The course and prognosis of pemphigus in 47 Tunisian patients.

BACKGROUND: Pemphigus is a severe and life-threatening autoimmune bullous dermatosis. OBJECTIVE: We have analysed parameters that may influence prognosis of pemphigus (P). METHODS: It was a retrospective study (2002-2010), with pemphigus considered as severe if body surface involvement ≥ 30%. Disease control and relapse-free survival (Kaplan-Meier) were analysed and compared according to several parameters (P < 0.05). RESULTS: 47 cases of pemphigus were collected, mean age 51 years ± 16.8 (F/H = 3.27). There were 30 pemphigus profundus and 17 superficial pemphigus. The median remission period was of 9 months (1.2 months-5 years). The mean healing time was of 40 days (6 days-4 months), which did not depend on type of P, its severity or infectious complications, whereas it was shorter in aged patient (≥ 65 years) compared to non aged ones (P = 0.018). 36.2% of patients had relapsed. Relapses were significantly more frequently observed only in the presence of mucosal involvement at presentation (P = 0.015). The median overall 1st relapse-free survival was of 2.33 years. Only mucosal involvement at presentation was associated with a shorter median 1st relapse-free survival time (1.28 years vs. 3 years) (P = 0.0017). Mortality rate was of 10.6% (n = 5); in four patients the death was directly related to pemphigus and occurred rapidly after the onset of lesions. CONCLUSION: Our study illustrates the poor prognosis of pemphigus by a long duration to disease control, a high initial dose of oral steroid, a high rate of relapse and a short remission period. Only mucosal involvement at presentation was identified as a poor prognostic factor.

A novel dysfunctional LHX4 mutation with high phenotypical variability in patients with hypopituitarism.

CONTEXT: LHX4 is a LIM homeodomain transcription factor involved in pituitary ontogenesis. Only a few heterozygous LHX4 mutations have been reported to be responsible for congenital pituitary hormone deficiency. SUBJECTS AND METHODS: A total of 136 patients with congenital hypopituitarism associated with malformations of brain structures, pituitary stalk, or posterior pituitary gland was screened for LHX4 mutations. RESULTS: Three novel allelic variants that cause predicted changes in the protein sequence of LHX4 (2.3%) were found (p.Thr99fs, p.Thr90Met, and p.Gly370Ser). On the basis of functional studies, p.Thr99fs mutation was responsible for the patients' phenotype, whereas p.Thr90Met and p.Gly370Ser were likely polymorphisms. Patients bearing the heterozygous p.Thr99fs mutation had variable phenotypes: two brothers presented somato-lactotroph and thyrotroph deficiencies, with pituitary hypoplasia and poorly developed sella turcica; the youngest brother (propositus) also had corpus callosum hypoplasia and ectopic neurohypophysis; their father only had somatotroph deficiency and delayed puberty with pituitary hyperplasia. Functional studies showed that the mutation induced a complete loss of transcriptional activity on POU1F1 promoter and a lack of DNA binding. Cotransfection of p.Thr99fs mutant and wild-type LHX4 failed to evidence any dominant negative effect, suggesting a mechanism of haploinsufficiency. We also identified prolactin and GH promoters as potential target genes of LHX4 and found that the p.Thr99fs mutant was also unable to transactivate these promoters. CONCLUSIONS: The present report describes three new exonic LHX4 allelic variants with at least one being responsible for congenital hypopituitarism. It also extends the phenotypical heterogeneity associated with LHX4 mutations, which includes variable anterior pituitary hormone deficits, as well as pituitary and extrapituitary abnormalities.

[Abdominal obesity and knee ostheoarthritis]. / Obésité abdominale et gonarthrose.

