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Studies of Rare Human Diseases Lead to Insights into Regulation of Human Beta-cell Proliferation

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Macrophage vesicles in antidiabetic drug action

Thiazolidinediones (TZDs) are potent insulin-sensitizing drugs, but their use is accompanied by adverse side-effects. Rohm et al. now report that TZD-stimulated macrophages release miR-690-containing vesicles that improve insulin sensitization and bypass unwanted side-effects.

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Published 08 May 2013

Doi 10.5772/46124

ISBN 978-953-51-1080-4

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This book covers a selected number of hot topics in endocrine and hormone-related pathologies, discussed by eminent scientists and clinicians coming from different countries of the world. It deals with advanced recent trends in the field, including neuroendocrine and pituitary tumors, thyroid dysfunctions, diabetes and a series of endocrine-related diseases, such as those related to the anabolic e...

This book covers a selected number of hot topics in endocrine and hormone-related pathologies, discussed by eminent scientists and clinicians coming from different countries of the world. It deals with advanced recent trends in the field, including neuroendocrine and pituitary tumors, thyroid dysfunctions, diabetes and a series of endocrine-related diseases, such as those related to the anabolic effects of testosterone, obesity, cancer, the liver complications of diabetes and the pediatric nonalcoholic fatty liver disease. The readers should be able to have a basic, as well as critic and advanced, overview of these selected hot pathologies of the endocrine system.

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On developing a thesis for Reproductive Endocrinology and Infertility fellowship: a case study of ultra-low (2%) oxygen tension for extended culture of human embryos

Daniel j. kaser.

1 Reproductive Medicine Associates of New Jersey, 140 Allen Road, Basking Ridge, NJ 07920 USA

2 Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107 USA

Fellows in Reproductive Endocrinology and Infertility training are expected to complete 18 months of clinical, basic, or epidemiological research. The goal of this research is not only to provide the basis for the thesis section of the oral board exam but also to spark interest in reproductive medicine research and to provide the next generation of physician-scientists with a foundational experience in research design and implementation. Incoming fellows often have varying degrees of training in research methodology and, likewise, different career goals. Ideally, selection of a thesis topic and mentor should be geared toward defining an “answerable” question and building a practical skill set for future investigation. This contribution to the JARG Young Investigator’s Forum revisits the steps of the scientific method through the lens of one recently graduated fellow and his project aimed to test the hypothesis that “sequential oxygen exposure (5% from days 1 to 3, then 2% from days 3 to 5) improves blastocyst yield and quality compared to continuous exposure to 5% oxygen among human preimplantation embryos.”

The scientific method revisited

While Sir Francis Bacon is commonly credited with the enumeration of the scientific method circa 1620 AD, its true origin dates back much further than the Enlightenment [ 1 ]. By most scholarly accounts, an Arabic physicist by the name of Ibn al-Haytham was the first to explicitly delineate what is now taught in grade-school science classrooms worldwide. In his 1021 AD “Book of Optics,” in addition to providing the basis for development of the pinhole camera centuries later, al-Haytham outlined three steps to scientific inquiry:

• State a problem based on observation
• Criticize a hypothesis through experimentation
• Interpret the resulting data to form conclusions.

Indeed, these central research tenets have withstood the test of time and still serve as a guide for the most seasoned of investigators.

The following article describes a practical approach to research, with tips and tricks aimed to simplify the process for those, like myself, who are just embarking upon a career that includes research. I recently completed my fellowship in Reproductive Endocrinology and Infertility, which includes an 18-month research requirement. Fellowship thesis projects can be clinical, basic, or now epidemiological in nature. My primary research compared the blastulation rates in human preimplantation embryos in two different conditions for extended culture: sequential oxygen (O 2 ) exposure (5% from days 1 to 3, then 2% from days 3 to 5) vs. continuous 5% O 2 exposure [ 2 ]. While my work was basic, the steps described below are generally applicable to all research. The specifics may vary based on your study, mentor, or institution, but the outline should still be relevant.

Finding a mentor

Identifying a mentor who is able to sponsor you as a fellow is paramount. Sometimes what seems to be an ideal mentoring situation turns out to be just the opposite. Early in my first year of fellowship, I rotated through a laboratory to learn more about the research opportunities there—the project I pursued was interesting and had the potential to lead somewhere, but the doctoral student I was working with was about to graduate and was not particularly interested in training me. On the scale from basic to translational to clinical, the lab was heavily anchored on the basic side with possibility to lead to more translational work years later. This is the reality of much research, and while clearly critical to advance knowledge, it felt too distant from the clinic for me personally. And perhaps most importantly, I knew the skills that I would learn there would not be relevant beyond fellowship, as I did not plan on continuing to do basic research.

I changed labs partway through my first year. My fellowship director was initially reluctant about this decision, because from the outside it looked like a perfect lab for a fellow—extremely well-funded, highly productive with visible publications in impactful journals, a star mentor. Ultimately, though, it was not a good fit for what I needed and where I wanted to go. Thankfully, I recognized this early on and still had time to pivot.

If your program allows you to do an abbreviated rotation in a laboratory or with a particular mentor, without having to commit for the duration if things do not pan out, I would encourage you to consider this option. It allows you a brief, but substantive experience to determine if the project is worth pursuing.

Following this false start, I began a rotation in the clinical IVF lab. This immediately was more in line with the type of work I wanted to do in fellowship and, indeed, for the rest of my career. Fortunately, the director of the IVF Laboratory, Dr. Catherine Racowsky, agreed to take me on for my thesis work. We had completed several other projects together during my residency and had grown to have a close working relationship.

Like any effective mentor-mentee arrangement [ 3 ], we deeply respected one another’s work, shared common values, communicated regularly and without reservation, were accountable to one another, and had a personal connection. Other attributes to consider when choosing a mentor include their availability, track record in mentoring other trainees to success, their willingness to challenge you to expand your goals, to take appropriate risks, and to think both critically and creatively. Just as mentees have different strengths and weaknesses, so do mentors. It is important to be honest with yourself about your own working style and to select a mentor that enhances your strengths and likewise complements your weaknesses.

Once I had identified a mentor, I immersed myself in the clinical IVF literature. My initial work in the lab involved quality control and dish preparation—checking incubator temperatures and pH at the start of each day, pouring media. I started there with my reading: media composition, the Henderson-Hasselbalch equation, buffering capacity, and incubator settings. I became interested in learning more about normal physiology of the peri-implantation period and how that was, or was not, reflected by laboratory conditions.

One of my most memorable professors from medical school used to say “Not reading equals death.” Perhaps his point was overstated, but the sentiment was spot on—without knowing the background for a topic backwards and forwards, it is hard to know a relevant question to ask, not to mention being sure that your idea has not previously been investigated.

When you start learning about a particular topic, do not limit yourself to the newest publications in the field. Read the old literature, too—the foundational works. During fellowship, I became on a first name basis with the medical librarian at my university. I would email her a reference that PubMed did not have linked, and she would either help track down the .pdf or scan the original version for me. I requested so many articles like this that I thought the library may stop honoring these requests. They never did. One time the librarian told me that I was one of the only trainees who regularly used this service. How could this be? It was like a virtual walk through the stacks of an old library, and my appetite for reading these early works was insatiable.

Rarely, you come across a finding in the literature that gives you pause, a finding that somehow seems to have been buried under other publications, in years of other work. You have to read it twice, three times for it register. This is the feeling that I had when I stumbled into Yedwab’s description of “The temperature, pH and partial pressure of oxygen in the cervix and uterus of women and uterus of rats during the cycle” in a 1976 volume of Fertility & Sterility [ 4 ]. It was right there in plain sight:

The mean peri- and postovulatory uterine PO 2 in the human was approximately 15 mmHg [ 4 ].

I calculated the conversion to atmospheres (atm); 15 mmHg divided by 760 mmHg/atm = 0.0197, or roughly 2%! Why were we culturing embryos, then, in 5% O 2 ? I double-checked my arithmetic. I asked my co-fellow down the hall to do the same thing and then an old Chemistry teacher. Two percent was unanimous. Maybe the research had not been done at sea-level? Tel Aviv, Israel, elevation 16.7 ft. Maybe it was a one-off finding that was never corroborated? I emailed for more articles. Thirty years after Yedwab’s initial description, another report of the uterine O 2 tension in the human was published, and the findings were remarkably similar: 18.9 mmHg or 2.5% [ 5 ]. Other mammals, including the rat, hamster, rabbit, and Rhesus monkey likewise have been reported to have uterine O 2 tensions of approximately 2%, as well [ 4 , 6 ].

