Hypopituitarism is defined as one or more pituitary hormone deficits due to a lesion in the hypothalamic-pituitary region. By far, the most common cause of hypopituitarism associated with a sellar ...mass is a pituitary adenoma. A high index of suspicion is required for diagnosing hypopituitarism in several other conditions such as other massess in the sellar and parasellar region, brain damage caused by radiation and by traumatic brain injury, vascular lesions, infiltrative/immunological/inflammatory diseases (lymphocytic hypophysitis, sarcoidosis and hemochromatosis), infectious diseases and genetic disorders. Hypopituitarism may be permanent and progressive with sequential pattern of hormone deficiencies (radiation-induced hypopituitarism) or transient after traumatic brain injury with possible recovery occurring years from the initial event. In recent years, there is increased reporting of less common and less reported causes of hypopituitarism with its delayed diagnosis. The aim of this review is to summarize the published data and to allow earlier identification of populations at risk of hypopituitarism as optimal hormonal replacement may significantly improve their quality of life and life expectancy.
Context:
We have recently reported somatic mutations in the ubiquitin-specific protease USP8 gene in a small series of adenomas of patients with Cushing's disease.
Objective:
To determine the ...prevalence of USP8 mutations and the genotype-phenotype correlation in a large series of patients diagnosed with Cushing's disease.
Design:
We performed a retrospective, multicentric, genetic analysis of 134 functioning and 11 silent corticotroph adenomas using Sanger sequencing. Biochemical and clinical features were collected and examined within the context of the mutational status of USP8, and new mutations were characterized by functional studies.
Patients:
A total of 145 patients who underwent surgery for an ACTH-producing pituitary adenoma.
Main Outcomes Measures:
Mutational status of USP8. Biochemical and clinical features included sex, age at diagnosis, tumor size, preoperative and postoperative hormonal levels, and comorbidities.
Results:
We found somatic mutations in USP8 in 48 (36%) pituitary adenomas from patients with Cushing's disease but in none of 11 silent corticotropinomas. The prevalence was higher in adults than in pediatric cases (41 vs 17%) and in females than in males (43 vs 17%). Adults having USP8-mutated adenomas were diagnosed at an earlier age than those with wild-type lesions (36 vs 44 y). Mutations were primarily found in adenomas of 10 ± 7 mm and were inversely associated with the development of postoperative adrenal insufficiency. All the mutations affected the residues Ser718 or Pro720, including five new identified alterations. Mutations reduced the interaction between USP8 and 14-3-3 and enhanced USP8 activity. USP8 mutants diminished epidermal growth factor receptor ubiquitination and induced Pomc promoter activity in immortalized AtT-20 corticotropinoma cells.
Conclusions:
USP8 is frequently mutated in adenomas causing Cushing's disease, especially in those from female adult patients diagnosed at a younger age.
Abstract Purpose of review To review original research studies and reviews that present data on changes of body compartments and its mutual cross-talk with respect to the failing heart predominantly ...in non-cachectic patients with chronic heart failure (HF). Recent findings Thanks to the integrative approach considering the whole organism, several recent studies suggested a complex network of communication between body compartments in respect to failing heart during the natural course of body wasting in non-cachectic patients with HF. Interestingly, recent studies suggest that failing heart trough secretion of natriuretic peptides acts on fat metabolism by inducing adiponectin secretion and lipolytic actions. Soluble myostatin released from the failing heart may induce skeletal muscle wasting in HF through an endocrine-like mechanism, as well. The likelihood that adipocyte-derived hormones influence bone status has been recently proven. Increased serum adiponectin was independently associated with reduced bone mass in elderly patients with non-cachectic HF. Summary The concept of body compartments cross-talk in respect to failing heart provides a very interesting paradigm of integrative physiology. Better understanding of body compartments changes and its complex biochemical interplay may provide more efficacious and forehand treatment to prevent and/or postpone disability and improve quality of life in patients with chronic HF.
