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Lipid Clinic Addresses Abnormal Cholesterol Levels in Children

Dr. Ambika Ashraf is the director of pediatric endocrinology at Children’s of Alabama.

Through early intervention, the lipid clinic at Children’s of Alabama is aiming to give kids with lipid problems a shot at healthier adulthoods.

The clinic used to be hosted as part of the weight management clinic at Children’s until leaders realized that lipid problems are not limited to children with obesity. Ambika P Ashraf, M.D., director of pediatric endocrinology at Children’s of Alabama, runs the clinic with nurse practitioner Erin Tuanama, N.P., and pediatric endocrinologist Christy Foster, M.D. Patients also receive nutritional counseling, recommendations for physical activity and lifestyle changes and, depending on their condition, genetic and cardiology consultations. The clinic meets weekly, and the team currently follows more than 1,000 patients.

Twenty-percent of children between ages 12 and 19 have some type of lipid disorder, and that rate jumps to 42% in children who are obese.[i] Ashraf calls pediatric dyslipidemia “a no man’s land” because different pediatric subspecialists take care of children with the condition.

As the only pediatric lipid clinic in the state—and one of the largest directed by pediatric endocrinologists in the Southeast—Children’s sees patients with familial hypercholesterolemia (FH). This genetic disorder affects about one in every 250 people and dramatically increases their risk of premature heart disease. The clinic receives referrals from throughout the South and treats patients with rare, genetically linked types of dyslipidemia, such as familial chylomicronemia (FCS), severe hypertriglyceridemia, familial combined hyperlipidemia and sitosterolemia. “Lipid problems start early in childhood, and it’s very important to intervene in a timely manner to prevent the cardiovascular risk,” said Ashraf, who is board certified in lipidology and is a fellow of the National Lipid Association.

Early diagnosis is critical for early intervention, which can prevent the heart disease and stroke that dyslipidemia can bring later in life. At the clinic, patients with high triglycerides or combined dyslipidemia (high LDL and triglycerides) are primarily managed with diet and lifestyle changes. Losing just 5-10% of their body weight can normalize cholesterol levels in children with dyslipidemia resulting from obesity. Those with high LDL levels and those with FH often need medications, such as statins, and lifestyle changes.

Science proves that this early intervention can lead to a healthier adulthood. One study compared adults with FH who started a statin when they were children to their parents with FH who didn’t start a stain until middle age. Just 1% of those receiving early treatment had experienced cardiovascular events by age 39, and none had died of cardiovascular causes. Conversely, 26% of their parents had experienced cardiovascular events by age 39, and 7% had died from cardiovascular causes.

“In the past, a lot of pediatricians thought they didn’t have to treat lipid problems,” Ashraf said. “We used to think we could wait to treat these children. But we have a window of opportunity to prevent later events. We can’t wait.”

In 1991, the National Institutes of Health’s National Cholesterol Education Program recommended selective cholesterol screening of children with certain risk factors or those with FH. Twenty years later, recognizing the power of prevention and the growing epidemic of obesity in the pediatric population—which often results in dyslipidemia—the American Academy of Pediatrics (AAP) and the National Heart, Lung and Blood Institute (NHLBI) recommended universal screening for all children ages 9-11 and again between ages 17 and 21.The AAP also provided criteria for when children should see a lipid specialist versus managing the condition with diet and exercise.

The AAP and NHLBI also recommended screening children ages 2-10 if they have high-risk factors, such as parents or grandparents who had heart attacks or other cardiovascular diseases before age 55 (for men) or 65 (for women).

A recently published study found that nationally just 17% of healthy children were screened, while between 22% and 77% of children with high-risk heart conditions were screened. When Ashraf began directing the lipid clinic in 2006, only about 10-20% of local pediatricians adhered to the screening guidelines, she said. But after intensive education, including setting metrics, holding grand rounds and instituting an annual day of education, now more than half of Alabama pediatricians follow the recommended guidelines.

[i] May AL, Kuklina EV, Yoon, PW. Prevalence of Abnormal Lipid Levels Among Youths — United States, 1999—2006. MMWR. 2010; 59(02);29-33.


