PEDBASE.org - The Pediatric Database - Detailed information of HYPOTHALAMIC HAMARTOMAS

HYPOTHALAMIC HAMARTOMAS

DEFINITION:

A congenital disorder of the central nervous system (CNS) characterized by gelastic seizures and true precocious puberty.

EPIDEMIOLOGY:

incidence: most common known etiologic cause of central precocious puberty:
- 16% of females with true precocious puberty
- 50% of males with true precocious puberty
age of onset:
- childhood (as early as 1 year of age)
risk factors:
- Lawrence-Moon-Biedl Syndrome

PATHOGENESIS:

1. Background

due to the premature awakening of the hypothalamic-pituitary-gonadal axis by direct compression of the hamartoma on the hypothalamus and/or the hamartoma may function as an autonomous neuroendocrine unit or as an accessory hypothalamus that secretes
GnRH
considered a true or central (complete) precocious puberty:
- gonadotropin-dependent
- development of all secondary sexual characteristics (isosexual)
- increased size and activity of gonads
the concurrence of gelastic (laughing) seizures, hypothalamic hamartomas, and true precocious puperty may constitute a specific epileptic syndrome

2. Pathology

considered to be a congenital malformation involving the CNS where neural tissue resembling nerve cells of the tuber cinereum are ectopically located
hamartomas are composed of heterotopic and hyperplastic tissue including neurons, fibres, and glia
hamartomas are small, static or slow growing and usually do not grow or involve surrounding structures
occasionally connected to the tuber cinereum by a stalk
cells of the hamartoma may contain GnRH, ACTH, or other hypothalamic peptides

CLINICAL FEATURES:

1. Endocrine Manifestations

1. Complete Precocious Puberty

development of all secondary sexual characteristics
- isosexual
increased size and activity of the gonads

2. Hypothalamic Manifestations

adipsia
cachexia
diabetes insipidus
obesity
hyperthermia

2. Neurological Manifestations

1. Gelastic Seizures

usually initial manifestation
stereotypic laughter:
- brief, uncontrolled, and unprovoked
may progress from gelastic seizures to complex partial seizures or generalized tonic-clonic seizures

2. Others

mental retardation
progressive impairment of cognitive function
neuropsychological deterioration
behavioural disorders - aggressive outbursts

INVESTIGATIONS:

1. Imaging Studies

1. Skeletal X-Rays

advanced bone age

2. MRI/CT

well defined mass in the inferior aspect of hypothalamus
MRI - isointensity (T1-weighted) and hyperintensity (T2-weighted) images
CT - isodense, nonenhancing, noninvasive spherical mass

3. Pelvic Ultrasound

enlargement of the uterus
multicystic appearance of ovaries

2. Serum

elevated testosterone (M) and estradiol (F)
elevated FSH and LH on serial determinations
pulsatile secretion of FSH and LH
LHRH stimulation test
- brief LH response as in puberty
- best test for evidence of central precocious puberty