Timing matters: diurnal variation of maximal fat oxidation and substrate oxidation rates in metabolic syndrome-a randomized crossover study.

PURPOSE: The aim of this study was to investigate if diurnal oscillation in maximal fat oxidation (MFO) and substrate oxidation rates during exercise exists in subjects with metabolic syndrome (MetS). METHODS: In a randomized crossover design, 14 MetS patients were assigned to two graded exercise tests conditions performed in the morning (between 7:00 and 9:00 a.m) and in the afternoon (between 4:00 and 5:00 p.m). MFO was defined as the highest absolute value of fat oxidation obtained from the average of last 2-min stages during an indirect calorimetry test. RESULTS: MFO increased by 20.6% from morning to afternoon (p = 0.0002, Cohen's d = 0.52). There was a significant time of day, (p < 0.0001, η2p = 0.76) and intensity effect (p = 0.002, η2p = 0.32) in fat oxidation (Fatox) rates indicating that Fatox was higher in the afternoon than in the morning. CONCLUSION: Our study extends previous findings on the existence of diurnal variation in maximal fat oxidation to MetS patients, highlighting the afternoon as a more favorable time for fat utilization during exercise. These findings have practical implications for optimizing training timing in MetS patients. TRIAL REGISTRATION NUMBER: PACTR202306776991260.

Unmasking the escalation: a comparative analysis of diabetic ketoacidosis severity before and during the COVID-19 pandemic in a Tunisian pioneer study.

BACKGROUND: The severity of diabetic ketoacidosis (DKA) at diagnosis increased during the global COVID-19 pandemic. This study aimed to analyze the impact of the pandemic on the clinical and biological severity of DKA in patients with new-onset diabetes mellitus (DM) in Tunisia. RESEARCH DESIGN AND METHODS: The study included patients hospitalized for new-onset DKA 2 years prior and 2 years during the COVID-19 pandemic. Data was collected retrospectively, and DKA severity was classified based on biological parameters like potential of hydrogen (pH) and HCO3-. RESULTS: The results showed that DKA was more severe during COVID-19, as evidenced by lower potential of hydrogen (pH) (p = 0.006), and serum bicarbonate (HCO3-) levels (p = 0,005). Despite the higher severity of DKA was higher during COVID-19, intensive care unit hospitalizations remained equivalent (p = 0.359). The prevalence of hyponatremia was also higher during COVID-19 (p = 0.024). CONCLUSION: The findings suggest that delayed diagnosis and COVID-19 May contribute to the increased severity of DKA and electrolyte imbalance during the pandemic. Further research is needed to better understand the underlying mechanisms and develop appropriate strategies to address this issue.

Explaining Long COVID: A Pioneer Cross-Sectional Study Supporting the Endocrine Hypothesis.

Context: In some patients, symptoms may persist after COVID-19, defined as long COVID. Its pathogenesis is still debated and many hypotheses have been raised. Objective: Our primary objective was to evaluate the corticotroph and somatotroph functions of patients previously infected with SARS-CoV-2 and experiencing post-COVID-19 syndrome to detect any deficiencies that may explain long COVID. Methods: A cross-sectional study was conducted including patients who had previously contracted SARS-CoV-2 with a postinfection period of 3 months or less to 15 months, divided into 2 groups. The first group (G1) comprised fully recovered patients, while the second group (G2) included patients experiencing long COVID. The primary outcome was the comparison of corticotroph and somatotroph functions. Results: A total of 64 patients were divided into 2 groups, each consisting of 32 patients. G2 exhibited more frequently anterior pituitary deficits compared to G1 (P = .045): for the corticotroph axis (G1: 6.3% vs G2: 28.1%) and for the somatotroph axis (G1: 31.3% vs G2: 59.4%). Baseline cortisol level was significantly lower in G2 (G1: 13.37 µg/dL vs G2: 11.59 µg/dL) (P = .045). The peak cortisol level was also lower in G2 (G1: 23.60 µg/dL vs G2: 19.14 µg/dL) (P = .01). For the somatotroph axis, the insulin growth factor-1 level was lower in G2 (G1: 146.03 ng/mL vs G2: 132.25 ng/mL) (P = .369). The peak growth hormone level was also lower in G2 (G1: 4.82 ng/mL vs G2: 2.89 ng/mL) (P = .041). Conclusion: The results showed that long COVID patients in our cohort were more likely to have anterior pituitary deficiencies. The endocrine hypothesis involving anterior pituitary insufficiency can be considered to explain long COVID.

