Salivary Cortisol Measurement Contamination After Oral Hydrocortisone: A Randomized Crossover Trial.

The study aimed to evaluate salivary cortisol (SC) contamination and determine the associated factors in secondary adrenal insufficiency (SAI) patients treated with hydrocortisone (Hc). A randomized crossover trial involved SAI patients. SC was measured before the morning Hc dose, then at one, two, and four hours after. The procedure was performed twice on two days of a week: one day while taking Hc in tablet form (tablet set) and one day while taking Hc in capsule form (capsule set). Area under the curve (AUC) of SC levels over time was calculated in each participant for the two sets. SC contamination was defined as AUCtablet above the 95th percentile of AUCcapsule. Thirty-four patients (24 females and 10 males) with a median age of 48 years were enrolled. Post-Hc dose SC levels were higher in tablet than in capsule set, particularly at one hour. Prevalence and extent of SC contamination were estimated to 32% and 88%, respectively. In capsule set, SC measured two hours after Hc intake showed the strongest correlation with AUC (r=0.88, p<0.001). In multivariate analysis, serum potassium≥3.9 mEq/l was the only predictor for SC contamination [multi-adjusted OR (95% CI): 7.1 (1.4-36.1); p=0.018]. SC measured during the two hours after Hc intake is inaccurate for glucocorticoid replacement therapy assessment in SAI patients treated with Hc in tablet form.

Metabolic disorders during endogenous Cushing's syndrome: prevalence, associated factors, and outcome after remission.

Objective. The prognosis of Cushing's syndrome (CS) is related to a higher cardiovascular morbidity and mortality. This study aimed to determine the prevalence of metabolic disorders in patients with CS, the associated factors, and the rate of remission of these disorders after the remission from CS. Methods. It is a retrospective study including 75 cases of CS followed up at the university hospital La Rabta of Tunis from 1987 to 2018. Clinical and paraclinical data were collected from medical files. Results. The mean age of the patients was 44.1±18.9 years and the sex ratio was 0.39. At CS diagnosis, the frequencies of obesity, hypertension, diabetes, dyslipidemia, and metabolic syndrome were 52, 75, 43, 83, and 73%, respectively. The age, gender, body mass index, waist circumference, and baseline serum cortisol level were not associated with the presence of diabetes, hypertension or dyslipidemia. Forty-eight patients were operated on. At one year, 38 patients were in remission from CS. The remission rates of hypertension, diabetes, and dyslipidemia were respectively 58% (p<0.001), 76% (p<0.001), and 17% (NS). Conclusion. Metabolic disorders were frequent during CS and their frequencies decreased after the remission from the syndrome.

Impact of hydrocortisone replacement on bone mineral density and bone turnover markers in patients with primary adrenal insufficiency.

Objective. The study was aimed to assess the effect of hydrocortisone (HC) replacement therapy on bone mineral density (BMD) and bone turnover markers in patients with primary adrenal insufficiency (PAI). METHODS: A cross-sectional study was conducted in 37 PAI patients treated with HC. BMD and selected bone turnover markers (ß-crosslaps and osteocalcin) were measured. A stepwise binary logistic regression model was applied to determine the independent variables associated with low BMD. RESULTS: Osteoporosis was noted in 14.3% and osteopenia in 34.3% of cases. These patients were older (p=0.01) and received higher daily HC dose compared to patients with normal BMD (p=0.01). BMD values in the lumbar spine and the femoral neck were negatively correlated with daily HC dose (r=-0.36, p=0.03 and r=-0.34, p=0.05, respectively). Plasma osteocalcin was negatively correlated with disease duration (r=-0.38, p=0.02) and cumulative HC dose (r=-0.43, p<0.01). In multivariate analysis, a daily HC dose ≥12 mg/m2/day was independently associated with a higher risk of osteopenia/osteoporosis [OR (95% CI), 9.0 (1.1-74.6); p=0.04]. CONCLUSIONS: Impaired bone mineralization in patients with PAI is correlated with HC dose. A daily HC dose ≥12 mg/m2/day was associated with an increased risk of osteopenia and osteoporosis in these patients.

