COMMENTARY

Updates From ENDO 2017: Part 2

Vitamin D in Kids; Pyrethroids; Levothyroxine

Charles P. Vega, MD; Bradley D. Anawalt, MD

Disclosures

August 11, 2017

Charles P. Vega, MD: Hello. I'm Dr Charles Vega. Welcome to Critical Issues in Endocrinology. I'm a clinical professor of family medicine at the University of California at Irvine. I'm delighted once again to be joined by Dr Bradley Anawalt, who is professor of medicine and an endocrinology specialist at the University of Washington. We have been talking about the critical issues that were presented at the ENDO 2017 conference, and we are going to jump right back in. We are going to cover three interesting studies briefly that may have a clinical impact in primary care.

Vitamin D in Kids

Our first subject for review is one of the most vexing issues for me in my primary care practice but in a new framework—it's about vitamin D in kids.

Vitamin D deficiency, as you know, has been associated with a broad range of negative health outcomes among adults. The protective effects of vitamin D supplements against important health outcomes, such as cardiovascular disease and cancer, are either minimal or they're largely unproven. Low levels of vitamin D are associated with obesity[1] and dyslipidemia[2] among adults.

Censani and colleagues[3] did something interesting. They assessed the potential association between vitamin D levels and serum lipids among children. They focused on 178 children who either had overweight or obesity. A really high percentage of that cohort, 55%, met the criteria for vitamin D deficiency. Vitamin D deficiency was associated with negative effects on serum triglycerides, LDL levels, as well as the total- to HDL cholesterol ratio.

Brad, I'm going to pitch it to you: What do you think are the clinical implications of this research? The average age of these kids was 12 years old. Is this really going to change the instructions we provide to overweight and obese children at this age or change our lab testing and other things we might do?

Bradley D. Anawalt, MD: I'm not sure that we need to change the diagnostic approach to boys and girls who are 11 and 13 years old. We do not need to order serum 25-hydroxy vitamin D measurements on all those kids. The study is clinically valuable because it reinforces the value of ensuring that adolescents consume enough vitamin D in their diet. These days there are a lot of teens and preteens avoiding milk and dairy products because they have heard that the high fat content may lead to obesity. The contrary appears to be true; higher consumption of milk, yogurt, and dairy products is associated with lower rates of obesity, lower body fat, and higher cardiopulmonary fitness.[4,5]

We need to ensure that adolescents have an adequate intake of dairy products that are rich in vitamin D. One of the implications of this study is not so much that we need to do more diagnostic evaluation for vitamin D deficiency, but we need to recognize that our teenagers are such that they prefer sodas and fruit drinks over milk. They should be encouraged to drink milk (or water) instead of sodas and fruit drinks.

Dr Vega: Right, and the sugared and sweetened beverages are a scary alternative. I cannot leave the subject of vitamin D, of course, without getting your take on vitamin D supplements overall, whether you are talking about kids or adults. What are your thoughts?

Dr Anawalt: It's a good time to be a maker of vitamin D. It makes it very easy to peddle the product when everywhere you turn you see another article suggesting that vitamin D deficiency is rampant and that vitamin D will cure all that ails you.

We need to focus on diet. People need to be sure that they have a healthy diet. Some people have bona fide vitamin D deficiency with very low levels of vitamin D. Bariatric surgery increases the risk for vitamin D deficiency. Conditions such as celiac sprue can also lead to vitamin D deficiency. Those individuals benefit from vitamin D supplements.

In general, particularly for adolescents, there is no need for supplemental vitamin D.

In general, particularly for adolescents, there is no need for supplemental vitamin D. If they take vitamin D supplements or a multivitamin with vitamin D, that is fine. But we often say that what they are doing is just really making expensive urine. They are excreting the water-soluble vitamins (although vitamin D is fat soluble). Vitamin supplements are really unnecessary for most of these adolescents.

Pyrethroids and Puberty

Dr Vega: Another interesting study <<coder please link underlined to /viewarticle/878085>> that came out of the 2017 ENDO Conference, focused on the effects of exposure to pesticides on the timing of puberty among boys.

Interestingly, there is a worldwide trend towards earlier puberty among both girls and boys. Environmental factors might be playing a role in this change.

Research in China analyzed 463 boys for a metabolite of what is called pyrethroid pesticides.[6] They found that moderate increases in urinary metabolite levels of this pesticide were associated with increased luteinizing hormone and follicle-stimulating hormone levels. Elevated metabolite levels were also associated with a twofold increase in a rate of early puberty.

