Sodium-Glucose Cotransporter 2 Inhibitor (SGLT2i) Associated Diabetic Ketoacidosis in Oncology Patients: A Case Series and Literature Review.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) use is associated with an increased risk of diabetic ketoacidosis (DKA). The clinical data regarding the use of SGLT2i and its potential side effects in oncology patients is limited. We are retrospectively reporting four oncology patients with type 2 diabetes mellitus using SGLT2i who were admitted with DKA. The mean age of the patients was 61.25 years, and male to female ratio was 1:1. The duration of type 2 diabetes ranged from 10 to 20 years (mean 15.75 years) and the types of SGLT2i used were empagliflozin 25 mg and dapagliflozin 10 mg. The types of malignancy in our case series included squamous cell carcinoma of the cheek, ovarian cancer, and two patients had laryngeal carcinoma (squamous cell carcinoma). Diabetic ketoacidosis was diagnosed in three patients following chemotherapy or concurrent chemo-radiotherapy. Poor oral intake and infections were the main risk factors in our patients. Mean blood glucose level, anion gap, and bicarbonate level were 11.7 mmol/l, 32.25, and 5 mmol/l, respectively. The majority had moderate DKA based on pH (mean 7.13). The hospital course was complicated by acute kidney injury (n=4), infections (n=4) (urinary tract infections, and pneumonia), and three patients required critical care. The mean length of hospitalization was 19.2 days and no mortality was reported among our patients. SGLT2i-related DKA is an emerging complication recognized in oncology patients. Some of the risk factors for this complication are starvation, poor oral intake, and infection which are quite prevalent in oncology patients. Temporary holding of SGLT2i medication during this period might have a potential preventive role.

Hypergonadotropic Hypogonadism Due to Transaldolase Deficiency: Two Cases and Literature Review.

Transaldolase deficiency is a rare autosomal recessive inborn error of carbohydrate metabolism caused by pathogenic/likely pathogenic biallelic mutations in the TALDO1 gene. This disorder is characterized by multisystem involvement with variable phenotypes, including intrauterine growth restriction; dysmorphic features; abnormal skin; hepatosplenomegaly; cytopenia; and cardiac, renal, and endocrine abnormalities. Herein, we present two Emirati patients with hypergonadotropic hypogonadism due to transaldolase deficiency and variable phenotypes of systemic involvement.

Impulse control disorders in patients with dopamine agonist-treated pituitary adenomas: a cross-sectional multicenter study.

BACKGROUND: Impulse control disorders (ICDs) have been described as underrecognized side effects of dopamine agonists (DAs) in neurological disorders but are not sufficiently understood in endocrine conditions. OBJECTIVE: To identify the prevalence of DAs induced ICDs and determine potential risk factors related to these disorders in patients with prolactinoma and non-function pituitary adenomas (NFPAs). METHODS: This is a cross-sectional multicenter study involving 200 patients with prolactinoma and NFPAs, who received follow-ups in tertiary referral centers. DA-induced ICDs were assessed using ICD questionnaires modified from prior studies. RESULT: At least one ICD was reported by 52% of participants, among whom 28.5% mentioned compulsive shopping, 24.5% punding, and 24.5% hypersexuality. Furthermore, 33% of the patients reported the presence of one type of ICD behavior, while 12% specified two and 7% had three types of such behavior. The multivariable logistic regression showed that the significant risk factors of ICD were younger age (adjusted odds ratio [AOR]: 0.92, 95% confidence interval [CI]: 0.88-0.97, p 0.001), being single (AOR: 0.15, 95%CI: 0.03-0.84, p 0.03), and a positive history of psychiatric illness (AOR: 7.67, 95% CI: 1.37-42.97, p 0.021). CONCLUSION: ICDs with a broad range of psychiatric symptoms are common in individuals with DA-treated prolactinoma and NFPAs. Endocrinologists should be aware of this potential side effect, particularly in patients with a personal history of psychiatric disorder.

Rare Coexistence of Acute Intermittent Porphyria With Systemic Lupus Erythematous: Case Report and Literature Review.