Can Diabetes Prematurely Age DNA in Teens and Adolescents?

Dr. Christy Ann Foster is a pediatric endocrinologist at Children’s of Alabama.

How does diabetes change a teenager’s gene expression? That’s the question researchers in the Endocrinology and Diabetes Division at Children’s of Alabama are exploring. The topic is vital given the stratospheric rise in Type 2 diabetes in adolescents.[1] In addition, the disease appears to be more aggressive than adult-onset diabetes, with adolescents losing up to 15 years of life expectancy due to comorbidities.

Research in adults shows that many complications of diabetes, including increased risk of cardiovascular and kidney disease, diabetic retinopathy, nerve damage and early mortality, appear to be related to epigenetic aging, in which gene expression changes while the underlying DNA remains the same. Epigenetic age is an indicator of biological aging, capturing the impact of environmental and behavioral influences across time on cellular function and the potential for disease. The higher a person’s epigenetic age acceleration, the higher their all-cause mortality and morbidity is. Ideally, a person’s epigenetic age corresponds to their chronological age; the epigenetic age of a patient with diabetes may be years older than their chronological age.

“I think the study of epigenetics is fascinating because it shows the way our genes can be changed by other influences,” Children’s pediatric endocrinologist and study leader Christy Anne Foster, M.D., said. “If we can understand these influences and how they can modify the impact of our genetics, there is potential for intervention.”

However, little research has been done on such epigenetic changes in children, and none in those with diabetes and/or obesity. Which is exactly what the study focuses on.

“With the impact of seeing such an increase in Type 2 diabetes in adolescents, and even pre-adolescents, we want to understand what developing this condition so early means for their long-term health,” Foster said.

The first step is a pilot study using the DNA of children and adolescents ages 12-18. Researchers are comparing the DNA of patients with diabetes and obesity to the DNA of those without either. They’re also comparing the DNA of patients with obesity to that of normal-weight children and adolescents. Researchers hope the study will establish that epigenetic aging occurs in adolescents with diabetes and/or obesity and will help them identify risk factors that can be addressed.. If the study is promising, researchers plan to do longitudinal studies to follow the impact of dietary and therapeutic interventions on epigenetic age acceleration.

One challenge will be determining whether the changes are the result of diabetes or something else, which is why the control group is so important, Foster said.

If the investigators do find a direct link between diabetes and DNA methylation, they may not be able to directly modify it, Foster said, but they could potentially support patients based on their social determinants of health and manage their risks that way.

Foster is partnering with Bertha Hidalgo, Ph.D., an associate professor at the University of Alabama at Birmingham’s School of Public Health. She’s also collaborating with researchers at the University of Minnesota, who are analyzing the DNA for epigenetic changes. “Given the prevalence of Type 2 diabetes in pediatric patients, understanding these changes in that population is critical,” Foster said. “These young people are at such high risk for complications with such a long-term diagnosis. The more we understand, the more we can hopefully improve their quality of life.”

[1] Lawrence JM, Divers J, Isom S, et al. Trends in Prevalence of Type 1 and Type 2 Diabetes in Children and Adolescents in the US, 2001-2017. JAMA. 2021;326(8):717-727. doi:10.1001/jama.2021.11165


A Multidisciplinary Approach to Metabolic Bone Disease

Drs. Margaret Marks (left) and Ambika Ashraf lead the metabolic bone disease clinic at Children’s of Alabama.

Treating metabolic bone disease in children involves a team of specialists including a pediatric endocrinologist, pediatric orthopedic surgeon, geneticist, physical medicine rehabilitation specialist and nutritionist. Where once patients and their families had to navigate this web of specialists, now the metabolic bone disease clinic at Children’s of Alabama assembles the entire care team, whom patients often see in one visit, thanks to a multidisciplinary approach.

“When we initially started out, we weren’t sure how many patients we’d have,” clinic director Ambika Ashraf, M.D., said. “Subsequently, we realized most of these patients were going out of state.” Today, the clinic follows more than 300 patients. Most are from Alabama, but patients also travel from Tennessee, Mississippi and Georgia.