I finally believed there might be something to this when I came across a 1992 study in Obstetrics and Gynecology [ 7 ], which elegantly described the O 2 tension in the uterus through the first and early second trimester of pregnancy among patients undergoing elective termination. Surprisingly, a polarographic microelectrode inserted into the placental bed confirmed that the fetus is exposed to a hypoxic environment (17.9 mmHG or 2.4%) through 10 weeks of gestation, and by the 12th week, the same measurement had significantly increased to 60.7 mmHg or 8.0%. This was consistent with histologic data from early pregnancy hysterectomy specimens, as well, which indicated that the fetal-placental circulation is not actually patent until 11–12-week gestation [ 8 ]. It seems that for the first trimester, Mother Nature had preserved the reducing, O 2 -poor atmosphere characteristic of early life on this planet. Now, we just had to turn down the setting on the incubators and follow her lead.

I next set out to determine when in normal development the human embryo traverses the tubal-uterine junction. While the traditional teaching is that the preimplantation embryo does not reach the uterus until the blastocyst stage, review of the sparse literature available suggests that the late cleavage-stage or early morula may in fact be the developmental stage that enters the endometrial cavity. This timing was first described by Croxatto et al., who serially ligated, transected, and flushed the oviducts in 54 women undergoing voluntary sterilization at various intervals following the LH surge [ 9 ]. The most advanced embryo recovered from the oviduct was a 7-cell; no morulae or blastocysts were found [ 10 ]. Furthermore, no embryos remained in the oviduct beyond 96 h post-LH peak (i.e., 80 h post-ovulation). From corresponding uterine flushing experiments, the earliest reported stages recovered from the uterus were a 12-cell and a 16-cell embryo [ 11 , 12 ].

Thus, the cleavage stage embryo is likely exposed to the O 2 tension characteristic of the oviduct (5 to 8% in mammals and non-human primates) [ 6 , 13 ], while the early morula and beyond is exposed to that of the uterus (2%).

Defining a question

The next step to any research project is to define a question that is feasible to investigate. Typically, the more specific the question is, the better. A specific question allows you to hone in on one aspect of a problem and to select appropriate methodology and outcomes.

In the context of developing my own project, I wondered whether it was possible that as our field moved from routine cleavage stage transfer to blastocyst transfer, our culture conditions, specifically the O 2 tension, had not been updated to reflect normal physiology. I was familiar with the vast literature comparing 20 vs. 5% O 2 and recent meta-analyses that demonstrated a modest improvement in both clinical pregnancy (OR 1.11, 95% CI 1.04–1.18; 9 RCTs, n  = 5,501) and live birth (OR 1.14, 95% CI 1.04–1.25; 8 RCTs, n  = 5,401) following culture in low oxygen tension [ 14 ]. However, to my knowledge, when I began my experiments, no one had examined what effect, if any, a further reduction in oxygen tension might have on human embryo development.

In defining my question, one could pose “how does lowering the incubator O 2 tension from 5% to 2% on day 3 affect in vitro blastulation rates in sibling human embryos?” Alternatively, one might ask “is 2% O 2 superior to 5% O 2 for clinical IVF?” Both are certainly reasonable questions to ask; however, the former is more specific and provides a clearer framework than the latter as to how the experiment will be executed. This targeted thinking is important early on in study design. By committing yourself to a specific question, you will have already considered the feasibility of performing the investigation, you will have narrowed down the required methods, and identified study endpoints from the outset.

Forming a hypothesis

In an era of big data, do not overlook the power of a simple hypothesis. The hypothesis is very similar to the research question—it is just typically phrased as an affirmative or negative statement. That is, the null hypothesis for this research question is “There is no difference in blastulation rates of sibling human embryos when the incubator O 2 tension is reduced on day 3 of development.” Stated this way, your reader might be expecting a non-inferiority design with corresponding power analyses. In contrast, the alternative hypothesis might be “Reducing the incubator O 2 tension on day 3 is associated with increased (or decreased) blastulation rates in sibling human embryos.” Here, the reader might expect a study that was powered to show superiority. Ideally, a research project should be selected that is publishable whether or not the null hypothesis is rejected. Accordingly, if you choose a biologically plausible question to answer, even if you get negative results, the data are still valuable in guiding future research efforts.

Whenever you find yourself lost about how to proceed (either with designing your next experiment, choosing an appropriate statistical test, interpreting results, etc.), go back to your original hypothesis. Say it out loud. What is it, specifically, that you are testing? It is easy to get caught up in methodology and to lose sight of the original research goal. In those uncertain times, remind yourself of your hypothesis. It is your compass home.

Designing the study

Just as a hypothesis will serve as your compass, a well-crafted research proposal will serve as your map. Such a proposal is invaluable and well worth the time and effort required for development. Therefore, even if your program does not require it, I would encourage you to write one for your project. The basic format provides the hypothesis, background and significance, and study design (including inclusion and exclusion criteria, variables, primary and secondary outcomes, power calculations, proposed statistics, interim analyses, and stopping criteria). Empty or “shell” tables and figures are also helpful to organize how you anticipate presenting the data and writing the manuscript. Depending on your research background, it may be worthwhile to meet with a biostatistician early and often to discuss the proposal and incorporate feedback in real-time prior to even starting the study. Ask other more senior investigators, including your mentor, to review and revise the proposal as well. By investing time in this process upfront, not only will it clearly set up the planned analyses but also when you are ready to synthesize the paper, it will practically write itself.

Ultimately, for my O 2 tension study, I chose to perform a randomized study of sibling embryos that had been donated to research. The sibling pairs, in which one embryo from each pair would remain in 5% O 2 for the duration of culture and the other would be placed into a pre-equilibrated media drop at 2% on day 3, was critical to eliminate patient variability in embryo development, as each patient served as a control for herself. Variables between the pairs that we could control for, such as method of insemination, number of pronuclei, and whether or not the embryo had previously been cryopreserved, were included in a model using generalizing estimating equations to account for multiple embryos from the same patient. Power calculations determined how many embryos I might expect to need in order to determine if there was a significant difference in the number of usable blastocysts between the treatment groups based on the effect size observed when comparing 20 to 5% oxygen.

While it likely would have been more straightforward to use an animal model, and certainly easier to accrue pairs of sibling embryos, any finding (positive or negative) would have to be extrapolated to the human. That is, I had what seemed to be a biologically plausible hypothesis, and anything short of using human embryos would not directly answer the research question. This created numerous challenges relating not only to ensuring that we had a sufficient number of embryos for the project but also to the funding opportunities available. Due to the paucity of donated two pronuclei zygotes, in the end, the vast majority of embryos were tripronuclear, 3PN. And the choice to study human embryos informed how the research could be funded and where it legally could be conducted. Indeed, the Dickey-Wicker Amendment, a rider attached to a 1995 congressional bill, specifies that federal funds cannot be used for human embryo research [ 15 ]. This applies to all personnel, reagents, equipment, and even physical laboratory space supported by federal dollars. As a result, the research was performed in a non-federally funded laboratory and secondary outcomes for this study (mass spectrometry of spent culture media and multiplexed real-time PCR of O 2 -regulated genes in the inner cell mass and trophoectoderm) were contracted out—the former to a private company out-of-state and the latter to a university core lab that was entirely funded by the Howard Hughes Medical Institute.

All of the above is to say, be creative about study design (in the case study described, using human 3PN embryos instead of an animal model) and be cognizant of how these choices will affect eligibility of study funding and how it might affect your selection of outcomes.

Getting funding

Research is typically expensive. Depending on the type and scale of the study, funding requirements may be minimal or grow to be quite considerable. This will largely be driven by study design, so again, take time in drafting a solid research proposal.

Various sources for funding are available for fellows, including extramural grants from the National Institutes of Health (e.g., T32, K grant, Loan Repayment Program for Contraception and Infertility Research, or the Reproductive Scientist Development Program); professional organizations or non-profits (e.g., American Society for Reproductive Medicine KY Cha Award in Stem Cell Technology, the Young Investigator’s Achievement Award from the Jones Institute for Reproductive Medicine, or the March of Dimes); private grants (e.g., Foundation for Embryonic Competence or pharmaceutical companies); and finally, internal funding from your local institution.

Most universities have a grants administration department that is responsible for managing grant applications and awards. When preparing a new application, be sure to notify your grant officer of any deadlines—otherwise, you may find yourself in a situation in which your portion of the application is complete, but the corresponding administrative work required to submit the grant on behalf of the institution cannot be completed by the submission deadline.

