches in managing AI during pregnancy. DESIGN: Retrospective anonymized data collection from 19 international centers from 2013 to 2019. SETTING AND PATIENTS: 128 pregnancies in 113 women with different causes of AI: Addison disease (44%), secondary AI (25%), congenital adrenal hyperplasia (25%), and acquired AI due to bilateral adrenalectomy (6%). RESULTS: Hydrocortisone (HC) was the most commonly used glucocorticoid in 83% (97/117) of pregnancies. Glucocorticoid dosage was increased at any time during pregnancy in 73/128 (57%) of cases. In these cases, the difference in the daily dose of HC equivalent between baseline and the third trimester was 8.6 ± 5.4 (range 1-30) mg. Fludrocortisone dosage was increased in fewer cases (7/54 during the first trimester, 9/64 during the second trimester, and 9/62 cases during the third trimester). Overall, an adrenal crisis was reported in 9/128 (7%) pregnancies. Cesarean section was the most frequent mode of delivery at 58% (69/118). Fetal complications were reported in 3/120 (3%) and minor maternal complications in 15/120 (13%) pregnancies without fatal outcomes. CONCLUSIONS: This survey confirms good maternal and fetal outcome in women with AI managed in specialized endocrine centers. An emphasis on careful endocrine follow-up and repeated patient education is likely to have reduced the risk of adrenal crisis and resulted in positive outcomes.

Unfavorable Hormonal and Psychologic Profile in Adult Women with a History of Premature Adrenarche and Pubarche, Compared to Women with Polycystic Ovary Syndrome.

If circulating adrenal androgens levels rise before the age of 8 years in girls, this phenomenon is termed premature adrenarche (PA), while the concomitant appearance of pubic hair is called premature pubarche (PP). Girls with PA-PP display an unfavorable hormonal profile compared to their normal peers and have an increased risk of developing polycystic ovary syndrome (PCOS) features peripubertally. However, the sequelae of premature adrenarche remains unclear. We assessed metabolic, hormonal, psychologic profiles, and ovarian morphology in 21 women of mean age (±SD) 21.3±3.3 years, BMI: 23.6±4.4 kg/m2 with PA-PP, 45 women with PCOS and 26 controls, matched for age and BMI. PA-PP women displayed a favorable lipid profile compared to PCOS and controls. Insulin resistance index (HOMA-IR), however, were similar in PA-PP and PCOS women (2.09±1.42, 2.08±0.83) and higher than controls (1.13±0.49, p <0.05). Circulating androstenedione levels did not differ between PA-PP and PCOS women (0.11±0.05 vs. 0.12±0.03), but was higher than that of controls (0.02±0.0 nmol/l, p <0,05). Ovarian volume was increased in PA-PP and PCOS (11.14±3.3 vs. 10.99±4.61) compared to controls (6.74±1.83 cm3). PA-PP women had a higher score of state/trait anxiety and depressive and eating disorder symptoms than controls, with a pattern that matched that of PCOS women. Only 14% of the PA-PP group fulfilled the Rotterdam PCOS criteria. Some women with a history of PA-PP displayed hormonal and psychologic profile similar to PCOS, and accordingly a regular monitoring of these girls during adulthood is advised.

Management of the Female With Non-classical Congenital Adrenal Hyperplasia (NCCAH): A Patient-Oriented Approach.

Non-classical congenital adrenal hyperplasia (NCCAH) is considered to be a common monogenic inherited disease, with an incidence range from 1:500 to 1:100 births worldwide. However, despite the high incidence, there is a low genotype-phenotype correlation, which explains why NCCAH diagnosis is usually delayed or even never carried out, since many patients remain asymptomatic or are misdiagnosed as suffering from other hyperandrogenic disorders. For affected adolescent and adult women, it is crucial to investigate any suspicion of NCCAH and determine a firm and accurate diagnosis. The Synacthen test is a prerequisite in the event of clinical suspicion, and molecular testing will establish the diagnosis. In most cases occurring under 8 years of age, the first symptom is premature pubarche. In some cases, due to advanced bone age and/or severe signs of hyperandrogenism, initiation of hydrocortisone treatment prepubertally may be considered. Our unifying theory of the hyperandrogenic signs system and its regulation by internal (hormones, enzymes, tissue sensitivity) and external (stress, insulin resistance, epigenetic, endocrine disruptors) factors is presented in an attempt to elucidate both the prominent genotype-phenotype heterogeneity of this disease and the resultant wide variation of clinical findings. Treatment should be initiated not only to address the main cause of the patient's visit but additionally to decrease abnormally elevated hormone concentrations. Goals of treatment include restoration of regular menstrual cyclicity, slowing the progression of hirsutism and acne, and improvement of fertility. Hydrocortisone supplementation, though not dexamethasone administration, could, as a general rule, be helpful, however, at minimum doses, and also for a short period of time and, most likely, not lifelong. On the other hand, in cases where severe hirsutism and/or acne are present, prescription of oral contraceptives and/or antiandrogens may be advisable. Furthermore, women with NCCAH commonly experience subfertility, therefore, there will be analysis of the appropriate approach for these patients, including during pregnancy, based mainly on genotype. Besides, we should keep in mind that since the same patient will have changing requirements through the years, the attending physician should undertake a tailor-made approach in order to cover her specific needs at different stages of life.

