Cardiothyreosis: Prevalence and risk factors.

Cardiothyreosis (CT) or thyrotoxic heart disease is associated with higher morbidity and mortality than the other forms of hyperthyroidism. Its risk factors have been analyzed in a limited number of studies. The aims of our study were to investigate the prevalence of CT and its risk factors in patients with hyperthyroidism. METHODS: We identified 538 patients with a hospital discharge diagnosis of hyperthyroidism from January 2000 to December 2015. Among them, 35 patients were diagnosed as having CT. Their demographic, clinical and biological characteristics were studied and compared with those of 72 controls (patients admitted for hyperthyroidism without CT) randomly selected using univariate and multivariate analysis. RESULTS: The prevalence of CT in patients hospitalized with overt hyperthyroidism was 6.5%. The cardiac complications seen were atrial fibrillation (AF) in 33 cases (6.1%) and cardiac heart failure (CHF) in 11 cases (2%). The risk factors of CT were age greater than 50 years (OR=13.1; 95% CI [4.9-34.4]), low socioeconomic status (OR=2.8; 95% CI [1.2-6.7]), low educational level (OR=3.1; 95% CI [1.2-8.3]), personal history of hypertension (OR=3.5; 95% CI [1.1-11.2]) and a multinodular toxic goiter as the etiology of hyperthyroidism (OR=4.6; 95% CI [1.6-13.9]). After multivariate analysis, age greater than 50 years was the only independent risk factor of CT (adjusted OR=11.6; 95% CI [2.7-49.5]). Severe biological hyperthyroidism (FT4 >3 times normal) was associated with a lower risk of CT (adjusted OR=0.2; 95% CI [0.1-0.9]). CONCLUSIONS: The prevalence of CT in patients with overt hyperthyroidism was relatively low. Cardiac complications were AF and CHF with a clear predominance of AF. Advanced age was the only independent risk factor of CT. Cardiac complications may be seen even if hyperthyroidism is not biologically severe.

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.

The rs9939609 polymorphism in the fat mass and obesity associated (FTO) gene is associated with obesity in Tunisian population.

CONTEXT: Variations in the fat mass and obesity-associated gene (FTO) has been associated with obesity in many populations, but the results are conflicting. OBJECTIVE: The aim of this study was to evaluate the effect of the rs9939609 polymorphism in the FTO gene on obesity risk and plasma leptin, adiponectin, insulin and lipid concentrations in Tunisians. MATERIALS AND METHODS: Four hundred and ninety-four subjects with obesity and 334 non-obese participated in this study. The rs9939609 (T/A) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: Significant differences in genotype frequencies were observed between cases and controls. In the separate analysis by gender, the association between the AA genotype and obesity was statistically significant in women but not in men. After stratification by obesity class this association remains only with obesity class III. DISCUSSION: Our study is in agreement with studies on Caucasian, Portuguese and Cebu Filipino populations where a gender-specific association was found between rs9939609 polymorphism and obesity. It is also in agreement with studies on Mexican, Spanish and European populations, where an association was found with obesity class III. CONCLUSION: The rs9939609 polymorphism of FTO gene is associated with obesity, especially obesity class III in women.

The risk for hypoglycemia during Ramadan fasting in patients with adrenal insufficiency.

OBJECTIVES: The risk for hypoglycemia during Ramadan fasting in patients with adrenal insufficiency (AI) is not fully known. The aims of this study were to evaluate this risk objectively and to determine the associated factors. METHODS: This prospective case-crossover study included 25 women and 5 men with known and treated AI and a median age of 38.5 y. Patients underwent clinical examination and a fasting blood sample was collected to measure glucose, urea, creatinine, sodium, potassium, cortisol, growth hormone and free thyroxine. A 24-h continuous glucose monitoring system (CGMS) using iPro2 (Medtronic, Parsippany, NJ, USA) with Enlite sensor (Medtronic) was performed for each patient during a Ramadan fasting day then again during a nonfasting day. RESULTS: Interstitial glucose levels during the 24-h period, the fasting period, and the fasting period after exclusion of the 5 postprandial hours were significantly lower during the fasting day than on the nonfasting day. Hypoglycemia occurred in three patients (10%) during the fasting day but not during the nonfasting day (P = 0.23). Hypoglycemia was asymptomatic in two cases. Male sex was significantly associated with the occurrence of hypoglycemia. CONCLUSION: Interstitial glucose levels were lower during fasting in patients with AI. However, the risk for hypoglycemia was not increased.

