Identifying the First Val281L Mutation Causing Nonclassic Congenital Adrenal Hyperplasia in the Central-East Region of Tunisia.

Nonclassic congenital adrenal hyperplasia (NCAH) is a genetic disorder characterized by mutations in the genes encoding enzymes involved in cortisol production, most commonly the 21-hydroxylase enzyme. Unlike classic congenital adrenal hyperplasia (CAH), NCAH typically presents later in life with milder symptoms. The diagnosis of NCAH can be challenging due to its nonspecific symptoms and variable presentation. Early detection is crucial for timely intervention and management, particularly in families with a history of the condition. We report a case of NCAH in a patient from the Central-East Region of Tunisia, in whom the subsequent genetic testing revealed a Val281Leu (V281L) mutation in the CYP21A2 gene. A 26-year-old female presented with facial hirsutism and irregular menstrual cycles. Physical examination revealed mild hirsutism and laboratory tests showed elevated levels of testosterone and 17-hydroxyprogesterone (17-OHP). A provisional diagnosis of NCAH was made, subsequently confirmed by an adrenocorticotropic hormone (ACTH) stimulation test demonstrating an exaggerated 17-OHP response. Genetic testing revealed heterozygosity for the V281L mutation. Family testing showed the patient's mother to be homozygous and the father heterozygous for the mutation. This report highlights the importance of recognizing subtle symptoms of NCAH for early diagnosis and management. Genetic testing aids in confirming the diagnosis and identifying carriers within families. Treatment with glucocorticoids aims to suppress adrenal androgen production and manage symptoms. Regular follow-up is essential to monitor treatment response and adjust medication as needed. NCAH can present with subtle symptoms, necessitating a high index of suspicion for a proper diagnosis. Genetic testing plays a crucial role in confirming the diagnosis and identifying carriers within families. Early intervention and regular follow-up improve outcomes in affected individuals. This report also underscores the significance of genetic testing in the management of NCAH and highlights the need for increased awareness about this condition among healthcare providers.

Medical and Surgical Approaches for a Non-functioning Pituitary Adenoma During Pregnancy.

Non-functioning pituitary adenomas (NFPA) are most commonly found in post-menopausal women and men above the age of 50. They are mainly revealed by a tumor syndrome. The incidence of symptomatic NFPA during pregnancy is rare, with only nine documented cases in the literature. The patient was 39 years old with no previous medical or surgical history and was 17 weeks pregnant. A large pituitary macroadenoma measuring 17 x 18 x 19 mm was discovered radiologically in the presence of a pituitary tumor syndrome. Clinical examination revealed no signs of hormone deficiency or hypersecretion. A corticotropic and thyrotropic deficit was ruled out following a hormonal workup. Ophthalmological examination revealed reduced visual acuity and bilateral visual field damage. Treatment with cabergoline at a dose of 3 mg/week was initiated following written consent from the patient. The patient underwent vaginal delivery of a healthy newborn at term. Hormonal assessment at three months postpartum definitively ruled out hormonal hypersecretion. She underwent transsphenoidal surgery, with a histological examination of the resection specimen revealing a pituitary adenoma binding adrenocorticotrophic hormone (ACTH), prolactin (PRL), and growth hormone (GH). The postoperative evaluation revealed a corticotropic and somatotropic deficit with the presence of an adenomatous residue on imaging. Substitutive treatment was then initiated along with therapeutic education. To the best of our knowledge, this is the third case in which cabergoline treatment was initiated. Cabergoline treatment enabled the pregnancy to continue, improved the patient's clinical condition, stabilized the size of the adenoma, and prevented potential apoplexy.

Determination of the Contributing Factors and HbA1c Cutoff Leading to Glucose Tolerance Abnormalities Following Gestational Diabetes.