Porphyrias, particularly acute intermittent porphyria (AIP), are rare, inherited disorders of heme synthesis. On the other hand, systemic lupus erythematosus (SLE) is an uncommon autoimmune disease that affects women predominantly. The coexistence of AIP and SLE is rare. We report a case of concomitant diagnosis of AIP and SLE in a 21-year-old woman who presented with recurrent acute abdominal, chest, and back pain associated with nausea and vomiting, followed by arthralgia, multiple joint pain, and rash. Investigations revealed severe hyponatremia related to SIADH (syndrome of inappropriate antidiuretic hormone secretion) with a positive SLE antibody panel and a positive urine screen for porphobilinogen. Molecular test confirmed the diagnosis of AIP with a pathogenic mutation in the HMBS gene.

Clinical Characteristics and Outcomes of Diabetic Ketoacidosis in Patients With Type 2 Diabetes using SGLT2 Inhibitors.

Background: Sodium glucose cotransporter 2 inhibitors (SGLT2i) use is associated with an increased risk of diabetic ketoacidosis (DKA). Objective: This study evaluated and compared the DKA characteristics and outcomes of users and non-users of SGLT2i. Methods: We retrospectively studied patients with type 2 diabetes mellitus (T2DM) admitted with DKA to Tawam Hospital, Al Ain City, UAE between January 2017 and March 2021. Demographic data, clinical, and laboratory findings were extracted from the electronic medical records. Results: A total of 55 patients with T2DM (62% UAE nationals, 50% women) were admitted with DKA. The average age was 54.0 ± 18.9 years and average diabetes duration of 15.7 ± 15.1 years. Seventeen patients (31%) were using SGLT2i. Infection was the main precipitating factor for DKA in (8 out of 17) SGLT2i users. Compared to non-users, SGLT2i users had lower systolic blood pressure (119.9 vs 140 mmHg; P = .012) and serum glucose levels (16.2 vs 24.9 mmol/L; P < .001) and higher Na level (137.5 vs 132.6 mmol/L; P = .005). Additionally, 56.3% of SGLT2i users had euglycemic DKA compared to 2.6% of nonusers (P < .001). Acute kidney injury (AKI) occurred more in SGLT2i users compared to non-users (94.1% vs 67.6%, P = .043). Further analysis revealed that SGLT2i users were about five times more likely to have prolonged hospital length of stay (⩾14 days) when compared with non-users (adjusted OR: 4.84; P = .035). Overall, there was no difference between the two groups with regards to DKA complications and mortality. Conclusions: SGLT2i related DKA is associated with lower blood glucose levels, lower SBP, worse hypovolemia, increased risk of AKI, and longer hospital stay when compared to non SGLT2i related episodes. Since the benefits of SGLT2 inhibitors far outweigh potential risks, there is a need to raise healthcare professionals and patients' awareness about this potential association.

Continuous subcutaneous insulin infusion is associated with a better glycemic control than multiple daily insulin injections without difference in diabetic ketoacidosis and hypoglycemia admissions among Emiratis with Type 1 diabetes.

AIMS: To characterizes Emiratis patients with Type 1 diabetes (T1D) and compares outcomes between continuous subcutaneous insulin infusion (CSII) versus multiple daily insulin injections (MDI) users. The WHO-Five Well-Being Index (WHO-5) score was used to screen for depression. METHODS: In this cross-sectional study; sociodemographic, clinical characteristics and insulin replacement regimens were collected on patients with T1D between 2015-2018. RESULTS: 134 patients with mean age of 20.9±7.5 years were included. Females constitute 56.7% and 50.7% had diabetes duration of >10 years. Diabetic ketoacidosis (DKA) at presentation was reported in 46.3%. Average glycemic control over preceding 12months was satisfactory (less than 7.5%), suboptimal (7.5-9%), and poor (more than 9%) in 26.6%, 42.7% & 30.6% of the patients, respectively. Higher proportion of patients using CSII achieved satisfactory or suboptimal glycemic control compared to patients with MDI (P = 0.003). The latest median /IQR HbA1c was significantly lower (P = 0.041) in patients using CSII (8.2 /1.93%) compared to MDI (8.5/2.45%). There was no significant difference between two groups in DKA, severe hypoglycemia or total WHO-5 score. CONCLUSIONS: CSII usage was associated with better glycemic control than MDI, although no difference in DKA and severe hypoglycemia. The overall glycemic control among Emiratis subjects with T1D is unsatisfactory and needs more rigorous patient counseling and education.