Insulin-induced edema: an unusual complication in a patient with diabetic ketosis.

The insulin-induced edema is a rare complication of insulin therapy. Two mechanisms are known, the sodium and water retention and vasoactive mediator's release. We report the case of a 32 years-old patient, with a history of diabetes for one month treated with metformin. He was hospitalized for diabetic ketosis and developed lower legs edema and scrotum edema, few hours after the insulin injections. Biologic tests showed hypoprotidemia without proteinuria and hyponatremia. The abdominal ultrasound showed a liver steatosis. Chest radiography was normal. Transthoracic echocardiography showed a moderate pericardial effusion. Edema resolved spontaneously one month later. Protidemia and natremia were normalized. The natural history of insulin-induced oedema was observed in our patient and the accountability of insulin is likely, but invetstigations are often needed to eliminate other causes of edemas.

Ramadan fasting in patients with adrenal insufficiency.

AIM: The risks of fasting during Ramadan in patients with adrenal insufficiency are unknown. The aims of this study were to evaluate these risks in such patients, to determine the risk factors and finally to set some recommendations. METHODS: It is a cross-sectional study about 180 patients with known and treated adrenal insufficiency. The patients responded to a 14-item questionnaire concerning their knowledge about the disease and fasting during the last month of Ramadan. RESULTS: There were 132 women and 48 men. The mean age was 47.6 ± 15.0 years (14-79). One hundred and thirty eight patients (76.7 %) were advised by their physician not to fast. Ninety-one patients (50.5 %) tried to fast. Complications occurred in 61 cases (67.0 %): asthenia in 88.5 % of cases, intense thirst in 32.8 %, symptoms of dehydration in 49.2 % and symptoms of hypoglycaemia in 18 %. One patient was hospitalized. Fifty-five patients (60.4 %) were able to fast for the whole month. Age, gender, duration of the disease, its primary origin, associated hypothyroidism, diabetes mellitus, hypertension or diabetes insipidus and daily dose of hydrocortisone did not significantly differ between fasters and non-fasters, full-month-fasters and partial-month-fasters, and fasters with complications and fasters without complications. The frequency of adequate knowledge about the disease was significantly higher in full-month-fasters vs. partial-month-fasters, and in fasters without complications vs. those with complications. CONCLUSION: In patients with adrenal insufficiency, fasting can cause complications especially if the level of knowledge about the disease is low.

Lack of association between FokI polymorphism in vitamin D receptor gene (VDR) & type 2 diabetes mellitus in the Tunisian population.

BACKGROUND & OBJECTIVES: The impact of several environmental and genetic factors on diabetes is well documented. Though the association between the vitamin D receptor (VDR) gene polymorphisms and type 2 diabetes mellitus (T2DM) has been analyzed in different ethnic groups, the results have been inconsistent. The aim of this study was to evaluate the possible association between VDR FokI polymorphism and genetic susceptibility to T2DM in Tunisian population. METHODS: A total of 439 unrelated patients with T2DM and 302 healthy controls were included in the study. Genomic DNA was extracted from blood and genotyped for the single nucleotide polymorphism (SNP) of FokI (T/C: (rs2228570) by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) analysis. RESULTS: The genotype distribution and the relative allelic frequencies for the FokI polymorphism were not significantly different between T2DM and controls: in T2DM patients the frequencies of the CC, CT, and TT genotypes were 52.6, 41.0, and 6.1 per cent, respectively, and in controls the genotype frequencies were 55.6, 38.7, and 5.6 per cent, respectively. In our study, the TT genotype of the FokI polymorphism was not associated with T2DM (OR =1.19, 95% CI 0.63 - 2.25, P=0.577). INTERPRETATION & CONCLUSIONS: Our study showed no significant association of the FokI polymorphism in the vitamin D receptor gene with type 2 diabetes mellitus in Tunisian population.

