Despite a variety of studies on the tropical cyclone (TC) response to climate change, few of them have examined the projected damages of future TCs. Here we quantify the impact of anthropogenic warming on TC-induced damages in the late twenty-first century along the coasts of Southeast China based on convection-permitting TC simulations and machine-learning-based damage models. We found that if the area’s 10 super typhoons between 2013 and 2019 were to occur at the end of the century under the high emissions RCP8.5 scenario, they would have on average a 12% ± 4% increase in landfall intensity, 25% ± 23% increase in precipitation, and 128% ± 70% increase in economic losses, compared to historical simulations. We also found a significant increase in the full risk profile. The estimated typhoon loss with a 50-year return period for Zhejiang, Fujian, Guangdong, and Hainan (four most typhoon-prone provinces among the seven provinces in the region) would increase by 71%, 170%, 20%, and 85%, respectively, towards the end of the century even under the lower emissions RCP4.5 pathway. Our findings imply the need to design effective local hazard mitigation measures to reduce future typhoon risks. Lekima produced the record of daily rainfall accumulation in both Zhejiang and Shandong Province since the weather observation system in China was first established in 1949, with the resultant flooding a primary cause of fatalities and property damages. Besides Lekima, the recent high typhoon activity in WNP has posed a serious threat to Southeast China. For instance, there were 16, 10, and 9 super typhoons  in the 2015, 2016, and 2018 WNP typhoon seasons, respectively, in comparison to 8 on average over 1948–2017.The Western North Pacific Ocean (WNP) is the most active tropical cyclone (TC) basin, accounting for almost one-third of the world’s annual TCs. Severe TCs, also called typhoons (with maximum 10-m wind speed at least 32.7 m/s) in WNP, cause devastating losses of life and property in Southeast China, where both the population and economy are growing rapidly. One of the most prominent examples is Typhoon Lekima (2019), which made landfall in mainland China with a major hurricane intensity and caused 56 fatalities and a direct economic loss of 53.72 billion CNY  are also important factors for increased coastal flood hazards15.A number of studies have been devoted to the long-term trend in TC activity in the WNP16, given various emission scenarios17 and socioeconomic development pathways18. For example, a climate change signal has been identified in historical U.S. hurricane losses from an economic point of view by a regression-based approach19. A statistical relationship linking the maximum 10-m wind speed of hurricanes and the economic losses was developed for the U.S. Atlantic and Gulf Coasts and used to assess the influence of climate change on TC damages with the aid of a synthetic TC model20. The Community Earth System Model was combined with the TC damage model to estimate future changes in TC-induced damages on the global scale21. The study found that the global TC damage is mostly dominated by East Asia due to a large number of strong Pacific storms1, which indicates that the regional impact studies are urgently needed22 to guide policy makers to take appropriate risk-reduction actions and hence limit the impact of climate change.With the advances of dynamical modelling of TCs, changes in TC damages can be assessed by combining atmospheric science and economics24), the mesoscale Weather Research and Forecasting (WRF) model26, and machine-learning-based damage models. The damage models on a regional level are developed based on the deep neural network (DNN) to establish links between typhoon damages in Southeast China and six meteorological variables including storm intensity  and maximum 10-m wind speed), storm size , daily site-maximum precipitation, daily area-mean precipitation, and astronomical high tide using historical data and are employed for estimating future socioeconomic typhoon impacts on Southeast China  High-Resolution Forecast-Oriented Low Ocean Resolution (HiFLOR24) experiments or the Coupled Model Intercomparison Project Phase 5 (CMIP5) models. Changes in storm activity including intensity and rainfall for the 10 SuperTYs are further used to drive the DNN models to investigate how the damages from the SuperTYs would respond to climate warming. Because HiFLOR shows good skill in simulating the intensity spectrum of TCs including Categories 3–5 TCs24, we also couple the landfalling typhoon samples directly simulated from a 70-year HiFLOR experiment24 under the RCP4.5 scenario with the DNN damage models to estimate the full hazard risk profiles in Southeast China by the end of the twenty-first century.We conduct convection-permitting WRF control simulations for a collection of 10 historical super typhoons that produced devastating damages in Southeast China (referred to as SuperTYs hereafter). We also simulate pre-industrial and future episodes of the same 10 storms by placing them in the climate conditions of 1860–1880 or at the end of the twenty-first century under the RCP4.5 and RCP8.5 scenarios. This analysis is achieved through the so-called pseudo-global warming (PGW) approach26 was developed especially for the research on typhoon/hurricane simulation and real-time prediction. Based on the AHW model (Version 3.7), the convection process of the inner typhoon center is explicitly resolved with high-efficiency movable 4-km grids while the interaction between the atmospheric environment and the typhoon circulation is also considered in the outer large computational domain. We perform the 10-member ensemble simulation using the stochastic kinetic energy backscatter scheme (SKEBS)29, which captures the uncertainties in unresolved convection scales by introducing temporally and spatially correlated perturbations to the rotational wind components and potential temperature.As a module of the WRF system, the Advanced Hurricane Weather Research and Forecasting (AHW) model28. The PGW simulations were conducted by adding perturbations to the initial and boundary conditions for historical control simulations. For pre-industrial typhoon simulations, the climate perturbations were computed as the differences between 1860 and 1880 monthly climatology  and 2000–2020 monthly climatology  from general circulation models (GCMs). For future climate simulations, the climate differences between 2080 and 2100 monthly climatology (future climate) and 2000–2020 monthly climatology were used as perturbations. The climate perturbations from two individual GCM models (FGOALS-s2 and CCSM4), 10-GCM model ensemble mean from the CMIP5 project, and HiFLOR24 were used in the future typhoon PGW simulation under low (RCP 4.5) or high (RCP 8.5) emission scenarios  towards the climatological SST over the period 1986–200523. Future “early” and “late” climate HiFLOR experiments were conducted to project the storm climatology during 2016–2035 and 2080–2100, respectively, with the climatological SST derived from a multi-model mean of 17 CMIP5 models for the RCP4.5 pathway24. Here we focus on the “late” (2081–2100) HiFLOR experiments because their differences are more significant to reflect the climate change response of TCs in HiFLOR. For scenario analysis, we used the “late” HiFLOR climate conditions to drive the AHW model for the simulations of the 10 SuperTYs in the future climate condition. To estimate future typhoon damage risks in Southeast China during the late twenty-first century, we identified landfalling typhoon events in Southeast China from the HiFLOR “late” experiments. Typhoon meteorological variables of the identified typhoon events served as direct inputs to estimate typhoon damages by the developed DNN typhoon damage models . The landfall details of the 10 SuperTYs, i.e., landfalling locations and affected provinces of Chinese coast, are given in Supplementary Table The 10 historical storms selected over 2013–2019 are landfalling SuperTYs with a lifetime maximum 10-m wind speed no less than 51 m/s, approximately equivalent to major hurricanes. The 10 SuperTYs  for Lekima  compared to the historical record is observed for Typhoon Lekima under the HiFLOR RCP4.5 climate. We note that for Lekima, the future storm under the HiFLOR RCP4.5 experiment intensified more than those under the CMIP5 RCP4.5 and RCP8.5 experiments. The greater intensification of Lekima under HiFLOR RCP4.5 is also shown by the greater decrease in minimum SLP at landfall  climate scenarios  for historical typhoons, and the daily area-mean precipitation is calculated by averaging the daily precipitation from the meteorological stations located in the same province. To match with each observational site, the daily site-maximum and area-mean precipitation from the WRF simulations are evaluated over a square region of 25 km × 25 km centered on the corresponding observational site. The WRF model is capable of capturing the timing and magnitude of maximum precipitation at the observational sites  before using those TC meteorological variables to estimate the direct economic loss. TC frequency in the HiFLOR control simulation is bias-corrected against the CMA typhoon observations during the period 1986–2005  to Zhejiang Province in 2019, translating to a return period of 22 years in the historical period see Fig. a. AccordSuperTY Lekima in 2019 produced catastrophic damages in Zhejiang province. There is an urgent need to project future typhoon activity under climate change and assess its impact on Southeast China as the TC precipitations and the TC intensity are, with growing confidence, projected to increase under anthropogenic warming. Here, for the first time, we quantify the increase in typhoon damage at the province level by the end of twenty-first century for Southeast China due to TC climatology change.28. In addition, our regional-scale “worst-case-scenario” studies of climate change effects on TCs are indeed consistent with those from the high-resolution global models24, which also show robust increases of TC intensity and precipitation in a warming climate.The increase of typhoon damage risk under future climate could be attributed mainly to stronger storm intensity  and heavier precipitation , as evidenced in Tables The typhoon damage may vary significantly along the Southeast coast of China, which is impacted by the combined effects from socioeconomic exposures and mitigation measures taken by the coastal provinces. Such regional-scale differences are captured by the ensemble DNN damage models, trained by historical typhoon meteorological data and damage records at a