Incretin System: New Pharmacological Target in Obese Women with Polycystic Ovary Syndrome

Introduction: Obesity is highly prevalent in polycystic ovary syndrome (PCOS). It aggravates adverse features of the syndrome. Weight management by lifestyle intervention is often insufficient. We reviewed studies addressing the use of agents mediating through incretin system in obese PCOS

Interplay between Oxidative Stress and Chronic Inflammation in PCOS: The Role of Genetic Variability in PCOS Risk and Treatment Responses

PCOS is often accompanied by insulin resistance, which is associated with the pathogenesis of the syndrome and increases the risk of developing the metabolic syndrome, type 2 diabetes, and cardiovascular complications. All these processes are characterized by chronic inflammation, which may be associated with an increased formation of reactive oxygen species and activation of inflammatory pathways that may further aggravate the function of pancreatic beta-cells. It has been shown that PCOS treatment improves metabolic indexes, while at the same time lowering inflammatory indicators. This chapter summarizes the latest findings about the role of oxidative stress and chronic inflammation in pathogenesis of PCOS. It also provides information on genetic variability in these pathways that may lead to interindividual differences in the risk for PCOS-related metabolic complications. Furthermore, genetic variability in these pathways may influence response to different treatment options in PCOS patients

Strokovna stališča Združenja endokrinologov Slovenije o obravnavi glukokortikoidne osteoporoze

Zdravljenje z glukokortikoidi je najpogostejši vzrok sekundarne osteoporoze. Za glukokortikoidno osteoporozo je značilno zelo hitro zmanjšanje mineralne kostne gostote z naglim zvišanjem tveganja za osteoporozne zlome, zato priporočamo ob uvedbi glukokortikoida oceniti bolnikovo tveganje za zlom in mu svetovati glede zdravega načina življenja ter vnosa kalcija, vitamina D in beljakovin. Če je indicirano, uvedemo tudi eno od zdravil za zaščito kosti, s čimer povečamo mineralno kostno gostoto in zmanjšamo tveganje za zlome vretenc. Večinoma predpišemo bisfosfonate, bolj ogroženim bolnikom, ki so zlome že utrpeli, lahko tudi teriparatid

Adrenal vein sampling for primary aldosteronism

Background Adrenal vein sampling (AVS) is essential for diagnostics of primary aldosteronism, distinguishing unilateral from bilateral disease and determining treatment options. We reviewed the performance of AVS for primary aldosteronism at our center during first 15 years, comparing the initial period to the period after the introduction of a dedicated radiologist. Additionally, AVS outcomes were checked against CT findings and the proportion of operated patients with proven unilateral disease was estimated. Patients and methods A retrospective cross-sectional study conducted at the national endocrine referral center included all patients with primary aldosteronism who underwent AVS after its introduction in 2004 until the end of 2018. AVS was performed sequentially during Synacthen infusion. When the ratio of cortisol concentrations from adrenal vein and inferior vena cava was at least 5, AVS was considered successful. Results Data from 235 patients were examined (168 menage 32%73, median 56 yearsBMI 18%48, median 30.4 kg/ m2). Average number of annual AVS procedures increased from 7 in the 2004%2011 period to 29 in the 2012%2018 period (p < 0.001). AVS had to be repeated in 10% of proceduresit was successful in 77% of procedures and 86% of patients. The proportion of patients with successful AVS (92% in 2012%2018 vs. 66% in 2004%2011, p < 0.001) and of successful AVS procedures (82% vs. 61%, p < 0.001) was statistically significantly higher in the recent period. Conclusions Number of AVS procedures and success rate at our center increased over time. Introduction of a dedicated radiologist and technical advance expanded and improved the AVS practice

Individualizacija magistralnog hormonskog liječenja kod bolesnice s kemoterapijom induciranom prijevremenom insuficijencijom jajnika i smanjenom jetrenom funkcijom: prikaz slučaja

Although the use of commercially manufactured hormone therapy (HT) to treat menopausal symptoms has declined during the past 12 years, the use of custom compounded HT seems to have increased. A 39-year-old woman with refractory anemia sustained premature ovarian insufficiency following allogeneic stem cell transplantation. After systemic biologic treatment (azacitidine) and corticosteroid therapy, besides extreme climacteric symptoms (Green Climacteric Scale, 59) and impaired quality of life, she also had elevated liver enzymes. Therefore, she was not a candidate for oral HT. Treatment was started with 17-beta estradiol patch 0.5 mg (Climara) together with micronized progesterone intravaginally, 2x100 mg (Utrogestan) for 3 months. She was not satisfied, so the custom compound HT started with 17-beta estradiol 0.5 mg gel 2x/day and micronized progesterone in liposomal gel 100 mg/daily. She was much better but she complained of low libido, decreased sex drive and emotional instability, so 1% testosterone gel was added. Now she was completely satisfied, Green Climacteric Scale was 8 and liver enzymes were normal. In conclusion, custom compound HT has the possibility of tailoring and adjusting therapy to the individual need, which has been the everlasting goal in menopause medicine and should be a good option for special clinical cases.Premda je upotreba komercijalno pripravljene hormonske terapije u liječenju klimakteričnih simptoma u posljednjih 12 godina u padu, čini se da je upotreba magistralnih hormonskih pripravaka u porastu. Žena u dobi od 39 godina s refraktornom anemijom doživjela je prijevremenu insuficijenciju jajnika nakon transplantacije matičnih stanica. Nakon sistemskog biološkog liječenja azacitidinom i kortikosteroidima, uz izrazite klimakterične tegobe (Greenov indeks 59) i smanjenu kvalitetu života imala je povišene jetrene enzime. Zbog toga nije bila kandidat za oralnu hormonsku terapiju. Započeto je liječenje 17-beta estradiolom u obliku naljepka od 0,5 mg (Climara) zajedno s mikroniziranim progesteronom intravaginalno 2x100 mg (Utrogestan) kroz 3 mjeseca. Nije bila zadovoljna terapijom pa su joj propisani magistralno pripravljeni hormoni. Započelo se s primjenom 17-beta estradiola u obliku 0,5 mg gela 2x/dan i mikroniziranog progesterona u liposomalnom gelu 100 mg/dnevno. Bolje se je osjećala, ali još uvijek se žalila na smanjeni libido i emocionalnu nestabilnost pa je dodan 1% testosteron. Sad je bila potpuno zadovoljna terapijom, Greenova klimakterijska ljestvica bila je 8, a jetreni enzimi su se normalizirali. U zaključku, magistralni hormonski pripravci pružaju mogućnost titracije i prilagođavanja terapije individualnim potrebama, što je stalni cilj u menopauzalnoj medicini i mogao bi biti dobra mogućnost za posebne slučajeve