Typically, a project proposal, timeline, and itemized budget are required for application. Many funding sources likewise request an interim milestones report to ensure that the recipient is on-track and often a final presentation of findings. The funding source may also dictate how the awarded money may or may not be spent. For example, as described above, federal monies cannot be used for human embryo research. Other grants, particularly those from private sources, stipulate that the award may only be used for direct, and not indirect, costs. Direct costs are those that are spent to perform the specific project, while indirect costs (otherwise known as facilities and administration, F&A) are those that are not and are used for overhead costs, such as general office equipment, laboratory maintenance and infrastructure, utilities, and so on. If a grant is subject to indirect costs, a percentage of the direct cost amount (as determined by the institution or funding agency) is added to the final budget line and earmarked for overhead, so is not available for research. These indirect cost rates are independently negotiated by institutions with the Department of Health and Human Services, and the rates can vary considerably from institution to institution [ 16 ]. Some private grants specifically forbid that the award can be applied to indirect costs, effectively ensuring that all money is used for the research project itself and not moved into general funds “to keep the lights on.”

Sometimes it is necessary to apply for multiple grants before being awarded funding. It is easy to become discouraged, but use any feedback from a rejection as a source for improving your project and next proposal. Continue to put your name in the hat; with time, thoughtful research design, and perhaps most importantly, identifying the most appropriate funding source, your efforts will pay off.

Executing the project

After so much preparation, performing the actual study may be the easiest, and hopefully, the most rewarding, part of your research. Clearly, it depends on the work you are doing. Most will be relieved, however, to see all of their efforts finally in motion once the first experiment is done or the first patient is recruited. The specifics of how you execute the research will be guided by your hypothesis and your study design, but will always be shaped by external pressures such as time and funding. Recognizing these external constraints allows you to address them proactively so you can focus on the research at hand.

Depending on the type of research, data may become available for analysis on a continuous basis, episodically at predetermined interim analyses (and only accessible to a Data Safety Monitoring Board) or at the conclusion of the study. Throughout this process, be sure to keep thorough records of your work and back up your data often. Once the final dataset is available, it will likely require data cleaning to ensure accuracy and to confirm outliers. In addition, if you are working with a biostatistician, compile a data dictionary that defines each variable and how it is coded in the dataset; this will be used for coding purposes and will ensure accuracy of the statistical analyses. Finally, review your study proposal one last time and confirm that all of the planned data are included in the dataset for analysis.

Publishing your work

Research is meant to be shared. This may occur at local research-in-progress meetings, regional professional organizations, or national or international conferences. All of these forums are aimed to critically evaluate the presented work and to offer suggestions for improvement or future study. I always consider feedback from the audience after a presentation as the first round of reviewer comments for a paper, and I make sure that all of these points are addressed in the final submission.

The success of a project may not only depend on the quality of the work but also how it is packaged into a story. Certainly, if the research is low quality or low impact, no amount of spin will change that; however, a good project may be made better with effective communication of a clear, take-home message.

One example of how to do this is to devise a memorable name for the project. When I first proposed “Ultra-low” O 2 to my mentor, she cringed, but with some explanation, ultimately came round. It was an accurate portrayal of the study, distinguished it from the conventional “low” O 2 moniker for 5%, sounded contemporary, and allowed people to immediately understand where this work fit within the literature. It further delineated a progression from atmospheric to low to ultra-low O 2 , and anyone familiar with the antecedent work would immediately understand the motivation for the current study.

Following presentation at a conference, the next and final step for a project is to submit the work for publication. Again, incorporate feedback from meetings into the final revision of the paper in an attempt to anticipate reviewer comments. The choice of where to submit your work depends on the novelty and/or clinical significance of the findings, the intended audience (subspecialty vs. general medical interest), and its place within the existing literature. Your mentor often has the best perspective on the most appropriate journal for submission. Include key references in your citations, as reviewers are often familiar with the landmark studies in a particular field and expect to see them cited or they are the primary researchers who have conducted the previous important studies themselves.

Repeating and/or translating the findings

The hallmark of science is that it is reproducible. Your manuscript should provide sufficient detail such that an outside researcher in the same field should be able to replicate your methodologies. Data using human embryos in experimental conditions are limited, and so ultimately, larger multicenter studies or meta-analyses are often required to arrive at a definitive answer for a particular research question. As a follow-up of my preliminary findings, an ongoing laboratory study is currently being performed at Reproductive Medicine Associates of New Jersey (ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT 02919384","term_id":"NCT02919384"}} NCT 02919384 ) in which we are assessing the effect of ultra-low O 2 on the development of sibling embryos used in clinical IVF. To be involved in this project from its inception, and to see its potential for clinical application, has been a rewarding experience. Ultimately, whether or not this will translate into a paradigm shift in how human embryos are cultured in vitro remains to be determined.

Concluding remarks

While the scientific method can be summarized by al-Haytham’s three postulates: (1) state a problem based on observation, (2) criticize a hypothesis through experimentation, and (3) interpret the resulting data to form conclusions, scientific inquiry often does not occur so smoothly or in such a linear fashion. There will be starts and stops, detours, and U-turns along the way. Young investigators should rest assured, though, that meaningful work is possible with the help of an experienced mentor, a research question that is informed by both biology and the historical literature, and a thoughtful study proposal and design.

Everyone’s research experience is unique. This is just one version of the story, and the specifics provided here may need to be tailored to your own work. What is important to recognize is that the purpose of all research is to cast light where there previously was none. Accordingly, make sure you are testing a novel, unexplored hypothesis. Do not be afraid to question something that is currently accepted dogma. You might be surprised by what you find.

On developing a thesis for Reproductive Endocrinology and Infertility fellowship: a case study of ultra-low (2%) oxygen tension for extended culture of human embryos

• Fellow's Forum
• Published: 04 February 2017
• Volume 34 , pages 303–308, ( 2017 )

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• Daniel J. Kaser 1 , 2  

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Fellows in Reproductive Endocrinology and Infertility training are expected to complete 18 months of clinical, basic, or epidemiological research. The goal of this research is not only to provide the basis for the thesis section of the oral board exam but also to spark interest in reproductive medicine research and to provide the next generation of physician-scientists with a foundational experience in research design and implementation. Incoming fellows often have varying degrees of training in research methodology and, likewise, different career goals. Ideally, selection of a thesis topic and mentor should be geared toward defining an “answerable” question and building a practical skill set for future investigation. This contribution to the JARG Young Investigator’s Forum revisits the steps of the scientific method through the lens of one recently graduated fellow and his project aimed to test the hypothesis that “sequential oxygen exposure (5% from days 1 to 3, then 2% from days 3 to 5) improves blastocyst yield and quality compared to continuous exposure to 5% oxygen among human preimplantation embryos.”

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Kaser, D.J. On developing a thesis for Reproductive Endocrinology and Infertility fellowship: a case study of ultra-low (2%) oxygen tension for extended culture of human embryos. J Assist Reprod Genet 34 , 303–308 (2017). https://doi.org/10.1007/s10815-017-0887-5

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DOI : https://doi.org/10.1007/s10815-017-0887-5

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Use of thyroid hormones in hypothyroid and euthyroid patients: a THESIS* survey of Belgian specialists *THESIS: treatment of hypothyroidism in Europe by specialists: an international survey

• Maria-Cristina Burlacu 1 ,
• Roberto Attanasio 2 ,
• Laszlo Hegedüs 3 ,
• Endre V. Nagy 4 ,
• Enrico Papini 5 ,
• Petros Perros 6 ,
• Kiswendsida Sawadogo 7 ,
• Marie Bex 8 ,
• Bernard Corvilain 9 ,
• Chantal Daumerie 1 ,
• Brigitte Decallonne 8 ,
• Damien Gruson 10 ,
• Bruno Lapauw 11 ,
• Rodrigo Moreno Reyes 12 ,
• Patrick Petrossians 13 ,
• Kris Poppe 14 ,
• Annick Van den Bruel 15 &
• David Unuane 16  

Thyroid Research volume  15 , Article number:  3 ( 2022 ) Cite this article

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Hypothyroidism is a topic that continues to provoke debate and controversy with regards to specific indications, type of thyroid hormone substitution and efficacy. We investigated the use of thyroid hormones in clinical practice in Belgium, a country where currently only levothyroxine (LT4) tablet formulations are available.

Members of the Belgian Endocrine Society were invited to respond to an online questionnaire. Results were compared with those from other THESIS surveys.

Eighty (50%) of the invited 160 individuals, completed the questionnaire. LT4 was the first treatment of choice for all respondents. As secondary choice, some also prescribed liothyronine (LT3) and LT4 + LT3 combinations (2 and 7 respondents, respectively). Besides hypothyroidism, 34 and 50% of respondents used thyroid hormones for infertile euthyroid TPOAb positive women and the treatment of a growing non-toxic goiter, respectively. Had alternative formulations of LT4 to tablets been available (soft gel or liquid L-T4), 2 out of 80 (2.5%) participants would consider them for patients achieving biochemical euthyroidism but remaining symptomatic. This proportion was higher in case of unexplained poor biochemical control of hypothyroidism (13.5%) and in patients with celiac disease or malabsorption or interfering drugs (10%). In symptomatic euthyroid patients, 20% of respondents would try combined LT4 + LT3 treatment. Psychosocial factors were highlighted as the main contributors to persistent symptoms.