province level. We found that Guangdong Province seems to have lower sensitivity to future typhoon hazard than other coastal provinces. As shown in Fig. We should expect an uneven risk distribution of typhoon hazard in the future since local populations can adapt to climate change in numerous ways. The province-level DNN models were developed to capture various forms of adaptation to the extent that populations have historically employed them. For example, if local farmers of Guangdong have been adjusting their planting conditions based on recent typhoon activity, the effects of these previous adaptation would be captured by the DNN damage models. Our study applies a “top-down” data-driven macro-level approach that estimates the economic impacts of climate changes without requiring the knowledge of the underlying mechanisms responsible for those losses. Such an approach assumes no future changes of exposure to typhoons and focuses on the direct effects of climate change.21 (hereafter G2018). In G2018, the change in mean annual damage due to future storms was projected to increase by about 70% for East Asia, which dominates the global changes. Our estimated 75% increase in the 50-year typhoon damage for all four coastal provinces in China is consistent with G2018. The DNN damage model in our study advances the G2018 study by considering multiple typhoon meteorological variables. The G2018 study does not account for adaptation in the estimates of damage while we capture the adaptation in various provinces with the province-level damage model. Our finding is essentially within the range of those found in existing studies, but our results provide more useful insights for the region of Southeast China, particularly on the changes in potential typhoon-induced damage arising from climate change. On the other hand, our study does not consider future changes in exposure and adaptation. We may overestimate the future typhoon impact as the studies34 indicate that societies continue to adapt to TCs, so the exposure could be reduced. Despite the limitations, our regional impact study can be used to identify locally appropriate risk reduction (adaptation) measures and provide evidence to facilitate policy and decision making.The conventional wind-speed dependent TC damage model has been used to project future TC damage with a high-resolution global climate model18 (hereafter T2019) projected economic impacts of climate change on the global scale considering both climate change mitigation pathways and socioeconomic development pathways34, which describe alternate evolutions of the socio-economic system and the eco-environment. T2019 adopted a bottom-up approach by conducting process-based impact simulations for each modeled sector and aggregating the monetized impacts. The economic impact of climate change could be calculated by different impact models for various sectors18, e.g., energy, water, transportation, and agriculture. The monetized impacts reported in T2019 were based on only one impact model for each sector; thus the uncertainty associated with variation between the impact models was neglected in T2019. The DNN damage model ensemble developed here is data-driven and are computationally highly efficient. On the other hand, unlike the impact model in T2019 that can be applied more broadly, the data-driven province-level model may be applicable for only the study region in China. Our study does not directly account for TC-induced storm surge, which is expected to increase TC flood hazards under global warming15, although storm surge is strongly correlated with wind intensity and storm size. Thus, future studies should evaluate the effect of TC-induced storm surge. The effect of different socioeconomic pathways, i.e., sustainable development or fossil-fueled development, may also be investigated. In addition, the DNN damage models could be refined to make independent estimates of economic impact for individual sectors, e.g., agriculture, power, building, etc. The effective and local hazard mitigation measures could then be designed and taken to reduce risks of future typhoon hazards threatening Southeast China.A previous study43 used in the WRF experiments are also listed in Supplementary Table 40, New Thompson et al. scheme41 (Thompson), and Morrison double-moment scheme42 (Morrison). The air-sea flux parameterization43, which describes the aerodynamic drag between air and sea, is an important part of the momentum balance in modeling the development of typhoons in the AHW model and is set through the namelist variable of isftcflx  corresponding to three different air-sea flux schemes. The ensemble-means of historical typhoon simulations are compared with the observed best track data from the CMA45, in terms of typhoon tracks and time series of minimum SLP and maximum 10-m wind speed  Operational Global Analysis data at 1° resolution from the National Centers for Environmental Prediction (NCEP) are used for initial and boundary conditions to drive the WRF model for the historical control simulations. We apply a set of parameterization schemes of physical processes through sensitivity experiments for the meso-scale WRF simulation of the 10 SuperTYs to improve the accuracy of simulated TC tracks and intensity. The physical parameterization schemesFor the PGW method, atmospheric variables including air temperature, relative humidity, and geopotential height at all tropospheric levels from climate model simulations are used for lateral boundary condition perturbations. The surface variables from climate model simulations, i.e., surface temperature, 2-m air temperature, 2-m specific humidity, SLP, and surface pressure, are used to adjust initial conditions in the PGW experiments. These changed thermodynamic fields are applied to the initial and boundary conditions used in the AHW model to generate “past” or “future” episodes of the 10 SuperTYs. Grid configurations and parameterization schemes of physical processes remain the same as in the historical hindcast simulation for each SuperTY.23 and the future “early” and “late” climate HiFLOR experiments24 were conducted, and the outputs of these simulations and projections were used in this study. The prescribed climatological SST in the HiFLOR control simulation was the monthly varying climatology from the Met Office Hadley Centre Sea Ice and SST dataset (HadISST1.1)46.HiFLOR was developed at the Geophysical Fluid Dynamics Laboratory (GFDL). Seventy-year control HiFLOR simulations23. In the detection algorithm, SLP and the temperature anomaly averaged between 300 and 500 HPa were the main variables used to locate the local minima of SLP and the warm core of a candidate TC.We used the HiFLOR “late” experiments to drive the AHW model for the simulations of the 10 SuperTYs in the climate conditions at the end of the twenty-first century under the RCP4.5 scenario. For future typhoon risk estimation, landfalling typhoon events in Southeast China were identified from the HiFLOR “late” RCP4.5 experiments by the TC detection algorithm as described in the literature24, we applied the bias correction to the frequency of genesis (FOG) and the TC wind speed obtained from the original HiFLOR experiments. Since the FOG bias can be estimated by subtracting observed values from simulated control values in each segmented 2° × 2° grid, the FOG of HiFLOR RCP4.5 experiment could be corrected when assuming that the model biases are inherited by the future projections32. Supplementary Figure 47 was applied to adjust the projected maximum 10-m wind speed of HiFLOR. The QDM is commonly used for correcting systematic errors in distributions of a modeled series (HiFLOR data) compared to the control simulation or observation data while preserving model-projected relative changes in quantiles. Supplementary Figure Because of the simulation bias of HiFLOR experimentshttp://data.cma.cn/data) of the CMA. The daily area-mean precipitation for a landfalling site is calculated by averaging the daily precipitation from available meteorological stations within the province of the landfalling site. The maximum 2-min sustained wind speed at 10-m height and the minimum SLP of typhoons are derived from the CMA-STI best-track dataset45. The tropical cyclone size dataset is derived from Satellite Observations48. Different data sources have been used to acquire a reliable record of typhoon damages, i.e., direct economic losses, collapsed houses, death tolls, and flooded croplands due to landfalling TCs on coastal provinces of China49. The data sources include documents of meteorological disaster for Zhejiang, Fujian, Guangdong, and Hainan provinces50, China Meteorological Yearbook (1986–2017)51, and the Yearbooks of Meteorological Disaster (2006–2017)52. The overall impact of each observed landfalling typhoon has been quantified in terms of the number of deaths, the number of collapsed houses, the area of flooded croplands, and the direct economic losses (CNY). The direct economic loss is the most important damage measure that is estimated by costs of repair and replacement to restore properties  to the states before typhoon landfall. We present direct economic losses for the 10 SuperTYs recorded by Department of Civil Affairs of China. The direct economic loss is adjusted by the consumer price index (CPI) of 2013. The CPI data is obtained from the National Bureau of Statistics of China (http://data.stats.gov.cn/search.htm?s=CPI).Daily precipitation during historical typhoon is taken from the National Meteorological Information Center  is used to describe astronomical tide activity, which is set as “1” when the typhoon made landfall on the 2nd, 3rd, 17th and 18th day of the lunar calendar. These variables serve as input data to train DNN damage models. Typhoon-induced damage data are represented by direct economic losses. To better train the province-level DNN damage models, the direct economic loss is transformed into economic loss index (ELI) with a range of 0 to 1, which is a normalization of direct economic losses by a given loss threshold, by employing the following conversion function of 53, has been widely applied in a variety of scientific fields58. The advantages of DNN models over other regression methods include independent learning and adaptive ability, memory association, and parallel processing of data. The multivariate input–output relationship between landfalling-typhoon characteristics and province-level damages can be readily established in DNN models without explicitly describing the underlining physical and economic theory. Specifically, we develop province-level BP-DNN models for typhoon-prone regions of Southeast China to