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.

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.

Clinical, immunological, and genetic investigations in a rare association of type 1 diabetes with xeroderma pigmentosum.

Xeroderma pigmentosum (XP) is a rare genodermatosis predisposing to skin cancers. Autoimmune diseases related to XP are rarely discussed in the literature. Type 1 diabetes (T1D) has been associated with other genodermatoses like Cockayne syndrome, but it has never been described in XP. In the present study, we report the rare occurrence of T1D in XP patients. Five XP patients belonging to 4 consanguineous families originating from different regions of Tunisia were investigated. Their ages ranged between 8 and 18 years. All the patients had a severe hypovitaminosis D. All the patients had positive GAD antibody levels, and 4 of them had familial history of other autoimmune diseases. The spectrum of XP was variable in all the patients, with dermatological and neurological symptoms, and the occurrence of some cancers. Various hypotheses have been proposed to explain this association, among of which we cite the role of immunomodulation and down-regulation of ATP-dependent DNA excision repair protein genes, implying that impaired DNA repair may contribute to the development of some autoimmune diseases. Vitamin D3 deficiency secondary to sun protective measures was found in all patients and thus may play a role in increasing T1D risk in these patients.

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.

Disorders of sodium balance in COVID-19 patients: two Tunisian patients report.

Coronavirus disease 2019 (COVID-19) was first reported in December 2019. The disease is caused by severe acute respiratory syndrome virus corona virus 2 (SARS-CoV-2). Mild respiratory symptoms are the most common manifestations of SARS-CoV-2, but new signs are constantly being discovered as it spreads. Disorders of sodium balance are increasingly described in patients with SARS-CoV-2. We report, here, the cases of two patients presented with COVID-19 and in whom we discovered sodium disorders. The first patient is a 74-year-old man who presented with fatal hypernatremia. The second patient is a 66-years-old man presented with COVID-19 and euvolemic hyponatremia attributed to syndrome of inappropriate anti-diuretic hormone secretion (SIADH). This hyponatremia persisted long after the respiratory signs disappeared. Sodium balance disorders are increasingly described in the literature; special attention should be paid to the electrolyte status of COVID-19 patients. Pathophysiological mechanisms associating SARS-CoV-2 with these disorders are being studied.

Association of an empty sella and grave´s disease in a patient with acromegaly: a case report.

Acromegaly is, in most cases, caused by growth hormone secreting pituitary adenomas. Those patients often develop different pathologies of the thyroid gland, however, the occurrence of Grave´s disease is quite a rare situation. We report a case of a 64-year-old female patient who presented with signs of hyperthyroidism and imbalance of her diabetes mellitus. On physical examination, she had facial features of acromegaly. Biochemical testing confirmed the suspicion of acromegaly and Grave´s disease, with an elevated insulin-like growth factor-1 and a suppressed thyroid stimulation hormone (TSH) with positive TSH-receptor antibodies. A pituitary Magnetic Resonance Imaging (MRI) was performed, revealing a macro-adenoma and an empty sella. The patient successfully underwent a transsphenoidal surgery and obtained a remission of her hyperthyroidism under anti-thyroid drugs.

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.

Clinical patterns of third nerve palsies in diabetic patients.

BACKGROUND: Neuropathy is a frequent complication in diabetic patients with variable clinical presentations and evolutions. AIM: The purpose of the study was to specify the clinical features of diabetic third nerve palsy, to assess the risk factors and to observe its evolution. METHODS: We report a series of 11 diabetic patients with oculomotor paralysis collected in the department of endocrinology and diabetology of FarhatHached Hospital of Sousse between 1996 and 2005. RESULTS: Our study was about 6 men and 5 women with an average age of 63.6 ± 13.7 years. All patients had type 2 diabetes.  Eight patients presented with diplopia, three with periocular pain and 6 with headache. The oculomotor palsy was unilateral in all cases. All patients were in glycemic imbalance at the time of the diagnosis of ptosis and they were at high cardiovascular risk. The evolution under optimal equilibrium of diabetes and control of cardiovascular risk factors was marked by regression and disappearance in 4 patients, homo or contralateral recurrence in 4 patients and persistence of the palsy in 1 patient. CONCLUSION: Glycemic equilibrium and ischemic phenomena due to cardiovascular risk factors are at the root of these oculomotor paralyses in diabetic patients. The evolution of diabetic mononevritis remains unpredictable despite the control of blood glucose levels and cardiovascular risk factors.

Correlation between superficial and intra-operative specimens in diabetic foot infections: results of a cross-sectional Tunisian study.

OBJECTIVE: To determine the correlation between superficial, and intra-operative specimens in diabetic foot infections (DFIs). METHODS: We conducted a cross-sectional study in patients with DFIs hospitalized in a Tunisian teaching hospital. Superficial specimens were collected for all patients, and intra-operative specimens were collected in operated patients. The specimens were processed using standard microbiology techniques. Antimicrobial susceptibility testing was carried out according to the protocol established by the European Committee on Anti-microbial Susceptibility Testing. Intra-operative and superficial specimens were considered correlated if they isolated the same microorganism(s), or if they were both negative. RESULTS: One hundred twelve patients, 81 males and 31 females, mean age 56 years, were included. Superficial samples were positive in 77% of cases, and isolated 126 microorganisms. Among the positive samples, 71% were monomicrobial. The most frequently isolated microorganisms were Enterobacteriaceae (53%), followed by streptococci (21%) and Staphylococcus aureus (17%). Nine microorganisms (7%) were multi-drug resistant. Intra-operative samples were positive in 93% of cases. Superficial specimens were correlated to intra-operative specimens in 67% of cases. Initial antibiotic therapy was appropriate in 70% of cases. The lower-extremity amputation and the mortality rates were 41% and 1%, respectively. CONCLUSION: In our study, DFIs were most frequently caused by Enterobacteriaceae and superficial specimens were correlated to intra-operative specimens in only two thirds of cases. Clinicians should emphasize on the systematic practice of intraoperative specimens in all patients with DFIs treated surgically, while well-performed superficial specimens could be useful for prescribing appropriate antibiotic therapy in other patients.