Conclusions

LT4 tablets is the preferred treatment for hypothyroidism in Belgium. A minority of the respondents would try combined LT4 + LT3 in symptomatic but biochemically euthyroid patients. Thyroid hormones are prescribed for euthyroid infertile women with thyroid autoimmunity and patients with non-toxic goiter, a tendency noted in other European countries, despite current evidence of lack of benefit.

Introduction

Hypothyroidism is the consequence of insufficient thyroid hormone (TH) action on target tissues [ 1 ]. Five percent of the European population, increasing with advancing age, has some degree of hypothyroidism [ 2 ]. In Belgium in 2012, more than 500,000 patients were treated with TH [ 3 ]. This number has been increasing (Fig.  1 ), a trend also noted in other European countries [ 4 ]. The thresholds of serum TSH when initiating TH treatment are falling, and this may be driven by attributing common and non-specific symptoms such as weight gain, fatigue, mood disorders and poor memory to hypothyroidism [ 5 , 6 ]. The unjustified prescription of TH could partially explain why a significant proportion of the treated patients are not satisfied with their treatment, but the efficacy and tolerability of different TH formulations or combinations have also been implicated [ 7 , 8 ].

Number of Belgian patients treated by year with thyroid hormones between 2005 and 2019. Source: National Institute of Diseases (INAMI-RIZIV, https://www.inami.fgov.be )

New LT4 formulations (liquid and soft gel capsules), approved by the European Medicines Agency and the American Food and Drug Administration, are claimed to improve bioavailability, presumably by facilitating absorption, but large-scale randomized studies are needed before these formulations can be prioritized over classical ones, at least in patients without gastrointestinal diseases and/or no concomitant medications [ 9 ]. Moreover, these new formulations are more expensive and are not commercially available in a number of European countries. In Belgium, the two LT4 branded tablet formulations (L-Thyroxine®, Takeda and Euthyrox®, Merck) are the only TH currently marketed and reimbursed.

Approximately 10% of patients treated with LT4 for hypothyroidism report persisting hypothyroid symptoms despite biochemical euthyroidism [ 7 ]. One of the hypothesis to explain this finding is the inability of LT4 to restore normal TH physiology [ 5 ], opening the way to the alternative of LT3 treatment. However, current European guidelines, endorsed by Belgian professional societies, recommend monotherapy with LT4 as the first line treatment of hypothyroidism, due to lack of evidence of superiority of LT3 + LT4 treatment with respect to hypothyroid symptoms and quality of life [ 10 ]. Nevertheless, persisting symptoms are a strong determinant of the physicians’ prescribing preferences, independent of biochemical control of hypothyroidism [ 11 ].

This survey is part of THESIS (Treatment of Hypothyroidism in Europe by Specialists: An International Survey), an international initiative investigating whether differences in practice between 28 European countries impact management of hypothyroidism [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ]. The aim of our survey was to identify current attitudes on the treatment of hypothyroid and euthyroid patients with thyroid hormones in Belgium.

We used an English language web-based survey constructed with Survey Monkey, an open-access platform that provides various question templates. The questionnaire included 26 questions of which 9 related to the professional characteristics of the respondents (Additional File  1 ). An invitation e-mail, including an electronic link to the questionnaire, was sent to the 160 members of the Belgian Endocrine Society (BES), followed by two reminders between October 15 and December 31, 2020. Anonymized responses were stored electronically. The survey service automatically blocked repeat submissions from the same IP address.

The survey was approved by the Ethics Committee (Comité d’Ethique) Hospitalo-Facultaire des Cliniques Universitaires St-Luc, Université Catholique de Louvain, Brussels, Belgium.

Statistical analyses

Results are presented as absolute numbers and percentages of respondents. The characteristics of respondents (years of practice < 10 years, 10–30 years, > 30 years, specialty Endocrinology vs. other, and place of practice University center vs. other, shown in Table  1 ) were compared according to the answers to questions B1 (Indications for TH in biochemically euthyroid patients) and B13 (The use of combined LT4 and LT3 treatment) using a Chi-square test or Fisher’s exact test. Binary logistic regression analysis was performed to identify, among the characteristics of responders (years of practice < 10 years, 10–30 years, > 30 years, specialty Endocrinology vs. other, and place of practice University center vs. other), those that influence the level (high score 5–8 vs low score 1–4) of the score given to each of the eight potential reasons of question B17 (Persisting symptoms in LT4 treated patients achieving normal TSH). All covariates with a p -value less than 0.20 in univariate analysis were introduced into a multivariate model. A backward elimination strategy was used to estimate the best model. Analyses were done using SAS V9.4 software (SAS Institute Inc., Cary, NC, USA). All p -values are two-sided and values less than 0.05 were considered statistically significant.

Respondent characteristics

All eighty respondents (50% of the BES members), representing five different clinical specialties (Endocrinology, Internal Medicine, Pediatric Endocrinology, Nuclear Medicine and Family Medicine) completed the survey. Endocrinologists represented 74% of the respondents. Four endocrinologists with multiples specialties were characterized as endocrinologists in the statistical analyses.

Forty-six (57.5% of the respondents) were members of other national and/or international endocrine or thyroid associations and nearly half of them (38 participants, 47.5%) practiced in non-university centers. All the participants were clinically active. The demographic characteristics of the respondents are listed in Table 1 .

Fifty participants (62.5%) treated hypothyroid patients on a daily basis, 29 (36%) on a weekly basis, whereas only one rarely managed hypothyroid patients. More than 100 hypothyroid patients/year were treated by 32 (40%) respondents, 51–100 annually by 28 (35%), and 20 (25%) treated less than 50 hypothyroid patients/year.

Choice of thyroid hormones

LT4 was the first treatment of choice for hypothyroidism for all respondents with none opting for LT3, LT4 + LT3 combination or desiccated thyroid extract. Nevertheless, some physicians also use LT3 and LT4 + LT3 combinations in their clinical practice (2 and 7 respondents, respectively). Combination therapy was considered by 20% of respondents for patients with normal serum TSH complaining of persistent symptoms suggestive of hypothyroidism, but this therapy would never be used by 74% of the respondents due to low quality evidence of superiority over LT4 monotherapy. There were no significant associations between use of combination treatment for symptomatic euthyroid patients and years in medical practice or physician working environment. Endocrinologists tended to prescribe LT4+ LT3 treatment more often than other colleagues (26% of endocrinologists vs. 6.3% of the other specialists, p  = 0.056).

The majority of respondents (92.5%) stated that their patients were using the type of LT4 that they recommended.

Clinical indications for treatment with thyroid hormones

A significant proportion of participants responded that TH treatment is indicated in biochemically euthyroid but infertile females with high levels of antithyroid antibodies and in euthyroid patients with benign goiter growing over time (34 and 50% of respondents, respectively) (Fig.  2 ). Other clinical conditions in euthyroid patients (depression resistant to antidepressant medications, obesity resistant to lifestyle intervention, severe hypercholesterolemia and unexplained fatigue) were considered as indications for TH treatment by less than 5%of respondents. Forty percent of respondents never treated euthyroid patients with TH. There were no significant differences, in terms of specialty or type of practice (university vs. other), between physicians who treated or did not treat (for any reason) euthyroid patients. Physicians who had practiced for more than 30 years were more prone to treat than those with shorter clinical practice (41% with less than 10-year practice vs. 60% with 10–30-year practice vs. 83% with more than 30-year practice, p  = 0.024). This difference was greater for TH treatment of benign euthyroid goiter (27% vs. 50% vs. 77%, respectively, p  = 0.009) (Fig.  3 ). Specialty (endocrinology vs. other) and place of practice (university vs. other) did not influence the treatment of benign euthyroid goiter ( p  = 0.638 and p  = 0.958, respectively).

Reasons for prescribing thyroid hormones in euthyroid patients. Multiple answers were possible. Columns represent the percentage of respondents who prescribe LT4 for the given condition

Percentage of respondents, in relation to length of clinical practice, who treat biochemically euthyroid infertile females with high levels of antithyroid antibodies or euthyroid patients with benign goiter growing over time, with thyroid hormones

After initiating LT4 treatment for hypothyroidsm, 57.5% of physicians would re-check serum TSH level after 4 to 6 weeks, and 42.5% after 8 weeks. In case of switching to a different formulation or change from one manufacturer’s LT4 tablet to another, 45% would still re-check the TSH after 4 to 6 weeks, 52.5% after 8 weeks but 2.5% (2 out of 80 individuals) would rely on a clinical evaluation for choice of this interval.