Detection and localization of hyperfunctioning parathyroid glands on [18F]fluorocholine PET/CT using deep learning – model performance and comparison to human experts

In the setting of primary hyperparathyroidism (PHPT), [18F]fluorocholine PET/CT (FCH-PET) has excellent diagnostic performance, with experienced practitioners achieving 97.7% accuracy in localising hyperfunctioning parathyroid tissue (HPTT). Due to the relative triviality of the task for human readers, we explored the performance of deep learning (DL) methods for HPTT detection and localisation on FCH-PET images in the setting of PHPT. Patients and methods. We used a dataset of 93 subjects with PHPT imaged using FCH-PET, of which 74 subjects had visible HPTT while 19 controls had no visible HPTT on FCH-PET. A conventional Resnet10 as well as a novel mPETResnet10 DL model were trained and tested to detect (present, not present) and localise (upper left, lower left, upper right or lower right) HPTT. Our mPETResnet10 architecture also contained a region-of-interest masking algorithm that we evaluated qualitatively in order to try to explain the model’s decision process. Results. The models detected the presence of HPTT with an accuracy of 83% and determined the quadrant of HPTT with an accuracy of 74%. The DL methods performed statistically worse (p < 0.001) in both tasks compared to human readers, who localise HPTT with the accuracy of 97.7%. The produced region-of-interest mask, while not showing a consistent added value in the qualitative evaluation of model’s decision process, had correctly identified the foreground PET signal. Conclusions. Our experiment is the first reported use of DL analysis of FCH-PET in PHPT. We have shown that it is possible to utilize DL methods with FCH-PET to detect and localize HPTT. Given our small dataset of 93 subjects, results are nevertheless promising for further researc

Glucagon-like peptide 1 and taste perception

Preclinical studies provided some important insights into the action of glucagon-like peptide 1 (GLP-1) in taste perception. This review examines the literature to uncover some molecular mechanisms and connections between GLP-1 and the gustatory coding. Local GLP-1 production in the taste bud cells, the expression of GLP-1 receptor on the adjacent nerves, a functional continuum in the perception of sweet chemicals from the gut to the tongue and an identification of GLP-1 induced signaling pathways in peripheral and central gustatory coding all strongly suggest that GLP-1 is involved in the taste perception, especially sweet. However, the impact of GLP-1 based therapies on gustatory coding in humans remains largely unaddressed. Based on the molecular background we encourage further exploration of the tongue as a new treatment target for GLP-1 receptor agonists in clinical studies. Given that pharmacological manipulation of gustatory coding may represent a new potential strategy against obesity and diabetes, the topic is of utmost clinical relevance

Genetic variability in antioxidative and inflammatory pathways modifies the risk for PCOS and influences metabolic profile of the syndrome

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder of multifactorial etiopathology likely to involve the interactions between genetics and lifestyle. Chronic inflammation and oxidative stress (OS) may participate in the pathophysiology of the syndrome. The question of the extent to which OS and inflammation are causally related to the development of the syndrome and metabolic complications remains unanswered. By our knowledge, the role of the NLR family pyrin domain containing 3 (NLRP3) inflammasome as an important trigger of inflammatory pathways and NLRP3 and CARD8 polymorphisms has never been addressed in PCOS yet. We conducted a case-control study conducting of total 169 Slovenian PCOS patients and 83 healthy blood donors. They were genotyped for polymorphisms in antioxidative (SOD2 rs4880, CAT rs1001179, PON1 rs854560, and rs662) and inflammatory pathways genes (NLRP3 rs35829419, CARD8 rs2043211, TNF rs1800629, IL1B rs1143623, and rs16944, IL6 rs1800795) using competitive allele-specific polymerase chain reaction (PCR). Logistic regression and the Mann–Whitney test were used in the statistical analysis. SOD2 rs4880, CARD8 rs2043211, and IL1B rs16944 were associated with the risk of developing PCOS. Furthermore, the interactions between CARD8 rs2043211 and IL6 rs1800795 and between IL1B rs1143623 and IL6 rs1800795 also significantly affected the risk for PCOS. With regard to glucose homeostasis, CAT rs1001179, SOD2 rs4880, PON1 rs854560, NLRP3 rs35829419, and TNF rs1800629 were significantly associated with response to the glycemic load. Our data indicate that the genetic variability in the antioxidative and inflammatory pathways influences the development of PCOS and glucose homeostasis in PCOS patients