Relationship between lipid profile, inflammatory and endothelial dysfunction biomarkers, and type 1 diabetes mellitus: a case-control study.

OBJECTIVE: Inflammation is a major factor in endothelial dysfunction (ED) which is the earliest predictor of cardiovascular disease and premature mortality in type 1 diabetes mellitus (T1DM) patients. This study aimed to describe the possible relationship between plasma lipids and inflammatory and ED biomarkers in young Emirati patients with and without T1DM. METHODS: This case-control study included 158 patients with T1DM and 157 healthy controls from the local population of the United Arab Emirates (UAE). Anthropometric data, clinical variables, lipid profiles, liver enzymes, HbA1c, inflammatory, and ED biomarkers were measured for all participants using sophisticated techniques and assays. RESULTS: The mean ages ± SD of patients with T1DM and healthy controls was 19.3 ± 6.4 years (59.5% females) and 9.2 ± 6.8 years (61.5% females), respectively. The mean duration of T1DM was 9.3 ± 5.7 years, with HbA1c of 8.9 ± 2.1%. BMI, WC, SBP, and DBP significantly differed between the two groups. The mean lipid profiles (HDL, TG, TC, ApoA, and ApoB), liver enzymes (GGT, ALT), inflammatory (IL-6, adiponectin, TNF-α, hs-CRP), and ED biomarker levels (ICAM-1, VCAM-1, selectin, and ET-1) were also significantly different between patients and controls. Based on Spearman's rank and logistic regression analysis, there was a significant association between elevated lipid profile, liver enzymes, inflammatory markers, and ED markers in T1DM patients compared to controls. Among the biomarkers studied, ApoA, ApoB, and TC were significantly increased in T1DM patients compared to controls. CONCLUSION: This study revealed a strong association between an elevated lipid profile and inflammatory and ED markers with T1DM, which could lead to cardiovascular events in the UAE population.

Severe Prolonged SGLT2i-induced Euglycemic Diabetic Ketoacidosis Refractory to Standard Therapy and Dialysis: Case Report and Literature Review.

Sodium-glucose cotransporter type 2 inhibitors (SGLT2i) are oral hypoglycemic agents that have insulin-independent glucose-lowering effects mediated by increasing the renal excretion of glucose by inhibiting the SGLT2-mediated renal glucose reabsorption. An increasingly recognized complication induced by SGLT2i is euglycemic diabetic ketoacidosis (eDKA). Here, we describe the case of a 26-year-old male patient with type 2 diabetes mellitus and morbid obesity. Prior to presentation he was on multiple oral hypoglycemic agents including SGLT2i. He developed life-threatening severe prolonged eDKA associated with SGLT2i (Canagliflozin), precipitated by adenovirus infection. The acidosis was not responding to standard DKA therapy and renal replacement therapy but was managed effectively with insulin titration based on capillary ketone measurements. After reviewing the literature on severe prolonged eDKA induced by SGLT2 and treatment modalities used, we present previously reported cases similar to ours.

Clinical and biochemical characteristics of diabetic ketoacidosis in adults with type 1 or type 2 diabetes at a tertiary hospital in the United Arab Emirates.