Use of different LT4 formulations

Several questions explored different clinical scenarios where alternative formulations (soft-gel capsules and liquid solution) could be preferred over classical LT4 tablets in patients taking interfering drugs or food, or presenting with coeliac disease, malabsorption, lactose intolerance, or intolerance to common excipients (Additional File  2 ). Had alternatives for LT4 tablet formulations been available, only 2 out of 80 (2.5%) participants would consider them for patients achieving biochemical euthyroidism but remaining symptomatic. This proportion was higher for patients with unexplained poor biochemical control of hypothyroidism (13.5%) and gastrointestinal diseases or interfering drugs (10%).

Use of dietary supplements

Fifty-one percent of respondents would never use dietary supplements. Selenium or iodine were recommended in addition to TH replacement by 7.5% in case of coexisting autoimmune thyroiditis, by 11% for subclinical hypothyroidism and by 30% if requested by the patients.

Management of symptomatic patients despite achieving a normal TSH

Most of the respondents considered that the percentage of symptomatic patients despite obtaining a normal TSH is less than 5% (34% of participants) or between 6 and 10% (32.5%). In the opinion of 51% of respondents, this population is unchanged in the last 5 years, while 24% thought it is growing. According to the majority, the most likely explanation for persistent symptoms is psychosocial factors (ranked 6.3 on a scale from 1 to 8), followed by patients’ unrealistic expectations (5.7), presence of comorbidities (4.8), burden of having to take medication (4.4), burden of chronic disease (3.8), chronic fatigue syndrome (3.7), inability of LT4 to restore normal physiology (3.5), and, finally, presence of underlying inflammation due to autoimmunity (3.4) (Fig.  4 ).

Presumed explanations for persistent symptoms in hypothyroid patients despite achievement of a normal TSH under LT4 treatment. Participants were asked to rank the potential explanations. Higher columns represent greater presumed importance

In univariate analyses, the specialty, the type of practice or the years in medical practice did not modify the way the respondents ranked the above reasons, except for patients’ unrealistic expectations which received higher scores from the non-endocrinologists (odds ratio 3.27; 95% CI: 1.10–9.68; p  = 0.032). This difference was maintained in a multivariate analysis.

This is the first survey on the use of TH by Belgian specialists. As elsewhere in Europe [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ] and in agreement with international guidelines, the survey confirmed that LT4 is the treatment of choice for Belgian hypothyroid patients. However, a significant proportion of respondents also use TH for more controversial indications, such as infertile euthyroid TPOAb positive women and a growing benign goiter. A similar or even greater preference for the treatment of infertile euthyroid women in the presence of thyroid autoimmunity was reported by French (31.7%), Greek (31.9%), Romanian (36.4%), Italian (37.3%), Danish (42.1%), Swedish (47.3%), Spanish (48.5%) and Polish (63.4%) endocrinologists who responded to this question, respectively [ 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 ], although the limited available evidence does not support this approach. In the case of assisted reproductive technology, all large randomized controlled trials in this population concluded that there is no benefit from LT4 treatment [ 21 , 22 ], which was confirmed in the recent TABLET trial including euthyroid TPOAb positive women with a medical history of (recurrent) miscarriage or receiving treatment for infertility [ 23 ]. The ETA guidelines on thyroid disorders prior to and during assisted reproduction published in 2021 [ 24 ] state that association with adverse fertility outcomes appears to emerge at TSH levels above 4.0 mIU/L, when LT4 treatment should be started. Nevertheless, limited data indicate that LT4 treatment optimized the ovarian reserve, fertilization and embryo development. Therefore, it has been suggested to consider LT4 treatment in infertile women with thyroid autoimmunity and serum TSH > 2.5 mIU/L on a case-by-case basis, taking into account factors such as ovarian causes of subfertility, older age (> 35 years), a history of recurrent miscarriage, or high levels of thyroid antibodies [ 24 ].

In contrast to current evidence, a surprisingly high proportion of Belgian specialists (50%) consider TH treatment in patients with a euthyroid benign goiter growing over time, a rate similar to Bulgarian (55%), Polish (40.9%) and French (40.2%) colleagues [ 14 , 15 , 19 ], but higher than 24.2% of Greek [ 18 ], 21.2% of Spanish [ 17 ],18% of Italians [ 12 ],14% of Swedish [ 20 ] and 12.5% of Danish endocrinologists who responded to this question [ 13 ]. This response may be related to adherence of older endocrinologists to outdated clinical practices, no longer recommended by recent guidelines [ 25 ]. Among these outdated ideas, one may be reminded of the misbelief that LT4 is a source of iodine in previously iodine-deficient areas. Euthyroid goiter is more prevalent in populations with low or borderline iodine intake and evolves from a diffuse thyroid enlargement at younger ages to an autonomous nodular disease in elderly. A number of studies show that goiter size is at best marginally reduced by LT4 [ 26 , 27 ], and that lowering TSH is associated with osteoporosis and cardiovascular morbidity [ 28 ] and mortality [ 29 ] in a dose-dependent way [ 30 ]. A diffuse goiter might benefit from TSH-lowering treatment [ 27 ], but surgery or radioiodine are more effective [ 26 , 27 , 31 ]. In Belgium, radioiodine is not traditionally used for the treatment of nontoxic goiter. Although radioiodine does lead to significant thyroid volume reduction, relatively high activities of radioiodine are needed [ 32 ], because of a frequent finding of a low thyroid radioiodine uptake, especially since the iodine salt addition policies have been largely implemented. Moreover, in Belgium, radioiodine can be given in outpatient clinic only up to 15 mCi. Thyroid radioiodine uptake can be enhanced by using recombinant TSH [ 27 ] but the product is not reimbursed in Belgium for this indication. Belgian specialists might also fear that thyroid autoimmunity, including thyroid-associated orbitopathy, might be induced or exacerbated by radioiodine administration. These limitations of alternative treatments may explain the choice of Belgian specialists for thyroid hormones in the management of simple euthyroid goiter. At contrast, in Denmark, where radioiodine is the preferred treatment for nontoxic goiter [ 33 ], only one in ten specialists recommend thyroid hormone for this indication [ 13 ].

Contrary to other European countries, LT3 and combination of LT4 + LT3 are not available on the Belgian market, but may be ordered from other European countries. This might be the reason why less than 10% of Belgian specialists use these therapies, compared with e.g. 58.6% of their Danish colleagues [ 13 ]. However, a higher number of respondents (20% of Belgians) are willing to switch to combination treatment in patients with normal TSH and persisting symptoms of hypothyroidism on LT4, a tendency noted in other THESIS surveys (25% of Greeks [ 18 ], 32.2% of Polish [ 15 ], 40% of Italians [ 12 ]. This proportion was even higher in Danish (71%) and Swedish (78.5%) specialists [ 13 , 20 ], despite the lack of evidence of superiority of combined treatment over LT4 and lack of long-term safety data. The preference towards combined treatment was more frequent in Belgian endocrinologists than other Belgian physicians, but was not influenced by the physician working environment or years of practice. We can only speculate that the endocrinologists may be more aware of the LT4 monotherapy controversies and the alternative of combination LT4 + LT3 treatment. As an example, in Polish THESIS, physicians who believed that persistent symptoms are not due to inability of LT4 to restore normal physiology were less likely to prescribe combination LT4 + LT3, than physicians who believed that LT4 does not restore normal physiology [ 14 ]. A recent expert consensus stated that a new clinical trial of LT4 + LT3 therapy is justified but should be correctly designed to address unsettled questions, such as: effect of deiodinase and TH transporter polymorphisms, inclusion of patients taking significant doses of LT4 and use of multiple daily doses or slow-release LT3 [ 34 ]. In the meantime, specialists should be aware that current guidelines suggest that a trial of LT4 and LT3 combination treatment may be considered only in symptomatic patients achieving biochemical euthyroidism for at least six months and after the exclusion of interfering conditions and comorbidities [ 10 ], the latter being very prevalent in patients with hypothyroidism [ 35 ]. Furthermore, combination treatment should be discontinued after a few months if there is no clinical improvement.

Although hypothyroid patients dissatisfied with their treatment represent a minority, our survey suggests, as other investigations of this type [ 12 , 13 , 14 , 20 ], that their proportion is either stable or increasing over time. The reasons for this dissatisfaction are much debated and include a number of contributors other than hypothyroidism per se, among them psychosocial factors, comorbidities and aspects of the patient-physician communication [ 5 , 36 , 37 ]. In this respect, our survey did not enquire about patient compliance with treatment.