Uncovering the alarming rise of diabetic ketoacidosis during COVID-19 pandemic: a pioneer African study and review of literature.

Introduction: Reports around the world indicate that COVID-19 pandemic may be contributing to an increase in the incidence of new onset diabetic ketoacidosis (DKA). This has yet to be studied in Africa. We aimed to compare the incidence trend of new onset DKA before and during the COVID-19 pandemic, with a focus on the type of diabetes mellitus (DM).Materials and methodsThis was a cross sectional analytical study, over a 4-year period, between March 2018 until February 2022 conducted in the referral center: diabetology department of university hospital Farhat Hached Sousse, Tunisia. The study population included patients hospitalized for new onset DKA divided in two groups: G1: before COVID-19 pandemic and G2: during COVID-19 pandemic. Patients younger than 14, new onset DM not presenting with DKA, other types of diabetes (monogenic, secondary or pancreatic diabetes) were not included. A statistical analysis of the monthly incidence trend was conducted using the Jointpoint software providing the average monthly percentage of change (AMPC). Results: a total of 340 patients were included:137 registered before the pandemic and 203 during the pandemic, representing a 48.17% increase. The mean monthly incidence of new onset DKA during COVID-19 pandemic was statistically higher than that before COVID-19 pandemic (8.42 ± 4.87 vs 5.75 ± 4.29 DKA per month) (p=0.049). The temporal trend of DKA during the 4-year study showed a significant upward trend with a change in AMPC of +0.2% (p=0.037). The incidence of type 1 diabetes (T1D) and type 2 diabetes (T2D) increased by 50% and 44% respectively during COVID-19 pandemic. Anti-glutamic acid decarboxylase (anti-GAD) antibodies' titers significantly increased in G2 compared with G1 (median of 330[Q1-Q3]=[58.5-1795]vs 92.5[Q1-Q3]=[22.5-1074] respectively)(p=0.021). Discussion: The incidence trend of DKA showed an increase during the COVID-19 pandemic along with an increase of T1D and T2D implying that the pandemic may have been the underlying factor of this upward trend.

Secondary Amenorrhea Revealing a Giant Hamartoma of the Tuber Cinereum.

Hypothalamic hamartomas are benign tumors composed of ectopic neural and glial tissue. They have a low prevalence and are usually associated with central precocious puberty or epilepsy with gelastic seizures. The presentation beyond childhood is rare, and the symptoms are not the same as in childhood. Here, we report the case of a woman who presented with secondary amenorrhea and headaches revealing a giant hamartoma of the tuber cinereum (TC). The hormonal assessment showed moderate hyperprolactinemia. Synacthen testing was normal. Magnetic resonance imaging revealed a suprasellar hamartoma on the TC measuring 20 mm with sellar extension. The optic chiasma and cavernous sinuses were clear. Hyperprolactinemia was explained by mechanical compression of the pituitary stalk. The patient started cabergoline orally (1 mg per week) with an improvement of the prolactin levels and had a natural pregnancy six months later without incident. Surgery was not indicated due to the difficult transsphenoidal access and the absence of major clinical symptoms.

Predictive Factors for Lower Limb Amputation in Type 2 Diabetics.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is a major public health problem. Foot-related complications are common in diabetic patients. The aim of this study is to identify predictive factors for lower limb amputation (LLA) in order to better identify this at-risk population. METHODS: This was a cross-sectional study involving 134 patients who were hospitalised for the management of T2DM complicated by diabetic foot, in the department of endocrinology and diabetology. We included patients with T2DM whose diabetes was diagnosed 10 years ago or more, and who had a diabetic foot problem. Statistical differences between predictors of amputations were tested using: t-tests for numerical variables and chi-square tests for categorical variables. Significant variables were analysed by logistic regression to determine significant predictors. RESULTS: The mean duration of diabetes was 17±7 years. We found that 70% of patients with LLA were older than 50 years (p<10-3). The prevalence of LLA was higher (p=0.015) in patients with diabetes for more than 20 years. We noted that 58% of patients who underwent LLA were hypertensive (p<10-3). The majority of patients with LLA (58%) had abnormal micro-albuminuria (p<10-3). We found that 70% (n=12) of patients with LLA had low-density protein cholesterol levels above the target value (p<10-3). Diabetic foot grade ≥4 (4 or 5) according to Wagner's classification, was present in 24% of amputee patients. Based on a 95% confidence interval level, the independent significant predictive factors for LLA in our patients were: T2DM for more than 20 years, hypertension and diabetic foot grade ≥4. CONCLUSIONS: After multivariate analysis, the significant independent predictive factors associated with LLA were: T2DM for more than 20 years, hypertension, and diabetic foot grade ≥4. Early management of diabetic foot problems is therefore recommended to avoid amputations.

