Unlocking the power of synergy: High-intensity functional training and early time-restricted eating for transformative changes in body composition and cardiometabolic health in inactive women with obesity.

OBJECTIVE: The purpose of this study was to examine the long-term effects of time-restricted eating (TRE), with or without high intensity functional training (HIFT), on body composition and cardiometabolic biomarkers among inactive women with obesity. METHODS: Sixty-four women (BMI = 35.03 ± 3.8 kg/m2; age = 32.1 ± 10 years) were randomly allocated to either: (1) TRE (≤8-h daily eating window, with ad libitum energy intake) group; (2) HIFT (3 sessions/week) group; or (3) TRE combined with HIFT (TRE-HIFT) group. The interventions lasted 12 weeks with a pre-post measurement design. A HIFT session consists of 8 sets of multiple functional exercises with self-selected intensity (20 or 30s work/10s rest). RESULTS: TRE-HIFT showed a greater decrease of waist and hip circumferences and fat mass compared to TRE (p = 0.02, p = 0.02 and p<0.01; respectively) and HIFT (p = 0.012, p = 0.028 and p<0.001; respectively). Weight and BMI decreased in TRE-HIFT compared to HIFT group (p<0.001; for both). Fat-free mass was lower in TRE compared to both HIFT and TRE-HIFT groups (p<0.01 and p<0.001; respectively). Total cholesterol, triglyceride, insulin, and HOMA-IR decreased in TRE-HIFT compared to both TRE (p<0.001, p<0.01, p = 0.015 and p<0.01; respectively) and HIFT (p<0.001, p = 0.02, p<0.01 and p<0.001; respectively) groups. Glucose level decreased in TRE-HIFT compared to HIFT (p<0.01). Systolic blood pressure decreased significantly in both TRE-HIFT and HIFT groups compared to TRE group (p = 0.04 and p = 0.02; respectively). CONCLUSION: In inactive women with obesity, combining TRE with HIFT can be a good strategy to induce superior effects on body composition, lipid profile and glucose regulation compared with either diet or exercise intervention alone. TRIAL REGISTRATION: Clinical Trials Number: PACTR202301674821174.

Metabolic Disorders During Prolactinomas.

The metabolic profile during prolactinoma may be subject to significant changes. We aimed to describe the different metabolic aspects in patients monitored for prolactinoma and to study the correlations between the size of the prolactinoma and the metabolic parameters. We conducted a retrospective, descriptive, and analytical study of 77 cases of prolactinomas collected and monitored at the endocrinology and diabetology department of the Hedi Chaker Hospital in Sfax between 2000 and 2017. Our patients were divided into three groups according to the size of their prolactinomas. Statistical correlations were sought between tumor size and clinical and biological parameters. The mean age of our patients was 38.3 ± 14.2 years. They were divided into 51 women (66.2%) and 26 men (33.7%). Pituitary tumor syndrome was the most common circumstance of discovery in our population (62.3%). The clinical examination revealed an average waist circumference of 95.71 cm. Android fat distribution was observed in 25 women (49%) and 12 men (46.1%). A statistically significant positive correlation was objectified between waist circumference and tumor size (r = 0.29 and P = 0.019). The average body mass index was 28.08 kg/m2. Obesity was noted in 56 cases (72.7%). Glucose tolerance disorders and hypertriglyceridemia were also more evident each time prolactinoma size increased in contrast to the level of high-density lipoprotein cholesterol which decreased with adenoma size. Our study highlighted the metabolic and hormonal repercussions of prolactinomas. Metabolic syndrome was more common in patients with larger prolactinoma. These results should guide the initial assessment and therapeutic management of prolactin adenomas.

Diabetes Distress and Illness Perceptions in Tunisian Type 2 Diabetes Patients.