UNLABELLED: The objective of our study was to determine whether waist circumference (WC) is a more reliable indicator than body mass index (BMI) of the presence of knee osteoarthritis in obese subjects. PATIENTS AND METHODS: We performed an observational study of obese patients with no other risk factors for knee osteoarthritis. For each patient, we evaluated BMI, WC, duration of obesity and knee pain. Two groups were identified: "asymptomatic patients" (AG), without knee pain, and "symptomatic patients" (SG). For the SG, we measured pain intensity (visual analog scale [VAS], 0-100 mm) and functional repercussions (using the Lequesne and WOMAC indexes). Patients with knee pain underwent standard radiographic procedures to search for signs of osteoarthritis, and the SG was divided into two subgroups: with radiological signs of osteoarthritis (SG-1) and without radiological signs of osteoarthritis (SG-2). The AG and SG groups and SG-1 and SG-2 groups were compared for age, sex, and duration of obesity. Comparisons of BMI, WC, and function involved the Student's t-test. RESULTS: We recruited 56 patients for the study (82.5% females; mean obesity duration (13+/-6.5 years; mean age 43.21+/-9.58 years). The mean BMI was 39.6+/-7.23 kg/m(2) and mean WC was 113+/-14.3 cm. We found 33 patients (59%) with knee pain. Independent of age, sex, duration of obesity and BMI, the SG showed more significant WC (117.27+/-14.71 cm vs. 107+/-11.75 cm for the AG, P 0.01). In the same group and independent of the already mentioned factors, the patients with radiological signs of osteoarthritis showed significant WC [122+/-15.57 cm (SG-1) vs. 108+/-6.88 cm (SG-2) (P 0.01)]. Moreover, the VAS score of pain at rest and during effort and the WOMAC and Lequesne scores were 16+/-25.7 mm, 75+/-18.3 mm, 12.3+/-8.92 and 11.5+/-5.44 (SG-1) and 7+/-18.4 mm, 70+/-19.2 mm, 5.7+/-3.05, and 6.9+/-3.79 (SG-2), respectively. The difference between SG-1 and SG-2 was significant only for the WOMAC (P=0.015) and Lequesne (P=0.026) scores. CONCLUSION: Independent of BMI, WC appears to be a factor associated with the presence of knee pain and osteoarthritis in obese patients. Furthermore, a high WC is associated with significant functional repercussion.

[Paradoxal growth hormone and cortisol response to hypoglycemia caused by endogenous hyperinsulinemia: a case report]. / Inhibition paradoxale de la réponse somatotrope et corticotrope à l'hypoglycémie par hyperinsulinisme endogène: à propos d'une observation.

Growth hormone (GH) together with cortisol are two important counter-regulatory hormones maintaining normal glycemia. Hyperinsulinemic hypoglycemia is a disorder of this counter-regulation described in neonates. We report here a rare case of reversible dissociated hypopituitarism secondary to an insulinoma in a 38-year-old man referred for investigation of hypoglycemic episodes. Hormonal investigations were in favour of dissociated anterior pituitary failure, with growth hormone and corticotroph deficiency. The hypothalamic-pituitary MRI was normal. The fasting test argued in favour of a hyperinsulinemic hypoglycemia. The abdominal scan and the endoscopic ultrasound showed a mass within the tail of the pancreas. Distal pancreatectomy was performed. Histology disclosed an insulinoma. On follow-up, no hypoglycemic episodes recurred and cortisol and GH response to induced hypoglycemia was normal. Our clinical case shows that hyperinsulinemia and hypoglycemia in patients with insulinoma can give rise to functional growth hormone and corticotrophin deficiency. The pathophysiological mechanism of this defective counter-regulation remains to be clarified; some studies suggest it could be related to hyperinsulinemia-induced decreased in CRF secretion and GHRH pulse.

[Rare complication of diabetic acidoketosis: the pneumomediastinum]. / Complication rare de l'acidocétose diabétique: le pneumomédiastin.

Pneumomediastinum is a rare condition with an incidence of 1/33,000. It can be a rare complication of diabetic acidoketosis. We present the cases of two diabetic patients and review the literature, focusing our analysis on the interrelationships between these two diseases. Both patients were young subjects, a 21-year-old woman and an 18-year-old man with type 1 diabetes who were admitted for acidoketosis. Clinically, the patients presented the cardinal signs of diabetes and a flu-like syndrome associated with dyspnea and chest pain. Physical examination revealed a poor general health status, tachycardia and polymnea, as well as a painful diffuse tumefaction of the neck with subcutaneous emphysema. Blood tests disclosed elevated glycemia and urine was positive for acetone. The diagnosis of severe metabolic acidosis was retained. The chest x-ray demonstrated the subcutaneous emphysema and air in the anterior mediastinum. On the computed tomography scan obtained in the second patient, the heart was silhouetted with a hyperlucent zone laterally. Treatment consisted in strict bed rest with oxygen therapy, fluid replacement, insulin and heparin. The pneumomediastinum resolved in both patients within three days on average. The causal effect of diabetic acidoketosis in the development of pneumomediastinum in our two patients was retained after ruling out all other potential causes, including chest trauma and asthma.