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.

[Posttraumatic type 1 diabetes in an army soldier]. / Diabète de type 1 post-traumatique chez un soldat de l'armée.

The influence of stress as a precipitating factor associated with the onset of type 1 diabetes have been widely studied in the literature. The relationship between physical and psychological traumas and diabetes has been rarely studied in the military environment. Posttraumatic diabetes is a controversial topic. We here report the case of a Tunisian soldier, with no previous medical and family history of autoimmune disease who was diagnosed with Type 1 diabetes after a physical aggression occurred during a social conflict between the forces of law and order and the citizens.

[Study of acute inaugural ketosis-prone diabetes in a Hospital in Central-Eastern Tunisian]. / Etude sur le diabète aigu cétosique inaugural dans un hôpital du Centre-Est Tunisien.

Ketosis-prone diabetes is an acute complication of diabetes resulting from ketone accumulation in the blood. Despite the high rate of ketosis-prone diabetes described, there is very little information on the epidemiology of this inaugural complication of diabetes in Tunisia. This study aims to determine the epidemiological and clinical features and the laboratory tests parameters of inaugural ketoses in a Hospital in Tunisian. We conducted a retrospective, cross-sectional exhaustive study of patients admitted with inaugural ketosis over the period January 2010 - August 2016. The study population was divided into 2 groups according to the presence or not of anti-pancreatic autoimmunity: the DAI group consisted of all patients with autoimmunity, the DNAI group consisted of all patients without autoimmunity. Our study included 391 patients, with a sex ratio of 226 men/125 women, the average age was 34 ± 14.33 years. There was a male predominance (68%) in the general population. The age of disease onset was significantly lower in the DAI group. A factor that contributed to ketosis onset was found in 77.7% of the overall study population, it was significantly more frequent in the DAI group than in the DNAI group. The most common factor was viral infections. Thyroid antibodies were significantly higher in the DAI group. Ketosis is a common factor leading to inaugural decompensation of diabetes in Tunisia. Young adult male is the most affected group of population reported in the literature, with the absence of autimmunity, and a clinical profile of type 2 diabetes.

Macroprolactinemia and Empty Sella Syndrome.

Macroprolactinemia is a polymeric form of prolactin-release, causing mildly symptomatic clinical pictures. The former can be isolated or associated with other causes of hyperprolactinemia. The association with an empty sella syndrome is rare. We report a case of a female patient discovered with this association. It's about a female patient 47 years old, followed up since the age of 31 years for bilateral galactorrhea and a spaniomenorrhea. There has been no associated drug intake. Her exploration has showed a serum prolactin level of 635 mIU/L. Thyroid test results were normal T4 = 10,2ng/L and TSH = 1.76 mIU/L. A brain scan has showed an empty sella turcica. Despite the unchanged levels of prolactinemia, the evolution under dopaminergic 5 mg /D has been marked by the occurrence of a pregnancy with persistent moderate hyperprolactinemia in the postpartum. Chromatography has showed a predominance of the macroprolactin form with: Prolactin monomer at 4.8%, Big Prolactin at 5% and Big Big Prolactin at 83%, thus stopping bromocriptine. Our observation suggests that macroprolactinemia can be associated with conventional etiologies of moderate hyperprolactinemia as the empty sella syndrome. Its detection would prevent the use of dopaminergic therapy which seems not useful.

[Prolactin-secreting microadenoma in menopausal women]. / Micro adénome à prolactine à l'âge de la ménopause.

Prolactin-secreting adenoma is rare in elderly women. Patient's clinical picture may be confused with that of menopause, making diagnosis sometimes difficult. We report the case of a 57-year old woman with a 2-year history of secondary amenorrhea without hot flushes associated with galactorrhea in order to highlight the peculiarities of prolactin-secreting microadenomas. Physical examination confirmed the diagnosis of galactorrhoea and biology showed hyperprolactinemia at mIU/L, FSH = 15.1 IU/L and LH = 4,1 IU/L. Pituitary MRI showed left adenoma measuring 8 mm. Patient's evolution under dopaminergic treatment was marked by the recovery, for a transitional period, of mestrual cycles and the occurrence of hot flushes, normalization of prolactin levels and reduction of adenoma size.

Lipid management in ramadan.

During Ramadan fast, Muslims must refrain from smoking, eating, drinking, having sexual activity, and consuming oral medications from sunrise to sunset. It has been previously shown that Ramadan fasting induces favourable changes on metabolic parameters, reduces oxidative stress and inflammation and promotes cardiovascular benefits. Although ill people are exempted from fasting, most patients with chronic diseases are keen on performing this Islamic-ritual. During recent years, Risk stratification and treatment adjustment during Ramadan are well known and structured in several guidelines for patients with diabetes mellitus. Data related to the effect of Ramadan fast on lipid profiles are less known and several controversies have been reported. Here, we focus on lipid profile and lipid management during Ramadan taking into account comorbidities and cardiovascular risk.