Purpose: Diabetes distress (DD) refers to the negative emotions and burden of living with diabetes. Illness perceptions are among the factors that can influence self-management and psychological distress in diabetics. This study aimed to determine the prevalence and the associated factors of DD in Tunisian patients with type 2 diabetes mellitus. We also studied the relationship between DD and illness perceptions in diabetics. Patients and Methods: This was a cross-sectional study conducted among individuals with type 2 diabetes, followed up at the outpatient endocrinology unit at the Hedi Chaker University Hospital, Tunisia. DD was assessed using the Diabetes Distress Scale (DDS-17). The Brief Illness Perception Questionnaire (Brief-IPQ) was used to assess diabetes illness perceptions. Multivariate logistic regression was used to determine independent factors associated with the presence of DD. Results: A total of 103 patients were recruited. The mean age was 59.31 (±10.83) years; 54.4% were female. In total, 70.9% had DD. Using regression analysis, we demonstrated that the illness perceptions of personal control, HbA1C, absence of comorbidities, lower age at diabetes diagnosis, and socioeconomic status were significantly associated with DD. Conclusion: This study sheds light on the high prevalence of DD among patients with type 2 diabetes in Tunisia. Illness perception-focused psychological intervention would be efficacious in reducing diabetes distress in patients with type 2 diabetes mellitus.

Diagnosis and management of pituitary apoplexy: a Tunisian data.

BACKGROUND: Pituitary apoplexy (PA) is defined as the hemorrhage or the infraction of a pituitary adenoma. Aiming to determine the epidemiological, clinical, paraclinical characteristics as well as management and outcomes of PA in our population, we conducted this cross-sectional study. METHODS: This cross-sectional study was conducted at the Department of Endocrinology of Hedi chaker university hospital, Sfax. Data was collected from medical charts of patients with pituitary apoplexy admitted in our department between 2000 and 2017. RESULTS: We included 44 patients with PA. Their mean age was 50 ± 12.6 years. Among them, 31.8% had a known pituitary adenoma, and it was in all cases a macroadenoma, predominantly a prolactin secreting tumor (42.8%). A triggering factor of PA was encountered in 31.8% of cases and it was mainly: head trauma, dopamine antagonists, and hypertension. The clinical presentation of PA encompassed headaches (84.1%), visual disturbances (75%), and neurological signs (40.9%). Gonadotropin deficiency was the most frequent form of hypopituitarism noted (59.1%), followed by corticotropin deficiency (52.3%), thyrotropin deficiency (47.7%), and somatotropin deficiency (2.3%). Hormonal assessment at PA onset, concluded that 23 had a secreting adenoma: 18 prolactinomas, 3 ACTH-secreting adenomas, and 2 GH-secreting adenomas. In the 21 remaining cases, the tumor was non-functioning (47.7%). Pituitary MRI was performed in 42 cases (95.5%), revealing infraction and or hemorrhage in the pituitary gland in 33 cases; a heterogenous signal or a fluid level within the adenoma, in nine cases. Urgent administration of intra venous hydrocortisone was required in 19 cases. Mannitol administration was mandatory in a patient who had severe intracranial hypertension. Surgical management of the PA was imperative in 24 patients (54.5%): 15 suffered from severe visual impairment, 4 had an intracranial hypertension, 2 cases demonstrated an impaired consciousness, 2 patients experienced a tumor enlargement and one case had a severe Cushing's disease. Operative complications found were rhinorrhea attributable to cerebral spinal fluid leakage, insipidus diabetes associated with rhinorrhea, isolated insipidus diabetes, and hydrocephalus in one case each. Long-term follow-up concluded that headaches persisted in five cases, owing to the tenacity of a macroprolactinoma regardless of cabergoline treatment in one case, the recurrence of an adenoma in two cases and its persistence despite the medical and the surgical treatment in two patients. Concerning the visual acuity defects, only two patients had persistent diminished visual acuity at long-term follow-up. Among 25 patients, 13 were diagnosed with definitive thyrotropin deficiency. Similarly, 14 patients had persistent corticotropin deficiency (CD). Additionally, CD was de novo diagnosed in two patients. Otherwise, gonadotropin deficiency prevailed in all cases. Persistent prolactin deficiency was seen in two patients. Disappearance of the pituitary tumor was encountered in 11 out of 24 cases at long-term follow-up. Overall, surgery was associated with better outcome than conservative management. Pituitary apoplexy is a challenging condition due to its variable course, its diagnosis difficulty and management, as gaps remain to determine the best approach to treat this condition. CONCLUSIONS: To conclude, pituitary apoplexy is a challenging condition due to its variable course, its diagnosis difficulty and management, as gaps remain to determine the best approach to treat this condition. Further studies are thus needed.