[Panhypopituitarism revealing metastasis of small-cell lung carcinoma associated with sarcoidosis]. / Panhypopituitarisme révélateur d'une métastase d'un carcinome à petites cellules associée à une sarcoidose.

Pituitary metastasis and sarcoidosis are two causes of pituitary stalk thickening. Their association has been described ago three decades. In this setting, we report a case of panhypopituitarism revealing pituitary metastasis from a small-cell lung carcinoma associated with sarcoidosis. A 49 year-old smoking patient with type 2 diabetes was admitted for acute adrenal failure with polyuria polydipsia syndrome and a pituitary tumor syndrome. Hormone explorations confirmed anterior pituitary insufficiency. Water restriction revealed central diabetes insipidus. The hypothalamic-pituitary MRI revealed a 1-cm sellar mass with nodular thickening of the stalk. The chest radiograph showed a heterogeneous opacity in the left lung. The thoraco-abdominal scan demonstrated a mass in the left lung highly suggestive of malignancy and many enlarged mediastinal nodes, hepatic nodules, and hypertrophy of the left adrenal. Bronchoscopy was performed three times and showed infiltration of the left bronchial tree but histological examination of the bronchial biopsies was negative for all samples. Ultrasound-guided biopsy of the liver was achieved and histology demonstrated sarcoidosis. The diagnosis of sarcoidosis was incompatible with the deterioration of the patient's general status. Subsequent radiographic explorations showed an increase in the size of the tumor mass and histological evaluation of a scan-guided trans-thoracic biopsy demonstrated small-cell carcinoma. Small-cell lung carcinoma is the most common cancer with pituitary metastasis. The proposed link between sarcoidosis and malignancy has remained controversial but has not been proven false.

[MRI pituitary stalk abnormalities: etiology aspects in 11 patients]. / Anomalies de la tige pituitaire à l'IRM: aspects étiologiques à propos de 11 cas.

Newer techniques of magnetic resonance imaging (MRI) describe more accurately pituitary stalk abnormalities such as infections, infiltrative lesions and tumors. In absence of all the above mentioned etiological factors, genetics defects are suspected, mainly when other malformations are equally present. We attempt to show through 11 observations the variability of pathologies involving the pituitary stalk with their respective clinical and radiological features and associated endocrine abnormalities. This is a retrospective study of 7 men (67%) and 4 women (33%), mean age of 28 year (range: 15 to 53) in whom pituitary MRI was performed for hypopituitarism, diabetes insipidus or hyperprolactinemia. Three patients had brain MRI for an extra-pituitary condition. The pituitary MRI showed a stalk section in 3 cases (27%), atrophy in 1 case and thickening in 7 cases (67%). The pituitary stalk anomaly was associated with hyperprolactinemia in 3 cases (27%), central diabetes insipidus in 4 cases (36%), growth hormone deficiency in 4 cases (36%), adrenal insufficiency in 5 cases (45%), hypogonadism in 5 cases (45%) and hypothyroidism in one case (9%). Established diagnoses were: sellar metastasis in 2 cases (18%), Langerhans' histocytosis, tuberculosis and autoimmune hypophysitis respectively in 3 cases (9%). In 6 cases (54%), no clear etiology was found. Given the multitude of pituitary stalk pathologies, a detailed etiologic inquiry must be performed in order to detect elements able to reclassify an initially idiopathic disorder.

[Imaging of rhinocerebral mucormycosis]. / L'imagerie dans la mucormycose rhinocérébrale.

PURPOSE: Rhinocerebal mucormycosis is a rare life threatening fungal infection observed in immunocompromised patients. We report six cases of patients with rhinocerebral mucormycosis confirmed histologically. Our study confirms the necessity of early diagnosis when clinical and CT findings are suggestive. MATERIALS AND METHODS: This is a retrospective study including 6 diabetic patients (3 women and 3 men) aged from 28 and 63 years. Five patients had ethmoiditis evolving for a few days (3 to 5 days), and one patient was in an ketoacidotic coma and had a severe infectious syndrome with purulent rhinorrhea evolving for 4 days. All of our patients underwent computed tomography (CT) scan of the paranasal sinuses. MRI was performed in two patients with neurological findings. RESULTS: Unilateral ethmoido-maxillary sinusitis was noted in 5 cases. Only one case of pansinusitis was found. All patients presented orbital involvement. Cerebral involvement was noted in 4 cases (cerebral venous thrombosis: 2 cases; abscess: 2 cases; cerebral ischemia: 2 cases). The diagnosis of mucormycosis was based on endonasal biopsy. When available, MRI allowed a more precise evaluation of the orbital and cerebral extension. CONCLUSION: Mucormycosis is an opportunist mycosis due to mucoralis fungus. It is very invasive with a highly aggressive potential in diabetic or immunocompromised patients. Imaging study particularly CT scan, plays an important role in diagnosis especially to evaluate cerebral extension.