predict direct economic losses in terms of ELI. Neuron number and hidden layer number are respectively adjusted for each model. For each run, or epoch, the BP-DNN model60 checks for the mean square error (MSE), or the objective function, and makes efforts to minimize it by altering the biases and weights with a reverse propagation process. The iterations for the optimal weight and bias parameters of the DNN keep going until the MSE decreases to the lowest level or the number of maximum iteration times reaches a predetermined value. To further improve the robustness or the generalization ability of the DNN models, we referred to the committee\ensemble method61 to establish ensemble modeling for each province. The way to construct a committee is to average the predictions of a set of individual DNN models. At least 10 DNN models are independently developed to form a model ensemble for predicting typhoon damage for each province.DNNs trained with backpropagation (BP), which is the most representative DNNIt is worth noting that possible overfitting could be a problem for the neural network model due to limits of the typhoon damage data. That is why we adopted the committee\ensemble method to alleviate possible overfitting problems. Furthermore, we adjusted the network structure and hyperparameters for each DNN member of the ensemble model, and out-of-sample tests were performed for each DNN damage model. To evaluate the model ensemble, the historical damages of Lekima (Zhejiang), Soudelor (Fujian), Usagi (Guangdong), and Haiyan (Hainan) are then estimated for each province by the corresponding 10-model ensemble and compared to the observed values. The mean of predictions from the model ensemble exhibits a good performance with a maximum error of 4.1% in the case of Soudelor for Fujian Province  serve as inputs for the DNN typhoon damage models to estimate the typhoon-induced loss in the future climate. The maximum 2-min sustained wind speed at 10-m height, the minimum SLP, daily site-maximum, and daily area-mean precipitation of serve as predicting variables in the DNN typhoon damage models to predict future typhoon damage of each future typhoon sample from the HiFLOR RCP4.5 experiment.63:64. We determine the economic loss threshold value for each province to separate the tail from the rest of the distribution by trial and error to achieve the overall minimum error of tail fitting. The CDF of the generalized Pareto distribution with the shape parameter k, the scale parameter σ, and the threshold parameter μ, is given as64:We apply the same extreme value analysis to both the historical typhoon damage data and the predicted damage data of future typhoons. Since the future typhoon damage is predicted using the corrected HiFLOR “late” projection data, differences between historical typhoon damage and the predicted future damage as presented in Fig. Supplementary Information.


Rapid reviews have emerged as an approach to provide contextualized evidence in a timely and efficient manner. Three rapid review centers were established in Ethiopia, Lebanon, and South Africa through the Alliance for Health Policy and Systems Research, World Health Organization, to stimulate demand, engage policymakers, and produce rapid reviews to support health policy and systems decision-making. This study aimed to assess the experiences of researchers and policymakers engaged in producing and using rapid reviews for health systems strengthening and decisions towards universal health coverage (UHC).n = 16). The topics covered included the process and experience of establishing the centers, stimulating demand for rapid reviews, collaborating between researchers and policymakers, and disseminating and using rapid reviews for health policies and interventions and the potential for sustaining and institutionalizing the services. Data were analyzed using thematic analysis.Using a case study approach with qualitative research methods, experienced researchers conducted semi-structured interviews with respondents from each center (Major themes interacted and contributed to shape the experiences of stakeholders of the rapid review centers, including the following: organizational structural arrangements of the centers, management of their processes as input factors, and the rapid reviews as the immediate policy-relevant outputs. The engagement process and the rapid review products contributed to a final theme of impact of the rapid review centers in relation to the uptake of evidence for policy and systems decision-making.The experiences of policymakers and researchers of the rapid review centers determined the uptake of evidence. The findings of this study can inform policymakers, health system managers, and researchers on best practices for demanding, developing and using rapid reviews to support decision- and policymaking, and implementing the universal healthcare coverage agenda. Changing Mindsets  within the team to be able to do these rapid reviews succinctly but also to do it well. …………. There is need for capacity to be able to write well and to package it well…………. You need dedicated capacity to search efficiently to identify evidence and then to be able to go through the evidence and be able to make sense of it. Most of the researchers were qualified and well trained, particularly in systematic review and rapid review methodologies, but they reported that they needed additional training to respond to the policymaking process, relevantly and comfortably. The respondents noted that the training should not be a single occurrence, as one session may not leave people feeling confident enough to continue on their own. Respondents also noted that additional support or mentorship was necessary to ensure that they applied what they learned into practice. Given this, it was important for all the teams to have access to training and make appropriate choices about who to invite to the trainings. The South African center included people from several collaborative institutions in addition to their internal team, while the centers in Ethiopia and Lebanon focused on groups within one organization. The South African group’s approach allowed them to continually draw on people from outside of their immediate team for different parts of the rapid response process. One of their researcher’s said: “The people who came for [mentions name]’s training we involve them like whenever we have a question. We put it out on to this mailing list of people who came for training and those who are interested in that topic volunteer to work on it.” It is rare that these capacities will be seen in one individual, and so, one may look to formulate a team with several individuals with one or some of the desired knowledge and skills. The policymakers also mentioned the need to set up structures to support use of evidence and having skilled individuals within the ministry who will be able synthesize and translate the evidence provided.In addition, the teams realized that there were other capacities outside of the traditional technical ones that were needed. These included the capacity to engage with, negotiate review questions, and understand the policymaking process, as described by a policymaker from Ethiopia: “And I think the other important thing is to understand the decision makers’ world because if you are a researcher you don’t always understand what is on pressure and the issues on the policymakers’ side.”So I think for me the critical thing about these kinds of projects going forward is that it needs dedicated capacity. It can’t be something that somebody adds on in the day and do it for the last or after hours for instance. You need dedicated people that can foster the relationship. That can even be in the policy maker space to understand the question that is coming up .To be efficient, respondents noted that there must be dedicated capacity for this kind of work. Several respondents from both the supply and demand side felt that this was critical for the survival of such a service:……………She [a policymaker] was very specific and clear and I think it is because: one; she has got a background in training in research and two; she came for the training with [mentions name] so she sort of understood what a rapid synthesis is and can provide. Whereas with [mentions name and background] and there is [mentions name and background], I think they are both …………..I am not sure how much of research background they have because we struggled a lot with moving their questions from operational to reviewable questions .There was general consensus amongst the respondents that the actors in the policymaking arena needed a certain set of knowledge and skills  to be able to use the rapid review findings effectively and efficiently. It was also beneficial for policymakers to attend the review centers’ trainings as they developed a better understanding and level of engagement with the process.When the participants were asked about what the needs of the policymakers were, one policymaker emphasized the need for them to also be capacitated to make use of the service. She noted, “It is how to make use of the information because you can generate a whole lot of questions but how do you use the information that was generated” . Another policymaker highlighted that one of the barriers to the rapid review services is “our capacity in interpreting the response report,” which needs to be addressed to ensure that the center is successful.A policymaker from Ethiopia, who had been using evidence in the form of surveys for decision-making, felt that the rapid reviews produced by the centers were less resource consuming in terms of time and funds as compared to the alternative sources.Participants felt that the determining factor for a good experience with the service was the evidence itself in terms of availability, relevance, and timeliness. Overall, the respondents felt that the rapid review centers were able to provide policy-relevant evidence in this way.Partnerships and collaborations were credited for different strengths brought to the process. These contributions included improved capacity, strengthened methods, and improved demand.A researcher from South Africa noted that collaboration strengthened the methods and the guidance to be able to implement the project. Specifically, they were drawing on several people from partner organizations outside of their group who participated in the training. Respondents also mentioned that the relationships between the researchers and policymakers were important for RRS work. They pointed out that several factors were involved in building and maintaining these relationships, particularly trust