The prevalence of gestational diabetes mellitus (GDM) has been steadily increasing over the past years. It is a major risk factor for glucose intolerance and type 2 DM (T2DM). The American Diabetes Association recommends that women whose pregnancy was complicated by GDM be screened for persistent glucose abnormalities at six to 12 weeks postpartum with either a fasting plasma glucose test alone or with a fasting 75-g, two-hour oral glucose tolerance test. This study aimed to identify the main predictive factors of glucose tolerance disorders in early postpartum women with a recent history of GDM. In this retrospective descriptive study, we identified 400 women who met the eligibility criteria for the study. The mean age was 34.54 ± 5.51 years. A total of 70% had a family history of DM, 16% had a personal history of GDM, and 23% had fetal macrosomia in previous pregnancies. The overall incidence of postpartum carbohydrate tolerance disorders was 36.4%, including 12% prediabetes and 24.4% DM. The prevalence of prediabetes and T2DM after delivery was higher with older maternal age, multigravidity, a higher BMI, a history of GDM, and fetal macrosomia in previous pregnancies. Furthermore, the persistence of this impaired glucose tolerance in postpartum was associated with a higher term of diagnosis, a higher glycated hemoglobin (HbA1c) percentage (the discriminant cutoff value with the best sensitivity/specificity ratio was 5.25%), the use of insulin therapy, cesarean section delivery, and fetal macrosomia. After adjusting for confounders, only prior GDM, a higher HbA1c level, macrosomia, and gestational term were found to significantly affect postpartum glucose tolerance. Although postpartum screening for T2DM is recommended for all women with GDM, a significant number of patients fail it. A better knowledge of predictive factors for this outcome is therefore needed for a more effective and targeted medical intervention.

Factors associated with severe diabetic ketoacidosis in patients diagnosed with type 1 diabetes: a decade-long cross-sectional analysis.

OBJECTIVE: The aim of this study was to identify factors associated with severe diabetic ketoacidosis (DKA) at the onset of type 1 diabetes mellitus (T1DM) in adult patients. METHODS: We conducted a retrospective analysis over a 10-year period including adults newly diagnosed with T1DM. Eligible participants were diagnosed with DKA at the time of T1DM diagnosis. DKA severity was categorized as mild, moderate, or severe. Data were collected on age, body mass index, family history of diabetes and autoimmune disorders, lifestyle habits, delayed diagnosis, and preceding factors. RESULTS: A total of 305 participants (69.8% men) with T1DM were included. Overall, 63 patients were admitted with severe DKA (Group 1) and 242 with non-severe DKA (Group 2). Factors associated with severe DKA at diagnosis of T1DM were a long period between symptom onset and first hospitalization, preceding infection, tachypnea, thrombocytopenia, anemia, hepatic cytolysis, polyuria, and tachycardia. CONCLUSIONS: The present findings highlight the need for improving awareness about diabetes symptoms among physicians and the public to reduce the occurrence and severity of DKA at the onset of T1DM.

The Growing Understanding of the Pituitary Implication in the Pathogenesis of Long COVID-19 Syndrome: A Narrative Review.

Long COVID-19, also known as post-acute sequelae of SARS-CoV-2 infection, is a condition where individuals who have recovered from the acute phase of COVID-19 continue to experience a range of symptoms for weeks or even months afterward. While it was initially thought to primarily affect the respiratory system, it has become clear that Long COVID-19 can involve various organs and systems, including the endocrine system, which includes the pituitary gland. In the context of Long COVID-19, there is a growing understanding of the potential implications for the pituitary gland. The virus can directly affect the pituitary gland, leading to abnormalities in hormone production and regulation. This can result in symptoms such as fatigue, changes in appetite, and mood disturbances. Long COVID-19, the persistent and often debilitating condition following acute COVID-19 infection, may be explained by deficiencies in ACTH and Growth hormone production from the pituitary gland. Corticotropin insufficiency can result in the dysregulation of the body's stress response and can lead to prolonged feelings of stress, fatigue, and mood disturbances in Long COVID-19 patients. Simultaneously, somatotropin insufficiency can affect growth, muscle function, and energy metabolism, potentially causing symptoms such as muscle weakness, exercise intolerance, and changes in body composition. Recently, some authors have suggested the involvement of the pituitary gland in Post COVID-19 Syndrome. The exact mechanisms of viral action on infected cells remain under discussion, but inflammatory and autoimmune mechanisms are primarily implicated. The aim of our study will be to review the main pituitary complications following COVID-19 infection. Moreover, we will explain the possible involvement of the pituitary gland in the persistence of Post COVID-19 Syndrome.

