[Growth hormone deficiency and pituitary stalk interruption in Fanconi anemia]. / Déficit en GH par interruption de la tige pituitaire dans l'anémie de Fanconi.

Fanconi anemia is a rare disorder inherited by recessive autosomic transmission belonging to the group of chromosomal instability syndromes. It is characterized by progressively developing medullary aplasia, various congenital malformations and especially a high risk of cancer, particularly acute myeloblastic leukemia and certain solid tumors. The association is quite common in patients with endocrine disease which constitutes an additional factor of morbidity and must be diagnosed and treated. We report a case of Fanconi anemia revealed by severe delay in statural growth and primary amenorrhea with a 21-year-old girl. The diagnosis was suggested by asymptomatic pancytopenia caused by a medullary hypoplasia and confirmed by a cytogenetic investigation using cross-linking agents that showed a large number of chromosomal breaks. Hormonal exploration revealed hypopituitarism with complete growth hormone (GH) deficiency and hypogonadotrophic hypogonadism caused by interruption of the pituitary stalk. The aim of this case report is to illustrate the importance of early exploration of retarded growth which, in some patients, can reveal potentially serious, and treatable, disease.

[Hypertension and insulin treatment in type 2 diabetes]. / L'hypertension artérielle au cours de l'insulinothérapie du diabétique de type 2.

UNLABELLED: Insulin resistance and endogenous hyperinsulinemia are associated with blood hypertension. OBJECTIVE: The aim of this analysis is to estimate the prevalence of blood hypertension one year after insulin treatment in type 2 diabetic patients. MATERIAL: and methods: This is a retrospective clinical study of 178 type 2 diabetic patients (57 men and 121 women) insulin treated since at least one year. Mean age is 62 +/- 10 years and mean duration of diabetes is ten years. All patients had a clinical and biological control before treatment with insulin and at least three controls during the first year of insulin treatment (anthropometric measurements, blood pressure, fasting plasma glucose, HbA1C). WHO definition of hypertension is used (blood pressure >or=140 / 90 mmHg). RESULTS: At baseline, 48% of patients have hypertension. After insulin treatment, the prevalence of hypertension significantly increase to 53% (94 / 178) three months later (p=0.008), to 54.5% (98 / 178) six months later (p=0.001) and to 55.6% (99 / 178) twelve months later. This increase in hypertension frequency is associated with a significant weight gain and a better blood glucose control. CONCLUSION: Insulin therapy may contribute to the development of blood hypertension. It promotes renal sodium retention and increases sympathetic nervous system activity. In the UKPDS intensive blood glucose control with insulin is not associated with an increase of macro vascular complications. These observational data suggest the need for further study of the relationship between exogenous insulin and hypertension.

Prevalence of metabolic abnormalities in the Tunisian adults: a population based study.

AIMS: To estimate the prevalence of individual metabolic abnormalities and the cluster of metabolic abnormalities in a representative sample of the Tunisian adult population and to identify their relationship with gender, age and residency. The definition used is an adaptation of the NCEP ATP III definition, using total cholesterol>or=5.2 mmol/l instead of HDL-cholesterol. MATERIALS AND METHODS: We used a sample of the Tunisian National Nutrition Survey (TNNS), a cross-sectional health survey conducted in 1996, to estimate the nutritional status of the population. The TNNS included 2 927 adults aged 20 years or older who had measurements of height, body weight, waist circumference, blood pressure, fasting plasma glucose, total cholesterol and triglycerides. The cluster of metabolic abnormalities was defined as the presence of three or more metabolic abnormalities. RESULTS: The prevalence of abdominal obesity, hypertriglyceridemia, high total cholesterol, high blood pressure and high fasting plasma glucose was, respectively, 9%, 23%, 24%, 45% and 15% in men and 33%, 19%, 29%, 44% and 15% in women. The prevalence of the cluster was more frequent in women than in men (18% versus 13%, P<0.001) and in those living in urban communities (21% in women, 16% in men) rather than rural communities (11% in women, 8% in men) (P<0.001). The prevalence also increased significantly with age (P<0.001). CONCLUSION: The cluster of metabolic abnormalities and its components are common in the Tunisian adult population and prevalence increases significantly with female sex, urban residency and age.

