Cushing's disease in childhood as the first manifestation of multiple endocrine neoplasia syndrome type 1.
OBJECTIVE
To describe three cases of Cushing's disease in children with multiple endocrine neoplasia type 1 (MEN1), as clinical manifestations of MEN1 are very rare in childhood.


METHODS
A retrospective review of three cases of Cushing's disease diagnosed between 1997 and 1999. Genetic screening for MEN1 gene mutation was performed in each patient.


RESULTS
An ACTH-secreting microadenoma was diagnosed in three children, aged 11-13 years, presenting with growth retardation and weight gain over a period of 3-4 years. All patients had successful transsphenoidal adenomectomies. Primary hyperparathyroidism was subsequently diagnosed in two of the patients, and in the monozygotic twin of one of the patients. A new mutation in the MEN1 gene (Tyr351His) was identified in two of the patients and the affected members of their families. In the third patient a de novo MEN1 gene mutation (Leu444Pro) was found.


CONCLUSIONS
MEN1 has to be considered in all children with tumours of the pituitary gland, and in those presenting with primary hyperparathyroidism. The children and their families should be advised to seek genetic counselling. We suggest that careful growth records be kept for children at risk of developing inherited MEN1 and, in the event of a decelerating growth rate, further diagnostic evaluation be undertaken with regards to ACTH-secreting pituitary tumours.
Rix
M
M
Department of Paediatrics, Aalborg University Hospital, 9000 Aalborg, Denmark. mariane.rix@dadlnet.dk
Hertel
N T
NT
Nielsen
F C
FC
Jacobsen
B B
BB
Hoejberg
A S
AS
Brixen
K
K
Hangaard
J
J
Kroustrup
J P
JP
D000236:Adenoma / Q000150:complications / Q000000981:diagnostic imaging / Q000601:surgery; D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D002648:Child; D003480:Cushing Syndrome / Q000209:etiology* / Q000235:genetics; D004252:DNA Mutational Analysis; D003907:Dexamethasone; D005260:Female; D005938:Glucocorticoids; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D006961:Hyperparathyroidism / Q000150:complications; D008279:Magnetic Resonance Imaging; D008297:Male; D018761:Multiple Endocrine Neoplasia Type 1 / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics; D009765:Obesity / Q000188:drug therapy / Q000209:etiology; D010911:Pituitary Neoplasms / Q000150:complications / Q000473:pathology / Q000601:surgery; D011859:Radiography; D014427:Twins
D005938:Glucocorticoids; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone