Dr. Pinnaro is part of the leadership team that has created a new national registry to track the health of persons with Turner syndrome. The initiative has been named the “Inspiring New Science to Guide Healthcare in Turner Syndrome (InsighTS)” Registry. The leadership group of the InsighTS Registry has now published their study’s design and goals. The publication’s abstract can be found on PubMed at the following link. Persons with Turner syndrome have unique health risks, and ideally should be seen regularly in a clinic with Turner syndrome expertise, such as the one at the University of Iowa Stead Family Children’s Hospital (2023 link to the Turner syndrome clinic) headed by Dr. Alexandrou and Dr. Pinnaro.
The majority of women with Turner syndrome experience primary ovarian failure, meaning that their ovaries never produce estrogen in normal quantities. For this reason, normal puberty does not occur. Estrogen production is not only important for a feminizing puberty to occur but also is important for overall health and wellness. Dr. Eirene Alexandrou heads the Turner syndrome clinic (clinic homepage link) at the University of Iowa Stead Family Children’s Hospital. She is a published expert in Turner syndrome care. Recently, on April 4, Dr. Alexandrou gave an invited webinar entitled “Estrogen Replacement Therapy in Turner Syndrome” (announcement link) for the Turner Syndrome Foundation. She reviewed the prevalence of primary ovarian failure in Turner syndrome, the benefits of estrogen replacement therapy, and the timing of such replacement including initiation.
Although it has long been known that persons with Turner syndrome have increased risk of developing diabetes, the reasons are not well understood. Relatedly, there are no known preventative strategies and no directed therapies. Dr. Pinnaro and Dr. Alexandrou from our Division have teamed up to review published knowledge in this area and map out critical gaps in understanding. Their review, entitled “Hyperglycemia in Turner syndrome: Impact, mechanisms, and areas for future research” has just been published in the peer reviewed literature. Also contributing to the manuscript were student Cameron Mitsch and division member Dr. Norris. The paper appears in the journal Frontiers in Endocrinology and can be found here (doi: link or pubmed link ). Dr. Pinnaro is leading a team working to find the root causes of diabetes linked to Turner syndrome. It remains important for persons with Turner syndrome to receive expert endocrine care, such as can be obtained from Dr. Alexandrou; see this link for contact information for her Turner syndrome clinic .
Teaming up, Dr. Alexandrou and Dr. Pinnaro from our division have worked hard to create the first dedicated clinic in the region for persons with Turner syndrome (TS). TS is a genetic condition that occurs when one of the X chromosomes is fully or partially lost from cells before birth. Symptoms of TS almost always include short stature and lack of pubertal progression. Both of these conditions can benefit from expert treatment from a pediatric endocrinologist. Additionally, TS symptoms often also include subtle structural body changes such a webbed neck, structural heart defects, autoimmune disorders, hearing loss, frequent ear infections, kidney defects, and selective learning difficulties. For this reason, it is crucial to have other pediatric sub-specialty services involved and/or available. The new clinic includes pediatric endocrinology, pediatric cardiology, clinical psychology, medical genetics, pediatric nephrology, reproductive endocrinology, dietician services, and a clinical pharmacist. In addition, Dr. Pinnaro is involved with clinical trials for which some patients may qualify. The current (2023) website for the clinic, including contact information, can be found here : https://uihc.org/childrens/services/turner-syndrome .
Growth hormone is required for children to realize their full potential to grow taller. Those children who are unable to make normal amount of growth hormone do not grow well. Fortunately, daily growth hormone injections are an available therapy and robustly restore growth in these children. More rarely, some children can make growth hormone but can not respond to it properly due to various genetic reasons. One such reason is mutation of a gene termed PAPPA2. This gene produces a protein required for growth hormone to work. Specifically, the PAPPA2 protein liberates IGF-1 — the major growth hormone induced growth factor — to allow it to promote growth. Persons who lack a proper PAPPA2 gene thus do not grow well. An active question in the field regards whether giving IGF-1 supplements might overcome this issue and promote growth in children with this condition. Dr. Eirene Alexandrou from our Division was part of a team that studied this question and have now published their findings. Their results suggest that indeed IGF-1 can improve growth in children with genetic mutations in PAPPA2, but that the therapy may not completely normalize growth. Because IGF-1 therapy can have side effects, they suggest weighing pros and cons with each family when considering treatment. Their findings have been published in the journal Hormone Research in Paediatrics. The abstract has been indexed in Pubmed and can be found here.