[Etiological diagnosis of central diabetes insipidus: about 41 cases]. / Diagnostic étiologique du diabète insipide central: à propos de 41 cas.

The occurrence of polyuria-polydipsia syndrome with hypotonic urine requires careful diagnostic strategy. This study aims to evaluate diagnostic modalities for central diabetes insipidus. We conducted a retrospective study of 41 cases with central diabetes insipidus (CDI). Data were collected at the Department of Endocrinology, University Hospital La Rabta, Tunis, from 1990 to 2013. We identified the circumstances for detecting CDI, the abnormalities in anterior pituitary assessment and pituitary imaging. CDI occurred in the postoperative period in 20 patients. The average urine 24-hour volume was significantly higher in patients with CDI outside a surgical setting. Water deprivation test was successful in all patients who benefited from it. Outside of neurosurgery, infiltration causes were found in 6 patients and tumor causes were found in 6 patients. CDI was associated with empty sella turcica in 1 case and idiopathic sella turcica in 3 patients. Hypothalamic-pituitary magnetic resonance imaging and anterior pituitary balance sheet are systematic outside pituitary surgery setting and obvious primary polydipsia.

Bone Mineral Density in Sheehan's Syndrome; Prevalence of Low Bone Mass and Associated Factors.

Hypopituitarism is a known cause of bone mineral loss. This study aimed to evaluate the frequency of osteopenia and osteoporosis in patients with Sheehan's syndrome (SS) and to determine the risk factors. This is a retrospective study of 60 cases of SS that have had a bone mineral density (BMD) measurement. Clinical, biological, and therapeutic data were collected. The parameters of osteodensitometry at the femoral neck and the lumbar spine of 60 patients with SS were compared with those of 60 age-, height-, and weight-matched control women. The mean age at BMD measurement was 49.4 ± 9.9 yr (range: 25-76 yr). The mean duration of SS was 19.3 ± 8.5 yr (range: 3-41 yr). All patients had corticotropin deficiency and were treated with hydrocortisone at a mean daily dose of 26.3 ± 4.1 mg. Fifty-seven patients (95%) had thyrotropin deficiency and were treated with thyroxine at a mean daily dose of 124.3 ± 47.4 µg. Thirty-five of the 49 patients, aged less than 50 yr at diagnosis and having gonadotropin deficiency (71.4%), had estrogen-progesterone substitution. Osteopenia was present in 25 patients (41.7%) and osteoporosis in 21 (35.0%). The BMD was significantly lower in the group with SS than in the control group (p < 0.001). The odds ratio of osteopenia-osteoporosis was 3.1 (95% confidence interval: 1.4-6.8) at the femoral neck and 3.7 (95% confidence interval: 1.7-7.8) at the lumbar spine. The lumbar spine was more frequently affected by low bone mineral mass (p < 0.05). The duration of the disease and the daily dose of hydrocortisone were independently and inversely associated with BMD at the femoral neck. The daily dose of thyroxine was independently and inversely associated with BMD at the lumbar spine. Estrogen-progesterone replacement therapy was not associated with BMD. Low bone mineral mass was very common in patients with SS. The lumbar spine was more frequently affected. The duration of the disease and the doses of hydrocortisone and thyroxine were involved in bone mineral loss.

The Gly482Ser polymorphism of the peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) is associated with type 2 diabetes in Tunisian population.

BACKGROUND AND AIMS: Peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α) is a transcriptional co-activator involved in adaptive thermogenesis, skeletal muscle metabolism, fatty acid oxidation, and gluconeogenesis. Several studies have suggested that the common PGC-1α polymorphism Gly482Ser (rs8192678) may be associated with risk of type 2 diabetes (T2D), with conflicting results. The aim of this study was to analyze whether the Gly482Ser variant is a risk factor for development of T2D in Tunisian population. METHODS: In a case-control study 487 unrelated patients with type 2 diabetes and 402 apparently healthy controls were recruited from January 2008 to August 2010. The Gly482Ser polymorphism was determined by PCR-RFLP analysis. RESULTS: A significant difference in genotypes distribution was observed between patients (Gly/Gly: 34.1%; Gly/Ser: 47.1%; Ser/Ser: 18.5%) and controls (Gly/Gly: 43.8%; Gly/Ser: 42.3%; Ser/Ser: 13.9%) (χ(2)=9.44, p=0.009). The T2D patient group showed a significant higher frequency of the Ser allele compared to the controls (43% vs. 34%; OR: 1.35, 95% [CI]: 1.11-1.65, p=0.002). The association between the Gly482Ser polymorphism and T2D remained significant after adjustment for other well-established cardiovascular risk factors. CONCLUSIONS: In the current study, a significant and independent association between the Gly482Ser polymorphism (rs8192678) of the PGC-1α gene and T2D in the Tunisian population was found.