Insulinoma with equivocal imaging.

Summary: A 55-year-old patient was admitted to our department for the management of a repetitive alteration of consciousness. Biological investigation results were consistent with endogenous hyperinsulinemic hypoglycemia. Insulinoma was therefore suspected. Abdominal computed tomography and endoscopic ultrasound showed no obvious pancreatic mass.Somatostatin receptor scintigraphy showed abnormal radioactive uptake in both the pancreatic tail and the uncinate process. Contrariwise, abdominal magnetic resonance imaging showed a unique lesion in the pancreas tail. The patient was then proposed for pancreatic surgery. Both intraoperative manual palpation and intraoperative ultrasonography of the pancreas showed a single corporal lesion of 1.5 cm. No lesion was found in the uncinate process. After a left pancreatectomy, the lesion was histopathologically confirmed to be a well-differentiated neuroendocrine tumor. The symptoms of the patient resolved almost immediately following the surgery. The follow-up is one and a half years to date. Learning points: The exact preoperative localization of the pancreatic mass remains the most challenging part of insulinoma diagnostic workup. The radiologist's experience is the best warrantor to a precise localization of the tumor. 111In-DTPA-octreotide uptake in the pancreatic uncinate process may be physiological and its interpretation must, therefore, be vigilant. Manual palpation along with intraoperative ultrasonography is considered as the most effective method for the localization of insulinomas during open surgery.

Case report: Management challenges of late diagnosed 17-alpha hydroxylase deficiency.

Herein we report the intriguing case of a 42-year-old woman presenting with grade three hypertension, severe hypokalemia and primary amenorrhea, which revealed to be the complete form of 17 alphahydroxylase deficiency. We also discuss the challenging therapeutic approach as well as the outcomes and the follow-up of this patient.

Analysis of ProP1 Gene in a Cohort of Tunisian Patients with Congenital Combined Pituitary Hormone Deficiency.

Background: Non-syndromic combined pituitary hormone deficiency (CPHD) occurs due to defects in transcription factors that govern early pituitary development and the specification of hormone-producing cells. The most common mutations are in the Prophet of Pit-1 (ProP1) gene. This work aims to (1) report findings of genetic analyses of Tunisian patients with non-syndromic CPHD and (2) describe their phenotype patterns and their evolution through life. Methods: Fifteen patients from twelve unrelated families with variable clinical phenotypes were included after excluding autoimmune and acquired forms of non-syndromic CPHD. Detailed pedigree charts and auxological, hormonal, radiological, and therapeutic details were recorded. Sanger sequencing was performed, and sequences were analyzed with a specific focus on coding and splice site regions of the ProP1 gene. Retained variants were classified using several in silico pathogenicity prediction tools and the VarSome platform. Results: We identified the common p.Arg73Cys mutation in seven patients from four unrelated pedigrees. We found a novel homozygous mutation (c.340C>T) in one sporadic case. This mutation generates a truncated ProP1 protein, predicted to be non-functional, lacking the last 112 codons (p.(Gln114Ter)). We confirmed by polymerase chain reaction (PCR) the absence of large exon deletions or insertions in the remaining sporadic patients (7/8). Conclusions: We report two mutations {one newly identified [p.(Gln114Ter)] and one previously reported (p.Arg73Cys)} in five unrelated Tunisian families with non-syndromic CPHD. This work is of clinical importance as it reports the high frequency of the p.Arg73Cys mutation in Tunisian CPHD families. Our study also illuminated the involvement of novel gene(s) in the emergence of non-syndromic CPHD.