Turner syndrome affects over 70,000 women in the United States. Turner syndrome is caused by loss genetic material from one X chromosome in a process that happens long before birth. Turner syndrome increases the risk of a variety of physical and medical changes such as shorter stature, subtle changes in facial structure, delayed puberty, congenital heart disease, and frequent ear infections. It has more recently been recognized that Turner syndrome also increases the risk of anxiety and depression. To better address the situation, Dr. Eirene Alexandrou recently developed an approach by which medical providers can screen persons with Turner syndrome using a simple questionnaire. She found that a high proportion, over half, of women with Turner syndrome had elevated anxiety levels. The results of Dr. Alexandrou’s study have been published this month in the journal “Hormone Research in Paediatrics” after peer review. The abstract of the work can be found on Pubmed (link). The results highlight the importance of multidisciplinary specialty clinics for persons with Turner syndrome, such as the clinic here led by Dr. Alexandrou and Dr. Pinnaro.
There are a number of reasons for growth failure in a child. There are a variety of genetic conditions that cause inherited forms of growth failure. One of these that is being increasingly recognized is aggrecan deficiency. This is a genetic condition that is passed from parent to child in a dominant pattern. To better understand aggrecan deficiency and its impact on growth and bone health, Dr. Eirene Alexandrou studied multliple families. She has now published her findings in the American Journal of Medical Genetics (PubMed link here). This work indicates that aggrecan deficiency is associated with moderate but progressive growth failure. Arthritis was very common among adults with aggrecan deficiency. With increased knowledge and awareness about this condition, the hope is to improve outcomes from earlier detection and treatment.
Growth failure resulting in short stature has a variety of causes. One uncommon cause of short stature relates to mutations in the aggrecan gene. This conditions runs in families in an autosomal dominant pattern and causes severe short stature. Dr. Alexandrou is part of a team that now reports that growth hormone treatment can help improve improve the growth rate in children with this condition. She helped co-author their scientific report, which is being published in the prestigious Journal of Clinical Endocrinology and Metabolism (PubMed link to their publication). The publication reiterates the importance of having children who are growing poorly be evaluated by a pediatric endocrinologist to help determine the potential causes and to consider the relative merits of treatment.
It takes years of training to become a pediatric endocrinologist, requiring at least a decade of studies after college. You could consider this to be the equivalent of completing the “26th grade”. The final step is to pass the Pediatric Endocrinology board exam. We are pleased to report that the three newest doctors in our Division have just passed their Board Exam. Congratulations to Drs. Alexandrou, Pinnaro, & Ramakrishna for becoming Board Certified Pediatric Endocrinologists. Their years of hard work and study have enabled them to become well qualified to diagnose and treat pediatric endocrine conditions.
Treatment-Induced Neuropathy of Diabetes (TIND) is a insufficiently recognized complication, usually temporary, that can occur after rapid correction of severe hyperglycemia. Its occurrence in the pediatric-aged population has not been well studied. Dr. Eirene Alexandrou has just published a paper describing 7 cases of TIND among children and young adults. She published the work in the Journal of the Endocrine Society (link to paper). The cases occurred in both type 1 and type 2 diabetes, and in each case followed a rapid improvement from severe hyperglycemia. All but 1 of the cases were transient. Symptoms included pain, often burning in nature, numbness, and autonomic disturbance. Management included stabilization of glycemia and medical therapy.