Tumor necrosis factor-α (TNF-α) -863C/A promoter polymorphism is associated with type 2 diabetes in Tunisian population.

AIMS: Tumor necrosis factor α (TNFα) plays a key role in orchestrating the complex events involved in inflammation and immunity. Accordingly, TNF α has been implicated in a wide range of autoimmune and infectious diseases, but also in conditions such as obesity and insulin resistance. The aim of the present study was to investigate the association between the -863C/A polymorphism in the promoter of the TNFα gene and type 2 diabetes in the Tunisian population. METHODS: The polymorphism -863C/A in the TNFα gene was determined in 211 type 2 diabetes patients and 345 healthy controls using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) analysis. RESULTS: A significant difference in genotype distribution and allele frequency was observed between patients and controls. Patients with type 2 diabetes had significantly higher frequency of the CA+AA genotypes compared to controls [35.5% vs. 22.3%; OR (95%CI), 1.91 (1.31-2.8); p=0.001]. The type 2 diabetes patient group showed a significant higher frequency of the A allele compared to the controls (0.19 vs. 0.11; p=0.001). After adjustment by a stepwise logistic regression method, hypertension, dyslipidemia, and CA+AA genotype were found to be significantly associated with T2D. CONCLUSION: The present study showed a significant and independent association between the -863C/A polymorphism of the TNFα gene and type 2 diabetes in the Tunisian population.

Abnormal circulating levels of matrix metalloproteinases and their inhibitors in diabetes mellitus.

BACKGROUND: The aim of this study was to determine plasma levels of matrix metalloproteinases (MMPs) 2, 3, and 9 and their tissue inhibitors (TIMPs) 1 and 2 in type 2 diabetic patients (T2DM) compared to healthy subjects. METHODS: The study involved 54 patients with T2DM and 57 age and gender matched healthy adults as controls. MMPs 2 and 9 were analyzed by gelatin zymography and MMP-3 and TIMPs 1 and 2 by ELISA. RESULTS: For technical feasibility, MMPs 2 and 9 were expressed in pro forms. Pro-MMP-9 was significantly higher (p < 0.05), whereas TIMP-1 and TIMP-2 levels were significantly decreased (p < 0.01) in patients with T2DM compared to controls. The MMP-3/TIMP-1 and the MMP-3/TMP-2 ratios were significantly higher in T2DM patients than controls (p < 0.05). Fasting plasma glucose was inversely correlated with TIMP-1 (r = -0.412, p < 0.01) and TIMP-2 (r = -0.315, p < 0.001), but was not associated with MMPs. CONCLUSIONS: The present study identified abnormalities in plasma markers for extracellular matrix metabolism in T2DM. The new parameters would constitute an effective approach to explore the complications of uncontrolled diabetes.

Unilateral agenesis of internal carotid artery associated with congenital combined pituitary hormone deficiency and pituitary stalk interruption without HESX1, LHX4 or OTX2 mutation: a case report.