and credibility.I think if you have a clear terms of reference in the agreement as to what from both sides. What is your role and responsibilities as the policy maker and what is your role and responsibility as the service provider? ………………. it will serve to guide to say this is how we will work together.A participant stated that it was important for expectations and responsibilities of each party to be clearly outlined:If we train for example the mass media about evidence synthesis . . . I think the mass media could play a pivotal role by linking the researcher, the evidence synthesis [team] with the policy makers. And if the mass media is provided with this synthesized evidence, they can make it public and they can go to the policy makers to also with this evidence and ask the policy makers whether they have used it or not. Or the other way around [to the researchers], saying the policy makers and decision maker are noting this evidence .Other relationships were highlighted as important. For example, one policymaker from Ethiopia noted that it was important to involve the media in understanding rapid review work as they would in turn foster linkages between the researchers and policymakers. He said:Policymakers frequently act as champions spreading the word amongst their colleagues and other potential users. For example, a South African policymaker from the State Department of Health who used the service mentioned that he heard about the RRS “From [name], my colleague who attended a training.” A researcher from Ethiopia also commented on champions: “So otherwise, the methods are very clear. Once we get a champion within the ministry of health we will establish that place and strengthen that relationship and we will push that structure is also created at the ministry of health.”……………….if it has to be sustainable the way forward is through permanent structures not committees. And advisory councils get to advise not to synthesize evidence. We have made it in black and white for [the ministry]. …………………….. But for the policy makers around the ministry of health, it’s always the council. Because of that it isn’t working [very well yet].All respondents agreed that the activities involved in the RRS should be institutionalized and made more permanent and sustainable. A policymaker from Ethiopia emphasized the following:…………………. so the one [level] we are currently at is what we call the middle level. And we are in the strategic unit so we are responsible for the planning and designing of service delivery. But then we also have a macrostructure which is responsible for policy development . . . So for me I find it valuable because we need to take policy and make it operational and implement it . . . so we look at what is the evidence based on feasibility, sustainability looking at making things work within your specific context. …………..at National department of Health level they are responsible for setting policy………………. So at that level it would make sense to have access to such a service because by the time it comes down to us they should have gone through all those thinking processes The respondents suggested that skilled staff and permanent platforms for rapid review centers were primarily needed for sustainability. However, they argued that it was important to determine where and how the service added value to each institutional level.In order for the structure to be functional, processes and their management must be in place that support policy and systems decision-making. As the centers carry out activities to build demand, they continuously engage with policymakers, which leads to increased demand and knowledge of policy needs and contributes to institutionalization.Rapid review services are ideally demand driven and aim to respond to the concerns and queries of the policymaking process. Therefore, research questions are typically generated by policy and other decision-makers and presented to the review team. To facilitate this process, the researchers from the RRS must build a relationship with the policymakers based on trust and credibility. One center noted, “It may take time, it’s like change of culture. Cultures don’t change overnight.”To begin building new bridges, one center described how they leveraged their existing relationships: “Other relationships we already have, [we] tried to use them to get more people to seek our service.” Another method of stimulating demand is to invite policymakers to rapid review training. Respondents also reported that researchers needed to leverage the results from completed reviews to gain credibility. For example, a researcher from Lebanon stated: “I think for a time being the researcher should go and show them that these are the results that show that evidence can be synthesized within a month or so. The advantages of decisions based on evidence is more higher than decision without any evidence.”The issue of process responsibility arose. The policymakers submitted their queries and utilized the final information, but the researchers conducted the reviews and synthesized the data to respond to the research question. Therefore, some clarity was needed around who held the responsibility to lead and see the knowledge translation (KT) process through. The responsible party — supply or demand side — would need to be well equipped to manage the process and would be liable if it did not evolve appropriately. This would also assist in evaluating and improving processes.The first person we engaged with ……………… the objective was to actually conduct the full rapid synthesis review in two weeks……….he gave us the question ……….. but when we read about it we realized that there were missing parts and there were things which we did not understand so we went back to him. But at that point we [had] not seen us going back and forth as part of the whole package, it was [originally] like all just a minor thing to help us……… Developing methods and standard operating procedures (SOPs) is an iterative process that is supported by the growing experience of the team. For example, teams realized that continuous engagement with the policymakers was required and should be deliberately planned for with clear objectives. A respondent noted:Centers recognized that the RRS model, which was presented to them during the trainings, needed to be adapted to their own contexts and capacities. One researcher indicated, “We actually changed our model from trying to come up with the 15 days finished product to actually starting small rapid responses” .The kind of questions we were asking are practical questions and it is important that the researchers understand the health system’s workings. Clarifying the question took time; we kept coming back and forth. It was good that they brought in an expert to clarify the question Both the researchers and policymakers were in agreement that the initial clarification process needed to be standardized to ensure that the needs of the policymakers and the research questions were well understood. A policymaker pointed out:The clarification process may take time, but it is an important step, and as the policymaker noted, the review team should have sufficient health systems’ knowledge and skills.So the first meeting when we were negotiating the question we asked them which is the best form of communication and most have said emails. But we also understand that they are very busy people sometimes they do not respond at all and we might have to make a phone call to follow up. The review centers and policymakers faced challenges with engaging and communicating with each other. For example, a researcher recalled their initial attempts at communication with policymakers:Referring to the same incident, a policymaker said, “We had some meetings and used email but you know emails can get lost in the day to day mails that come in so it took some time” . Furthermore, policymakers suggested that the researchers meet with them and interact with the policymaking processes to determine needs and learn more about how each side works. Respondents highlighted that time was a big factor in this kind of engagement. Both parties were quite busy as they were usually engaged in several activities in addition to their day-to-day work. It was important that both sides appreciated this right from the start. Continuous engagement on any given piece of work was also identified as one way of getting both groups to understand and contribute fully to the RRS processes. In Ethiopia, a co-production model was used when addressing a particular policy question through a rapid review. Policymakers worked alongside the research team to produce the findings. One respondent described their experience: “From our side we assigned focus for each research question and from their side they assigned like a Principal Investigator on this research question. And they communicate with the focus and the PI. They need like some document some guidelines from our side. They call, they email from the focus, from the PI”(sic) .… providing additional towards the salary, additional money could be helpful. We have put for example in our proposal we have put some incentives as an increase to the budget. And the other is for example the rapid review products should be used for promotion within the institute. And they have to be properly trained, training by itself could be considered as an incentive on people get new skills when they get say confidence. So training them, providing them with some additional incentives, money and considering the products for promotion at the institute .All participants agreed that the supply side human resource  were vital to the review center’s success. These resources needed to be mobilized in terms of the number of team members and their time commitment to the RRS. All of the centers in this study utilized researchers who were working on the projects part time or in addition to their usual work, but one researcher highlighted that these individuals would have to be incentivized  to ensure efficiency. Such incentives could include the following:Yeah so actually one thing that I mentioned previously using the routine information system as one way of like triangulating the findings that maybe good….it’s good if they use the routine data. In fact it is rapid but sometimes it may be good if they use like primary source of data. They use like research. The rapid actually, yeah. They can add some types of qualitative tools probably like interviewing with programs people, one or two program people and then they can add onto their report. The rapid review products generated by these rapid review centers were secondary outputs of