Pituitary tuberculosis presented with pituitary coma.

BACKGROUND: Pituitary tuberculosis is very rare. Its diagnosis is difficult unless a bacteriological or histological evidence of tuberculosis. OBSERVATION: We report the case of a 54 years old woman who presented with a pituitary coma that occurred two weeks after the initiation of antituberculous therapy for cervical lymph node tuberculosis. Resonance magnetic imaging showed a pseudotumoral aspect of the pituitary gland. She had hormonal replacement and anti-tuberculous therapy. Outcome was favourable with the normalization of both the pituitary function and the pituitary volume. However, an acute hypopituitarism happened eight months after the withdrawal of antituberculous, which were taken during 12 months. The re initiation of anti tuberculous therapy and its extension to two years leaded to a prolonged remission. CONCLUSION: the three-phase outcome confirms the tuberculous origin of the hypophysitis in our patient.

Edinburgh questionnaire in the screening for peripheral artery disease in type 2 diabetic patients.

AIM: to analyze Edinburgh questionnaire (EQ) screening performance for peripheral artery disease (PAD) in type 2 diabetic patients. METHODS: Cross sectional study including 150 type 2 diabetic patients without PAD history. All patients responded to EQ and had peripheral pulse checkup and measurement of the ankle/brachial index (ABI). PAD was considered to be present when the ABI was ≤ 0.9 Results: Participants mean age was 57.46 ± 8.04 years and sex-ratio (men/women) was 1.3. EQ has revealed intermittent claudication in 18 patients (12%). On examination, 42 patients (28%) had at least one weakened or abolished pulse in upper limbs. ABI has revealed the presence of PAD in 16% of patients. The EQ sensibility specificity, positive and negative predictivevalueswere 29, 91,39 and 87%, respectively. Among patients with false negative results (n=17), nine had peripheral neuropathy. CONCLUSION: In diabetic patients, EQ had a very low sensibility for the PAD screening. In fact, the important false negative rate, due to the coexisting of peripheral neuropathy, had limited the use of this questionnaire.

Benzylthiouracil induced ANCA associated glomerulonephritis in patients with graves' disease.

BACKGROUND: Renal complications in Graves' disease are rare and may be related either to the disease itself or secondary to antithyroid drugs. AIM: We report 6 cases of renal damage in patients with Graves' disease treated with Benzylthiouracil collected over a period of 14 years. METHODS: There were 6 women with a mean age of 37.86 ± 14.25 years. All patients developed renal vasculitis associated with ANCA. The signs were dominated by renal proteinuria and renal failure associated with hematuria in all cases. The lung involvement was the most common extrarenal manifestation occurred in 4 patients (alveolar hemorrhage in 2 cases, lymphocytic alveolitis in 1 case and pleurisy in 1 case). The benzylthiouracil was discontinued in 3 patients still under treatment. Corticosteroid therapy was used alone or in combination with cyclophosphamide in all cases. Plasmapheresis sessions were made during the alveolar hemorrhage. A complete remission was obtained in one case and incomplete remission in 2 cases. The other 3 patients required chronic hemodialysis. One patient died of sepsis. CONCLUSION: The possibility of renal impairment in antithyroid drugs treated Graves' disease requires monitoring to detect urinary abnormalities in order to early initiate therapy and improve patient's outcome.

Metformin-Induced Vitamin B12 Deficiency in Patients with Type 2 Diabetes: A Narrative Review with a Practical Approach for Screening, Diagnosing, and Managing Vitamin B12 Deficiency.

Metformin is the most widely used antihyperglycemic drug in patients with type 2 diabetes (T2D). Over the past 2 decades, several studies have highlighted a substantial increase in the risk of vitamin B12 deficiency in patients with T2D on metformin therapy. This can lead to several complications and induce or exacerbate peripheral neuropathy. Despite these data, there are no definite guidelines for screening, diagnosing, and treating vitamin B12 deficiency in patients with T2D on metformin therapy. Therefore, in this narrative review, we aimed to suggest a practical diagnostic and therapeutic strategy to address vitamin B12 deficiency in patients with T2D receiving metformin treatment. Clinical evidence supporting an increased risk of vitamin B12 deficiency in patients with T2D on metformin therapy and its risk factors and potential complications are also discussed.