[Hypertension in polycystic ovary syndrome]. / L'hypertension artérielle au cours du syndrome des ovaires polykystiques.

UNLABELLED: Polycystic ovary syndrome (PCOS) is associated with multiple cardiovascular risk factors. The aims of this study are to investigate the prevalence of hypertension in a female population with PCOS and to correlate hypertension with her clinical and hormonal profile. MATERIALS AND METHODS: it is a transversal study of 79 PCOS patients with mean age of 25 +/- 7 years (range 13-44). PCOS diagnosis is made by Rotterdam consensus criteria's (2003). WHO definition of hypertension is used (BP 140/90 mmHg). Blood pressure is measured three times in each patient. Ovarian echography and biochemical assays (GnRH test, androgens, cholesterol, triglycerides, and oral glucose tolerance test) are made before the 5th day of the menstrual cycle. RESULTS: 12% of PCOS women have hypertension. Family history of hypertension is not a predictive factor of hypertension in our study. PCOS patients with hypertension are not significantly older than those without hypertension (28.4 +/- 6.5 vs. 25.2 +/- 7; p = 0.12). If compared to PCOS women without hypertension, those with hypertension have a significantly higher BMI (39.2 +/- 7 vs. 29.6; p = 0.0004). PCOS patients with and without hypertension do not differ significantly in their level of androgens and total cholesterol. Triglycerides level is higher in PCOS patients with hypertension (p = 0.06). In oral glucose tolerance test, areas under the curve of insulin and glucose are significantly higher in PCOS patients with hypertension (respectively p = 0.06 and 0.02). The area under the curve of LH during GnRH test is lower in PCOS patients with hypertension (p = 0.04).

[Prevalence of celiac disease serological markers in Tunisian type 1 diabetic adults]. / Prévalence des marqueurs sérologiques de la maladie coeliaque chez des adultes tunisiens diabétiques de type 1.

OBJECTIVE: to evaluate the prevalence of celiac serological markers; anti-transglutaminase (ATGt), anti-endomysium (AE), anti-gliadin (AGD) and anti-reticulin (AR) antibodies; in type 1 diabetic Tunisian adults. SUBJECTS AND METHODS: 261 type 1 diabetic patients aged from 16 to 60 years were enrolled in this prospective study. IgG and IgA transglutaminase and gliadin were measured with ELISA. IgA AE were tested by indirect immunofluorescence using 2 substrates; monkey oesophagus and human umbilical cord. AR were detected by indirect immunofluorescence on rat liver, kidney and stomach. Sera IgA level was measured by turbidimetry. RESULTS: 83/261 of diabetics were positive for at least one antibody, 5.7% had ATGt-A, 3.4% AE on monkey esophagus, 3.1% AE on umbilical cordon, 18% AGD-A, 19.5% AGD-G and 3.1% AR. There was an excellent concordance between AE and ATGt (r = 0.9). Out of the 261 diabetics, 5 had an IgA deficiency and one of them has IgG AE and ATGt. CONCLUSION: serological markers of celiac disease seem to be frequent in diabetics. Nevertheless, diagnosis must be confirmed by histological studies which allow us to know the real prevalence of celiac disease in diabetic adults.

[Imaging of cerebrotendinous xanthomatosis]. / Imagerie de la xanthomatose cérébrotendineuse.

Cerebrotendinous xanthomatosis is a rare lipid storage disorder due tocaused by an autosomal recessive inherited defect of the hepatic mitochondrial sterol 27 hydroxylase. It's characterized by accumulation of cholestanol and cholesterol in many tissues, in particular tendons and brain, with tendon xanthomas, juvenile cataracts, and neurological abnormalities. MR imaging showed typical bilateral and symmetrical involvement of the dentate nuclei. Early and long- term treatment may improve neurologic function. The authors present a case of cerebrotendinous xanthomatosis and describe ultrasound, computed tomography, and magnetic resonance findings.