Organic farming preserve and upgrade the biodiversity of the soil and biodiversity of the entire ecosystem by protecting the environment, plants, and human health. This study analyses organic plant ...production worldwide and in Montenegro (2000-2020) and discusses the prospects and challenges in developing organic plant production. Geographically, Montenegro has a diverse climate, suitable for the production of more types of fields crops, vegetables and fruits throughout the year. The paper compares the area of organic farms, the number of farmers, and share of organic in the overall agricultural land in the world and Montenegro, Europe, and several European countries similar to Montenegro in terms of relief or area (Switzerland, Slovenia, Slovakia, Estonia, Serbia, and Cyprus). Data were also analysed for a mountainous state, such as Switzerland, and a Mediterranean one, as Cyprus, as by its position and relief, Montenegro is at the same time a mountainous (northern) and a Mediterranean country (southern region). Shows are trends in plant production areas in Montenegro since it gained independence (2006) and comparison with the EU countries. Grassland production prevails in Montenegro with 85.89%, followed by fruit (12.26%) and cereals (1.62%). The total area under organic vegetable covered a small area compared to the production of fodder crops (3951.84 ha), fruit (563.98 ha), medicinal and aromatic plants (232.46 ha) and field crops (74.49 ha). Organic fruit production has the largest share in the northern part of Montenegro. Certified organic production brings benefits because health-safe products are a condition for preserving the environment and health.
Pituitary adenohypophyseal tumors are considered as benign and termed “adenomas”. However, many tumors are invasive and a proportion of these exhibit an “aggressive behavior” with premature death due ...to progressive growth. Only very rare (0.2%) tumors with metastases are considered malignant and termed “carcinomas”. Taking into account this variability in behavior and the oncological definition, pathologists have proposed changing the term adenoma to tumor. Here we explain why use the term tumor instead of adenoma and identify tumor characteristics, associated with a high risk for poor prognosis. In a cohort of 125 tumors with aggressive behavior (APT) and 40 carcinomas with metastases (PC), clinical and pathological features were very similar. The comparison of this cohort (APT+PC) with a reference surgical cohort of 374 unselected patients clearly shows that the two cohorts differ greatly, especially the percentage of tumors with Ki67 ≥ 10% (35%vs3%;
p
< 0.001). A five-tiered prognostic classification, associating invasion and proliferation, identified grade 2b tumors (invasive and proliferative), with a high risk of recurrence/progression. Because half of the APT+ PC tumors have a Ki67 index ≥10%, and 80% of them show 2 or 3 positive markers of proliferation, we suggest that tumors that are clinically aggressive, invasive and highly proliferative with a Ki67 ≥ 10%, represent tumors with malignant potential. The percentage of grade 2b tumors, suspected of malignancy, which will become aggressive tumors or carcinomas is unknown. It is probably very low, but higher than 0.2% in surgical series. Early identification and active treatment of these aggressive tumors is needed to decrease morbidity and prolong survival.
Hematological neoplastic mass lesions of the sellar region are rare. We identified five cases of hematological malignancy with first presentation in the sellar region from our departmental database ...of 1,405 patients (0.36%) with sellar lesions diagnosed over the 17-year period (2005–2021). All patients were females (mean age 55.2 ± 3.4 years). One patient had multiple myeloma (MM), one patient had acute myeloid leukemia (AML), while three other patients had lymphoma (intravascular lymphoma (IVL, n = 1) or non-Hodgkin’s lymphoma (NHL, n = 2). Most patients presented with ophthalmoplegia, and one patient with diabetes insipidus (DI), with short duration of symptoms (median 30 days). All patients had an elevated erythrocyte sedimentation rate and altered blood count, while patients with lymphoma had elevated lactate dehydrogenase (LDH). Sellar mass was demonstrated in three patients while the patient with IVL had an empty sella and in the AML patient posterior lobe T1W hyperintensity was lost. Two patients (IVL and NHL) presented with multiple anterior pituitary deficiencies and one patient (AML) had DI. All patients were treated with chemotherapy. Two patients responded well to treatment (one had reversed hypopituitarism), while three patients died. Differential diagnosis of sellar-parasellar pathology should include suspicion of hematological malignancy, particularly in patients with short duration of nonspecific symptoms, neurological signs (ophthalmoplegia), blood count alterations and LDH elevation, pituitary dysfunction and imaging features atypical for pituitary adenoma. Early diagnosis is crucial for timely initiation of hematological treatment aimed at inducing disease remission and partial or full recovery of pituitary function.