Long-term complications of permanent hypoparathyroidism in adults: prevalence and associated factors.

INTRODUCTION: Patients with Chronic hypoparathyroidism (CHPT) receiving conventional treatment are exposed to several long-term complications including basal ganglia calcifications, posterior subcapsular cataract, kidney stones, and renal insufficiency. The aim of this study was to assess the prevalence and the associated factors of these complications in patients with CHPT. METHODS: We conducted a cross-sectional study including 58 patients with CHPT. All participants underwent physical examination, biochemical assessment (total serum calcium, serum phosphorus, serum albumin, intact-PTH, serum magnesium, 25-hydroxy-vitamin D, serum creatinine, thyroid stimulating hormone (TSH), and 24-hour urinary calcium), slit lamp examination, brain computed tomography scan (CT-scan), and renal ultrasound. RESULTS: Participants had a mean age of 52.6 ± 16.4 years and a gender ratio (women/men) of 3.5. Fahr syndrome, cataract, urolithiasis, and renal failure were found in 55%, 62%, 12%, and 17% of cases, respectively. CHPT duration >15 years (Adjusted-OR = 43.1, 95-CI: 2.63-703.06, p = 0.008) and poor adherence to treatment (Adjusted-OR = 8.04, 95%-CI: 1.52-42.42, p = 0.014) were independently associated with the risk of Fahr syndrome. Age >55 years (adjusted-OR = 5.07, 95-CI: 1.10-23.42, p = 0.037), disease duration >15 years (adjusted-OR = 20.21, 95-CI: 1.54-265.84, p = 0.022), and magnesium level <0.8 mmol/l (adjusted-OR = 36.46, 95-CI: 3.75-354.08, p = 0.002) were independently associated with the risk of subcapsular cataract. Only hypercalciuria (Adjusted-OR = 21.27, 95-CI: 2.31-195.91, p = 0.007) was an independent risk factor for kidney stones. Renal failure was not associated with kidney stones (p = 1). However, creatinine clearance was negatively correlated with age (r = -0.784; p < 10-3) and disease duration (r = -0.352; p = 0.007). CONCLUSION: Our results revealed high prevalences of neurological, ocular, and renal complications in patients with CHPT and emphasized the importance of regular biological monitoring, therapeutic adjustments, screening, and adherence to treatment in the prevention of these complications.

Persistent hypernatremia secondary to adipsic central diabetes insipidus in a patient with herpes-induced meningoencephalitis and COVID-19 infection: a case report.

Central diabetes insipidus (CDI) typically manifests as a polyuria-polydipsia syndrome, in which normonatremia is generally maintained through the polydipsia. A 53-year-old woman presented with diabetic ketosis and hyperosmolar hyperglycemic syndrome. Her medical history included herpes meningoencephalitis, which was associated with confusion and amnesia. On physical examination, she was apyretic, confused, and had signs of extracellular dehydration. Her capillary glucose concentration was high and her urine was positive for ketones. Laboratory investigations revealed severe hyperglycemia, hypernatremia (plasma hyperosmolarity of 393.6 mOsm/L), and mild acute renal failure. In addition, she had a paucisymptomatic COVID-19 infection. Intravenous rehydration with isotonic saline solution and insulin therapy were effective at controlling the ketosis and ameliorating the hyperglycemia, but failed to normalize the hypernatremia and hyperosmolarity. She was not thirsty and had a urine output of 1 L/day, with urinary hypotonicity. Desmopressin administration reduced the hypernatremia and hyperosmolarity to within their normal ranges, and the patient's urinary osmolarity increased to 743 mOsm/L. Therefore, adipsic CDI was diagnosed. Endocrine investigations revealed isolated central hypothyroidism. The results of pituitary magnetic resonance imaging were normal. Thus, patients with impaired thirst may have an atypical presentation of CDI. In addition, the diagnosis of adipsic CDI is particularly challenging.

