Dr. Lee, in addition to your clinical practice, you do research on reproductive development and the effects of endocrine disruptors on growth and puberty. You’re a great resource for us because, as child psychiatrists, we have a lot of overlap between our practice and endocrinology, and often we’re not sure what to do. Our biggest issue is often the thyroid, because lithium suppresses it, and because thyroid disorders can cause psychiatric symptoms, right?Dr. Lee: Sometimes thyroid disorders do present with psychiatric symptoms. With Graves’ disease behavioral manifestations are very common, and can be the presenting symptoms. In children, these manifest as moodiness, irritability, and labile behavior. Therefore a child with hyperthyroidism may have mood swings, school performance issues, and difficulty concentrating that might be confused with ADHD.

If we have a child who is presenting with symptoms that we are concerned might be thyroid, what kind of history do we need to ask about?Dr. Lee: Let’s talk about the two forms of thyroid disease separately. For hypothyroidism, the symptoms are very subtle and maybe something as simple as constipation. Poor growth in height is often the major finding. Children don’t usually have excess weight gain or obesity, because although hypothyroidism slows metabolism, it also decreases appetite.

And hyperthyroidism?Dr. Lee: Hyperthyroidism tends to be more symptomatic. One of the behavioral signs is mood swings where they burst out crying, for example. Deterioration in school performance is a big complaint—inability to concentrate and distractibility. There is often a history of diarrhea, weight loss or difficulty gaining weight, and hyperphagia.

What about the contribution of a family history of thyroid disease? Is that something that we should ask about?Dr. Lee: Thyroid disease is so common that that you often hear that a distant relative has thyroid disease, and there definitely is a genetic component. I think the relevant point in child psychiatry is that, particularly for lithium, there is limited data suggesting that those patients who have a family history of thyroid disease or who have thyroid autoantibodies themselves have a higher risk of developing thyroid dysfunction with lithium therapy. So the relative risk is greater if you have a baseline genetic risk (Bochhetta A et al, J Clin Psychopharm 2001;21(6):594–598; Baethage C et al, J Psych Neurosci 2005;30(6):423–427).

So if we wanted to test for a thyroid problem, what tests do you recommend?Dr. Lee: For hypothyroidism, the most important is TSH, and that will measure if the pituitary gland senses that the body is not receiving enough thyroid hormone. To measure thyroid hormone levels, depending on your local lab, you can request either free T4 or total T4. For hypothyroidism, you don’t need to measure total T3, because that tends to be well preserved in the normal range even in children who are profoundly hypothyroid. However, for Graves’ disease, you do need to measure all three hormones—TSH, either free T4 or total T4, and total T3. There is hardly ever any need to measure free T3, because it is very short lived and serum concentrations are not meaningful.

We all know that lithium suppresses thyroid. What is the danger of that and over what time course?Dr. Lee: Lithium has direct effects on the thyroid gland. It causes suppression of thyroid hormone synthesis as well as thyroid hormone release. If someone is being started on lithium, I think it is important to obtain baseline labs, then to retest every six months, or sooner if the lithium dose is being increased significantly. This is because thyroid hormone has such a profound effect on children’s growth. If someone is on lithium for the long term, I would start thyroid hormone replacement as soon as the TSH becomes abnormal. Thyroid hormone is easy to give and the goal is to maintain a euthyroid status.

So would we be better off starting our own thyroid hormone or referring to an endocrinologist? What are the risks if we get it wrong? Dr. Lee: I think a referral to an endocrinologist for management is preferable. However, this depends on how comfortable individuals feel with management of thyroid dysfunction. If your patient is thyrotoxic, he or she won’t be comfortable, and you could have behavioral consequences of the elevated thyroid hormone. If you use a subtherapeutic dose, then the child is still symptomatic.

What do you usually start at for thyroid?Dr. Lee: Dosage starts at 12 mg/kg for an infant and changes through childhood. An adolescent receives approximately 1.5 mg/kg, so the dosing is both age and weight based.

Let me switch hormones. How cautious do we need to be about prolactin?Dr. Lee: If prolactin is only minimally elevated, and there has been no clinical effect on reproductive function, then you don’t needto address it. For example, a woman may have serum concentrations that are one to two times the normal range with absolutely normal cycling. If prolactin becomes more elevated, for example, greater than three times the normal level, you are likely to see some effects on reproductive function.

And does too much prolactin in a boy affect puberty?Dr. Lee: Yes. It can delay the progression of puberty.

While we are in the reproductive realm, can we talk a little bit about Depakote and how it may cause polycystic ovarian syndrome. What should we monitor for?Dr. Lee: What has been reported with valproate is irregular menstrual cycles. So it may be a good idea for adolescents who are already menstruating to keep track of the first and last days of their cycles when they are started on a drug such as valproate. This way you can identify abnormal menstrual patterns early. Other symptoms such as hirsutism or acne are due to elevated androgens.

Adolescents hate Depakote and most other mood stabilizers because they cause acne and weight gain. There is evidence that metformin can prevent weight gain associated with antipsychotic use. Do you think that metformin is appropriate to use in children?Dr. Lee: Unless you have clear insulin resistance, there is no good data showing metformin’s efficacy for weight loss in children on antipsychotics. For teenage girls with PCOS, there is some benefit (Ojaniemi M et al, Horm Res Paediatr 2010;74(5):372–375).

Is metformin risky to use?Dr. Lee: The major side effect is lactic acidosis, which has symptoms of nausea and weakness, but it is fairly rare. There are frequent acute side effects of GI distress and discomfort, which sometimes lead to kids stopping it soon after starting or being nonadherent to therapy.

Let’s talk about growth hormone. Do you know of any link between growth hormone deficiency and psychiatric symptoms?Dr. Lee: In general most of the kids that I follow on growth hormone do very well and don’t have psychiatric symptoms. However, there has been some association with growth hormone deficiency and depression (Okumura A et al, J Paediatr Child Health 2009;45(11):636–640).

Are there other endocrine problems that we should consider when we see a child with psychiatric symptoms that don’t quite fit the usual?Dr. Lee: Sometimes Cushing’s syndrome can cause a psychosis and is a very, very difficult endocrine condition to diagnose. Cushing’s in children is a diagnosis that often is made two or three years after initial symptoms. So that is one possibility if you have a child who has had excess weight gain and poor linear growth. Excessive glucocorticoids will compromise linear growth. If a child who is still growing has weight gain that isn’t accompanied by normal growth, as you’d typically see with obesity, then you should consider Cushing’s disease. Poor growth in height, combined with subtle hirsutism and muscle pseudohypertrophy should signal that it might be an endocrine cause.

Thank you, Dr. Lee.