[Adrenal metastasis of a papillary thyroid cancer]. / Métastase surrénalienne d'un cancer papillaire de la thyroïde.

Adrenal metastases of the papillary thyroid carcinoma (PTC) are very rare. We report one case. A 63-year-old woman had undergone 15 years earlier left lobo-ishmectomy for a papillary thyroid cancer (PTC) and 7 years earlier right adrenalectomy for a tumor. Histologic examination showed a benign cortical tumor. In 1999, when the patient was admitted for worsening of glycemic control, a recurrence of the adrenal mass was detected. According to the hormone evaluation it was a non-functional tumor. Adrenalectomy was performed in June 2002 because the patient had initially declined surgery. Histologic examination and thyroglobulin immunochemistry identified metastatic PTC. Re-reading the histology slide of the first adrenalectomy agreed with the diagnosis. Thyroidectomy was completed in March 2003. Although iodine-131 therapy and thyroxine treatment were given, bone metastases were detected in August 2004. PTC usually spreads to the cervical and mediastinal lymph nodes. Distant spread may occur to bone or lung, but exceptionally to the adrenal gland. The adrenal localization is often associated with lung or bone metastasis. In our patient, the adrenal metastasis remained isolated for many years. It has been reported that survival rate decreases considerably after appearance of a distant metastasis. Although given delayed radical treatment, our patient remained alive 13 years after.

[Ramadan fasting in type 2 diabetes mellitus]. / La pratique du jeûne du mois de Ramadan chez le diabétique de type 2.

This study was designed to assess the effects of fasting during Ramadan on weight, blood pressure, metabolic control and plasma lipoproteins in diabetic patients. This study was conducted in December 2000 (Ramadan 1421) when the length of fasting was 12 hours a day. It included 38 type 2 diabetic patients (20 males and 18 females). Mean patient age was 51.410.5 years and mean body mass index (BMI) 28.94.7kg/m2. Three patients were treated with diet and 35 with oral hypoglycemic agents. Clinical and biochemical parameters were evaluated during three periods: three weeks before Ramadan (T0), at the fourth week of Ramadan (T1) and three weeks after the end of Ramadan (T2). During the month of Ramadan, a decrease in weight (0.52kg) and no change in blood pressure were observed. No metabolic complication occurred in our patients. A significant effect of Ramadan fasting was observed on glycemic control and lipoprotein levels. In patients whose fructosamine level before Ramadan was higher than 340micromol/l, plasma fasting glucose and serum fructosamine increased during Ramadan (p<0.003) and returned to initial levels at the end of Ramadan T2; in these patients also, a decrease of HDL-cholesterol (p<0.01) associated with an increase of LDL-cholesterol (p<0.003) were observed at T1 and disappeared at T2. But, in patients whose fructosamine level at T0 was lower than 340micromol/l, no effect on glycemic control and no significant effect on serum lipoprotein levels were found during Ramadan month. Ramadan fasting in type 2 diabetic patients seems to cause slight effects on glycemia and lipoprotein levels when previous metabolic control is quite good; but fasting induces more deterioration when previous control is poor.

[Toxic nodular goitre associated with papillary thyroid carcinoma and primary hyperparathyroidism]. / Association d'un goitre multinodulaire toxique, d'un carcinome papillaire de la thyroïde, et d'une hyperparathyroïdie primaire.

The association of a toxic multinodular goitre with papillary thyroid carcinoma and primary hyperparathyroidism is very rare. Only one case is reported in the literature, we present the second one. It is a 51 year old woman, who initially presented with a toxic nodular goitre. The diagnosis of primary hyperparathyroidism was made following renal complications and the discovery of papillary thyroid carcinoma was incidental during the surgical treatment of parathyroid adenoma. Whilst the association of those three diseases is exceptional, the coexistence of any two of them is relatively frequent without any known common etiopathogenetis. It is recognised that hyperparathyroidism can be found in hyperthyroid patients, but the diagnosis of hyperparathyroidism in these cases is very difficult. The fortuitous discovery of papillary thyroid carcinoma during parathyroid surgery has already been reported but in most cases it is a microcarcinoma. In patients presenting with hyperthyroidism the risk of an associated carcinoma is generally felt to be negligeable. However, this associations is not rare. The association of primary hyperparathyroidism, hyperthyroidism and papillary carcinoma of the thyroid is rare. However, the authors suggest that the presence of any of the pathologies should trigger a search for the other two.