An invasive nasopharyngeal carcinoma with extension to the pituitary gland mimicking an invasive pituitary macroadenoma: A case report.

Herein, we report a rare case of invasive nasopharyngeal carcinoma with extension to the pituitary gland misdiagnosed as a pituitary macroadenoma. A 50-year-old woman was referred to our department with a diagnosis of pituitary macroadenoma. She presented with headache, visual disturbances, weakness, nausea, vomiting, and hypoglycemia. Polyuria was not reported. On pituitary magnetic resonance imaging, a large mass was observed to extend from the sella turcica to the sphenoid sinus, optic chiasm, and nasopharynx, leading to the initial diagnosis of an invasive pituitary macroadenoma. Biochemical investigations revealed corticotropin deficiency, secondary hypothyroidism, hypogonadotropic hypogonadism, and moderate hyperprolactinemia. Hormone replacement therapy was initiated. After hydrocortisone initiation, diabetes insipidus was revealed. Subsequent magnetic resonance imaging showed an infiltration of the nasopharynx with an extension to the pituitary gland. An endoscopic biopsy confirmed the diagnosis of undifferentiated nasopharyngeal carcinoma. The patient was referred to the oncology department for chemo and radiotherapy. Invasive nasopharyngeal carcinoma presenting with pituitary extension is very rare. It should be considered in the differential diagnosis of pituitary macroadenoma with hypopituitarism. Proper management of such cases requires a multidisciplinary approach.

Effects of high-intensity statin therapy on steroid hormones and vitamin D in type 2 diabetic men: A prospective self-controlled study.

The study aimed to assess the effect of high-intensity statin therapy on testicular and adrenal steroids and vitamin D levels in type 2 diabetic men. A prospective study, conducted between March 2021 and July 2022, including 60 men with type 2 diabetes, aged 40-65 years, statin-free, and in whom treatment with high-intensity statin was indicated. The patients had two visits, before and 6 months after a daily intake of 40 mg of atorvastatin. During each visit, they underwent a clinical examination, and a fasting blood sample was collected for biological and hormonal measurements. There was a significant increase in the prevalence of decreased libido (from 22% to 47%, p = 0.001) and a significant decrease in the frequency of sexual intercourse (from 4 [1-8] to 3 [0-4] per month, p = 0.005). The median ADAM's score significantly increased (from 4 [2-7] to 6 [3-8], p = 0.000). Twenty-two percent of the patients developed gynecomastia. The median total, bioavailable and free testosterone significantly decreased from 15.1 (11.4-17.4), 6.3 (5.0-7.8), and 0.27 (0.22-0.33) nmol/L to 12.7 (10.7-15.9), 5.7 (4.4-7.0), and 0.24 (0.19-0.30) nmol/L, respectively, with no change in FSH and LH levels. Three patients (5%) developed hypogonadism (testosterone <8 nmol/L). There was a significant decrease in DHEAS from 4.5 (2.8-6.1) to 3.8 µmol/L (2.6-5.6) and no change in cortisol and vitamin D levels. High-intensity statin therapy decreased androgen levels in type 2 diabetic men with significant clinical impact.

Secondary xanthogranulomatous hypophysitis mimicking a pituitary macroadenoma: a case report.