existing research and evidence. The policymakers felt that this might be a limitation, and that the centers could consider producing more forms of evidence:But then when we went to talk to [mentions name] about her question what we found out is that actually the information which we had gathered and given …was actually used as part of the decision making. And just a few days ago we talked to [mentions name],……..he also said yeah the information which we did give to [mentions name] was part of the decision making. We are not sure how much it influenced the decision but it actually made a difference [for us]. So I think there is a part for the service in policy making. We just need to find out how much is actually used. The researchers indicated that the products and the evidence they provided were generally used in the decision-making process. One researcher said:Knowing this, the researchers were motivated to continue with the rapid review work despite feeling that the process was difficult.Both the researchers and the policymakers noted that there were changes in knowledge, attitudes, and practices during their engagement with the rapid review centers. In this case, the researchers reported how the process helped them gain clarity on the different rapid synthesis processes and products. For example, several researchers and academics noted that there was enhanced clarity from the more academic rapid reviews, that they were more conversant with and could relate to better, towards the user-side oriented rapid responses, and that there were more than just the synthesis but were an outcome of an interaction process and engagement with the user side. “So it has changed from the first rapid synthesis we had. And I think also with that said it’s not an official name change but we have started calling it more of a rapid response as opposed to [just a rapid review]” .The researchers and policymakers also gained a better understanding of health systems and their application and different components related to the rapid review work: “So I know the difference between health systems and epidemiology but until I started working here it was more theory based ” .…….. when we find gaps like when we are looking at what [mentions name] really wanted; …………..there was no study at all which was done in South Africa and so what then? So now we know and what do we do with that information? So how do we go a step further may be working with UWCT and UCT to actually use our findings to the stuff which masters students or PhD students can fill the gap so that it becomes the whole around system…….. because I know that the department of health they are trying to work more with Universities to create research which is relevant to their questions. So we can try to fit into that.The review center teams found that the results of their research fed back into the process of research generation. For example, researchers in South Africa reported that the evidence from the reviews was often missing localized data. As such, they worked towards filling in those gaps with the available opportunities and partnerships. One researcher from South Africa reported:I think there is a key role in if they find for example when they find very little evidence of or very little reviews if I can go to the systematic reviews out there. It’s to feed that information back to your research institutes to say this is a gap in evidence that we found. Possibly these are the type of questions that has been asked. Start directly employing more role in agenda setting for primary researcher as well .The policymakers also recognized the gaps in evidence and the need to fill them. One policymaker suggested:On our part we were constrained by time, the SAMRC …..we received a report from them which was good quality…... Timeliness…on the first question, it was a bit slow but it was understandable since this was a first time for them, but time for the second question was good…it took about 2 weeks Despite facing some challenges throughout the pilot period, the review centers were successfully established and were able to conduct demand-driven rapid reviews. One method of measuring success is user satisfaction or appreciation. In general, policymakers were pleased with the review centers’ responsiveness and final products. In South Africa, for example, a policymaker described the deliverables as being of “good quality” and completed relatively timely:We were satisfied with the quality of the work. There is no complaints related to that and unfortunately the work we have asked there wasn’t a lot of primary studies and a whole lot of synthesis already being done on this. So a no answer is also a good answer . …. if a policy maker does not have a good research understanding, they have to understand that your answer that you are getting is also an answer. It is not a reflection of a poor outcome or a poor result ….. Another policymaker noted that the provided evidence enabled their unit to know and understand the gaps in evidence, which was important for determining how they would execute their proposed program. This also applied to situations in which no evidence was found to answer the research question directly. One policymaker reported:Of course so, these are some of the benefits. That we got from them and they give like some 2 or 3 recommendations from policy makers like us. Yeah, it’s you know doable just to give 2 or 3 recommendation areas. That this is you know I don’t think that we reached on matched states .The policymakers also described some limitations to the RRS and provided suggestions for improvement during their interaction with the researchers. For example, the policymakers felt the RRS should have a wider scope and not just focus on health system questions. The policymakers appreciated the value of the rapid response service and focus on the questions but suggested that the summaries add recommendations for them to act on.Yeah………… I feel that that’s a very good way of like getting information for decision. Because when I say survey - survey is good but we have two problems with survey. The first thing is survey is resource intensive. You need to have huge resource ………… to invest millions of pounds or dollars.………….. The other problem is time because these surveys take like a year or more than a year or something like that. So, if you are in urgency or if you need an urgent decision this survey may not be the way. All surveyed policymakers agreed that there were many instances where they needed evidence in an urgent manner, and they felt that the rapid review centers provided an appropriate, timely, and cost-effective avenue for them to access evidence in these situations.Another policymaker felt that there were many opportunities in the policymaking cycle in which the RRSs could be useful. She emphasized the need for the researchers to stay in touch and connected with the policy process. For example, there are political windows when specific issues are addressed and are on the agenda. The researchers need to be more involved to get to know these opportunities and be able to provide support when it is relevant.MSF came up with the idea - they came up with adherence clubs for HIV positive patients. So they are not a research centre they do not go through whole what research would say is rigorous and so most about 70 percent of the information which we getting was through MSF, through funders’ reports ……….. And so if you are in a research institute that might not be seen as rigorous but it might be the only information which exists. So do you then say there is no information or do you actually include that? .Although there was satisfaction registered amongst the policymakers, there were some challenges identified by both the researchers and policymakers. “Yes, I would use the services but rapid response should be quicker, policy many times needs quick responses” . The researchers felt that some of the activities involved in the rapid review process were onerous and could be streamlined or eliminated, “So I think our biggest thing right now is finding ways for people to seek the product without us having to do all the hard work of knocking on their doors. I think that would be really great for our sustainability” . In addition, researchers found it challenging to reconcile their knowledge and definition of good evidence with the needs of the decision and policy-making processes that may not necessarily align with that knowledge:So I think the challenge is staff turnover. That’s the major challenge we have as researchers and policy makers especially the policy makers. For example last time there was this guy who was a secretary of health systems research advisory council and I was a chairperson of that group, and when we were trying to come up with terms of reference (for the rapid review centre), the next meeting I couldn’t ….. because the secretary who was located at the ministry office had left the ministry .Both the researchers and policymakers were faced with the issue of high staff turnover in the ministries. Since the majority of the rapid response work was dependent on building long-term relationships with policymakers to facilitate behavior change, the staff turnover impeded on this process. In Ethiopia’s case, this issue threatened to derail the RRSs altogether.Resources and capacity were limitations mentioned by both researchers and policymakers. The review centers were not able to meet the high demand for the RRSs because of their limited capacity: “Probably the short comings are related to I don’t know probably the financial capacity. Because we received like more than 20 questions but we select some yeah because of the limitation of the resources” .Together, the organizational structural arrangements, the management of processes, and the products of the RRS shaped the outcome and/or influence and/or impact of the RRS. For example, the interaction and engagement of these components allowed the demand side to understand the needs of policymakers, while the policymakers understood the benefits and modalities of how to work with evidence. Additionally, feedback loops may develop between the structure and process management. The continuous engagement between these two mechanisms means that whatever is learned in the process is fed back into the structures. This leads to the creation of a built-in check system that ensures that the system is continually improving, learning from itself, and correcting the gaps.Our study highlights that policymakers welcome the idea of being engaged in platforms and strategies to ease the reported barriers that they face as they attempt to use evidence to inform