Pediatric Endocrinology

Seema Kumar, M.D., Pediatric Endocrinology and Metabolism, Mayo Clinic: One in three children are overweight or obese in the United States right now.

Vivien Williams: That says Mayo Clinic pediatric endocrinologist Dr. Seema Kumar puts kids at risk of adult diseases such as high blood pressure, high cholesterol and diabetes. A study in Annals of Internal Medicine reports it's not just being overweight that's the problem.

Dr. Kumar: What they found is that lower aerobic capacity and low muscle strength were associated with increased risk for type 2 diabetes in adulthood.

Vivien Williams: Even if study participants, 18-year-old males, were of average weight. So what does this tell us?

Dr. Kumar: It does suggest that improvement of muscle strength and improvement of aerobic capacity in our teenagers might be one way we can develop that we can prevent type 2 diabetes from developing in adulthood.

Vivien Williams: Physical activity strengthens bones, helps maintain weight and boost confidence plus it lowers stress, anxiety and depression.

Dr. Kumar: Children who are physically active tend to do better in school.

Vivien Williams: Any fun activity that gets kids moving is good for their health.

For the Mayo Clinic News Network, I'm Vivien Williams.

Seema Kumar, M.D., Chair, Division of Pediatric Endocrinology and Metabolism, Mayo Clinic: Hi. I'm Dr. Seema Kumar from the Mayo Clinic Children's Center in Rochester, Minnesota. I am the medical director of our pediatric weight management program. Our program is truly multi-disciplinary and offers services to children that are obese or have obesity-related complications. As we all know, childhood obesity is a significant health problem facing a country right now. Eighteen percent of children between the ages of 6 and 11 are obese and another twenty-one percent of adolescents between the ages of 12 and 19 are obese. We have put together a multidisciplinary team that includes a pediatric bariatrician with expertise in obesity management, psychologists, nutritionist and physical therapy. We offer a variety of services including psychological services, nutrition counseling, physical activity support and, in a selected number of children, medications and bariatric surgery. Our treatment is multidisciplinary, however comprehensive and individualized. We try to determine what is contributing to weight gaining your child. Our program is successful and we look forward to seeing you.

Vivien Williams: Weight-loss surgery helps many obese adults lose weight and improve their health but is it right for kids? Mayo Clinic endocrinologist, Dr. Seema Kumar says in some cases, yes.

Seema Kumar, M.D., Pediatric Endocrinology and Metabolism, Mayo Clinic: Severely obese adolescents that have health complications that are related to their weight.

Vivien Williams: Complications such as type 2 diabetes, sleep apnea, decreased mobility, joint pain and high cholesterol. Like any surgery, weight-loss operations are not risk-free.

Dr. Kumar: We want to offer the surgery only to teenagers that have really hard tried hard with medical measures aimed at cutting down caloric intake and increasing physical activity before we proceed with a surgical procedure.

Vivien Williams: If the decision is reached to have surgery, there are two options: the Roux-en-Y gastric bypass, which reduces the size of your stomach and the amount of food to absorb, and sleeve gastrectomy, which reduces your stomach to the size of a man's thumb. And, again, Dr. Kumar says surgery is not the answer for all obese kids but for some it can mean improvement in health and self-esteem and an improved quality of life.

For the Mayo Clinic News Network, I'm Vivien Williams.

Siobhan T. Pittock, M.B., B.Ch., Pediatric Endocrinology, Mayo Clinic: Hello, I'm Siobhan Pittock. I'm a pediatric endocrinologist at Mayo Clinic Children's Center and today I'd like to talk to you about hypothyroidism.

To have a better understanding of hypothyroidism, I think it's important that you understand what the thyroid gland does and how it's regulated. So thyroid gland is a gland that sits here in the neck, in front of the airway, and it's shaped like a butterfly. It makes a hormone called thyroid hormone or T4. T4 is what we call it for blood tests and the function of thyroid hormone or T4 is to regulate the speed of the cells of that the body is working. So if there's too much T4, that we call that hyperthyroidism. Everything in the body is sped up, so you have lots of energy. You have a shake potentially. You have fast heart rate. You have a lot of sweating. You lose weight easily and it's not very healthy.