Agenesis of internal carotid artery (ICA) is an unusual finding in subjects with congenital Combined Pituitary hormone deficiency (CPHD) with only nine cases being reported to date but to our best knowledge none of them was genetically investigated. A 10-years old girl presented with severe growth failure (height 103 cm) with substantial bone age delay (3 years). She had no history of perinatal insults or familial CPHD. There was no evidence of mental retardation or craniofacial dysmorphism or ophtalmological abnormalities. She was first diagnosed with GH and TSH deficiency. Cerebral magnetic resonance imaging (MRI) showed hypoplastic anterior pituitary, flat sella turcica, absent pituitary stalk with ectopic posterior pituitary as well as agenesis of the left ICA and the left carotid canal. Genomic analysis of pituitary transcription factor HESX1, LHX4 and OTX2 showed no mutations. Treatment with GH and thyroxine was started. The patient remained free of neurovascular symptoms for 5 years but she presented at the age of 15 years with delayed puberty related to an evolving gonadotropin deficiency. ICA agenesis associated with CPHD is unusual and is often asymptomatic in children. Since the CPHD with pituitary stalk interruption cannot be due to HESX1, LHX4 or OTX2 mutation in our case, other pathogenetic mechanisms may be responsible for CPHD associated with unilateral ICA agenesis.

[Ambulatory blood pressure measurement and control in hypertensive diabetic patients]. / Appréciation du profil tensionnel par mesure ambulatoire de la pression artérielle chez les diabétiques hypertendus traités.

BACKGROUND: Good blood pressure control is one of the recommended targets in diabetic patient's management. AIM: To evaluate blood pressure (BP) control in hypertensive treated diabetic patients using ambulatory blood pressure measurement (ABPM). METHODS: Two hundred and six hypertensive treated diabetic patients were enrolled in this study (83 men and 123 women). Mean age were 60.3±9.6 years-old with mean diabetic duration of 9.1±8.2 years. All of them underwent 24 hours ABPM. Intervals between measurements were 20 minutes at diurnal period and 30 minutes at nocturnal period. RESULTS: 28 patients (13.6%) only were at recommended target levels of blood pressure control (mean diurnal BP<130/80 mmHg and nocturnal BP<115/65 mmHg) and 137 patients were at the most bed control levels (mean diurnal BP ? 140/90 mmHg or nocturnal BP ? 125/75 mmHg). Bed controlled patients had mildly higher waist circumference (p=0.08). Poor BP control was associated with non dipper character (p<0.001), diabetic nephropathy (p<0.01) and diabetic retinopathy (p<0.01). CONCLUSION: Our hypertensive treated diabetic patients were far from good blood pressure control. ABPM showed that the loss of nocturnal blood pressure fall was the most associated abnormality with poor BP control. Diabetic microangiopathy were more frequent in poor controlled patients.

[Erythrocyte abnormalities in thyroid dysfunction]. / Les anomalies ertyrocytaires au cours des dysthyroïdies.

BACKGROUND: Erythrocyte abnormalities are frequently associated with thyroid dysfunction. However, they are rarely investigated and related to the thyroid. AIM: This study was aimed to determine the nature and frequency of erythrocyte abnormalities in thyroid disease and look for their evolution after thyroid function restoration. METHODS: This retrospective study included 412 patients with peripheral thyroid disease; hyperthyroidism (n=235) or hypothyroidism (n=177). Hyperthyroidism was considered for TSH<0.10 ÌUI/ml and hypothyroidism for TSH>5.0 ÌUI/ml. Anemia was defined by hemoglobin level<13 g/dl in men and <12 g/dl in women, microcytosis by mean corpuscular volume (MCV)<80 fl, macrocytosis by MCV>98 fl, and hypochromia by mean corpuscular hemoglobin (MCH)<25 pg. Restoration of euthyroid state was considered in patients with normal TSH levels for at least 3 months. RESULTS: Anaemia was observed in 40.9% of patients with hyperthyroidism and 57.1% of patients with hypothyroidism. Among these, normocytic or macrocytic anaemia was present in 46.3% of cases. Whereas, microcytosis, with or without anaemia, was noted in 87.7% of patients with hyperthyroidism. FT4 was positively correlated with the number of red blood cells and haemoglobin, and inversely correlated with MCV and MCH. After restoration of euthyroid state, most erythrocyte abnormalities were corrected. CONCLUSION: Thyroid diseases are frequently associated with erythrocyte abnormalities, including normocytic anaemia in hypothyroidism and microcytosis in hyperthyroidism. These abnormalities should be investigated and corrected. Their presence could steer towards subclinical thyroid dysfunction, allowing its early management.