policies, decisions, and practice. Researchers also benefit from similar strategies for the purposes of understanding, accessing, and engaging with the policy arena. As such, knowing about the experiences of both sides stimulates attitudes towards the use of evidence for decision-making in general.Our research sought to appraise and understand the experiences of rapid review centers in Ethiopia, Lebanon, and South Africa in conducting and using review findings to support policy- and decision-making processes in their countries and to understand the issues around the nexus between rapid reviews and policymakers’ needs for evidence. A study exploring the views and KT experiences of 14 Australian public health academics found that the capacity to engage in KT was influenced by factors within the academic context and the interaction of the academic and policy environments . We expeCherney and colleagues  describeA departing point in our study is the interaction of themes and emergence of the outcome and influence category, which was seen as an endpoint, but may also be a factor that influences or contributes to the endpoint. This highlights that there are often no single endpoints  or a well-defined one in processes related to KT. Indeed, the process involves all kinds of activities between generation and use of the evidence, which should culminate into better use of evidence. In many cases, this is thought of as a single process ending in use, but this may not be the case. For example, the influence of engagement during the rapid review process may result in a change of attitudes or incite curiosity in a policymaker who may use evidence as part of another process. The same policymaker could later act as a champion, leading peers and colleagues into considering EIDM. This endpoint is a byproduct of the main process and does not necessarily happen at the defined end.In this study, it is also necessary to understand the fact that rapid reviews and systematic reviews are still largely viewed as an academic exercise. Therefore, it is not surprising that researchers were still struggling with issues around rigor and quality and methods of knowledge syntheses as may be required to support policymaking. Many studies have documented that rapid reviews and knowledge syntheses in general are not well accepted by academic peers particularly in the policymaking domain. This could be a result of the absence of an agreed methodology for conducting rapid reviews to support policymaking or the fact that rapid reviews are perceived as inferior to other traditional research methods . ContrarA recurring and important factor that determines the experience of both researchers and end users is the capacity on both sides to interact and make sense of the rapid review process. On the researchers’ side, the capacity to work beyond the academics of the review and interpret or contextualize the review questions with the policy process in mind calls for particular skills that they may not have on the onset. If these skills are not developed, there is a potential for the review centers to fail to progress, which the respondents in this research highlighted very well. Researchers at the SAI reported having minimal experience interacting with policymakers, and on one occasion, this affected the demand or willingness for a policymaker to accept the RRS that was offered. All models of knowledge transfer recognize that KT of evidence especially research findings requires active engagement between researchers and users. However, this is often also cited as a barrier because of the two communities running on parallel agendas with minimal engagement or understanding of each other’s needs and norms –16. SimiMijumbi and colleagues have emphasized the need for resources to support KT activities to ensure that they are adequate and, most importantly, sustained . HoweverAs governments and their stakeholders including researchers and knowledge brokers push forward with the EIDM agenda, it is important that they all create an enabling environment for the practice. Knowing the factors that affect the experience of both researchers and users of evidence as presented by this study is helpful in ensuring this enabling environment, which would eventually contribute to uptake of evidence and a culture of EIDM. This study also highlights the importance of policymaking institutions ensuring that their staff and other stakeholders involved in the policy processes are well equipped to allow for efficient engagement and use of synthesized evidence. The same applies for the supply side, which includes research and knowledge-brokering institutions. Lastly, this research presents elements supporting the experience of producers and users of rapid reviews in response to policy and decision-making.The strengths of this research include utilizing methods of implementation research, implementing an intervention in real-life settings, and evaluating and learning from it. This is one of very few studies on rapid review services preparing rapid reviews for policy- and decision-making in LMICs, thereby increasing our understanding of the field of EIDM in these settings. The main limitation of this study is that it is based on pilot rapid review center; therefore, it remains to be seen if the same results would be observed at scale. In addition, case studies are the main method used in this study, with inherent limitations pertaining to external validity and application in other LMIC settings. However, we find that case studies are appropriate for pilots of this nature given that the research is exploratory and we are attempting to generate an illustrative theory about the experiences of individuals .The experiences of policymakers and researchers during the setup of rapid review centers and the process of providing rapid review products determine the uptake of evidence. These factors interact at different stages to influence the impact of the rapid review centers and evidence. The findings of this study can inform policymakers, health system managers, and researchers on best practices for demanding, developing, and using rapid reviews to support decision- and policymaking and implementing the universal healthcare coverage agenda.


A physical examination represents a fundamental step in diagnosing diseases. Due to the role that hormones play in the regulation of numerous biological processes in various organs and systems, endocrine diseases cause a variety of clinical manifestations that can be easily identified with a careful physical examination and can guide the clinician to specific diagnoses. Furthermore, the presence of specific clinical signs in various endocrine-metabolic diseases can predict the risk of developing comorbidities and serious adverse events. In this article, we present some of the main clinical signs of endocrine-metabolic diseases and the risk of comorbidities, summarizing the pathogenetic mechanisms that lead to their formation. The aim is to highlight how the identification of these specific signs can reduce the number of dynamic tests and the costs necessary to reach the diagnosis and allow the early identification of any complications associated with these diseases, improving the clinical management of affected patients. Physical examinations represent a milestone in the clinical management of a patient, guiding the clinician towards better use of diagnostic tests and a reduction in the demand for unnecessary laboratory and instrumental tests . Does thPhysical examination certainly plays a key role in the diagnosis of thyroid diseases. The presence of goiter, suitable correlated to the patient’s symptoms, allows us to suspect the presence of thyroid functional abnormalities (hypothyroidism or thyrotoxicosis) which can then be confirmed by hormonal tests. A palpable, painful goiter in patients with fever and initial symptoms of thyrotoxicosis suggests the presence of subacute thyroiditis. Adequate palpation can also identify the presence of nodules although it is not possible to distinguish a cystic nodule from a solid one by simple palpation. However, palpation of a very hard and firm nodule, possibly associated with later cervical lymphadenopathy, increases the suspicion of neoplastic disease. The presence of several palpatory nodules associated with symptoms of thyrotoxicosis suggests the presence of a toxic multinodular goiter, while a single nodule with symptoms of thyrotoxicosis suggests the presence of Plummer’s adenoma. Finally, the presence of Pemberton’s sign positivity, characterized by the appearance of facial congestion and respiratory distress when the patient is asked to raise his arms, may be indicative of an endothoracic goiter that compresses the veins and trachea due to the narrowing of the superior thoracic entrance caused by the maneuver. Therefore, thyroid palpation cannot be neglected in the management of patients with symptoms referable to thyroid dysfunction .Palpation of the neck may also reveal the presence of thyroglossal duct cysts that present as a painless, mobile mass of the midline of the neck, 75% of cases located inferior to the hyoid bone and showing movement with protrusion of the tongue .Another important palpatory sign associated with thyroid dysfunction is pretibial myxedema. Its presence increases the suspicion of hyperthyroidism and, in particular, of Graves’s disease (GD). This form of non-pulsating edema is not limited to the pretibial region and can also appear in other locations such as forearms, shoulders, arms, palms, upper back, and neck. Therefore, it can also be referred to as thyroid dermopathy. It has a prevalence of 4.3% of patients with GD rising to 15% in patients who also have ophthalmopathy. It is characterized by the presence of bilateral, asymmetrical, non-puncturing, painless, and erythematous nodules and plaques due to the deposition of mucopolysaccharides, in particular, hyaluronic acid in the papillary and reticular dermis with extension into the subcutis [For the evaluation of the infertile male, one of the signs that most correlates with sperm function is the low testicular volume (<12 mL). Most of the testicular volume depends on the proliferation of germ cells and the enlargement of seminiferous tubules during puberty. Therefore, spermatogenic impairment can be suspected in the presence of low testicular volume. The lower the testicular volume, the greater the damage to the germ cell component . FurtherIn addition to assessing testicular volume, scrotal palpation allows for the detection and suspicion of many other abnormalities. For example, the presence of acute scrotal pain associated with the sensation of