On the other hand if you have not enough thyroid hormone, we call that hypothyroidism. Everything is slowed down and when things are slowed down, you feel very tired. Your heart rate is slow. You may feel colder than you should feel, want to wear extra jackets in the summertime. You often have dry skin or dry hair and you may have constipation. So it's important that the body really functions at the right speed, neither too fast nor too slow, and because that is such an important function, the body has the thyroid regulated not just by itself but by a higher body called the pituitary gland.

The pituitary gland sits in the brain, in the center between the eyes, just behind the eyes and in the center, and the pituitary gland regulates lots of glands around the body not just the thyroid gland. How it regulates things is that the pituitary gland is what tells the thyroid gland what to do and how it does this is by secreting a hormone called thyroid stimulating hormone or TSH for short. Under the influence of this TSH, the thyroid gland makes thyroid hormone. The pituitary gland is constantly aware of how much thyroid hormone there is in the body, and we call that a feedback loop. So the pituitary gland knows how much stimulation the thyroid gland needs by recognizing how much thyroid hormone there is in the system. So what happens in hypothyroidism, it can be caused by two separate events. Either your thyroid gland gets sick and that's the most common situation by far. The thyroid gland gets sick we call that primary hypothyroidism. If the thyroid gland is sick, it doesn't make enough thyroid hormone so we get a low T4 level. Because we have a low T4 level, the pituitary gland recognizes that and says, "Hey thyroid, wake up make more hormone" and increases the amount of stimulation it's giving. So in primary hypothyroidism, we have a low T4 because of a sick thyroid gland which results in the pituitary gland shouting louder at the thyroid and increasing the TSH, and that can be confusing for people because we talk about hypothyroidism, people know that it's underactive, and yet we talk about a high blood test. This is why. It's because it's a high TSH.

The second situation where we can get hypothyroidism is if your pituitary gland itself is sick. If your pituitary gland itself is sick, it isn't going to make the TSH, and so even a healthy thyroid gland can't respond because it's not being told what to do and so you have a low T4 level. That's much less common. We call that secondary hypothyroidism.

Whether you have primary hypothyroidism or secondary hypothyroidism, the treatment is the same. What we do as physicians as providers is we give you the replacement. This is what you need the T4 and we have a really good chemical substitute for that. It's called levothyroxine and we give you the levothyroxine and it's a once daily pill and then we figure out how you're doing based on your symptoms but also based on measuring these two blood tests. We can tell that very easily if we have given you the right amount of medication by checking those blood tests. It doesn't take very frequent monitoring. We check it more frequently in children because they're growing and their doses need to be adjusted more frequently, and then in adulthood, generally people only need to have their thyroid blood tests checked once a year. For the most part, primary care providers, whether they be pediatricians or family doctors, are comfortable looking after hypothyroidism once the initial diagnosis has been made and once people have started on therapy.

Siobhan T. Pittock, M.B., B.Ch., Pediatric Endocrinology, Mayo Clinic: Hello, I'm Siobhan Pittock, pediatric endocrinologist at Mayo Clinic Children's Center, and today I'd like to talk about thyroid cancer in children. Cancer is a scary word. It's a scary word for everybody but thyroid cancer doesn't need to be as scary as other cancers if treated appropriately. Thyroid cancer is typically looked after by endocrinologists and surgeons rather than by the usual cancer doctors and the treatment for thyroid cancer is really quite different from other treatments of cancers.

How do you know or how would you suspect thyroid cancer? The thyroid gland sits here in the neck. It's a gland that produces thyroid hormone and the majority of thyroid cancers present with a lump either within the thyroid gland itself or in one of the lymph nodes in the neck. So it's essentially a lump in the neck is how most thyroid cancers present. Lumps in the neck are common in children. They occur because of ear infections or sore throats and many, many, many lumps in the neck are entirely normal and they're not in the least concerning. However, if lumps in the neck are very persistent, if they're large, if they are associated with a change in the voice, if they go on for a very long time, they really should be evaluated by your primary care provider who can then decide if your child's lump in the neck is something that's more worrisome than the usual type of lymphadenopathy.