Hypophysitis is an extremely rare inflammatory disease that can mimic the clinical and radiological features of a pituitary adenoma. In this case report, we describe a 45-year-old woman with secondary xanthogranulomatous hypophysitis (XGH) who presented with signs of a pituitary macroadenoma. The patient complained of headaches, visual impairment, and amenorrhea-galactorrhea syndrome. Her physical examination was normal. Laboratory investigation revealed corticotropin, thyrotropin, and gonadotropin deficiencies. She also had low visual acuity in her right eye and an altered visual field. Pituitary magnetic resonance imaging revealed an intra and suprasellar mass measuring 13 × 11 × 16 mm, with hemorrhagic necrosis, that was having a discrete mass effect on the patient's optic chiasm and pituitary stalk. The patient was treated with hydrocortisone and levothyroxine, and then transferred to the Neurosurgery department for total transsphenoidal resection of the mass. Histological examination of the tumor permitted a diagnosis of XGH of a remodeled Rathke's pouch cyst to be made. Systemic conditions such as tuberculosis, sarcoidosis, and other granulomatous diseases were excluded. The etiopathogenesis of XGH remains poorly characterized, but it may be a progressive form of lymphocytic hypophysitis or a remodeled Rathke's pouch cyst. Screening for autoimmune pathology and systemic diseases is essential to guide appropriate management.

De Novo Psychiatric Disorders in a Woman With Giant Prolactinoma Treated With Cabergoline.

Dopamine agonists are the first-line treatment of prolactinomas. The risk of developing de novo psychiatric symptoms during dopamine agonist therapy is low. Herein, we report the case of a 42-year-old woman with a giant prolactinoma who developed a psychiatric disorder after 1 day of cabergoline therapy initiation. She presented with amenorrhea, galactorrhea, headaches, and disturbed vision. Biological investigations revealed hyperprolactinemia (2975 ng/ml) with gonadotropin deficiency. Pituitary MRI showed a giant pituitary adenoma. The patient was treated with cabergoline at the dose of 1 mg twice weekly. One day after the treatment initiation, she developed acute delirium with temporospatial disorientation and compulsive medication use. These symptoms disappeared 1 week after the reduction of the dose of cabergoline. Patients with hyperprolactinemia receiving an initial high dose of cabergoline may develop changes in mood and behavior regardless of prior psychiatric history.

Assessment of quality of life in patients with permanent hypoparathyroidism receiving conventional treatment.

Introduction: Patients with permanent hypoparathyroidism suffer from multiple complaints and are exposed to long-term complications that might compromise their well-being. The aim of this study was to assess the quality of life (QoL) in patients with permanent hypoparathyroidism receiving conventional therapy and to determine the associated factors. Methods: This was a cross-sectional matched case-control study including 53 patients with permanent hypoparathyroidism and 53 matched controls. Biochemical blood parameters (calcium, phosphate, albumin, magnesium, 25-hydroxy-vitamin D, creatinine, TSH, and PTH) and 24-hours calciuria were measured in patients with hypoparathyroidism. QoL was assessed in all participants using the Short Form 36 Health Survey (SF-36). Results: The study included 53 patients (41 women and 12 men) with hypoparathyroidism receiving conventional therapy.Their mean age was 52.8 ± 16.5 years. In comparison with controls, patients with hypoparathyroidism had significantly lower scores in all eight domains of SF-36 (p < 10- 3). Patients with poor socioeconomic conditions had lower SF-36 scores than those with good conditions.The etiology of hypoparathyroidism, the disease duration, the control of the disease, and the body mass index did not significantly interfere with SF-36 scores. SF-36 total score was negatively correlated with age (r=-0.619, p < 10- 3) and symptoms of hypocalcemia (r=-0.284, p = 0.039), and positively correlated with creatinine clearance (r = 0.559, p < 10- 3), magnesium level (r = 0.345, p = 0.011), and 25 hydroxy-vitamin D level (r = 320, p = 0.021). No significant correlations were found between SF-36 scores and other biological parameters such as calcemia, phosphatemia, phosphocalcic product, PTH, TSH, and calciuria. Conclusion: Patients with permanent hypoparathyroidism had impairment in their QoL. Age, socioeconomic conditions, renal function, magnesium level, and 25 hydroxy-vitamin D level may interfere in the decline of the QoL of these patients.

A case of reversible hypoparathyroidism in a patient with Riedel's thyroiditis treated with glucocorticoids.

