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retardation of linear growth support the diagnosis of juvenile primary hypothy-
roidism. However, patients with panhypopituitarism may also have severe retarda-
tion of linear growth (due to combined defi ciency of GH and TSH), but lack
myxoedematous manifestations. This is because increased TSH is required for the
accumulation of glycosaminoglycans in interstitial tissues which is conspicuously
low in patients with secondary hypothyroidism. In addition, TSH-independent T 4
synthesis still continues in patients with secondary hypothyroidism; therefore, T 4
defi ciency is less severe in these patients as compared to patients with primary
hypothyroidism. The thyroid profi le in the index patient confi rmed the diagnosis
of juvenile primary hypothyroidism due to Hashimoto’s thyroiditis as she had very
high TSH and TPO antibody titer. Short stature and delayed puberty are the usual
presenting manifestations of juvenile primary hypothyroidism. Growth failure in
patients with juvenile hypothyroidism is a result of reduced GH secretion and
GH-mediated IGF1 generation as thyroxine is required for both GH secretion and
IGF1 generation. In addition, thyroid hormone has a direct effect on epiphyseal
growth plate and promotes differentiation of chondrocytes to hypertrophic chon-
drocytes which is required for growth of long bones. The mechanism of delayed
puberty in adolescents with hypothyroidism remains elusive; however, optimal
concentration of thyroxine may be required for initiation and maturation of GnRH
pulse generator activity and appropriate gonadal function. Further, elevated level
of prolactin in these patients may interfere with the development and maturation
of hypothalamo–pituitary–gonadal axis. Nevertheless, few patients with juvenile
hypothyroidism may present with gonadotropin-independent precocious puberty.
The index patient had one episode of vaginal bleed at the age of 12 years with
inappropriate development of secondary sexual characteristics (A − , P 1 , B 2 ) which
suggest aberrant production of estrogen by ovarian follicle resulting in estrogen
breakthrough bleed. This is usually seen in children with gonadotropin-indepen-
dent precocious puberty where the dichotomy between the breast development and
menarche can be observed as slow, and progressive priming with estrogen is
required for the breast development as opposed to the uterus which may respond
to sudden rise in estrogen. However, in the index case, this should not be termed
gonadotropin- independent precocious puberty, as she had menarche at the age of
12 years. The presence of multicystic ovaries in our patient can be explained by
increased TRH- mediated FSH secretion and decreased FSH clearance, thereby
resulting in increased FSH, and consequent follicular cyst formation. In addition,
high circulating levels of TSH also act on FSH receptor on ovarian follicle due to
specifi city-spillover, resulting in follicular growth and development. Presence of
thyro-lactotrope hyperplasia in our patient is a manifestation of long-standing,
untreated, severe primary hypothyroidism which occurs as a result of TRH-
mediated stimulation of thyro- lactotropes due to decreased negative feedback by
low levels of circulating thyroxine. Children and adolescents with long-standing,
3 Thyroid Disorders in Children