Celiac disease in adult patients with type 1 diabetes mellitus in Tunisia.

OBJECTIVE: Type1 diabetes mellitus may be associated with celiac disease. The prevalence of celiac disease as determined by screening among adult patients with type 1 diabetes is high with rates of 1.07.8% in Europe and U.S.A. The aims of the study are to determine the prevalence of celiac disease in adults with type 1 diabetes in Tunisia. METHODS: 348 consecutive adult patients with type1 diabetes were investigated prospectively and screened for celiac disease. The mean age was 28.45+/-10.74 years old. There were 176 females and 172 males. For the screening of celiac disease, we used immunoglobulin A (IgA) anti-endomysium (EMA) antibodies determined by an indirect immunofluorescence method. Anti-transglutaminase (tTG) antibodies were determined by an ELISA method. Those patients with positive results for anti EMA and or tTG were proposed for duodenal biopsy. RESULTS: 14 patients were positive for anti EMA and had high or a weak positive level of tTG antibodies. One patient from this group was already known to have celiac disease. Only 8 patients consented to biopsy and morphological changes were consistent with celiac disease in all cases. Prevalence of biopsy-proven celiac disease was 2.3% (95% CI=1.0-4.5%). CONCLUSION: The present study confirms that celiac disease of adults is prevalent in type 1 diabetic patients in Tunisia. Serological screening for celiac disease in type 1 diabetes is important because many patients are asymptomatic and most are detected by the screening.

Diabetic pregnancy in over 35 years old women.

87 pregnancies in diabetic women older than 35 years at time of conception were studied. 3% were insulin-dependent diabetes mellitus (IDDM), 52% non insulin-dependent diabetes mellitus (NIDDM) and 45% gestational diabetes mellitus (GDM). Mean age was 38 +/- 3 years; BMI was 33.2 +/- 7.0 kg/m2; gestation rate was 5 +/- 3 and number of alive children was 2 +/- 2. Only 3% of pregnancies were planned. Mean time of reference to diabetic care unit was 17 +/- 10 weeks. 95% of the women required human insulin. Mean total daily insulin dose was 0.49 +/- 0.28 UI/kg/d, increasing with gestational age. Mean fasting glycemia was 6.85 +/- 1.93 mmol/l and mean post-prandial glycemia was 8.29 +/- 2.52 mmol/l. Mean time of delivery was 38 +/- 2.1 weeks (less than 37 weeks in 9%). Cesarean section was performed in 44% of 34 cases. Death in utero occurred in 11% of 54 cases, postnatal death in 4%, congenital malformations in 4%, macrosomia in 40%. 9% of infants received intensive neonatal care. No difference was found between NIDDM and GDM about outcome of pregnancy. These results underlined importance of early screening for GDM as most cases seem to be undiagnosed pregravid diabetes mellitus (DM).

[Mesenchymal tumor associated with hypoglycemia and an elevated NSILP (author's transl)]. / Tumeur mésenchymateuse hypoglycémiante de la cuisse avec NSILP élevé.

An unusually located mesenchymal tumor with hypoglycemia is observed. Insulin, cortisol, growth hormone, glucagon levels are within the normals. The glucogenic aminoacids have also been measured, as well as the NSILP which was three times as high as the upper limit of normal values. The various processes which might have brought about the patient's hypoglycemia are discussed.

[Circadian rhythm of cortisol and its responsiveness to ACTH during Ramadan]. / Variations de la cortisolémie et de sa réponse à l'ACTH pendant le mois de Ramadan.