Levothyroxine Replacement Therapy and Overuse: A Timely Diagnostic Approach.

BACKGROUND: Levothyroxine (LT4) is one of the most prescribed drugs worldwide. Once started, approximately 90% of patients continue treatment long term. However, accumulating evidence suggests that many patients, for whom the indication for its administration is not adequately established and the diagnosis is not well documented, are overusing it. This study aimed to evaluate the necessity for and determine potential prognostic factors of long-term LT4 supplementation. METHODS: A prospective clinical cohort follow-up study was carried out. In 291 subjects (84% females) aged 48 ± 16 years on LT4 replacement therapy without a solid diagnosis of hypothyroidism being provided, the treatment was paused. At the beginning and after six to eight weeks of treatment discontinuation, thyrotropin (TSH) and free thyroxine levels were assessed, and thyroid ultrasound was performed. A TSH value of ≥4.5 IU/mL was considered as underlying hypothyroidism. RESULTS: Among the 291 individuals, 114 became hypothyroid (group A), while 177 subjects remained euthyroid off LT4 (group B; 39.2% vs. 60.8%, p < 0.001). The groups were comparable regarding sex, family history, age, body mass index, duration of treatment, basal TSH and free thyroxine values, thyroid volume, and presence of thyroid autoantibodies. However, diffuse inhomogeneous echogenicity on ultrasound examination was significantly higher (p < 0.001) in group A. CONCLUSIONS: These findings suggest considerable overuse of thyroxine therapy. The results underline the initial need to establish the diagnosis firmly before treatment initiation and to undertake periodic evaluation of all patients on chronic LT4 treatment as to the necessity for treatment continuation. In all patients on long-term LT4 therapy in whom the diagnosis has not been definitively established, it appears rational to introduce a six- to eight-week period of LT4 replacement therapy discontinuation, preceded and followed by TSH tests, as the first-line approach-a procedure that could be implemented as part of a common strategy among the scientific community to decrease current LT4 overuse.

Heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A1) can cause transient adrenal insufficiency and life-threatening failure to thrive.

The first and rate-limited step of steroidogenesis in all steroidogenic tissues is the conversion of cholesterol to pregnenolone, catalysed by P450scc side-chain cleavage enzyme (CYP11A1 gene-SCC). SCC deficiency has been characterised as an autosomal recessive disorder, although it may also be inherited as an autosomal dominant trait in humans. Here, we describe a family of three members carrying the same novel heterozygous CYP11A1 mutation, a c.235G > A missense variant in exon 1: pVal79Ile. A 46 XY boy (P1) was presented at the age of 3 months with early onset adrenal insufficiency and life-threatening failure to thrive, with low adrenal androgens but normal external genitalia. Five years later, the parents had twin girls, one of whom (P2) presented acute adrenal crisis a few hours after birth. The father (P3), born at term, was reported as having suffered from failure to thrive during the neonatal period, though not his only male sibling. This report of severe early adrenal insufficiency caused by a heterozygous mutation of the CYP11A1 gene clearly demonstrates that SCC deficiency may be inherited as an autosomal dominant trait in humans.

Successful Treatment of Severe Atopic Dermatitis with Calcitriol and Paricalcitol in an 8-Year-Old Girl.

Atopic dermatitis (AD) is a chronic inflammatory disease affecting children and adolescence. The traditional therapeutic options for AD, including emollients topically and immune modulatory agents systemically focusing on reducing skin inflammation and restoring the function of the epidermal barrier, are proven ineffective in many cases. Several studies have linked vitamin D supplementation with either a decreased risk to develop AD or a clinical improvement of the symptoms of AD patients. In this report, we present a girl with severe AD who under adequate supplementation with cholecalciferol was treated with calcitriol and subsequently with paricalcitol. She had significant improvement-almost healing of her skin lesions within 2 months, a result sustained for more than 3 years now. Because of hypercalciuria as a side effect from calcitriol therapy, treatment was continued with paricalcitol, a vitamin D analogue used in secondary hyperparathyroidism in chronic kidney disease. Calcitriol therapy may be considered as a safe and efficacious treatment option for patients with severe AD, particularly for those with refractory AD, under monitoring for possible side effects. Treatment with paricalcitol resolves hypercalciuria, is safe, and should be further investigated as an alternative treatment of atopic dermatitis and possibly other diseases of autoimmune origin.

Acute Bilateral Cataract in Type 1 Diabetes Mellitus.

We report a case of a 17-year old boy, who presented acute bilateral cataract and complete vision loss within six days, three months after the diagnosis of Type 1 Diabetes Mellitus (T1DM) under optimal metabolic control (HbA1c 6%). At presentation (HbA1c 10.4%) and after correction of diabetic ketoacidosis (pH 6.917) and the beginning of intensified insulin treatment with insulin glargine once daily and insulin aspart before meals,the patient underwent full ophthalmologic examination,which was completely normal. Only few cases with acute bilateral cataract - all relatively shortly after the diagnosis of T1DM - have been reported. Several hypotheses have been drawn but the exact mechanism of this phenomenon remains unclear. The interesting finding in our case was the clearly elevated insulin autoantibodies (IAA) at the time of cataract formation, negative however at presentation. The relation between the elevation of IAA and cataract formation should be further investigated in diabetic patients.