Neurosarcoidosis-Induced Hypophysitis Mimicking Pituitary Macroadenoma.

Sarcoidosis is characterized by the presence of noncaseating granulomatous inflammation in the affected organs. Isolated involvement of the hypothalamic-pituitary axis in patients with sarcoidosis is rare. We report a rare case of a female patient in whom hypophysitis, mimicking a pituitary macroadenoma, resulted in pituitary transsphenoidal surgery. A female patient had been complaining of bilateral temporal headaches for over a month. Brain MRI showed a pituitary adenoma of height 16 mm, width 16 mm, and depth 12 mm. Hormonal assay showed central hypothyroidism and elevated level of prolactin. Histological examination revealed granulomatous hypophysitis. A specific search for Mycobacterium tuberculosis was negative on the pituitary tissue. After the exclusion of differential diagnoses, the combination of clinical, laboratory and radiological tests led to the diagnosis of neurosarcoidosis. This report presents an uncommon case of a pituitary localization of neurosarcoidosis mimicking a macroadenoma. Understanding the different MRI aspects of neurosarcoidosis is essential to avoid interpretive blunders that could result in an incorrect diagnosis.

Gastrointestinal manifestations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) patient: major effect on treatment and prognosis.

Summary: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive inherited syndrome caused by mutations in autoimmune regulator (AIRE) gene. The three clinical components of this syndrome are mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. In addition to these frequent symptoms, many other components have been reported including gastrointestinal manifestations.We report a case of a 17-year-old Caucasian female patient diagnosed with APECED who presented with acute abdominal pain. Her medical history revealed chronic digestive discomfort without bowel movement disorders. The patient needed a significant increase in doses of calcium supplementation and hydrocortisone which appeared to be partially inefficient. Investigation with esophagogastroduodenoscopy and biopsy showed autoimmune atrophic gastritis. The patient eventually needed increasing doses of treatment received in order to achieve desired clinical and biological therapeutic goals. Learning points: Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive inherited syndrome caused by mutations in the autoimmune regulator (AIRE) gene. The three clinical components of this syndrome that appear in early childhood are mucocutaneous candidiasis, hypoparathyroidism, and primary adrenal insufficiency. In addition to these frequent symptoms, many other components have been reported including gastrointestinal manifestations like atrophic gastritis. They can be caused by many abnormalities including atrophic gastritis and the modification of intestinal biofilm and microbiota. Early diagnosis and treatment of gastrointestinal manifestations associated with APECED prevent multiple life-threatening consequences like acute adrenal crisis and severe symptomatic hypocalcemia.

Effect of Pre-Meal Metformin With or Without an Acute Exercise Bout on Postprandial Lipemic and Glycemic Responses in Metabolic Syndrome Patients: A Randomized, Open Label, Crossover Study.

INTRODUCTION: Both exercise and pre-meal metformin could lower postprandial glucose and lipid profiles. AIMS: To explore whether pre-meal metformin administration is superior to metformin administration with the meal in reducing postprandial lipid and glucose metabolism, and whether its combination with exercise confer superior benefits in metabolic syndrome patients. MATERIALS AND METHODS: In a randomized crossover design, 15 metabolic syndrome patients were assigned to 6 sequences including 3 experimental conditions: metformin administration with a test meal (met-meal), metformin administration 30 min prior to a test meal (pre-meal-met) with or without an exercise bout designed to expend 700 Kcal at 60% VO2 peak performed the evening just before pre-meal-met condition. Only 13 participants (3 males, 10 females; age: 46 ± 9.86, HbA1c: 6.23 ± 0.36) were included in the final analysis. RESULTS: Postprandial triglyceridemia was unaffected by any condition (all P > .05). However, both pre-meal-met (-7.1%, P = .009) and pre-meal-metx (-8.2%, P = .013) significantly reduced total cholesterol AUC with no significant differences between the two latter condition (P = .616). Similarly, LDL-cholesterol levels were significantly lower during both pre-meal-met (-10.1%, P = .013) and pre-meal-metx (-10.7%, P = .021) compared to met-meal with no difference between latter conditions (P = .822). Plasma glucose AUC was significantly reduced by pre-meal-metx compared to both pre-meal-met (-7.5%, P = .045) and met-meal (-8%, P = .03). Insulin AUC was significantly lower during pre-meal-metx compared to met-meal (-36.4%, P = .044). CONCLUSIONS: Metformin administration 30 minutes prior to meal seems to exert favorable effects on postprandial TC and LDL-Cholesterol levels compared to its administration with meal. Addition of one exercise bout only improved postprandial glycemia and insulinemia. TRIAL REGISTRY: Pan African clinical trial registry, Identifier PACTR202203690920424.