Background: Diabetes ketoacidosis (DKA) is a well-known acute complication of diabetes. This study aims to describe the sociodemographic, clinical, and biochemical characteristics of adult patients with different diabetes types and DKA severities attending a tertiary hospital in the UAE. Methods: We retrospectively extracted sociodemographic, clinical, and laboratory data from the electronic medical records of 220 adult patients with DKA admitted to Tawam Hospital between January 2017 and October 2020.Results: The average age was 30.6 ± 16.6 years of whom 54.5% were women, 77.7% were UAE nationals and 77.9% were Type 1 diabetes (T1DM). 12.7% were newly diagnosed with diabetes. Treatment noncompliance (31.4%), and infection (26.4%) were the main precipitating factors. Most patients presented with moderate DKA (50.9%). Compared to T1DM, patients with Type 2 diabetes (T2DM) were older (53.6 vs 23.9 years, p < 0.001), had longer hospital stay (12.1 days vs 4.1 days, p < 0.001), had more complications (52.1%, vs 18.9% p <0.001), and a higher mortality rate (6.3% vs 0.6%, p = 0.035). Patients with severe DKA had a shorter diabetes duration compared to mild and moderate DKA (5.7 vs 11.0 vs 11.7 years, respectively, p = 0.007), while complications were significantly lower in the mild group compared to both the moderate and severe groups (11.6% vs 32.1% vs 33.3%, respectively). Conclusion: The risk of DKA is higher for patients with T1DM than for those with T2DM. The clinical characteristics and outcomes of patients with T2DM differ from those with T1DM highlighting the importance of educating all patients about DKA.

Rare case of chemotherapy-refractory metastatic vaginal squamous cell carcinoma with complete response to concurrent pembrolizumab and radiotherapy- case report and literature review.

Primary vaginal cancer is a rare malignancy with a lack of international guidelines and supporting clinical trial evidence to guide decision making. Historical results have shown poor outcomes with chemotherapy for stage IVB vaginal squamous cell carcinoma (SCC). The evolving role of checkpoint inhibitors in rare gynaecological cancers prompted us to investigate the role of pembrolizumab in this setting. The efficacy of pembrolizumab in vaginal SCC has never been investigated in any clinical trial. There is established data to support the use of concurrent chemoradiotherapy in gynaecological cancers, however, the data for concurrent use of immunotherapy and radiotherapy is still lacking but is the subject of several clinical trials. We herein present the first reported case of chemotherapy refractory vaginal SCC with complete response to pembrolizumab and concurrent pelvic radiotherapy. We also present wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) as a rare but new immune related adverse event.

Utility of Cannulated Prolactin to Exclude Stress Hyperprolactinemia in Patients with Persistent Mild Hyperprolactinemia.

BACKGROUND: Stress-induced hyperprolactinemia can be difficult to differentiate from true hyperprolactinema and may result in patients having unnecessary investigations and imaging. We report the results of cannulated prolactin tests with serial prolactin measurements from an indwelling catheter to differentiate true from stress-induced hyperprolactinemia in patients with persistently mildly elevated prolactin levels in both referral and repeat samples. METHODS: Data were collected for 42 patients who had a cannulated prolactin test between January 2017 and May 2018. After cannula insertion, prolactin was measured at 0, 60, and 120 minutes. Normalization is defined as a decline in prolactin to gender-defined normal ranges. RESULTS: The mean age was 33.8 years (SD ± 9.9), and 37 (88%) were female. Menstrual irregularities were the main presenting symptom in 28.57% of the patients. Prolactin normalized in 12 (28.6%) patients of whom cannulated prolactin test was done. Repeat random prolactin levels were significantly higher in patients whose prolactin did not normalize during the cannulated prolactin test. MRI of the pituitary gland showed an abnormality in 23 out of 28 (82%) patients who did not normalize prolactin, a microadenoma in the majority of patients (18 patients). CONCLUSION: The cannulated prolactin test was useful in excluding true hyperprolactinemia in 28.6% of patients with previously confirmed mildly elevated random prolactin on two occasions, thus avoiding over-diagnosis and unnecessary imaging.

Synacthen Stimulation Test Following Unilateral Adrenalectomy Needs to Be Interpreted With Caution.