The clinical experience with LT4 formulations other than tablets is very limited in Belgium. Nevertheless, the percentage of specialists expecting no major clinical changes for a symptomatic euthyroid patient switching to another formulation was similar to the one observed in Italy (42.5% Belgians vs. 50.3% Italians). Italian specialists are familiar with soft-gel capsules and liquid solution alternatives which they prefer in patients with specific conditions (interfering drugs, actual or suspected malabsorption, inability to take LT4 in the fasting state, unexplained poor biochemical control of hypothyroidism) [ 12 ]. In these conditions, the use of alternative LT4 formulations may also be favored by some Belgian specialists, but more than one in three were unable to formulate an opinion in the absence of clinical experience.

Selenium supplementation in addition to thyroid hormones was recommended by some of our survey respondents, although there is insufficient evidence to support this approach. A decline in thyroid autoantibodies in patients treated with selenium [ 38 ], does not offer documented clinical efficacy in chronic autoimmune thyroiditis [ 39 ]. Nevertheless, one third of the respondents prescribed dietary supplements, including selenium, at the patients’ request. This trend was already noticed among physicians in Europe [ 40 ], and is not recommended by current guidelines on management of hypothyroidism [ 41 ].

The strength of our survey is an acceptable response rate of 50%, comparable to that of a previous national Belgian survey on thyroid nodule management [ 42 ], and one of the highest of all THESIS surveys (vs. 25.5% in France, 25.8% in Spain, 28.2% in Sweden, 31.2% in Denmark, 39.3% In Italy, 42.4% in Romania) [ 12 , 13 , 16 , 17 , 19 , 20 ], despite the constraints of the ongoing Covid-19 pandemic. Physician surveys performed anonymously can reveal important habits and practices that are not evidence-based, potentially harmful, and identify the extent to which these may need to be prioritized as educational unmet needs that require to be addressed by professional organizations and societies. Although the absolute number of participants in our survey is limited, they were experienced with TH treatment and mostly of them treated at least as many hypothyroid patients on a daily basis compared to larger countries participating to THESIS initiative (62.5% of Belgians vs. 57.8% of Italians, 49.1% of Swedish or 34.2% of Danish) [ 12 , 13 , 20 ]. Moreover, our survey, as the majority of THESIS surveys, identified similar trends and deviations in the treatment with TH, as the treatment of euthyroid TPO+ infertile women and the preference for combined LT4 + LT3 treatment in hypothyroid patients with persistent symptoms. In this respect, data generated by our survey could be relevant to many other countries with similar populations and health care systems.

Our survey has also limitations. It can be argued that physician surveys record opinions rather than real practice. While this is true, physician surveys are not worthless. Indeed in the field of hypothyroidism physician surveys have been published and cited widely, and have helped expand our knowledge about management of hypothyroidism [ 11 , 43 , 44 , 45 , 46 ]. The survey targeted members of the BES, mostly endocrinologists, although several medical specialties are involved in TH treatment in Belgium. According to the National Institute of Diseases (INAMI-RIZIV, https://www.inami.fgov.be ), 88% of thyroid hormones prescriptions made in Belgium in 2019 were made by general practitioners (GPs). However, this is not an isolated situation. For example, most Swedish patients with hypothyroidism are treated by GPs [ 20 ] and hypothyroidism is managed both in primary and secondary care in Denmark [ 12 ]. Although GPs were under-represented in THESIS surveys, it is likely that they follow recommendations issued by specialists via national guidelines or Continuing Medical Education sessions. As in Sweden, Belgian specialists and GPs are working in close relationship for the treatment of patients with thyroid hormones. Therefore, the indications for the prescription of TH by specialists probably impact and influence those of GPs and are worth studying.

As the proportion of specialists working in a university center was over-represented, we cannot exclude, as another limitation to our study, that the respondents represented physicians treating a high proportion of dissatisfied patients in search of alternatives to standard TH treatment.

Although our survey reflects mainly the experience with levothyroxine tablet monotherapy, that is the treatment that the vast majority of hypothyroid patients receive, and the evidence base for clinical outcomes is far more robust than other thyroid hormones.

In conclusion, in Belgium TH are generally used according to current guidelines, but we did note, as most of THESIS surveys, deviations from evidence-based recommendations. Thyroid autoimmunity in euthyroid infertile women and euthyroid benign goiter were common indications for LT4 treatment, constituting practices in need of further scrutiny as unjustified thyroid hormones treatment can lead to iatrogenic hyperthyroidism and be dangerous. In Belgium, choice of TH is relatively uninfluenced by demographic respondent variables such as clinical specialty, type of practice or years of medical practice, and reflects the availability of drug formulations and type.

Availability of data and materials

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We deeply acknowledge Roberto Negro, Division of Endocrinology, V. Fazzi Hospital, Lecce, Italy for his participation to THESIS questionnaire construction. We thank all colleagues who contributed to the study by answering the questionnaire.

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Additional file 1..

Belgium Hypothyroid Survey Questionnaire.

Additional File 2.

Preference for different LT4 formulations in different clinical situations.

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Burlacu, MC., Attanasio, R., Hegedüs, L. et al. Use of thyroid hormones in hypothyroid and euthyroid patients: a THESIS* survey of Belgian specialists *THESIS: treatment of hypothyroidism in Europe by specialists: an international survey. Thyroid Res 15 , 3 (2022). https://doi.org/10.1186/s13044-022-00121-9

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45 of the Best Diabetes Dissertation Topics

Published by Owen Ingram at January 2nd, 2023 , Revised On August 16, 2023

The prevalence of diabetes among the world’s population has been increasing steadily over the last few decades, thanks to the growing consumption of fast food and an increasingly comfortable lifestyle. With the field of diabetes evolving rapidly, it is essential to base your dissertation on a trending diabetes dissertation topic that fills a gap in research. 

Finding a perfect research topic is one of the most challenging aspects of dissertation writing in any discipline . Several resources are available to students on the internet to help them conduct research and brainstorm to develop their topic selection, but this can take a significant amount of time. So, we decided to provide a list of well-researched, unique and intriguing diabetes research topics and ideas to help you get started. 

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List of Diabetes Dissertation Topics

• Why do people recently diagnosed with diabetes have such difficulty accepting reality and controlling their health?
• What are the reactions of children who have recently been diagnosed with diabetes? What can be done to improve their grasp of how to treat the disease?
• In long-term research, people getting intensive therapy for the condition had a worse quality of life. What role should health professionals have in mitigating this effect?
• Why do so many individuals experience severe depression the months after their diagnosis despite displaying no other signs of deteriorating health?
• Discuss some of the advantages of a low-carbohydrate, high-fat diet for people with diabetes
• Discuss the notion of diabetes in paediatrics and why it is necessary to do this research regularly.
• Explain the current threat and difficulty of childhood obesity and diabetes, stressing some areas where parents are failing in their position as guardians to avoid the situation
• Explain some of the difficulties that persons with diabetes have, particularly when obtaining the necessary information and medical treatment
• Explain some of the most frequent problems that people with diabetes face, as well as how they affect the prevalence of the disease. Put out steps that can be implemented to help the problem.
• Discuss the diabetes problem among Asian American teens
• Even though it is a worldwide disease, particular ethnic groups are more likely to be diagnosed as a function of nutrition and culture. What can be done to improve their health literacy?
• Explain how self-management may be beneficial in coping with diabetes, particularly for people unable to get prompt treatment for their illness
• Discuss the possibility of better management for those with diabetes who are hospitalized
• What current therapies have had the most influence on reducing the number of short-term problems in patients’ bodies?
• How have various types of steroids altered the way the body responds in people with hypoglycemia more frequently than usual?
• What effects do type 1, and type 2 diabetes have on the kidneys? How do the most widely used monitoring approaches influence this?
• Is it true that people from specific ethnic groups are more likely to acquire heart disease or eye illness due to their diabetes diagnosis?
• How has the new a1c test helped to reduce the detrimental consequences of diabetes on the body by detecting the condition early?
• Explain the difficulty of uncontrolled diabetes and how it can eventually harm the kidneys and the heart
• Discuss how the diabetic genetic strain may be handed down from generation to generation
• What difficulties do diabetic people have while attempting to check their glucose levels and keep a balanced food plan?
• How have some individuals with type 1 or type 2 diabetes managed to live better lives than others with the disease?
• Is it true that eating too much sugar causes diabetes, cavities, acne, hyperactivity, and weight gain?
• What effect does insulin treatment have on type 2 diabetes?
• How does diabetes contribute to depression?
• What impact does snap participation have on diabetes rates?
• Why has the number of persons who perform blood glucose self-tests decreased? Could other variables, such as social or environmental, have contributed to this decrease?
• Why do patients in the United States struggle to obtain the treatment they require to monitor and maintain appropriate glucose levels? Is this due to increased healthcare costs?
• Nutrition is critical to a healthy lifestyle, yet many diabetic patients are unaware of what they should consume. Discuss
• Why have injuries and diabetes been designated as national health priorities?
• What factors contribute to the growing prevalence of type ii diabetes in adolescents?
• Does socioeconomic status influence the prevalence of diabetes?
• Alzheimer’s disease and type 2 diabetes: a critical assessment of the shared pathological traits
• What are the effects and consequences of diabetes on peripheral blood vessels?
• What is the link between genetic predisposition, obesity, and type 2 diabetes development?
• Diabetes modifies the activation and repression of pro- and anti-inflammatory signalling pathways in the vascular system.
• Understanding autoimmune diabetes through the tri-molecular complex prism
• Does economic status influence the regional variation of diabetes caused by malnutrition?
• What evidence is there for using traditional Chinese medicine and natural products to treat depression in people who also have diabetes?
• Why was the qualitative method used to evaluate diabetes programs?
• Investigate the most common symptoms of undiagnosed diabetes
• How can artificial intelligence help diabetes patients?
• What effect does the palaeolithic diet have on type 2 diabetes?
• What are the most common diabetes causes and treatments?
• What causes diabetes mellitus, and how does it affect the United Kingdom?