scrotal mass or swelling may lead to suspicion of testicular torsion or epididymitis-orchitis. However, in these cases, only a scrotal ultrasound scan allows a differential diagnosis of certainty.Another cause of acute testicular pain is torsion of the testicular appendage. In these cases, the pain is less acute and the scrotal edema less pronounced than in testicular torsion, and the sign of the blue dot, indicative of the necrosis of the testicular appendix, may sometimes be evident .In addition to the palpable masses associated with pain, testicular palpation may allow us to suspect, especially in young adults with a history of cryptorchidism or other risk factors, the presence of tumor masses that generally present themselves as single and firm nodularity . Among the scrotal palpable masses, the hydrocele, which can be differentiated from other testicular masses by transillumination of the fluid with a torch, and the varicocele are also recognizable . The latThe scrotal physical examination allows for the evaluation of the integrity of the epididymal structures and highlights the possible presence of epididymal cysts or vas deferens agenesis which could cause obstructive azoospermia . SimilarFinally, exploration of the inguinal canal during scrotal palpation may also allow for evidence of an inguinal hernia . In evaluating the child’s development, a key role is also played by the evaluation of the size of the penis. In particular, the presence of a penis diameter <2.5 standard deviation (SD) below the average for age is indicative of micropenis. For a correct measurement, the penis should be measured when it is fully extended, with the foreskin retracted and holding the glans between the thumb and forefinger. The measurement is taken from the pubic branch to the distal tip of the glans penis on the dorsal side. Crucial during the measurement is to press the suprapubic fat pad as much as possible inward to exclude a “buried penis”. Since penile development largely depends on adequate development of the hypothalamic-pituitary-gonadal axis, any conditions of hyper- or hypogonadotropic hypogonadism must be excluded in cases of micropenis. Furthermore, growth hormone deficiency/resistance or abnormalities of the androgen receptor function may also be associated with this condition. When all diseases are excluded, one can speak of idiopathic micropenis .2) [2 ratio and hence must be excluded. Other common causes include obesity, which increases estrogen levels due to the aromatase action of visceral fat. In turn, estrogens increase SHBG levels and exert negative feedback at the hypothalamic-pituitary level with a consequent decrease in testosterone levels and a further reduction in the T/E2 ratio. Other causes of gynecomastia are renal failure, which causes hypotestosteronemia and hyperprolactinemia, and liver failure, which is associated with increased SHBG levels and consequent reduction in testosterone levels and impaired estrogen metabolism. Furthermore, the use of anti-androgenic drugs, such as spironolactone, could play a role in these patients. Another serious condition, which can be suspected in presence of gynecomastia, is a testicular tumor secreting hCG. This hormone, having an LH-like action, stimulates the activity of testicular aromatase, increasing estrogen secretion that results in breast proliferation. Therefore, in the case of gynecomastia, a careful evaluation of the gonadal hormone profile , the hepatic and renal function, and a testicular ultrasound should be carried out for an early diagnosis of these diseases.Finally, a mention deserves gynecomastia. It is the benign proliferation of mammary glandular tissue in men. Although it is common and generally unrelated to abnormalities in childhood and adolescence, it can be a sign of many diseases in adulthood. Gynecomastia occurs when there is an imbalance between testosterone (T) and 17ß-estradiol (E2) ,13. Ther2 ratio, such as antiandrogens, and psychoactive drugs , protonic pump inhibitors, etc. Furthermore, the abuse of illicit substances, including cannabis and alcohol, which have a direct inhibitory effect on the hypothalamus-pituitary-testicular axis, must also be excluded [2 imbalance. On the other hand, hypothyroidism lowers testosterone levels by causing hyperprolactinemia [Furthermore, in the case of gynecomastia, a careful drug history is necessary to exclude the use of drugs that can alter the T/Eexcluded ,13. Finactinemia ,13. The Several dermatological signs contribute to orienting the suspicion towards an endocrine disease. For instance, striae rubrae and the buffalo hump are among the cutaneous signs with the greatest predictive diagnostic value. Both are strongly related to Cushing’s syndrome. The buffalo hump is caused by the relevant role of hypercortisolism in the reorganization of body fat, which leads to centripetal obesity and the accumulation of fat on the face , in the supraclavicular region, and the retronucal region . Striae rubrae are purple streaks characterized by a width >1 cm, commonly localized on the abdomen and lower flanks. They can also occur on the upper arms, shoulders, armpits, breasts, hips, buttocks, and upper thighs . Their pChanges in skin pigmentation play an important role in endocrine diseases. Several and even rare syndromes are associated with skin manifestations and endocrine dysfunctions. For example, café-au-lait macules are often found in numerous rare genetic syndromes that are associated with endocrinological abnormalities. They are often the first clinical manifestation of numerous RASopathies such as neurofibromatosis type 1 and Noonan syndrome . Also, iOther skin manifestations are much more common. For example, skin hyperpigmentation, mentioned above for ACTH-dependent Cushing disease, is also a sign of primary adrenal insufficiency. In this case, elevated levels of ACTH can cross-react with the melanocortin receptor 1 on melanocytes, stimulating them. Furthermore, since ACTH originates from proopiomelanocortin (POMC), an increase in melano-stimulatory hormones results from the cleavage of POMC. In detail, hyperpigmentation is usually generalized. However, it is more pronounced in the areas most exposed to the sun. Moreover, surface of the skin under pressure (elbows and knees), around the nipples, and the genital region, are also affected. It can also be present on mucosal surfaces such as the tongue, oral mucosa, and the inner part of the lips . AnotherSkin hypopigmentation and, in particular the presence of vitiligo, should also be an alarm sign for the patient in whom the endocrinologic disease is suspected. Vitiligo is closely associated with the development of autoimmune thyroiditis, so much so that in patients with this skin sign, the search for anti-thyroid antibodies and the evaluation of the function of this gland is recommended . HoweverAnother sign that is a frequent reason for endocrinological consultation, affecting between 4.3 and 10.8% of women, is hirsutism. It should be assessed using the Ferriman-Gallwey index (FGi). An FGi > 8 is indicative of hirsutism . HoweverHirsutism must be differentiated from hypertrichosis. While in hirsutism, there is an overgrowth of androgen-sensitive hair in a male pattern, in hypertrichosis there is a growth of terminal hair in areas where they are not normally present, regardless of whether they are regions sensitive to the effects of androgens. Therefore, in the management of a patient who comes to the clinician’s attention, it is first necessary to distinguish between these two conditions. There are several congenital and acquired causes of hypertrichosis and among them are also recognized endocrine causes. In particular, hypothyroidism can be associated mainly in children with an alteration of the hair on the scalp, which can become coarse, dull, and brittle. This condition reverses with the initiation of L-thyroxine replacement therapy. In addition, areas of hypertrichosis can be observed in hyperthyroidism at the plaques of pretibial myxedema. Another condition that can lead to hypertrichosis and is also associated with endocrine abnormalities is represented by the POEMS syndrome  .Unlike hirsutism, in men, the presence of a reduction in the percentage of body hair, especially in the pubic and axillary region, as well as a reduction in the growth rate of the beard and therefore in the frequency of shaving, could be signs of low testosterone levels. Therefore, in these cases, the clinician must investigate the presence of decreased libido, erectile dysfunction, and other signs and symptoms compatible with hypogonadism .Closely associated with hirsutism from the etiopathological point of view is acne. Indeed, this condition too can be seen in diseases that increase androgen production such as PCOS, NCCAH, and androgen-secreting tumors. Furthermore, in cases of hypercortisolism such as in Cushing’s syndrome, steroid acne can be observed. It is characterized by erythematous, monomorphic papules or small pustules distributed along the upper part of the trunk, the proximal upper extremities, the neck, and the face .Of extreme interest among the dermatological signs of endocrine disorders is acanthosis nigricans, described in Among the dermatological manifestations that best correlate with an endocrinological disease is the necrolytic migratory erythema (NME). Indeed, this is often the first sign that leads to suspect the presence of a glucagonoma, a rare endocrinologic disorder. It appears as a bullous and itchy dermatosis that evolves over a few weeks into patches or plaques with irregular edges, crusts ulcerations, and peeling. When these lesions fade, the skin sometimes takes on an eczematous and psoriasiform appearance. It may be diffuse or isolated to the perioral region, trunk, groin, intergluteal region, genital area, and lower extremities. The pathogenesis may in part be attributed to hyperglucagonemia, which results in increasing hepatocyte gluconeogenesis and lipolysis leading to hypoaminoacidemia, which in turn is associated with NME. Furthermore, hyperglucagonemia can contribute to increasing levels of arachidonic acid, prostaglandins, and leukotrienes, predisposing the inflammatory reaction typical of this dermatosis. Confirming the role of hyperglucagonemia, surgical removal of glucagonomas, or stabilization of glucagon levels with drugs helps resolve the rash. However, other mechanisms could also contribute to its pathogenesis and explain why even in pseudoglucagonoma syndrome, where glucagon levels are normal, NME may still be present. In particular, malnutrition can contribute to the development of NME. The deficiency of zinc, protein, amino