Since most of the conditions the clinic sees are complex and require multidisciplinary care, “getting to see the different specialists on the same day is a huge benefit,” Ashraf said. Otherwise, it could take six to eight months to get an appointment with individual specialists.

Patients have a varied spectrum of conditions including osteogenesis imperfecta; fibrous dysplasia; complex disorders of calcium, phosphorous and vitamin D metabolism; fragility fractures due to low bone density and osteoporosis; hypophosphatasia; and skeletal dysplasias.

Pediatric metabolic bone disease spans a spectrum from mild disease with a relatively low risk of fractures to disease so severe that just a small bump could result in a broken bone. Despite treatment, patients tend to be small in stature for their age, with multiple deformities resulting from fractures and poor healing, Ashraf said. They are also prone to problems in other areas, including cardiovascular and pulmonary complications. “We make sure they see those specialists, too,” she said.

The most common condition the clinic treats is osteogenesis imperfecta (OI), or brittle bone disease, a genetic defect that affects the body’s ability to make collagen, which is required for strong bones. These children may have dozens or even hundreds of fractures before they reach adolescence.Most patients with OI receive bisphosphonate infusions in the Children’s infusion center to strengthen their bones.

Physical medicine, or physiatry, plays an important part in managing these children, Ashraf said, because many have some type of abnormality related to muscle tone or movement, joint laxity, joint contractures or muscle weakness. They may also need help with a wheelchair, braces/splints or other mobility devices.

“This is a fascinating time for metabolic bone disease,” Ashraf said. Just a decade ago, there were few treatments beyond the supportive and palliative. For instance, until a few years ago, the only treatments for X-linked hypophosphatemic rickets were oral phosphate and calcitriol. They helped, but not enough, and patients still required frequent surgeries. With the availability of burosumab, a monoclonal antibody that binds to and inhibits the activity of fibroblast growth factor 23—which blocks phosphate absorption—children with the condition now need fewer surgeries and experience fewer limb deformities.

Bisphosphonate infusions help reduce the number and severity of fractures in OI patients, and physical therapy can help with deformities. For hypophosphatasia, enzyme replacement helps manage the condition. Caring for these children “is a joy,” Ashraf said. “Especially when we can make a difference in their quality of life.”

Endocrinology, Inside Pediatrics

High-Risk Diabetes Clinic Keeps Kids Out of the Hospital

Children’s of Alabama offers clinic to help high-risk diabetes patients.

The 2018 death of a teenage patient was a wake-up call for Children’s of Alabama pediatric endocrinologist Mary Lauren Scott, MD. The patient had type 1 diabetes and had been admitted numerous times over the previous few years with sky-high blood sugar. He died at home from diabetic ketoacidosis (DKA), a diabetic emergency in which the body breaks down fat for fuel because it doesn’t have enough insulin.

In response, Scott, who also has type 1 diabetes, took action. She and her team searched their data and found 10 patients in the previous year who had been admitted three or more times with DKA. Such admissions are a red flag that the patient isn’t taking their insulin doses at home and that they have a risk of dying or having a medical emergency they can’t recover from. 

“When you’re dealing with a chronic disease such as diabetes and patients have recurrent hospitalizations, we get burnt out too,” she said. “That makes it difficult to have the kind of positivity, motivation and drive to help them surmount the insurmountable and deal with what, for them, feels impossible. It’s hard, it’s complicated, and it’s not uplifting when you feel like you’re not able to help the patient.”

Scott, who was already directing a clinic for children and adolescents with type 2 diabetes, started another clinic in 2018 specifically for these high-risk patients. The primary goals of the clinic are to prevent hospitalizations and saving lives. The patients are all adolescents, at an age when they—instead of their parents—typically start handling their insulin injections and blood glucose tracking. 

The clinic meets half a day each month. The focus is on communication. Parents, social workers, nurses, nurse practitioners, diabetes educators and counselors work as a team to build trust with the teenagers. “We speak to them differently to get them to open up to us more than they perhaps ever have with other providers,” Scott said.