UNLABELLED: Changes in the nyctemeral pattern observed during Ramadan include diurnal fasting from sunrise to sunset and delayed and shortened periods of sleep. The purpose of the present study was to investigate the possible effect of these changes on the circadian rhythm of cortisol and its response to exogenous ACTH. SUBJECTS AND METHODS: Eleven healthy male volunteers aged 20 to 35 years were studied for two weeks prior to Ramadan. Two short ACTH stimulation tests (250 microg ACTH 1-24 intravenously) at 8 a.m. and 8 p.m. An average 17 days after the beginning of the month of Ramadan, basal cortisol was measured at 8 a.m. and a short stimulation test was performed at 8 p.m. RESULTS: Before Ramadan, cortisol level was higher at 8 a.m. (749.5 +/- 207 nmol/l) than at 8 p.m. (195.18 +/- 79 nmol/l, p<0.001) and the incremental cortisol response to exo genous ACTH was higher at 8 a.m. (peak at 1.167 +/- 46 nmol/l) than at 8 p.m. (peak at 950 nmol/l) (NS). During Ramadan, morning cortisol level (646.3 81 nmol/l) was lower than before Ramadan (NS). The 8 p.m. cortisol level (319 193 nmol/l) increased slightly during Ramadan (p=0.08) but remained lower than the morning level during Ramadan (p=0.001) and before Ramadan (p<0.001). There was not significant difference between cortisol responsiveness to exogenous ACTH at 8 p.m. during Ramadan (peak at 1.102 51 nmol) and at 8 a.m. and 8 p.m. during Ramadan. DISCUSSION: Changes in eating and sleeping schedule was found to reduce morning cortisol level and raise the evening cortisol level. Adrenal sensitiveness to corticotropin stimulation did not appear to be impaired during Ramadan.

[Post-traumatic anterior pituitary insufficiency. Apropos of 2 cases]. / L'insuffisance anté-hypophysaire post-traumatique. A propos de deux observations.

Post-trauma hypopituitarism is rare. The frequency of pituitary lesions observed at autopsy contrasts with small number of clinical cases. We report two cases in a 38 and a 25-year-old patients who developed hypopituitarism two years after severe craniofacial trauma followed by early onset but transitory poluria-polydypsia. Hormone explorations confirmed pituitary deficiency. Neuroradiological imaging, especially magnetic resonance imaging was normal with no intrasellar arachnoidocele.

Efficacy and safety of bromocriptine in the treatment of macroprolactinomas.

To assess the effectiveness of bromocriptine (BRC) as primary therapy in reducing the size of PRL-secreting macroadenomas with extra-sellar extension, we conducted a multicenter study in 29 patients without prior radiotherapy. Clinical presentation, response to medical treatment and long term follow-up of 29 patients with macroprolactinoma (pituitary mass more than 10 mm in diameter) were analysed. There were 19 women for 10 men. Mean age was 33 years. An hypogonadism was present in 94% of women vs 57% for men. Headaches and or visual abnormalities were present in 68% of women vs 90% of men. The mean basal serum prolactin level before treatment was 1 501 ng/ml: 202 ng/ml for women (range: 70-478 ng/ml) and 3 870 ng/ml for men (range: 100-20 476 ng/ml) and was correlated to tumoral size. 25 patients were treated with BRC as primary therapy with a mean dose of 9,7 mg/day (13 mg/day in men and 8 mg/day in women). BRC no malized serum PRL levels in all men and in 17/19 women over a mean period of 6 months, ranging from 3 to 72 months in both sexes. Tumor size was reduced by more than 50% in 18/29 patients (62%) with secondary empty sella in 5 patients and by less than 50% in 11 patients. Visual field improved in most of the patients in whom it was initially abnormal. Reduction in size was quite fast in most of patients but slower in some of them. The cumulative radiological response to BRC increased with time. Therefore, it appears that prolonged medical therapy is effective and safe in macroprolactinomas.

[Cortisol rhythm during the month of Ramadan]. / Rythme du cortisol pendant le mois de Ramadan.