Pheochromocytoma of the prostate: An unusual location.

Ectopic pheochromocytomas, also called paragangliomas, are defined as catecholamine -secreting tumors, which develop outside the adrenal medulla. Pheochromocytomas of the urinary tract represent less than 1% of all paragangliomas and are most commonly located in the bladder. Nevertheless, prostatic pheochromocytoma is an extremely rare clinical entity and only a few cases have been reported in the medical literature. Herein, we report a case of ectopic pheochromocytoma arising from the prostate, revealing with hypertensive crisis occurring immediately after ejaculation.

Tunisian Maturity-Onset Diabetes of the Young: A Short Review and a New Molecular and Clinical Investigation.

Introduction/Aims: Maturity-Onset Diabetes of the Young (MODY) is a monogenic non-autoimmune diabetes with 14 different genetic forms. MODY-related mutations are rarely found in the Tunisian population. Here, we explored MODY related genes sequences among seventeen unrelated Tunisian probands qualifying the MODY clinical criteria. Materials and Methods: The GCK and HNF1A genes were systematically analyzed by direct sequencing in all probands. Then, clinical exome sequencing of 4,813 genes was performed on three unrelated patients. Among them, 130 genes have been reported to be involved in the regulation of glucose metabolism, ß-cell development, differentiation and function. All identified variants were analyzed according to their frequencies in the GnomAD database and validated by direct sequencing. Results: We identified the previously reported GCK mutation (rs1085307455) in one patient. The clinical features of the MODY2 proband were similar to previous reports. In this study, we revealed rare and novel alterations in GCK (rs780806456) and ABCC8 (rs201499958) genes with uncertain significance. We also found two likely benign alterations in HNF1A (rs1800574) and KLF11 (rs35927125) genes with minor allele frequencies similar to those depicted in public databases. No pathogenic variants have been identified through clinical exome analysis. Conclusions: The most appropriate patients were selected, following a strict clinical screening approach, for genetic testing. However, the known MODY1-13 genes could not explain most of the Tunisian MODY cases, suggesting the involvement of unidentified genes in the majority of Tunisian affected families.

A Rare Cause of Refractory Chronic Diarrhea and Cachexia: A Case Report.

VIPoma is an unusual neuroendocrine neoplasm that autonomously secretes VIP. It is associated with secretory diarrhea and electrolyte disturbances. Herein we report a case of a male patient, who was hospitalized in the Department of Endocrinology in Hedi Chaker Hospital, Sfax, Tunisia. He presented VIPoma syndrome, with hepatic metastases at diagnosis. He had a history of chronic, watery diarrhea. He was dehydrated with many electrolytic disorders as hypokalemia, hyponatremia and metabolic acidosis. Abdominal CT scan showed a heterogeneous mass in the pancreatic head with multiple hepatic lesions. A high VIP hormone level was found. Histological study of a liver biopsy revealed hepatic metastases of neuroendocrine carcinoma. The patient received analogues of somatostatin and systemic chemotherapy, with a transient symptomatic relief. Sadly the patient was lost to follow-up.

Nonstop mutation in the Kisspeptin 1 receptor (KISS1R) gene causes normosmic congenital hypogonadotropic hypogonadism.