The Concealing Effect of COVID-19: Unveiling the Surge in Community-Acquired Infections and Its Association With Diabetic Ketosis During the Pandemic.

Background Some studies suggest that the SARS-CoV-2 pandemic has contributed to diverting attention from other community-acquired infections (CAIs), leading to an increase in their incidence and severity. Our study aimed to describe and compare clinical features of CAI before and during the pandemic as a factor precipitating diabetes ketoacidosis (DKA). Methodology We included 250 patients who presented with DKA due to CAIs, other than SARS-CoV-2, divided into two distinct groups: 100 patients (G1) who consulted two years before the pandemic, and 150 patients (G2) who consulted during the SARS-CoV-2 pandemic. Cases in both groups were matched for age and type and duration of diabetes. Primary outcomes were a longer diagnosis delay and more severe DKA in G2 during the pandemic. Secondary outcomes included blood test results, duration of ketosis, duration of antibiotic therapy, and diabetes treatment. Results The diagnosis and treatment delays were longer for patients seeking medical care during the pandemic (p < 0.001). The duration of DKA was also significantly longer in the G2 group (p = 0.007). During the pandemic, patients' blood tests showed more anomalies with higher glycated hemoglobin (p = 0.02), C-reactive protein (p = 0.001), and lymphocytosis (p = 0.016). The duration of antibiotic therapy was also significantly longer in G2 (p = 0.01). Conclusions This study showed the impact of the COVID-19 pandemic on the management of diseases other than SARS-CoV-2. Indeed, several factors played a part in the increased incidence of CAIs, which were more severe than in the pre-pandemic period. These included fear of contagion, confinement, and physicians' preoccupation with the pandemic.

Pilot Findings on SARS-CoV-2 Vaccine-Induced Pituitary Diseases: A Mini Review from Diagnosis to Pathophysiology.

Since the emergence of the COVID-19 pandemic at the end of 2019, a massive vaccination campaign has been undertaken rapidly and worldwide. Like other vaccines, the COVID-19 vaccine is not devoid of side effects. Typically, the adverse side effects of vaccination include transient headache, fever, and myalgia. Endocrine organs are also affected by adverse effects. The major SARS-CoV-2 vaccine-associated endocrinopathies reported since the beginning of the vaccination campaign are thyroid and pancreas disorders. SARS-CoV-2 vaccine-induced pituitary diseases have become more frequently described in the literature. We searched PubMed/MEDLINE for commentaries, case reports, and case series articles reporting pituitary disorders following SARS-CoV-2 vaccination. The search was reiterated until September 2022, in which eight case reports were found. In all the cases, there were no personal or familial history of pituitary disease described. All the patients described had no previous SARS-CoV-2 infection prior to the vaccination episode. Regarding the type of vaccines administered, 50% of the patients received (BNT162b2; Pfizer-BioNTech) and 50% received (ChAdOx1 nCov-19; AstraZeneca). In five cases, the pituitary disorder developed after the first dose of the corresponding vaccine. Regarding the types of pituitary disorder, five were hypophysitis (variable clinical aspects ranging from pituitary lesion to pituitary stalk thickness) and three were pituitary apoplexy. The time period between vaccination and pituitary disorder ranged from one to seven days. Depending on each case's follow-up time, a complete remission was obtained in all the apoplexy cases but in only three patients with hypophysitis (persistence of the central diabetes insipidus). Both quantity and quality of the published data about pituitary inconveniences after COVID-19 vaccination are limited. Pituitary disorders, unlike thyroid disorders, occur very quickly after COVID-19 vaccination (less than seven days for pituitary disorders versus two months for thyroid disease). This is partially explained by the ease of reaching the pituitary, which is a small gland. Therefore, this gland is rapidly overspread, which explains the speed of onset of pituitary symptoms (especially ADH deficiency which is a rapid onset deficit with evocative symptoms). Accordingly, these pilot findings offer clinicians a future direction to be vigilant for possible pituitary adverse effects of vaccination. This will allow them to accurately orient patients for medical assistance when they present with remarkable symptoms, such as asthenia, polyuro-polydipsia, or severe headache, following a COVID-19 vaccination.