We studied the nyctohemeral cortisol secretion rhythm and the cortisol response to 1-24 corticotropin during Ramadan in 11 healthy, male volunteers aged 20-35 years. Their response to 250 mg 1-24 corticotropin was investigated 2 weeks before Ramadan by testing daily at 08:00 and 20:00 hours. After 16-22 days of fasting, their cortisol levels were measured at 08:00 hours and their response to 1-24 corticotropin at 20:00 hours. Before Ramadan, the baseline cortisol level was significantly higher at 08:00 hours than at 20:00 hours and the cortisol response to 1-24 corticotropin was also higher at 08:00 hours but this difference was not significant. During Ramadan, the cortisol level at 08:00 hours was lower than at the same time before Ramadan; the level at 20:00 hours was slightly higher than at the same time before Ramadan. There was no significant difference between the cortisol response to 1-24 corticotropin at 20:00 hours during Ramadan and the responses before Ramadan at 20:00 hours and 08:00 hours.

[Metabolic effects of the month of Ramadan fasting on type 2 diabetes]. / Les effets métaboliques du jeûne du mois de Ramadan chez des diabétiques de type 2.

We assessed the effects of Ramadan fasting on metabolic control, particularly change of HDL-cholesterol in 25 type 2 diabetic patients treated with diet or oral agents, with good metabolic control. Clinical and biochemical parameters and food intake were evaluated 3 weeks before Ramadan, in the fourth week of Ramadan and 3 weeks after Ramadan.There were no changes in body weight and blood pressure nor any metabolic complications. The mean plasma fasting glucose, serum fructosamin and haemoglobin A1c did not change. We found a negative relation between cholesterol intake during Ramadan and the change of HDL-cholesterol. When cholesterol intake was lower than 400 mg/day, plasma HDL-cholesterol increased by 13% at the end of Ramadan and by 23% 3 weeks after Ramadan.

[Food intake, and anthropometrical and biological parameters in adult Tunisians during fasting at Ramadan]. / Apports alimentaires, paramètres anthropométriques et biologiques chez des sujets adultes tunisiens au cours du jeûne de ramadan.

We evaluated the effects of fasting during Ramadan on nutritional intake and plasma lipoproteins in 20 healthy adults of normal weight. A 5-day food questionnaire was completed for every participant. Clinical investigations, anthropometrical measurements and laboratory analysis were also undertaken. Body weight, blood pressure and blood glucose were not influenced by fasting but there were non-significant modifications in the plasma lipid fractions. The total cholesterol remained unchanged. Total daily energy intake was comparable before, during and after Ramadan despite the decrease in meal frequency during fasting. Thus fasting in Ramadan did not affect dietary intake, clinical, anthropometrical and most biological parameters.

[Prevalence and clinical aspects of superficial mycosis in hospitalized diabetic patients in Tunisia]. / Prevalence et aspects cliniques des mycoses superficielles chez le diabétique tunisien en milieu hospitalier.

OBJECTIVES: The prevalence of mycotic infection seems to be higher among diabetic patients than in the non-diabetic population. The aims of this study were to determine the frequency of mycosis and to compare clinical and fungal results. PATIENTS AND METHODS: This transversal study included 307 type 1 and 2 diabetic patients admitted between January 1998 and January 2000. A dermatologist examined all patients. The mean age was 44 +/- 17 years and the duration of diabetes 8 +/- 6 years. Patients with suspected lesions underwent mycological examination. RESULTS: Clinical signs of presumed fungal infection were found in 61% of patients, but mycosis was confirmed only in 30%. Fungal foot infection accounted 38% of the patients, mostly due to dermatophytes (94%). The commonest localizations of dermatophytes were interdigital (60%) followed by onychomycosis (30%). The main fungal agent was Trichophyton rubrum. The main risk factors for fungal infections were the age of patients (P = 0.0003) and duration of diabetes (P < 0.05). Interdigital foot localization of dermatophytes was correlated to age (P < 0.0001) and to the male gender (P < 0.01). The frequency of dermatophytes in nails was higher in type 2 diabetic patients (P < 0.01). Vulvovaginal candidosis and interdigital dermatophytes were more frequent in obese than in non-obese patients. The accuracy and specificity of direct examination were respectively 85% and 79%. CONCLUSION: The high frequency of mycosis in diabetic patients at hospital is demonstrated. The main risk factors were age, male gender and obesity.