[Hypothyroidism after external radiotherapy. Fifteen cases]. / Hypothyroïdie après radiothérapie externe. A propos de 15 cas.

Hypothyroidism frequency is estimated to be between 10 and 45% after radiotherapy alone, and 40 to 67% after radiotherapy associated with thyroidectomy. This hypothyroidism is infraclinical in 60% of the cases. Our study concerned 15 cases of hypothyroidism after external radiotherapy delivered between and 1991 and 1999. An irradiation of the cervical, cerebral and thorax regions was indicated for different types of cancers. Larynx carcinoma epidermoid was the most frequent cancer (seven cases); the radiation treatment used cobalt 60 with conventional fractionation, i.e., 2 Gy per treatment, five treatments a week. In nine cases, the hypothyroidism was discovered during a systematic examination; it was clinically evident in the six remaining cases. Hypothyroidism appeared after an irradiation dose average of 50 Gy (extremes 30-65 Gy). The average duration of the irradiation was about 7 weeks and the hypothyroidism appeared in a mean 22 months. In all cases, the substituting treatment was initiated with a favorable progression. Faced with the risk of hypothyroidism, it is necessary to check patients who have undergone external irradiation of the neck.

[Thyrotoxicosis hepatitis: a case report]. / Hépatite thyrotoxique.

Abnormal liver function in thyroid disorders may be secondary to thyrotoxicosis or to autoimmune injury to the liver. We report the case of a 36-year-old female who developed jaundice and pruritus with mild cholestasis and moderately elevated transaminase levels. The diagnosis of Graves' disease was made shortly thereafter. Laboratory findings were: alanine and aspartate aminotransferase 219 (IU/I (N: 9-50) and 102 IU/I (N: 10-15) respectively, alkaline phosphatase 336 IU/I (N: 40-135), bilirubin 24 micromol/I (N: 2-23), and gamma-glutamyl transpeptidase 232 IU/I (N: 9-43). Abdominal ultrasonography showed normal bile ducts; echocardiography ruled out heart failure; viral and autoimmune markers for hepatitis and cirrhosis were negative. Percutaneous liver biopsy showed moderate intrahepatic steatosis, anisokaryosis, lymphocyte infiltration in the portal areas, and Kupffer cell hyperplasia. Outcome was favorable after seven months of iodine therapy, confirming the diagnosis of thyrotoxicosis hepatitis.

[Ectopic thyroid: two cases]. / L'ectopie thyroïdienne: à propos de deux cas.

Ectopic thyroid is a rare condition (1/4000 to 1/8000 among patients with hypothyroidism). The underlying etiological pathogenic mechanisms remain unknown. Diagnosis is established on the basis of imaging findings. We report two cases of hypothyroidism in adult females who had ectopic sublingual thyroid glands. The first patient was a 20-Year-old woman who had been treated for hypothyroidism since the age of 13 Years before the diagnosis of ectopic thyroid 7 Years later. In both patients, the thyroid gland was palpable. In the first patient the physical examination revealed an ectopic sublingual gland. Scintigraphy confirmed the diagnosis in both patients. The CT-scan and MRI were positive in the second patient. Hormonal substitution therapy using L-thyroixine was given.

Pituitary stalk interruption syndrome in 83 patients: novel HESX1 mutation and severe hormonal prognosis in malformative forms.

BACKGROUND: Pituitary stalk interruption syndrome (PSIS) is a particular entity in the population of patients with hypopituitarism. Only rare cases have a known genetic cause. OBJECTIVES: i) To compare subgroups with or without extra-pituitary malformations (EPM) in a cohort of PSIS patients to identify predictive factors of evolution, ii) to determine the incidence of mutations of the known pituitary transcription factor genes in PSIS. Study design We analyzed features of 83 PSIS patients from 80 pedigrees and screened HESX1, LHX4, OTX2, and SOX3 genes. RESULTS: PSIS had a male predominance and was rarely familial (5%). Pituitary hypoplasia was observed only in the group with EPM. Multiple hormone deficits were observed significantly more often with versus without EPM (87.5 vs 69.5% respectively). Posterior pituitary location along the stalk was a significant protective factor regarding severity of hormonal phenotype. A novel HESX1 causative mutation was found in a consanguineous family, and two LHX4 mutations were present in familial PSIS. CONCLUSION: PSIS patients with EPM had a more severe hormonal disorder and pituitary imaging status, suggesting an antenatal origin. HESX1 or LHX4 mutations accounted for <5% of cases and were found in consanguineous or familial cases.