Concomitant coexistence of ACTH-dependent and independent Cushing syndrome.

We report a case of a patient who presented for ACTH-dependent Cushing after a confirmed hypercortisolism and an inadequate normal ACTH. A transsphenoidal surgery of a pituitary picoadenoma has been done. After surgery, the patient showed the persistence of hypercortisolism. CT scan revealed adrenal adenomas removed surgically and improved the patient.

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.

Efficiency of a multidisciplinary team care approach through a short hospitalization of patients with poorly controlled diabetes mellitus: a 12 months prospective monocentric study.

A multidisciplinary team is composed of various healthcare professionals that ensure a multifaceted approach on a group of patients. Standards for diabetes medical care note the importance of multidisciplinary diabetes care teams. We applied our model of multidisciplinary approach by structuring it in a determined five days hospitalization. The aim of this study was to determine if the interdisciplinary approach applied on a short hospitalization is of benefit in patients with poorly controlled diabetes mellitus. Sixty-seven patients were included and ensured a short hospitalization in which they received a multiple educational advice and a treatment adaptation. Sixty-one patients out of 67 (91%) were retained for evaluation with sufficient data at one year, i.e. 9% of patients with poor compliance. Evolution in glycosylated haemoglobin (HbA1c), weight and treatments was analyzed. After a 12 months follow-up, we observed significant improvement in HbA1c (-1.73%; p < 103) without weight loss (BMI=-0.42 kg/m2), p=0.28). HbA1c mean levels correlated negatively to body mass index (BMI) during the regular follow-up (r=-0.22, p=0.05). More than 90% of patients with poorly controlled diabetes mellitus responded to the multi-disciplinary approach with a decrease in HbA1c.

[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.

Assessing the adrenal axis by the glucagon stimulation test in children with idiopathic growth hormone deficiency.

Approximately 30% of children with idiopathic growth hormone deficiency (IGHD) also suffer from other pituitary hormone deficien-cies. Of children with IGHD, approximately 10% are unable to generate appropriate ACTH levels in response to stress. This study was prospectively designed to test the integrity of the adrenal axis in patients with an established diagnosis of IGHD using the glucagon stimulation test (GST). The study population comprised 39 patients with established childhood-onset IGHD. The diagnosis of GHD was established on the basis of failure of GH to increase over 10 ng/ml after two stimulation tests. The GST was performed by intra-muscular injection of 1 mg glucagon. The criteria followed to define adrenal deficiency was cortisol less than 167 ng/l in response to GST. The mean peak blood glucose level was 8.64 ±1.71 mmol/l. Analysing the cohort using the cut-off of 167 ng/ml to define adrenal insufficiency under GST, there were 25.64% of children diagnosed: 20% among males and 35.7% among females. Subjects with GH and ACTH deficiency had a mean peak GH of 2.07 ±1.79 ng/ml - significantly lower than GH peak of children with IGHD alone (p < 0,001). The frequency of children with combined somatotroph and corticotroph deficiencies with a GH peak < 3 ng/ml was 21% (p < 0,001). The current study identified a prevalence of adrenal insufficiency of 25.64%, which could predict greater risk for children if untreated, especially because a substantial proportion of patients do not present clinical symptoms.

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.