A couple of notes about the study. First of all, pyrethroids are very commonly used pesticides worldwide. They are used in the United States. Overall, they comprise about 30% of pesticides used around the world. Moreover, early puberty may be associated with some harm, mostly an increased risk for obesity.[7] However, a review of limited research suggested that early puberty may actually reduce the risk for hypertension and hyperglycemia versus a more normal average time.[8]

Turning it to you Brad, any comment on the potential mechanisms between these environmental factors and the risk for early puberty?

Dr Anawalt: Early puberty appears to be much more common in 2017 than it was 30, 40 years ago. The most important link to early puberty is related to obesity which clearly accelerates the onset of puberty. Importantly, we are now becoming aware of the fact that there appear to be compounds in the environment that have estrogen-like effects. Metabolites from pesticides are one example of this. There may be other metabolites that act as what we call endocrine disruptors, which can cause endocrine effects even at very low levels.

It's important for us to be aware of how we are poisoning the environment. There are health implications for that. If possible, I would avoid having children exposed to pesticides. I would not use them around the home. Children should avoid being around areas where pesticides have been applied. I cannot say that it's clearly a cause of early puberty, but evidence suggests that it might be.

None of us parents need children are who going through puberty earlier than necessary!

It is better to be prudent and avoid the exposure than to risk the possibility that you are going to have early onset of puberty. None of us parents need children are who going through puberty earlier than necessary!

Dr Vega: That's true. Hold off as long as we can.

Taking Levothyroxine With Milk

Dr Vega: Let's wrap up with something that is very simple and very practical. Millions of adults take levothyroxine on a regular basis. They probably do not pay much attention as to how they take it.

Chon and colleagues[9] presented data at the ENDO Conference from a small crossover study. They evaluated how taking levothyroxine with milk affects T4 concentrations among adults with normal thyroid function. They found that taking levothyroxine with milk significantly reduced T4 concentrations 6 hours after dosing.

This study really reinforced the recommendation to take levothyroxine on an empty stomach. I'll admit that this is not something I have always emphasized to my patients. I really have to do a better job of that.

What about the patient who cannot tolerate medications on an empty stomach? The author suggests that taking levothyroxine with the same diet each day is a workable alternative. Do you feel that is true? Do you have any particular advice for us in primary care who, I'm sure, prescribe the vast majority of levothyroxine?

Dr Anawalt: Yes, primary care providers are the primary prescribers of levothyroxine for most patients with hypothyroidism. On a practical note, I try to encourage my patients to take levothyroxine on an empty stomach because there are so many substances that interfere with the absorption.

It's often really hard for people to take a pill on an empty stomach 1 hour before they eat. If you are like me, I like to have a cup of coffee in the morning. Some of us like to adulterate our coffee with cream or milk which can interfere with the absorption of levothyroxine. Now these hypothyroid patients have to wake up an hour early before having their coffee to take their levothyroxine.

One practical thing you have already alluded to is, if a patient can take the levothyroxine at about the same time a day and in the same time relationship with a meal, then they may be able to get away with taking a levothyroxine with a little something in their stomach. If they maintain a normal TSH and are clinically and biochemically euthyroid on that particular regimen (meaning that they can maintain this clinically euthyroid state while taking levothyroxine on a full belly), I think that's okay.

[M]any patients can get away with taking [levothyroxine] on a full belly or with a little something in their stomach.

My patients, though, often have fluctuating TSH levels. Many primary care providers will see patients who have a TSH that's slightly low; then the patients return to clinic and the TSH is a little high (say, 10-15 mIU/L). In this clinical scenario, it is important to try to get the patient to take the levothyroxine on an empty stomach. Still, many patients can get away with taking it on a full belly or with a little something in their stomach.

Dr Vega: Patients generally want to keep their levels euthyroid—if nothing else, for very practical reasons. It results in fewer visits, less going to the lab, fewer blood draws. Taking the medication regularly at the same time of day, particularly on an empty stomach, can really help. It's definitely something to think about. When it comes to levothyroxine, we should not just ask, "Are you taking the medication?" but also "How are you taking the medication?"

Dr Anawalt: Many patients are going to be motivated by the fact that they want to feel well. They correctly identify that abnormal thyroid hormone levels in the blood might contribute to a decreased sense of well-being. That is often a big motivator for them to try to adhere to the advice to take the levothyroxine at the same time of day and ideally on an empty stomach.

Dr Vega: Brad, I love your highly practical yet strongly intellectual approach to these problems. I think if I ever have an endocrine issue, I'm going to fly up and try to see you. I really appreciate you taking the time to talk to me today.

Dr Anawalt: You would be welcome in Seattle anytime. We'll have a glass of milk to celebrate.

Dr Vega: That's right, yes. Then we'll take our levothyroxine.

That's it for Critical Issues today. Thanks very much for tuning in, and look for us next time.

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