A 48-year-old woman with a history of primary hypothyroidism, presented with compressive symptoms secondary to a rapid enlargement of a preexisting goiter. She had no clinical signs of hypocalcemia. Biological tests revealed hypoparathyroidism. Cervicothoracic computed tomography scan showed a heterogeneous compressive goiter. The patient was treated with levothyroxine, calcium, and alfacalcidol. A total thyroidectomy was not performed because of the hard adhesion to neighboring structures. Histopathological examination of the thyroid biopsy was consistent with the diagnosis of Riedel's thyroiditis (RT). The patient was treated with glucocorticoids. The outcome was marked by the resolution of compressive symptoms and the decrease of the thyroid gland volume. Serum calcium and parathyroid hormone levels reached normal ranges after the discontinuation of vitaminocalcic supplementation. Hypoparathyroidism may be clinically asymptomatic in a patient with RT as in our case. Early administration of glucocorticoids may be effective in reducing the fibrosclerotic process and lead to the recovery of parathyroid dysfunction.

[Cardiac abnormalities associated with hyperthyroidism: clinical, structural and rhythmic study]. / Anomalies cardiaques associées à l'hyperthyroïdie : étude clinique, structurelle et rythmique.

INTRODUCTION: The prevalence and nature of cardiac complications associated with hyperthyroidism vary considerably in the literature depending on the population studied and the means of investigation used to detect them. The aim of this study was to determine the structural, functional, and rhythmic cardiac abnormalities associated with hyperthyroidism and to identify their risk factors. METHODS: It is a cross-sectional study conducted in thirty adult patients with overt or subclinical hyperthyroidism. Each patient underwent a clinical cardiovascular examination, a cardiac Doppler ultrasound, a pulmonary ultrasound and a 24-hours rhythm holter. The diagnosis of cardiothyreosis (thyrotoxic heart disease) was retained if an arrhythmia, heart failure (HF) and/or pulmonary arterial hypertension (PAH) were noted following the investigations carried out. RESULTS: The mean age of the patients was 44.8 ± 14.4 years. The sex ratio (M/F) was 0.3. Five patients (17%) had subclinical hyperthyroidism and 25 (83%) had overt hyperthyroidism. Thirteen patients (43%) had cardiothyreosis. It consisted of a rhythm disorder in three patients (10%), PAH in twelve patients (40%) and HF in eight patients (27%). An age over 50 years and toxic nodular etiology were associated with atrial fibrillation (AF), p = 0.041 and p = 0.004 respectively. Tachycardia and a higher number of atrial extrasystoles were associated with HF, p = 0.039 and p = 0.007 respectively. A lower TSH, tachycardia and a higher number of atrial extrasystoles were associated with the presence of PAH, p = 0.004, p = 0.011 and p = 0.007 respectively. CONCLUSION: Cardiac complications should be sought in all patients with hyperthyroidism, especially in elderly and tachycardic patients. Specialized investigations such as echocardiography or 24 hours rhythmic holter should be requested in these cases.

Levothyroxine liquid oral substitution as an alternative treatment for refractory hypothyroidism due to gastrointestinal malabsorption: A case report.

Tablets of levothyroxine (LT4) are the most used form for the treatment of hypothyroidism. Some patients may present with refractory hypothyroidism despite a high daily LT4 dose. We report the case of a 49-year-old woman who was admitted to our department for refractory hypothyroidism. She was treated with 300 µg oral LT4 tablets daily (3.9 µg/kg/day). Despite good compliance and regular intake of high doses of LT4, she had persistent symptoms of hypothyroidism and a thyroid-stimulating hormone level of 92.4 mIU/L. LT4 absorption test was consistent with the diagnosis of malabsorption. Etiological investigations revealed Helicobacter pylori gastritis. Helicobacter infection was adequately treated, but symptoms of hypothyroidism and elevated thyroid-stimulating hormone persisted. Increased LT4 doses (400 µg) failed to normalize thyroid-stimulating hormone levels. Thus, she was put on LT4 liquid form at a dose of 80 drops/day per day (400 µg). Two weeks later, she presented with clinical and biological improvement with a normal free thyroxine level of 1.14 ng/dL. Patients with gastrointestinal disorders may present with refractory hypothyroidism despite increasing doses of LT4. Switching to liquid formulation may resolve this problem.