Positive myositis-specific autoantibodies during COVID-19: a case report.

Viral infection is known to be a trigger of autoimmune diseases. Numerous cases of coronavirus disease 2019 (COVID-19) with autoimmune manifestations have been reported and several authors have highlighted the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and autoimmune diseases. Autoimmune myopathies being one of these manifestations. A 27-year-old diabetic woman was admitted for management of acido-ketosis decompensation of her diabetes secondary to SARS-CoV-2 infection. During hospitalization, she developed muscle weakness and increased creatine kinase levels, which led us to assay the autoimmunity pattern which became positive for myositis-specific autoantibodies against single recognition particle (anti-SRP). The patient was treated with intense hydration with clinical and biological improvement and anti-SRP disappeared two months later. Positive myositis auto-antibodies are one of the autoimmune complications that could be seen during and after the SARS-CoV-2 infection.

Safety Assessment and Potential Risks of the Glucagon Stimulation Test in the Diagnosis of Secondary Adrenal Insufficiency.

BACKGROUND: Although it takes more time, the Glucagon Stimulation Test (GST) is a reliable measure for assessing growth hormone (GH) and Adrenocorticotropic Hormone (ACTH) secretion. The GST is considered to be a safe test; however, it still has mild side effects and potential risks. OBJECTIVES: The objective of this study was to analyze the side effects of the GST while testing adrenal-insufficient patients. METHODS: This was a prospective study in which GST was performed in eighty-one patients (44 men, 37 women, mean age: 35.83A9.62 years) with the pituitary disorder. The GST consisted of an intramuscular injection of 1 mg of glucagon. Blood samples were collected at baseline, and 30, 60, 90, 120, 150, 180, and 210 min after glucagon injection for cortisol measurements. All patients were asked to report side effects associated with this test. RESULTS: The mean peak blood glucose level under GST was 9.01A.03 mmol/L, and the mean glycemic nadir was 4.34A.75 mmol/L most frequently found during the 30th minute (p <10-3). During the test, 35 subjects (43.2%) had side effects with a mean age of 42.89 A19.75 years. Frequent side effects included: nausea (29.62%), vomiting (27.16%), abdominal cramps (18.51%) and hunger (13.58%). All patients tolerated the test until the end. Adverse effects were significantly more prevalent in patients older than 50 years (p=0.012). CONCLUSIONS: The GST is a reliable alternative to assess the hypothalamic pituitary adrenal axis but should be cautiously used especially in the elderly, despite minor side effects.

Pituitary apoplexy of a giant prolactinoma during pregnancy.

AIMS AND METHODS: Prolactinomas are a common cause of sexual dysfunction and infertility. We aimed, through this case report, to illustrate the difficulties of management of women with giant prolactinoma, especially in cases of desire of pregnancy. RESULTS: A 30-year-old woman was referred to our department for secondary amenorrhea. Investigations showed a prolactin level of 5168 ng/mL and giant pituitary adenoma of 4 cm in diameter. Cytoreductive surgery was performed after failure to normalize prolactin levels during three years with medical treatment by cabergoline. After seven months, menstrual cycles have resumed, and after 13 months, the patient became pregnant. At 22nd week of gestation, she was admitted in our hospital for pituitary apoplexy. Medical treatment with bromocriptine was chosen. The vaginal premature delivery at 28 weeks gave birth to twins weighing 1 Kg each who died on the 7th day of life. CONCLUSION: This is a relevant clinical case that illustrates the efficacy of cytoreductive surgery in case of insufficient response to dopamine agonists to restore gonadal function. The possibility of a pregnancy should be considered in these patients since it can be associated with high maternal and fetal risks.

Multiple endocrinological failures as a clinical presentation of a metastatic lung adenocarcinoma.