If we are concerned about thyroid cancer, the best test to start figuring out if this is something we should be concerned about is an ultrasound of the neck. It should be done by someone who has a lot of experience. Cancers in the neck look different from regular lymph nodes. Lumps within the thyroid gland themselves, we call those nodules, are very, very common in adults. Many, many adults have what we call benign or harmless nodules in the thyroid gland by the time they are 50 or 60 years of age. Nodules in children are not quite so common so when we see a nodule in the thyroid gland, we have a low threshold for testing that further. The next step, if we see a nodule in the thyroid gland or if we see a lymph node on ultrasound that looks suspicious, is to do what we call a fine needle biopsy, which basically consists of a needle--just the size of a needle that we would take blood from, that size needle--passed into the area, the concerning area either in the thyroid gland or in the lymph node, and drawing out some cells, putting them on a slide and seeing if there is anything concerning looking about them. Teenagers often do this without any anesthetic. Younger children sometimes need a little bit of anesthetic.

If thyroid cancer is diagnosed, the treatment is essentially surgical to remove the thyroid gland. It's very important to work with a surgeon who is very competent in removing thyroid glands. There are a lot of very important structures in the neck which can be damaged if an inexperienced surgeon takes out the thyroid gland, and then sometimes after the surgery, some additional therapy is needed like radioactive iodine. Therapy is not necessary for every patient but it's necessary for some patients who have more extensive disease and the mainstay then of treatment is thyroid hormone replacement, so the same thyroid hormone replacement that an adult or a child who has an underactive thyroid has. It's not chemotherapy. It's just a hormone. We place patients on that for life and then follow-up is accomplished by checking blood tests, by your endocrinologist having regular physical exams--feeling the neck, and also regular ultrasound exams of the neck. There are some newer modalities of treatment that we rarely have to resort to, things like ethanol ablation, and those are also available at specialized centers.

The thyroid cancer is a cancer. It does not need to be as scary as other types of cancers but it is important that if thyroid cancer is diagnosed or if there is concern for thyroid cancer, that appropriate testing happens so the treatment can occur as early in the course as possible.

Siobhan T. Pittock, M.B., B.Ch., Pediatric Endocrinology, Mayo Clinic: Hi, I'm Siobhan Pittock and I'm a pediatric endocrinologist at Mayo Clinic. Today I'd like to talk to you about Prader-Willi syndrome which is a rare genetic disorder that occurs in about one in 30,000 live births. It's caused by a lack of expression of patternly derived genes on Chromosome 15q11. The condition is characterized by very poor tone but with floppy babies who feed poorly and later development of obesity due to excessive appetite and short stature and poor gonadal function. These children require care from multiple subspecialists and the pediatric endocrinologist really plays a central part in their plan of care throughout childhood and adolescence. This is because the condition, unfortunately, is associated with several endocrine concerns. These children are short. If left untreated, boys of Prader-Willi syndrome grow to a mean final adult age of five foot, four and girls grow to about four foot, 11. Their short stature is due to a combination of growth hormone deficiency and also because of hypogonadism, they don't get that normal puberty growth spurt.

Prader-Willi syndrome is an FDA-approved indication for treatment with growth hormone therapy and children typically respond well. Initially the indication was just for short stature associated with Prader-Willi syndrome, but since it's been used, we are finding that the benefits of growth hormone treatment go beyond just improving final adult height. In children, they improve muscle tone and so improve motor development. They have an improvement in bone mineral density accrual and they also have improvement in lean body mass as it compares to fat mass. Some short-term studies in adults with growth hormone deficiency also show that they benefit lean body mass and also muscle tone.

Another big endocrine disorder in Prader-Willi syndrome is hypogonadism. Hypogonadism effects both boys and girls with Prader-Willi syndrome. It's a central cause of hypogonadism for both sexes but boys also have some primary testicular dysfunction. So these children often don't go into puberty at a normal time and we do our best to mimic normal adolescence through gradual introduction of sex steroids. Testosterone is given either transdermally or intramuscularly to boys and estrogen is given either orally or transdermally to girls. Often times, in adulthood, these patients will remain hypogonadal and will require treatment also. The estrogen level in girls is often not as low as we would expect and that's due to their obesity. They have amortization of androgens and so the estrogen levels are not as low as would be expected in other situations of hypogonadism. From the standpoint of fertility, fertility has been described in girls with Prader-Willi syndrome but there are no reports of paternity in males.