acids, and essential fatty acids can cause NME-like dermatitis .Finally, it should be mentioned the skin flushing, in particular on the face, telangiectasia, and pellagra-like lesions that, in a patient with profuse diarrhea and asthma-like symptoms, can orient the clinician toward the suspicion of a carcinoid syndrome .Among the anthropometric signs that best correlate with the presence of endocrine diseases is the eunuchoid habitus. Tall stature, underweight, long upper and lower limbs, and an arm span of more than 5 cm longer than height characterize this phenotype. It can also be associated with changes in primary and secondary sexual characteristics and/or metabolic parameters and altered fat mass distribution . RegardiThe presence of an increase in the size of the extremities, associated with pronounced protrusion of the frontal bumps, arching, and thickening of the eyebrows, enlargement of the nose and ears, thickening of the lips, skin wrinkles, nasolabial folds, and mandibular prognathism lead to dental malocclusion and increased interdental spacing, an acromegaly may be suspected. These alterations are partly attributable to soft tissue swelling which in turn is associated with the deposition of glycosaminoglycans, increased connective tissue collagen production, and the edema that occurs in this condition. Macroglossia is also common and contributes to the development of obstructive sleep apnea, which is a major complication of this disease. All of these signs are often subtle in their appearance and therefore general practitioner, as well as patients and their families, do not pay attention to these changes . When GH overproduction occurs before epiphyseal cartilage welding, a condition of gigantism is determined, characterized by a height greater than three SD per age or more than two SD beyond the target height calculated from the parental height. Furthermore, also in these patients, there is acral enlargement and alteration of facial features . In case of a reduction in height from four to ten standard deviations from the average height for age a GH deficiency or a resistance to its action like GH insensitivity syndromes (such as Laron syndrome) could be suspected. In detail, this reduction seems to be more marked in patients with GH insensitivity syndromes than in those with congenital GH deficiency. In addition, patients with Laron syndrome show an upper to lower segment ratio above normal for sex and age, denoting short limbs for the trunk size. Other signs that allow suspecting GH insensitivity syndromes, as well as GH deficiency, are some common facial abnormalities  . These sIn patients with periorbital edema and loss of the outer third of the eyebrows, a lowering of the upper eyelid, nose enlargement, lips thickening and macroglossia other signs and symptoms of hypothyroidism should be looked for. These signs are mostly attributable to the accumulation of mucopolysaccharides in the dermis, which cause the so-called myxedema or secondary to a decrease in sympathetic stimulation (such as lowering of eyelid) . The waist circumference is among the signs with an important role from the prognostic point of view. It is a useful tool for assessing the severity of obesity. Indeed, differently from the body mass index (BMI), waist circumference allows the identification of patients with an increased risk of developing obesity-related chronic complications, such as cardiovascular diseases and diabetes mellitus . Indeed,Similarly, increased waist-to-hip ratio (WHR) correlates significantly with cardiometabolic risk and the likelihood of developing myocardial infarction. It shows the presence of visceral adiposity even in those subjects where there is no obvious increase in body weight . In partMoreover, in women of childbearing age, an increase in these two indices would also appear to correlate with an increased risk of having polycystic ovary syndrome (PCOS), thus directing the clinician to study this condition .Acanthosis nigricans is another metabolic sign that correlates significantly with obesity and insulin resistance, allowing suspecting disorders related to this sign, such as diabetes mellitus, metabolic syndrome, and PCOS . Its preAs regards lipid metabolism, various signs direct the clinician towards the presence of dyslipidemia and in some cases towards the suspicion of a hereditary condition. These include xanthomas, which are lesions located in the connective tissue of the skin or tendons and fascia. They are made of macrophages that incorporate LDL cholesterol particles, leading to the formation of foam cells . The preThe most frequent form of xanthoma is eyelid xanthelasma. When present in children in association with corneal arch and tuberous or tendon xanthomas, autosomal dominant hypercholesterolemia maybe suspected. Generally, however, their frequency increases in the population over 50 years of age and their presence has a negative predictive role since they are associated with the presence of significantly higher levels of atherogenic LDL and a significantly higher risk of atherosclerosis than controls. Therefore, patients with these formations must be carefully monitored for the prevention of cardiovascular risk .Another sign related to hyperlipidemia is the corneal arch. This is caused by the deposition of lipids in the peripheral region of the corneal stroma. The width of the ring appears to be related to the severity of dyslipidemia and the duration of the condition. This deposition results in the formation of a gray-white or yellowish ring approximately 1 mm in diameter separated from the limbic margin by the Vogt lucid interval, a 0.3–1 mm wide area of the clear cornea. The deposition of lipids in the periphery of the cornea is due to the fact that this area is the one that receives most of the perfusion of the limbal vascular system. It is generally bilateral, whereas unilateral forms are seen on the contralateral side to that of a carotid artery occlusion, reinforcing the importance of limbic vascularity in the genesis of this condition. Prevalence increases with age and is higher in men. In addition to age, its presence is also related to alcohol intake, diabetes mellitus, smoking, blood pressure, BMI, and obesity. The correlation with dyslipidemia is demonstrated by the fact that ring extension appears to correlate with the duration and severity of LDL cholesterol levels and with an altered LDL/HDL cholesterol ratio . As withAgain, from the metabolic point of view, another sign with a prognostic and predictive role for severer diseases is hepatomegaly. It is often related to the accumulation of fat in the liver. When present, therefore, it is necessary to exclude the possibility of alcohol abuse and, if not, the presence of non-alcoholic fatty liver disease (NAFLD) can be suspected. This condition is strongly associated with obesity, metabolic syndrome, and an increased risk of developing serious diseases, such as liver cirrhosis and hepatocarcinoma. Furthermore, patients with NAFLD appear to have a higher prevalence of DM, which in turn is associated with worsening of the clinical condition. Diagnosis is generally based on ultrasound examination and evaluation of non-invasive scores, although the diagnosis of certainty can only be made by biopsy. Therefore, in obese patients, the presence of hepatomegaly is associated with an increased risk of metabolic and hepatic comorbidities . AnotherTrousseau and Chvostek signs are two fundamental signs to be sought in case of suspected hypocalcemia. Indeed, they are caused by the increased neuromuscular irritability, in turn related with the low calcium levels. When hypocalcemia-induced neuromuscular hyperexcitability is latent, looking for these two signs allows the diagnosis to be confirmed. The first can be evoked with a sphygmomanometer, which is inflated slightly above the patient’s systolic pressure. Ischemia resulting from occlusion of the brachial artery results in flexion of the wrist joint and metacarpophalangeal joints, flexion of the fingers, and adduction of the thumb (obstetrician’s hand). In the sign of Chvostek, on the other hand, the percussion of a point located in front of the earlobe and under the zygomatic process causes contraction of the muscles of the ipsilateral face .In patients who report reduced visual acuity up to bitemporal hemianopsia, compression of the chiasma by a pituitary adenoma may be suspected. Indeed, large adenomas can compress the optic chiasm and consequently the retinal nasal fibers, causing a reduction in the visual field. This reduction is often associated with diplopia. The presence of this additional sign indicates the extension of the adenoma towards the cavernous sinus and the consequent compression of the oculomotor nerves. Therefore, all of these signs also have a prognostic role regarding the radicality of a possible surgical removal, since they indicate the extension of adenomas towards important cerebral structures . In conclusion, physical examinations still play a key role in good endocrine clinical practice today. In fact, since hormones are essential in regulating the physiological processes of various organs and apparatuses of our body, their imbalance can lead to the onset of various physical signs that can guide the clinician towards specific diagnoses. This reduces the time and cost required to reach a diagnosis. Additionally, in some cases, they may be among the first physical signs of serious illnesses or play an important prognostic role in the development of future morbidity and mortality .


Accessory spleen is ectopic splenic tissue which can be either congenital or acquired. It is usually an asymptomatic incidental finding. In the context of known malignancy, accessory spleen can be mistaken for metastasis.Here, we share a case of ectopic spleen presenting as a gastric subepithelial lesion post splenectomy. Rare cases have been reported in the literature.Case Report and Literature ReviewCase:A middle age male with history of splenic rupture secondary to a motor vehicle accident and metastatic renal cancer was found to have a gastric subepithelial lesion on endoscopy. Endoscopic ultrasound (EUS) revealed a subepithelial mass coming off the submucosa or muscularis mucosa of the gastric wall with intact muscularis propria. EUS-guided core biopsy was performed and demonstrated splenic tissueSplenic tissue should be considered in the differential diagnosis when assessing gastric subepithelial tumors even in the context of previous trauma to the spleen. In addition, EUS-guided core biopsy may be required to rule out metastatic disease.NoneNone DeclaredESOPHAGEAL, GASTRIC & DUODENAL DISORDERS