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You can contact our 24/7 customer service for a bespoke list of customized diabetes dissertation topics , proposals, or essays written by our experienced writers . Each of our professionals is accredited and well-trained to provide excellent content on a wide range of topics. Getting a good grade on your dissertation course is our priority, and we make sure that happens. Find out more here . 

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How to find diabetes dissertation topics.

To find diabetes dissertation topics:

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• Consider cultural or demographic aspects.
• Consult experts or professors.
• Select a niche that resonates with you.

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Endocrinology Essay Examples and Topics

Type 2 diabetes, adult-onset type 2 diabetes: patient’s profile, diabetes mellitus: symptoms, types, effects.

• Words: 2190

Type 2 Diabetes as a Public Health Issue

• Words: 1667

Intervention Methods for Type 2 Diabetes Mellitus

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Overweight and Obesity Among Schoolchildren in Kuwait

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Health Promotion: Diabetes Mellitus and Comorbidities

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The Pathophysiology of Hashimoto’s Disease

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School Campaign Against Anaphylaxis

Diabetic leg ulcers: reflective account.

• Words: 1635

Diabetes Management: Case Study

Diabetes mellitus management in the elderly.

• Words: 2833

The Aboriginal Diabetes Initiative in Canada

• Words: 2857

Galactorrhoea: Diagnostics and Treatment

• Words: 1152

Blood Disorder: Disease Analysis

Epidemiology of type 1 diabetes, diagnoses for a patient with numbness in toes, the glucose control loss: case study, hypothyroidism: stages and symptoms, type 2 diabetes among rural hispanic (farmworkers), unraveling type 2 diabetes: insights into dynamics and dilemmas.

• Words: 4119

Testosterone deficiency for male health

Aspects of insulin-dependent diabetes, learning plan for patient anna with diabetes, type 2 diabetes and treatment approaches, gestational diabetes in a 38-year-old woman, type 2 diabetes mellitus and its implications.

• Words: 1340

Development of Comprehensive Inpatient and Outpatient Programs for Diabetes

• Words: 1106

Reflection on the Analysis of Process Recording

Improving glycemic control in black patients with type 2 diabetes, managing obesity as a strategy for addressing type 2 diabetes, tests and screenings: diabetes and chronic kidney disease, diabetes: treatment complications and adjustments, diabetes mellitus epidemiology statistics, affordable insulin now act: health policy and planning, the need for tracker device in diabetic patients, diabetes: risk factors and effects, barriers to engagement in collaborative care treatment of uncontrolled diabetes.

• Words: 2506

Hereditary Diabetes Prevention With Lifestyle Modification

Health equity regarding type 2 diabetes, diabetes mellitus: treatment methods, positive and negative feedback loops in endocrine system, diagnosing patient with insulin-dependent diabetes, human service for diabetes in late adulthood, diabetes: symptoms and risk factors, diabetes: types and management, advanced glycation end products and mortality among diabetic patients, type 2 diabetes’ impact on australian society, epidemiology of diabetes and forecasted trends.

• Words: 1107

Vitamin D and Dyslipidemia in Metabolic Syndrome

• Words: 1894

Communicating the Issue of Diabetes

The prevention of diabetes and its consequences on the population, addressing bloodstream infections, type 2 diabetes: prevention and education, the diabetes prevention articles by ford and mathe, type 2 diabetes in hispanic americans, diabetes mellitus as problem in us healthcare, prediabetes in the african-american population, diabetes mellitus: causes and health challenges.

• Words: 2020

Diabetes in Adults in Oxfordshire

Diabetes mellitus (dm) disorder case study analysis, diabetes mellitus in young adults, latino people and type 2 diabetes.

• Words: 1760

Diabetes Self-Management Education and Support Program

Diabetes mellitus care coordination.

• Words: 1246

Cushing Disease and Endocrine Control

• Words: 1110

Hyponatremia or Water Intoxication

Case study of patient with dka and diabetes mellitus.

• Words: 1444

Health Screening: Diagnosis and Management of Endometriosis

• Words: 1446

Diabetes: Statistics, Disparities, Therapies

Type 2 diabetes prescriptions and interventions, diabetes risk assessment and prevention, diabetes mellitus: preventive measures, type 2 diabetes in minorities from cultural perspective.

• Words: 1427

Ethics of Type 2 Diabetes Prevalence in Minorities

A strategic plan for diabetic management, type 2 diabetes in adolescents, analysis of diabetes and its huge effects, the impact of vegan and vegetarian diets on diabetes, “diabetes prevention in u.s. hispanic adults” by mccurley et al., diabetes disease of the first and second types, the trend of the higher prevalence of diabetes, thyroiditis among disorders of endocrine system, controlling blood glucose levels in diabetic patients, technological devices which help diabetic patients, diabetes mellitus as leading cause of disability.

• Words: 1653

Depression in Diabetes Patients

Type 1 diabetes: recommendations for alternative drug treatments, type 2 diabetes: a pharmacologic update, type 2 diabetes and its treatment, how to self-administer insulin injection.

• Words: 1872

Diabetes: Vulnerability, Resilience, and Care

• Words: 2230

Teaching Experience: Diabetes Prevention

• Words: 1659

Summary of Type 2 Diabetes: A Pharmacologic Update

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• Words: 1199

Diabetes Mellitus Type 2 and a Healthy Lifestyle Relationship

• Words: 1593

Sickle Cell Anemia: Causes and Treatment

• Words: 1553

What to Know About Diabetes?

• Words: 1004

Chronic Myelogenous Leukemia and Granulocytosis: Causes and Treatment

Blood transfusions in the management of hematological diseases.

• Words: 1134

Obesity and Overweight Prevention

Diabetes in saudi arabia, nutrition and physical activity for children with a diabetes, diabetes and hypertension avoiding recommendations, diabetes mellitus: types, causes, presentation, treatment, and examination.

• Words: 2366

Diagnosis and Classification of Diabetes Mellitus

Diabetes mellitus type ii: a case of a female adult patient.

• Words: 2965

Diabetes Insipidus: Disease Process With Implications for Healthcare Professionals

• Words: 1236

The Nature of Type 1 Diabetes Mellitus

• Words: 1706

Diabetes Risk Assessment

Aids, then and now.

• Words: 1447

Juvenile Diabetes: Demographics, Statistics and Risk Factors

Pheochromocytoma: a case study with a pheochromocytoma, covid-19: infection control and training program.

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Retinopathy in Diabetic Patients: Diagnosis and Treatment Options

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Catecholamines and Glucocorticoids

Prevention of complications in kendall regional medical center: thrombosis.

• Words: 2140

Changes in Thyroid Gland Functioning

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• UNC Chapel Hill

Research Topic: Reproductive Endocrinology

School of medicine > department of obstetrics and gynecology > division: reproductive endocrinology and infertility.

Anne Steiner is interested in infertility, in vitro fertilization (IVF), reproductive aging, hysteroscopy, amenorrhea (absent menses), biomarkers of ovarian aging, and reproductive potential. (Keywords: Amenorrhea, biomarkers, fertility, hysteroscopy, in vitro fertilization, infertility, ovarian aging, reproductive aging)

School of Medicine > Department of Psychiatry > Division: None

David Rubinow is interested in reproductive endocrine-related mood disorders. (Keywords: Endocrinology, mood disorders in women, reproductive health)

Steve Young is interested in the molecular biology of implantation and reproductive failure. (Keywords: Embryo implantation, infertility, molecular biology)

• [email protected]

Home » Blog » Dissertation » Topics » Clinics » 80 Clinical Endocrinology Research Topics

80 Clinical Endocrinology Research Topics

FacebookXEmailWhatsAppRedditPinterestLinkedInResearch topics in the realm of Clinical Endocrinology present a myriad of exciting opportunities for students embarking on their academic journeys at the undergraduate, master’s, or doctoral levels. These research inquiries not only broaden our understanding of physiological processes but also offer potential solutions to pressing medical issues. For students seeking to contribute to this […]

Research topics in the realm of Clinical Endocrinology present a myriad of exciting opportunities for students embarking on their academic journeys at the undergraduate, master’s, or doctoral levels. These research inquiries not only broaden our understanding of physiological processes but also offer potential solutions to pressing medical issues. For students seeking to contribute to this dynamic field, selecting the right research topics is crucial to advancing knowledge and fostering innovation in the realm of Clinical Endocrinology.