Adherence to glucocorticoid replacement therapy in Addison's disease: Association with patients' disease knowledge and quality of life.

Little is known about the quality of adherence to glucocorticoid replacement therapy in patients with Addison disease (AD). The aim of this study was to evaluate the quality of glucocorticoid treatment adherence in patients with AD and to assess its association with patients' disease knowledge and quality of life. METHODS: This is a cross-sectional study including 58 patients with AD. The Girerd questionnaire was used to assess the quality of adherence to glucocorticoid replacement therapy. A questionnaire was specially designed to assess patients' disease knowledge. The AddiQol questionnaire, specific to AD, was used to assess the patients' quality of life. Patients were considered non-adherent if they gave three or fewer than three negative answers to the Girerd questionnaire (score≤3/6). RESULTS: The mean age of the patients was 48.4±13.3 years (39 women and 19 men). Twenty-seven patients (46%) were non-adherent to glucocorticoid replacement therapy. An age below 48 years, poor adherence to comorbidity treatments, baseline cortisolemia at diagnosis>5µg/dl, history of adrenal crisis, poor knowledge about the disease, BMI<26.7kg/m2, waist circumference<90cm, low systolic blood pressure, fasting blood glucose<0.9g/l, and triglyceride<1g/l were the factors independently associated with non-adherence (respectively ORa [CI 95%]=4.8 [2.8-10.7], 5.0 [3.0-12.2], 2.3 [1.2-6.2], 4.1 [2.0-8.3], 3.9 [1.2-7.2], 3.9 [1.1-6.9], 1.8 [1.1-2.9], 4.8 [2.6-8.2], 2.5 [1.1-5.3], and 2.2 [1.1-5.1]). There was a positive correlation between the disease knowledge questionnaire score and the Girerd score (p=0.02, r=0.31). There was a positive correlation between the AddiQoL score and the Girerd score (p=0.01, r=0.32). CONCLUSION: Non-adherence to glucocorticoid replacement therapy was common in patients with AD and was associated with more frequent adrenal crisis and poorer quality of life. The quality of treatment adherence was correlated with patients' disease knowledge. Therapeutic education is essential to reduce the frequency of non-adherence, especially among young patients.

Vitamin B12 deficiency in long-term metformin treated type 2 diabetic patients: Prevalence and risk factors in a Tunisian population.

Objectives: To determine the prevalence of vitamin B12 deficiency in a Tunisian population with type 2 diabetes (T2D) on metformin treatment for more than three years and to identify its risk factors. Methods: This is a cross-sectional study conducted on 257 patients with T2D treated with metformin for at least three years. Patients were divided into two groups according to their vitamin B12 status. Low vitamin B12 was defined as ≤ 203 pg/mL. Results: The mean age of the patients was 59.8 ± 7.9 years. The mean duration of metformin use was 10.2 ± 5.2 years. The mean vitamin B12 level was 294.9 ± 156.4 pg/mL. The prevalence of vitamin B12 deficiency was 28.4%. Male gender, HbA1c < 7% and hyperhomocysteinemia were significantly associated with vitamin B12 deficiency (respectively p = 0.02, p < 0.001, p < 0.001). Homocysteine level was negatively correlated with vitamin B12 level (r = -0.2, p = 0.001). Dose and duration of metformin treatment, peripheral neuropathy and anemia were not associated with vitamin B12 deficiency. On multivariate analysis, HbA1c < 7% and hyperhomocysteinemia were independently associated with vitamin B12 deficiency (respectively OR = 3.2, 95%CI = [1.6-6.3] and OR = 2.3, 95%CI = [1.2-4.2]). Discussion: The prevalence of vitamin B12 deficiency in patients with T2D on metformin treatment was high. Hyperhomocysteinemia is associated with vitamin B12 deficiency suggesting that the deficit occurs at the tissue level.