Pituitary adenomas are benign neoplasms of the pituitary. The most prevalent are prolactinomas and non-functioning pituitary adenomas, followed by growth hormone- and ACTH-secreting adenomas. Most ...pituitary adenomas seem to be sporadic and their persistent growth is very atypical. No molecular markers predict their behavior. The occurrence of pituitary adenomas and malignancies in the same patient can be either pure coincidence or caused by shared underlying genetic susceptibility involved in tumorigenesis. Detailed family history on cancers/tumors in the first, second and third generation of family members on each side of the family has been reported in a few studies. They found an association of pituitary tumors with positive family history for breast, lung and colorectal cancer. We have reported that in about 50% of patients with pituitary adenomas, an association with positive family history for cancer has been found independent of secretory phenotype (acromegaly, prolactinoma, Cushing's disease or non-functioning pituitary adenomas). We also found earlier onset of pituitary tumors (younger age at diagnosis of pituitary tumors) in patients with a strong family history of cancer. In our recent unpublished series of 1300 patients with pituitary adenomas, 6.8% of patients were diagnosed with malignancy. The latency period between the diagnosis of pituitary adenoma and cancer was variable, and in 33% of patients, it was longer than 5 years. Besides the inherited trophic mechanisms (shared underlying genetic variants), the potential influence of shared complex epigenetic influences (environmental and behavioral factors - obesity, smoking, alcohol intake and insulin resistance) is discussed. Further studies are needed to better understand if patients with pituitary adenomas are at increased risk for cancer.
For agricultural production is used almost 40% of the global land from where it dominates conventional agriculture which uses large amounts of inputs in the form of fertilizers and pesticides leading ...to the contamination of soil, water resources, air pollution and land erosion, affects biodiversity and extinction of many plants and animals. On the other hand, the world's population is constantly growing and currently numbers more than 8 billion people and it is estimated that food production will have to double by 2050. In order to meet the future needs of the population for food raw materials, food production must significantly increase, and at the same time, the impact of agriculture on the environment and natural resources must be drastically reduced. Sustainable agriculture is emerging as one of the solutions. This way of agricultural practice refers to the management and preservation of natural resources through organizational and technological changes in modern agricultural production in order to satisfy human needs and preserve the environment. One of the most important natural resources on which the entire agricultural production relies is land. In intensively cultivated lands, there is a noticeable trend of intense degradation, which represents a major problem facing humanity. The paper reviews the decrease in soil fertility based on the samples collected during the five-year monitoring, as well as a proposal for measures to increase fertility and future preservation of this environmental resource.
The aim of the research was determination the efficiency of application 50 t ha-1 digestate from the process of anaerobic digestion on the productivity of sorghum (Sorghum bicolor L.) on moderately ...degraded (calcic gleysol) and fertile (chernozem) agricultural land, in southern Banat, Republic of Serbia. In the field experiment during three years digestate amendment led to an increase in the number of leaves by 28.56% and plant height by 5.34%, which led to an increase in yield by 3.40%. The maximum yield was 2018 (41.74 DM t ha-1) on chernozem. The yield of sorghum was lower on calcic gleysol compared to chernozem by 5.43% and was in positive, medium and very significant dependence on precipitation (0.61) and in positive significant correlation with digestate (0.53) and plant height (0.59). Biogas yield reach 157.05 Nm3 t-1 (9582 Nm3 ha-1) on chernozem with digestate. Digestate had a statistically significant positive effect on all tested characteristics of sorghum as well as biogas yield during all three experimental years. The use of digestate as a by-product in the process of producing biogas based on silage of sorghum, allows the substitution of mineral fertilizers and remediation of damaged soil, which contributes to sustainability from the bio-economic and environmental aspects.
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