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Endocrinology
Advances in the Diagnosis, Treatment and Molecular Genetics of
Pituitary Adenomas in Childhood
a report by
Margaret F Keil
1,2
and Constantine A Stratakis
1,2,3
1. Office of the Chief, Programme on Developmental Endocrinology and Genetics (PDEGEN); 2. Inter-institute Paediatric Endocrinology Training Programme,
National Institutes of Health (NIH); 3. Section on Endocrinology and Genetics (SEGEN), PDEGEN, National Institute of Child Health and Human Development (NICHD)
The pituitary gland has an essential role in the maintenance of menin, PRKAR1A, AIP and p27 (CDKN1B) mutations.
6,18–23
In late childhood,
homeostasis, normal growth and reproductive function. Although adolescence and adulthood, somato- and/or mammotropinomas are
pituitary tumours are rare in childhood and adolescence and are typically significantly more frequent than corticotropinomas.
24
histologically benign, significant morbidity may result due to their
location, mass effect and/or interference with normal pituitary hormone Corticotropinomas
functions.
1
The early identification of pituitary tumours in children is The most common type of pituitary adenoma in pre-pubescent children
necessary to avoid serious adverse effects on both physiological and is corticotropinomas; however, their frequency decreases during
cognitive outcomes as a result of pituitary hormone dysregulation during puberty and in late adolescence, when prolactinomas become more
the critical periods of growth in childhood and adolescence. In this article prevalent. The cumulative incidence of corticotropinomas (Cushing’s
we review recent findings on the diagnosis, evaluation, treatment and disease) in children does not exceed one-tenth of the annual incidence
molecular genetics of pituitary adenomas presenting in childhood. of two to five new cases of Cushing’s syndrome per million people per
year.
7,24,25
Typically, corticotroph adenomas are significantly smaller
Pituitary Adenomas than other types of pituitary tumours (usually 3mm or less). Rarely, they
Due to the rarity of pituitary tumours in children and adolescents, accurate can be exophytic, growing into the subarachnoid space, or invade the
information regarding the prevalence and incidence of these tumours is cavernous sinus or wall. In addition, there are case reports of tumours
lacking. Data from autopsy studies (primarily concerned with adults) show that originate in the posterior lobe.
26,27
that pituitary adenomas develop in approximately 17–25% of the
population.
1,2
In addition, studies using radiological imaging report a similar Clinical Presentation, Evaluation and Treatment
incidence of pituitary gland lesions in the general population (up to 20%) In children, the most characteristic clinical presentation of Cushing’s
with no gender predilection.
3
Approximately 3.5–8.5% of all pituitary disease is significant weight gain concomitant with a decrease in linear
tumours are diagnosed before 20 years of age and they account for height velocity. Other typical symptoms include headaches, delayed
approximately 3% of all diagnosed intracranial tumours in childhood.
4–8
pubertal development and amenorrhoea (despite significant virilisation
and hirsuitism), hypertension and glucose intolerance. Children and
The majority of pituitary tumours are sporadic; however, in children more younger adolescents usually do not report problems with sleep
commonly than in adults they can be part of a genetic condition disruption, muscle weakness or memory or cognition compared with
predisposing the sufferer to pituitary and other tumours. Even sporadic older adolescents and adults with Cushing’s disease.
28
tumours may harbour significant genetic abnormalities. Most
pituitary tumours are monoclonal lesions and modifications in expression of
Margaret F Keil is a Paediatric Nurse Practitioner and Director
various oncogenes or tumour suppressor genes, including GNAS, pituitary
of Clinical Services for the Paediatric Endocrinology
tumour transforming gene (PTTG), HMGA2 and FGFR-4, have been
Inter-institute Training at the National Institute of Child
identified.
9,10
Pituitary tumour development and cell growth are probably
Health and Human Development (NICHD). She is a doctoral
candidate at the Uniformed Services University of the Health
influenced by both pituitary and hypothalamic factors.
1,11,12
Other factors Sciences in Bethesda. Her research interests include pituitary
and genetic events seem to be implicated in pituitary cell clonal
and adrenal disorders and biobehavioural effects of early life
stress. Ms Keil received her nursing and master’s
expansion, and oncogene activation is necessary to propagate tumour
degree/nurse practitioner training at Georgetown University
growth.
9,13
An example of this secondary phenomenon is the widespread and the University of Colorado, respectively.
presence of GNAS-activating mutations in sporadic growth hormone
E: keilm@mail.nih.gov
(GH)-secreting pituitary tumours (in up to 40% of all such lesions).
14
Constantine A Stratakis is Chief of the Heritable Disorders
Branch and Director of the Paediatric Endocrinology
Adrenal corticotrophic hormone (ACTH)-producing adenomas are the most
Programme at the National Institute of Child Health and
common functional pituitary tumours in early childhood, although they are Human Development (NICHD). Dr Stratakis identified genes
still considerably rare. No genetic defects have been consistently associated
for Carney complex and other endocrine disorders. He was
Editor in Chief of the Journal of Endocrine Genetics and
with childhood corticotropinomas, which only rarely occur in the familial
serves on the Editorial Boards of many journals. Dr Stratakis
setting, and even then occur most commonly in the context of multiple
completed his residency and fellowships in paediatrics,
endocrine neoplasia type 1 (MEN1).
15–17
The second most frequently found
paediatric endocrinology and medical genetics at Georgetown
University. He received his medical and post-doctoral training
functional pituitary tumours in early childhood are GH- and/or prolactin at Georgetown University and the NICHD.
(PRL)-secreting, and in children these tumours almost always occur in the
familial setting or in the context of known genetic defects, i.e. GNAS,
© TOUCH BRIEFINGS 2008 53
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