Physical training combined with dietary measures in the treatment of adult obesity. A comparison of two protocols.

OBJECTIVE: Our objective was to study the effects of physical training combined with dietary measures in obese adults. In a second step, we sought to compare two training protocols and establish the additional contribution of strength training. METHODS: We performed a randomized, prospective survey from July 2004 to November 2007. Included patients were randomized into three groups: a control group (G1), a group (G2) performing dietary measures and a programme of treadmill training at 60% of each individual's maximum heart rate (HRmax) and a group (G3) who followed the G2 programme supplemented with strength training. All patients underwent an initial and final assessment of anthropometric & cardiovascular parameters, muscle strength, dyspnoea during activities of daily living, metabolic disorders, psychological status and quality of life. RESULTS: The greatest weight loss (7.24%) was observed in G3. Reduction in waistline measurement (WL) of 4.3% and 10.26% were noted in G2 and G3, respectively (p < 0.001). The percentage fat body mass fell by 10.4% in G3 (p < 0.001) and 8.6% in G2 (p = 0.03).We particularly noted an improvement in physical condition in groups 2 and 3, with lower HR and blood pressure values at rest and at maximum effort. The overall improvement in both arm and leg muscle strength was greater for G3 than for G2. Likewise, we noted an improvement in the metabolic parameters and depression & anxiety scores for the trained groups (G2, G3), relative to the control group (G1). We also noted improvements in the total impact of weight on quality of life (IWQOL) lite score of 15.2% in G2 and 18% in G3. CONCLUSION: Our survey demonstrated the beneficial effect of combining dietary measures and physical training in obese patients. In addition to weight loss, the programme enabled a reduction in the patients' body fat mass and abdominal obesity, a correction of metabolic disorders and an improvement in aerobic capacity. The improvement in all these parameters also enhanced the patients' psychological status and quality of life. The addition of strength training produced notable improvements in weight loss, arm muscle strength and abdominal obesity.

[Contribution of exercise and diet in the management of knee osteoarthritis in the obese]. / Apport de l'exercice physique et du régime dans la prise en charge de la gonarthrose chez l'obèse.

OBJECTIVE: Our objective was to determine whether exercise and weight loss are more effective either separately or in combination, in improving pain and physical function in obese adults with moderate knee osteoarthritis (OA). PATIENTS AND METHODS: Forty-five obese adults, with a body mass index greater than 35 kg/m2 or 30

Evidence for linkage and association between autoimmune thyroid diseases and the 18q12-q21 region in a large Tunisian family.

Many studies have shown linkage between IDDM6 locus on 18q12-q21 chromosome and several autoimmune diseases, suggesting that it might harbour susceptibility genes common to autoimmunity. Using 12 families deriving from a large Tunisian multiplex family (the Akr family) from which 38 people were affected with autoimmune thyroid diseases (AITD), and 193 unrelated AITD patients, tested against 100 healthy subjects, we tried to replicate the positive results previously reported for the IDDM6. Akr members were genotyped with eight microsatellite markers harbouring the IDDM6 region. Multipoint non-parametric linkage analysis have shown a clear peak values of NPL score around D18S41 marker (Z = 3.72, P = 0.0001). Family-based association test (FBAT) and transmission disequilibrium test (TDT) have confirmed linkage results. In particular, a significant association with allele 3 of D18S41 and allele 2 of D18S57 markers was found. Case-control studies, using one intragenic microsatellite (locus CTG18.1) marker in the immunoglobulin transcription factor (ITF2) gene, a 5' flanking AC repeat of the anti-apoptotic BCL-2 gene as well as two SNPs at positions +52 and +1955 from transcription start site of BCL-2, showed no significant association between neither genes and AITD. Our study is the first replication of the 18q12-q21 chromosome region as a potential candidate to AITD genetic susceptibility. The Akr family has shown evidence for linkage between IDDM6 locus and AITD. Moreover, case-control study does not support the involvement of ITF2 and BCL2 genes in AITD pathogenesis.