Another major clinical problem for patients with Prader-Willi syndrome is obesity. In fact these children in infancy tend to be thin because of poor feeding related to their poor tone, but in toddlerhood on into childhood, their tone improves to the point that they can eat well and they develop markedly increased appetite. If left unchecked, children with Prader-Willi syndrome, on average consume about three times the calories of their peers. The obesity is not only due, however, to their increased caloric intake, they also have poor muscle tone which results in decreased energy expenditure. Unfortunately, the obesity in Prader-Willi syndrome has been very difficult to treat. There have been multiple drug trials which have not really been very useful. The surgery has been tried in a limited number of patients and has again not found very useful mainly because, despite the surgery, the hyperphagia or insatiable appetite persists postoperatively. In fact surgical experience with Prader-Willi syndrome also shows a very high rate of complications in these patients really precluding its use in general.

One of the complications which is seen relatively frequently in patients with Prader-Willi syndrome after bariatric surgery is gastric perforation simply due to continued insatiable appetite, continued eating, and perforation of their surgical site. So really the mainstay of obesity management is diet and exercise and some very intensive dietary intervention programs have been found to be useful.

Another medical problem facing these patients is osteoporosis. The osteoporosis again can occur for many reasons and these children have growth hormone deficiency which is known to increase the risk of osteoporosis. They're also hypogonadal, another risk for osteoporosis. They also have poor muscle tone, yet another risk factor for osteoporosis. So in childhood, what we try and do is treat the growth hormone deficiency, if present, to treat the hypogonadism, if present, and encourage weight-bearing exercise as the patients can. We also feel that appropriate calcium and vitamin D intake is important just as it is for any other adolescent. In adulthood, osteoporosis needs to be screened for, and if bone mineral density is lower than expected or is falling, really providers should be considering either growth hormone treatment, if the patient is growth hormone deficient, or treatment of hypogonadism.

After growth hormone was in use for several years, there were multiple case reports of children with Prader-Willi syndrome who were on growth hormone treatment dying suddenly, usually in the context of a mild upper respiratory illness. This was very concerning. Obviously there was a worry that growth hormone was increasing the risk of sudden death. In fact no data was available up to this point rates of sudden death syndrome and it does appear from data gathered subsequently that these children are at increased risk of sudden death. Looking for potential causes of sudden death, sleep studies have been performed and these children do have very high rates of apnea and hypopnea and these apneas and hypopneas are both central and obstructive. When studies have been done both before growth hormone treatment and subsequent to growth hormone treatment, it appears that growth hormone does not cause any worsening in sleep disorder breathing. Because of this very high rate of sleep disorder breathing in Prader-Willi syndrome, we feel that it's very important that these children are evaluated by sleep specialists and many of our patients with Prader-Willi syndrome actually benefit from either CPAP or BiPAP.

In the quest to discover potential causes of sudden death in Prader-Willi syndrome, the concern has also arisen that these children may have adrenal insufficiency knowing that they do have other hypothalamic problems, and several small studies do show that there is a high rate of failure of the metyrapone test suggesting that they do have some degree of adrenal insufficiency. Larger studies have yet to be performed but certainly it seems like a low-risk treatment with potential great benefits so I advocate a treatment of these children with Prader-Willi syndrome with stress-dosage steroids during intercurrent illness.

While growth hormone was initially FDA-approved for treatment of short stature in Prader-Willi syndrome, more recent studies since we've been using it have shown that the benefits of growth hormone exceed just benefits as they relate to stature. In children, they also improve muscle tone and so improve motor development in young children. They also improve bone density and they improve lean body mass, improving the lean body-to-fat ratio. Several short-term studies and adults with Prader-Willi who have growth hormone deficiency also suggest improvement in lean body mass and improvement in bone mineral density. So the growth hormone has become a very important form of treatment for patients with Prader-Willi syndrome not only patients who are concerned about final adult height, but potentially lots of other very helpful areas too.

In summary, Prader-Willi syndrome is a complicated medical problem. There are many endocrine problems associated with the disorder and these children need to follow with pediatric endocrinologists through childhood along with multiple others subspecialists.