Clinical Endocrinology also known as “endocrine medicine” and “hormonal disorders research”, is the branch of medicine that specializes in the study of the endocrine system, encompassing hormone production, regulation, and their effects on the body’s functions and health.

A List Of Potential Research Topics In Clinical Endocrinology:

• Examining the influence of lifestyle factors on the occurrence and progression of endocrine disorders in the UK.
• Analyzing the cost-effectiveness of different treatment modalities for endocrine disorders in the UK.
• Assessing the correlation between vitamin D levels and insulin sensitivity in patients with metabolic syndrome.
• Investigating the effects of sleep disturbances on glucose metabolism in individuals with type 2 diabetes.
• Investigating the influence of androgen levels on the risk of developing cardiovascular disease in women.
• Understanding the role of the gut-brain axis in the regulation of appetite and energy balance.
• Analyzing the effects of hormonal fluctuations on pain perception and tolerance in women with endometriosis.
• Investigating the impact of hormonal changes during pregnancy on maternal metabolic health and offspring outcomes.
• Assessing the association between hormonal changes and the risk of developing gestational diabetes mellitus.
• Analyzing the role of adipose tissue-derived hormones in the pathogenesis of insulin resistance and metabolic syndrome.
• Investigating the association between hormonal changes and gastrointestinal motility in individuals with irritable bowel syndrome.
• Exploring the association between hormonal changes and cognitive decline in postmenopausal women.
• Exploring the potential therapeutic effects of hormone replacement therapy on bone health in postmenopausal women.
• Studying the healthcare utilization patterns and outcomes for endocrine disorders in the UK.
• Analyzing the effects of sleep duration and quality on hormonal regulation and metabolic outcomes in adolescents.
• Investigating the relationship between testosterone levels and muscle mass in aging men.
• Investigating the role of insulin-like growth factor-1 in the development and progression of prostate cancer.
• Assessing the role of thyroid hormones in the regulation of cholesterol metabolism and cardiovascular health.
• Assessing the association between growth hormone levels and cardiovascular risk factors in adults with acromegaly.
• Investigating the association between COVID-19 severity and endocrine dysfunction in affected populations.
• Investigating the impact of lifestyle modifications on insulin resistance in adolescents with polycystic ovary syndrome (PCOS).
• Exploring the effects of hormonal changes on immune responses and susceptibility to infections.
• Exploring the Interplay of Hormonal Imbalance and Cardiovascular Health in Clinical Endocrinology and Clinical Cardiology .
• Exploring the effects of insulin analogs on glycemic control and quality of life in individuals with diabetes.
• Evaluating the impact of sex hormone variations on bone density and fracture risk in postmenopausal women.
• Evaluating the relationship between thyroid function and mental well-being in individuals with bipolar disorder.
• Exploring the effects of hormonal imbalances on menstrual irregularities and reproductive health in women.
• Investigating the impact of endocrine-disrupting chemicals on male reproductive function and fertility.
• Assessing the association between thyroid dysfunction and mental health disorders in pediatric populations.
• Evaluating the impact of thyroid disorders on bone mineral density and fracture risk in postmenopausal women.
• Evaluating the association between hormonal changes and metabolic disturbances in women with polycystic ovary syndrome (PCOS).
• Investigating the role of thyroid hormones in modulating gut microbiota composition and function.
• Understanding the influence of COVID-19 on thyroid function and related disorders.
• Analyzing the role of endocrine dysfunction in the context of post-acute sequelae of COVID-19.
• Investigating the role of thyroid hormones in regulating cardiac function and cardiovascular outcomes.
• Analyzing the impact of endocrine-disrupting chemicals on human reproductive health and fertility.
• Investigating the disparities in access to endocrine healthcare services across different regions in the UK.
• Studying the interactions between gut microbiota and endocrine system in metabolic health.
• Analyzing the impact of gender-affirming hormone therapy on transgender individuals’ endocrine health.
• Investigating the relationship between testosterone levels and frailty in aging men.
• Analyzing the effects of hormonal changes on sleep patterns and quality of sleep in menopausal women.
• Reviewing the influence of endocrine disruptors on reproductive health and fertility.
• Evaluating the efficacy of combination therapy for managing thyroid cancer in elderly patients.
• Investigating the influence of hormonal fluctuations on appetite and food preferences during the menstrual cycle.
• Assessing the long-term effects of growth hormone therapy in adults with growth hormone deficiency.
• Investigating the association between insulin resistance and non-alcoholic fatty liver disease (NAFLD) in adolescents.
• Investigating the relationship between vitamin D deficiency and the development of autoimmune thyroid diseases.
• Evaluating the impact of the NHS framework on endocrine healthcare delivery and patient outcomes.
• Evaluating the impact of post-COVID-19 endocrine complications on metabolic health.
• Analyzing the impact of stress-induced cortisol levels on glucose metabolism and insulin sensitivity.
• Investigating the impact of maternal thyroid disorders on fetal development and neurocognitive outcomes.
• Analyzing the impact of glucocorticoid excess on metabolic parameters and cardiovascular risk.
• Reviewing the role of precision medicine in the management of endocrine disorders.
• Investigating the role of genetic factors in endocrine disorders prevalent in the UK.
• Analyzing the interplay between stress, mental health, and the endocrine system.
• Assessing the influence of thyroid hormones on neurodevelopment and cognitive function in infants and children.
• Exploring the effects of growth hormone therapy on metabolic parameters and cardiovascular risk in children with growth hormone deficiency.
• Analyzing the emerging technologies for early detection and management of endocrine disorders.
• Integrating endocrine biomarkers into clinical microbiology : a comprehensive approach for infection-endocrinopathy nexus.
• Reviewing the recent advancements in hormonal therapies for endocrine-related cancers.
• Evaluating the metabolic and endocrine effects of bariatric surgery in obesity management.
• Assessing the influence of hormonal imbalances on the development and progression of breast cancer.
• Investigating the genetic and epigenetic factors contributing to the development of congenital adrenal hyperplasia.
• Evaluating the impact of hormonal alterations on the development of autoimmune diseases in susceptible individuals.
• Examining the neuroendocrine effects of COVID-19 and their implications on mental health.
• Exploring the effects of environmental pollutants on endocrine function and reproductive health.
• Exploring endocrine disruptions in the aftermath of COVID-19 and potential therapeutic interventions.
• Studying the impact of COVID-19 on pituitary function and subsequent hormonal imbalances.
• Assessing the role of insulin-like growth factor binding proteins in the progression of cancer.
• Exploring the effects of hormone replacement therapy on muscle mass and physical performance in postmenopausal women.
• Assessing the hormonal alterations and implications in COVID-19 recovered individuals.
• Investigating the relationship between endocrine disruptors and the development of obesity in children and adolescents.
• Evaluating the role of leptin in appetite regulation and its potential as a therapeutic target for obesity management.
• Exploring the effects of thyroid dysfunction on male reproductive health and fertility.
• Understanding the role of gut microbiota in the development and progression of diabetes mellitus.
• Analyzing the effects of hormonal contraceptives on the regulation of mood and emotional well-being in young adults.
• Evaluating the effects of exercise interventions on hormone levels and metabolic health in postmenopausal women.
• Studying the long-term effects of childhood endocrine disorders on adult health and well-being.
• Investigating the molecular mechanisms underlying endocrine-related developmental disorders.
• Assessing the socioeconomic disparities in the prevalence and management of endocrine disorders in the UK.

In the fascinating world of Clinical Endocrinology, the journey of academic inquiry begins with the right research topic. Whether you’re an aspiring undergraduate, a determined master’s candidate, or an ambitious doctoral scholar, selecting a research topic that aligns with your interests and academic aspirations is pivotal. From investigating hormone-related disorders to exploring the role of endocrine signaling in various physiological processes, the options are diverse and enticing. Tailoring your research focus to your degree level and interests not only ensures academic growth but also contributes to the ever-evolving landscape of knowledge in Clinical Endocrinology. Choose wisely and embark on a journey of discovery that enriches both your academic path and the field of endocrine research.

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