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olfactory placode to hypothalamus during embryonic life. These hamartomas

may be located at hypothalamus, tuber cinereum, or mammillary bodies. This

occurs as a result of gain-of-function mutation of KAL1 gene with ectopic loca-

tion of GnRH neurons, contrary to Kallmann syndrome which is due to loss-of-

function mutation of KAL1 gene. In addition, TGF-α, a member of epidermal

growth factor family, has also been implicated in its pathogenesis. Pallister–

Hall syndrome, an autosomal dominant disorder, due to mutation of the GLP3

gene, can also be associated with hypothalamic hamartoma (Fig. 6.5).

T Posterior region

Anterior regionuberal region

Lamina

Te rminalis

Optic

chiasm

Optic

nerve

Tuberal part

Distal part

Intermediate part

Adenohypophysis

Neurohypophysis

Mammillary

body

Tuber

cinereum

Median

eminence

Infundibular

stalk

Posterior lobe

of pituitary

Hypothalamus

Fig. 6.5 Pictorial representation of anatomy of hypothalamo–pituitary region with focus on mammil-
lary body, tuber cinereum, and hypothalamus; the common sites for the development of hamartoma

33. How does hypothalamic hamartoma result in precocious puberty?

Ectopically placed GnRH neurons (accessory hypothalamus) escape the inhibi-

tory neuroendocrine regulation as opposed to eutopically placed GnRH neu-

rons in the arcuate nucleus of hypothalamus. TGF-α, a member of epidermal

growth factor family, has also been implicated in increasing the GnRH secre-

tion from ectopic GnRH neurons. Further, hamartoma may exert mass effect on

surrounding eutopic hypothalamic GnRH neurons; thereby, resulting in prema-

ture reactivation of GnRH pulse generator (Fig. 6.6).

6 Precocious Puberty