That means ensuring them there is no shame attached to missing insulin doses; what’s important is that they talk about it. “We tell them, ‘We need to know how to help you, so we can help you find success,’” Scott said. “We try to make the focus more about what’s working for [them] with [their] diabetes, what’s not working, and what [they] think would make things easier.” 

Patients must go six months without hospitalization before they graduate from the program.

The clinic is not just for patients, but for their families, as well. The patients are often drawn from minority and low-income backgrounds and have single parent households, Scott said. “The parent works and is also trying to manage a teenager who’s depressed or burnt out,” she said. “They can’t do everything.”

Because many of the parents have a history of interaction with child protective services, they rarely opened up to the staff about their child’s difficulties. With the new approach, parents are now more likely to talk about what’s happening at home and what they need help with. “That’s where we typically find success for these patients,” she said. 

The results have been impressive. 

  • 14 of the original 15 patients graduated. The one remaining is the youngest patient with significant home life issues. 
  • 8 of the 14 had a lower A1C when discharged. 
  • 6 of the 14 had no DKA admissions while in the clinic; all had three or more before joining the clinic. 
  • 12 of the 14 had fewer missed visits even though they came to clinic monthly instead of every three to four months.
  • Half had lower rates of DKA.
  • 12 of the 14 started continuous glucose monitoring while in clinic, and four also received insulin pumps, leading to a dramatic improvement in their health.
  • No patients died.

There are currently eight more patients enrolled, and more will be invited in the coming months, Scott said.

Endocrinology, Inside Pediatrics

PCOS Clinic Provides Holistic Care with a Multidisciplinary Approach

Doctor speaking with patient.

Excessive weight gain, acne, hirsutism, thinning hair, irregular menstrual cycles and insulin insensitivity –  these are some of the symptoms of polycystic ovary sydrome (PCOS), the most common reproductive condition in women and a risk factor for a plethora of metabolic diseases, including diabetes and cardiovascular disease, as well as infertility. It affects between 3% and 15% of women, who often wait years for a diagnosis, visiting numerous clinicians in the process.[i]

That’s changed for the young women of Alabama since pediatric endocrinologist Christy A. Foster, MD, started a multidisciplinary clinic in 2020 for adolescents with PCOS.

“Our goal is to try to improve the care patients receive in a more holistic manner,” she said. The clinic’s foundation is a multidisciplinary team that includes Foster, a pediatric gynecologist, a dermatologist, a social worker and family counselor, and a nutritionist. 

Many of these young women have been seen multiple times by their primary care doctor before they’re referred. “Coming to the clinic enables them to put a voice to what’s wrong—a feeling that they’re understood—which can be helpful,” Foster said. The multidisciplinary approach also provides expertise from several different providers. “That certainly helps with their care because otherwise they might have to make several different appointments and take more time to travel.” And most are just glad to have a home with providers who have expertise with PCOS. 

The physical manifestations of PCOS create a challenge at a particularly difficult time for young women, Foster said. “Their peers notice they ‘look different,’” she said. “That’s certainly a challenge for them from a mental health perspective.” That’s why it’s so important that the team includes counseling and mental health.

The Children’s clinic is one of only a limited number in the country, which is one reason Foster felt strongly about starting it. “I wanted to improve access to care in our region and address the patient as a whole person,” she said.

The team tailors treatment to address the patient’s greatest concerns, be it pre-diabetes, facial hair, severe acne or other repercussions of PCOS. “My hope is that when we start them on treatment, they feel their concerns are being addressed and heard and understood,” Foster said. Treatment options include birth control pills to regulate their menstrual cycles, an insulin sensitizer such as metformin, laser hair treatment and androgen receptor blockers. 

Another advantage of the clinic is that the team can follow the women longitudinally and, hopefully, prevent some of the metabolic conditions they’re at risk for.

After clinic, the team holds a debrief to discuss the patient as a whole, “There is a benefit to having everyone in the same place,” Foster said. “It improves communication.”