SUMMARY: Multiple endocrine metastases are a rare but possible complication of lung adenocarcinoma (LAC). Pituitary metastasis is a rare condition with poor clinical expression. Diabetes insipidus (DI) is its most common presenting symptom. Here we report an original case of a pituitary stalk (PS) metastasis from LAC presenting as central DI followed by adrenal insufficiency (AI) from bilateral adrenal metastasis, without known evidence of the primary malignancy. A 45-year-old woman whose first clinical manifestations were polyuria and polydipsia was admitted. She was completely asymptomatic with no cough, no weight loss or anorexia. Chest radiography was normal. Brain MRI showed a thick pituitary stalk (PS). DI was confirmed by water restriction test and treated with vasopressin with great clinical results. Explorations for systemic and infectious disease were negative. Few months later, an acute AI led to discovering bilateral adrenal mass on abdominal CT. A suspicious 2.3 cm apical lung nodule was found later. Histopathological adrenal biopsy revealed an LAC. The patient received systemic chemotherapy with hormonal replacement for endocrinological failures by both vasopressin and hydrocortisone. We present this rare case of metastatic PS thickness arising from LAC associated with bilateral adrenal metastasis. Screening of patients with DI and stalk thickness for lung and breast cancer must be considered. Multiple endocrine failures as a diagnostic motive of LAC is a rare but possible circumstance. LEARNING POINTS: Adrenal metastasis is a common location in lung adenocarcinoma; however, metastatic involvement of the pituitary stalk remains a rare occurrence, especially as a leading presentation to diagnose lung cancer. The posterior pituitary and the infundibulum are the preferential sites for metastases, as they receive direct arterial blood supply from hypophyseal arteries. Patients diagnosed with diabetes insipidus due to pituitary stalk thickness should be considered as a metastasis, after exclusion of the classical systemic and infectious diseases. The diagnosis of an endocrinological metastatic primary lung adenocarcinoma for patients without respiratory symptoms is often delayed due to a lack of correlation between endocrinological symptoms and lung cancer. The main originality of our case is the concomitant diagnosis of both endocrinological failures, as it was initiated with a diabetes insipidus and followed by an acute adrenal insufficiency.

Cortisol cut-points for the glucagon stimulation test in the evaluation of hypothalamic pituitary adrenal axis.

Diagnosis of adrenal insufficiency requires evaluation by dynamic stimulation tests. The insulin tolerance test (ITT) is accepted as the gold-standard test for the evaluation of hypothalamo-pituitary-adrenal (HPA) axis but the test is unpleasant and dangerous. Although it takes more time, glucagon stimulation test (GST) is a good alternative to ITT. The primary aim of this study was to compare the ITT and GSTs in the evaluation of HPA axe in patients with pituitary disorders. We conducted a prospective study in which ITT and GST were performed within 7 days in 81 patients. Serum cortisol was measured. We divided our population in Group 1 (G1): Adrenal Insufficiency (Peak cortisol under ITT <200 ng/mL) and Group 2 (G2): normal response (Peak cortisol under ITT >200 ng/mL). Receiver-operating characteristic (ROC) analysis was performed to identify the thresholds for GST. The mean peak of cortisol under GST was not significantly different from that obtained after ITT in the whole cohort (182.67 ± 89.07 ng/mL vs. 179.75 ± 79.01 ng/mL), and it was significantly reduced in patients of G1 (p < 10-3). ROC curve analysis showed that the best diagnostic accuracy was obtained with a peak cortisol cut-off to GST of 167 ng/mL (sensitivity, 89%; specificity, 79%). Using this cut-off, 86.4% of the patients were correctly classified. In our prospective series, GST is a potential accurate and safe alternative test for the assessment HPA. Test-specific cut-offs should be applied to avoid misinterpretation.

A case of Kallmann syndrome associated with a non-functional pituitary microadenoma.

Kallmann syndrome (KS) is a form of hypogonadotropic hypogonadism in combination with a defect in sense of smell, due to abnormal migration of gonadotropin-releasing hormone-producing neurons. We report a case of a 17-year-old Tunisian male who presented with eunuchoid body proportions, absence of facial, axillary and pubic hair, micropenis and surgically corrected cryptorchidism. Associated findings included anosmia. Karyotype was 46XY and hormonal measurement hypogonadotropic hypogonadism. MRI of the brain showed bilateral agenesis of the olfactory bulbs and 3.5 mm pituitary microadenoma. Hormonal assays showed no evidence of pituitary hypersecretion. LEARNING POINTS: The main clinical characteristics of KS include hypogonadotropic hypogonadism and anosmia or hyposmia.MRI, as a non-irradiating technique, should be the first radiological step for investigating the pituitary gland as well as abnormalities of the ethmoid, olfactory bulbs and tracts in KS.KS may include anterior pituitary hypoplasia or an empty sella syndrome. The originality of our case is that a microadenoma also may be encountered in KS. Hormonal assessment indicated the microadenoma was non-functioning. This emphasizes the importance of visualizing the pituitary region in KS patients to assess for hypoplastic pituitary malformations or adenomas.