PURPOSE: Congenital hypogonadotropic hypogonadism (CHH) is a rare genetic disorder mostly characterized by gonadotropins release and/or action deficiencies. Both isolated (idiopathic hypogonadotropic hypogonadism) and syndromic (Kallmann) forms are identified depending on the olfactory ability. Clinical and genetic heterogeneities of CHH have been widely explored, thus improving our understanding of the disease's pathophysiology. This work aims to (1) provide a detailed clinical and hormonal description of normosmic CHH patients and (2) identify the mutation linked to the studied phenotype. PARTICIPANTS AND METHODS: We investigated three affected patients with normosmic CHH, belonging to a consanguineous Tunisian family. Patients underwent an insulin-induced hypoglycemia test. We performed whole exome sequencing to identify the causal mutation. RESULTS: At first diagnosis, a total gonadotropic deficiency was identified in all patients. The insulin-induced hypoglycemia test has also revealed a reduced cortisol secretion and complete growth hormone deficiency. At 20.8 years, one female exhibited a spontaneous recovery of the hypothalamic-pituitary-adrenal axis function, unlike her affected siblings who still depend on corticosteroid replacement therapy. Herein, we identified a novel homozygous nonstop mutation (c.1195T>C) in KISS1R gene in all affected subjects. This mutation led to the substitution of the physiologic stop codon by an arginine (p.X399R). CONCLUSIONS: Our study highlights the importance of the KISS1R signaling, in gonadotropin-releasing hormone neurons, in the control of reproductive function. Additionally, our data suggests a complex central and peripheral metabolic control of puberty, through the hypothalamic KISS1R signaling. We suggest a mutual link between the hypothalamic-pituitary-gonadal, -adrenal, and -somatotropic axes.

Fahr's syndrome in Southern Tunisia: A broad spectrum of clinical and etiological features.

AIM: We describe the clinical and etiological profile of patients with Fahr's syndrome (FS). METHODS: Charts of sixteen patients diagnosed with FS between 1999 and 2014 were retrospectively assessed. RESULTS:   The mean age at diagnosis was 44.68 years (11-67 years). The most main presenting neurological features were seizures in 6 cases, headaches in 5 cases and parkinson's syndrome in 3 cases. Psychiatric disorders were observed in 2 patients including memory loss and iritability. Hypocalcemia clinical features were observed in 7 cases. The mean value of hypocalcemia was 1.69 mmol/l. Etiologies included idiopathic hypoparathyroidism in 4 patients, pseudohypoparathyroidism in 5 cases, secondary hypoparathyroidism, isolated hypovitaminosis D and cerebral radiotherapy in one case for each and Fahr's disease in 4 patients.  Oral calcium and vitamin D substitution were started in patients with parathyroid disturbances with favorable outcome. CONCLUSION: In this report, we propose to discuss the clinical manifestations of FS, its etiologies especially parathyroid disturbances and its therapeutic modalities.

Potential role of liver enzyme levels as predictive markers of glucose metabolism disorders in a Tunisian population.

The relationship between liver enzymes and T2D risk is inconclusive. We aimed to evaluate the association between liver markers and risk of carbohydrate metabolism disorders, as well as their discriminatory power, for T2D prediction. This cross-sectional study enrolled 216 participants classified as normoglycemic, prediabetic, newly diagnosed diabetics, and diagnosed diabetics. All participants underwent anthropometric and biochemical measurements. The relationship between hepatic enzymes and glucose metabolism markers was evaluated by analyses of covariance. The associations between liver enzymes and incident carbohydrate metabolism disorders were analyzed through logistic regression and their discriminatory capacity to predict T2D by ROC analysis. High AP, ALT, γGT, and AST levels were independently related to decreased insulin sensitivity. Interestingly, a higher AP level was significantly associated with an increased risk of prediabetes (p = 0.017), newly diagnosed diabetes (p = 0.004), and T2D (p = 0.007). An elevated γGT level was an independent risk factor for T2D (p = 0.032) and undiagnosed T2D (p = 0.010) in prediabetic and normoglycemic subjects, respectively. In ROC analysis, AP was a powerful predictor of incident diabetes and significantly improved T2D prediction. Liver enzymes within the normal range, specifically AP levels, are associated with increased risk of carbohydrate metabolism disorders and significantly improved T2D prediction.