The clinic is held once a quarter, although patients may see individual providers at other times. Since it began, about 50 young women have been seen, with about six to eight seen during each half-day clinic. “But certainly we’re looking to grow,” Foster said.

[i] Gibson-Helm M, Teede H, Dunaif A, Dokras A. Delayed Diagnosis and a Lack of Information Associated With Dissatisfaction in Women With Polycystic Ovary Syndrome. J Clin Endocrinol Metab. 2017;102(2):604-612. doi:10.1210/jc.2016-2963

Endocrinology, Inside Pediatrics

Managing Congenital Adrenal Hyperplasia With Precision

Nurse practitioner Leslie Pitts (left) and Dr. Gail Mick, director of the Children’s of Alabama endocrine newborn screening program.

Congenital Adrenal Hyperplasia (CAH)—a group of rare genetic disorders affecting the adrenal gland—occurs in approximately 1 in 16,000 children each year, and these rare cases present significant challenges for patients, parents and doctors. Without proper treatment, it can be a life-threatening condition, but treating it can be difficult for doctors. That’s why the endocrine team at Children’s of Alabama is participating in an international pediatric, phase 2 trial called CAHtalyst to investigate a new nonsteroidal treatment.

The treatment, Crinecerfont, may improve adrenal hormone balance by tamping down excess androgen production. The drug has already shown efficacy and safety in adult CAH trials, and Gail J. Mick, MD, director of the Children’s endocrine newborn screening program, says she’s delighted that Children’s can participate in the study. “The families are excited about new CAH research because they want new therapeutic options,” she said. 

CAH, which can occur in multiple forms, affects the adrenal gland’s ability to produce cortisol, a hormone critical for life; and aldosterone, a hormone that regulates salt and water balance. The most common form of CAH occurs due to a deficiency of the adrenal enzyme 21-hydroxylase. Without this enzyme, affected individuals are at risk of a life-threatening adrenal crisis as well as adrenal androgen overproduction. 

Doctors in the Children’s of Alabama’s endocrine newborn screening program specialize in helping newborns with CAH, which is one of more than 30 disorders screened for at birth by Alabama’s newborn screening program. At Children’s, newborns who screen positive for CAH are immediately evaluated for emergency care and management. To help parents and children with CAH, the Children’s Division of Endocrinology and Diabetes provides comprehensive care to nearly 100 CAH patients per year.

Treatment involves infusions of steroids and fluids, followed by carefully titrated doses of cortisol and mineralocorticoids. It’s not always easy. “It’s a very delicate balance to mimic normal adrenal function with oral medications,” Mick said. Give too much glucocorticoid, and you can suppress growth and expose patients to adverse steroid side effects. Give too little, and the adrenal gland overproduces androgens, which can spur early puberty and excess growth as well as other complications.

The adrenal imbalance is even more complex when children are sick and can’t take their medications. In those cases, parents must administer injectable glucocorticoids and seek emergency medical care. For this reason, routine childhood illnesses put a tremendous strain on parents. 

Extra support is essential, Mick says. CAH is challenging to manage, given individual nuances in adrenal insufficiency and the impact of growth and puberty on medical management.  “We offer special teaching and support for the parents in those early years as far as understanding how and when to give steroids and hormones to prevent adrenal crisis,” said nurse practitioner Leslie Pitts MSN, AC-PNP, CDE. 

The CAH and endocrine newborn screening clinic also serves as an important resource for pediatric providers throughout the region. “Providers consult with us when they have abnormal newborn screens on their patients,” Pitts said. “They know we’re available to answer questions and concerns regarding CAH diagnosis and management.”

Pitts and Mick stress the key role that parents play in managing their child’s CAH. “Hats off to the families of children with CAH,” Mick said. “They are a motivated community who support one another, advocate for CAH research and treatment, and have even put together a highly popular ‘Camp Cortisol’ at Children’s Harbor at Lake Martin.” 

“These are really quite extraordinary families,” Pitts said. And they may have a brighter future thanks to clinical trials like CAHtalyst. Mick predicts that in the next couple of years, they’ll have access to many more treatment options that will make the condition easier to live with.