Background: Cortisol levels in response to stress are highly variable. Baseline and stimulated cortisol levels are commonly used to determine adrenal function following unilateral adrenalectomy. We report the results of synacthen stimulation testing following unilateral adrenalectomy in a tertiary referral center. Methods: Data were collected retrospectively for 36 patients who underwent synacthen stimulation testing one day post unilateral adrenalectomy. None of the patients had clinical signs of hypercortisolism preoperatively. No patient received pre- or intraoperative steroids. Patients with overt Cushing's syndrome were excluded. Results: The median age was 58 (31-79) years. Preoperatively, 16 (44%) patients had a diagnosis of pheochromocytoma, 12 (33%) patients had primary aldosteronism and 8 (22%) patients had non-functioning adenomas with indeterminate/atypical imaging characteristics necessitating surgery. Preoperative overnight dexamethasone suppression test results revealed that 6 of 29 patients failed to suppress cortisol to <50 nmol/L. Twenty (56%) patients achieved a stimulated cortisol ≥450 nmol/L at 30 minutes and 28 (78%) at 60 minutes. None of the patients developed clinical adrenal insufficiency necessitating steroid replacement. Conclusions: Synacthen stimulation testing following unilateral adrenalectomy using standard stimulated cortisol cut-off values would wrongly label many patients adrenally insufficient and may lead to inappropriate prescriptions of steroids to patients who do not need them.

Burden, associated risk factors and adverse outcomes of gestational diabetes mellitus in twin pregnancies in Al Ain, UAE.

BACKGROUND: Gestational diabetes mellitus (GDM) in singleton pregnancies represent a high-risk scenario. The incidence, associated factors and outcomes of GDM in twin pregnancies is not known in the UAE. METHODS: This was five years retrospective analysis of hospital records of twin pregnancies in the city of Al Ain, Abu Dhabi, UAE. Relevant data with regards to the pregnancy, maternal and birth outcomes and incidence of GDM was extracted from two major hospitals in the city. Regression models assessed the relationship between socio-demographic and pregnancy-related variables and GDM, and the associations between GDM and maternal and fetal outcomes at birth. RESULTS: A total of 404 women and their neonates were part of this study. The study population had a mean age of 30.1 (SD: 5.3), overweight or obese (66.5%) and were majority multiparous (66.6%). High incidence of GDM in twin pregnancies (27.0%). While there were no statistical differences in outcomes of the neonates, GDM mothers were older (OR: 1.09, 95% CI: 1.06-1.4) and heavier (aOR: 1.02, 95% CI: 1.00 -1.04). They were also likely to have had GDM in their previous pregnancies (aOR: 7.37, 95% CI: 2.76-19.73). The prognosis of mothers with twin pregnancies and GDM lead to an independent and increased odds of cesarean section (aOR: 2.34, 95% CI: 1.03-5.30) and hospitalization during pregnancy (aOR: 1.60, 95% CI: 1.16-2.20). CONCLUSION: More than a quarter of women with twin pregnancies were diagnosed with GDM. GDM was associated with some adverse pregnancy outcomes but not fetal outcomes in this population. More studies are needed to further investigate these associations and the management of GDM in twin pregnancies.

A novel missense heterozygous mutation in MAP3K1 gene causes 46, XY disorder of sex development: case report and literature review.

BACKGROUND: Disorders of sex development (DSD) can result from congenital defect in sex determining pathway. Mitogen-activated protein kinase kinase kinase 1 (MAP3K1) is one of the commonest genes that has been identified to cause 46, XY DSD. It can present as complete or partial gonadal dysgenesis even within the same kindred. Few mutations in this gene have previously been identified in a high proportion of individuals with 46, XY gonadal dysgenesis. METHODS AND RESULTS: We report three siblings with same novel variant in MAP3K1 gene presenting with variable degrees of partial gonadal dysgenesis. Clinical and genetic assessments were performed for the three siblings, while endocrine evaluation was done for two of them. The identified mutation (p.Thr657Arg) was previously classified as a pathogenic variant, although apparently there are no reported humans with this mutation. CONCLUSION: This report adds to the genotype-phenotype correlation, highlighting the clinical importance of considering MAP3K1 gene defects as part of the differential diagnosis for complete or partial gonadal dysgenesis especially with multiple affected family members.