Hypothyroidism, Delayed Puberty, Mental Retardation

Question

Thank you very much for taking my questions. I have recently seen a 15 yo boy with severe hypothyroidism (TSH 506 uIU/ml and total T4 of 1.05 ug/dl). He also has significant short stature, being 4 feet 5 inches. He is Tanner 2 and has a low testosterone of 64. Unfortunately for him, his epiphysis are 90% closed by his bone age. I am concerned that if I treat him with thyroid replacement alone, he is going to go through an accelerated puberty, and will not end up with an acceptable height. So, we are contemplating starting him on a GnRH analog (leuprolide acetate) to shut down his puberty and supplement him with growth hormone at 0.37 mg/kg/week to improve his growth potential. Since this requires a lot of work and a lot of financial resources, I was wondering if I could ask you a few questions...

1. What is the mechanism for pubertal delay in boys with severe hypothyroidism (ie why do we see precocious puberty in girls with severe primary hypothyroidism, but see the opposite in boys)?

2. Are there any other studies (other than the one that I attached) that treated peripubertal boys with bone age delay in hypothyroidism with a GnRH analog and/or growth hormone? Do you think this is a reasonable approach?

3. This boy is also mildly retarded. Are there any syndromes that have mental retardation, severe short stature, hypogonadotropic hypogonadism and primary hypothyroidism? I thought of Laurence- Moon- Biedl syndrome, but this boy did not have polydactaly, he has no kidney or vision problems, so I think this particular diagnosis is unlikely for him.

I eagerly await your response. Thanks so much!

Alexandra L. Haagensen, MD, Children's Hospital Boston

Response

#1.--Thyroid hormone is essential for bone growth, and, therefore, bone age advancement. It appears that th CNS maturation that is necessary for puberty has the same determinants as those necessary for bone age maturation.; therefore, any disorder associated with delayed BA is associated with delayed puberty. In both sexes. The sex precocity seen in a tiny minority of hypothyroid children is poorly understood (see my chapter on female puberty in Sperling's textbook of pediatric endocrinology).

#2.--You can search PubMed as well as I for the latest. But this is a standard approach.

#3.--I wouldn't worry about DD unless he remains hypogonadotropic, which I presume he is (although polyclonal RIA's for LH and FSH may give inaccurate results in hypothyroidism) after thyroid replacement.

Robert Rosenfield,MFD, Pediatrics, Univ of Chicago 10 Nov 2004