hide
Free keywords:
gigantism, pituitary adenoma, somatotropinoma, growth hormone, aryl hydrocarbon receptor interacting protein gene, familial isolated pituitary adenoma (FIPA), X-linked acrogigantism
Abstract:
Despite being a classical growth disorder, pituitary gigantism has not
been studied previously in a standardized way. We performed a
retrospective, multicenter, international study to characterize a large
series of pituitary gigantism patients. We included 208 patients ( 163
males; 78.4%) with growth hormone excess and a current/previous abnormal
growth velocity for age or final height > 2 S.D. above country normal
means. The median onset of rapid growth was 13 years and occurred
significantly earlier in females than in males; pituitary adenomas were
diagnosed earlier in females than males (15.8 vs 21.5 years
respectively). Adenomas were >= 10 mm (i.e., macroadenomas) in 84%, of
which extrasellar extension occurred in 77% and invasion in 54%. GH/IGF1
control was achieved in 39% during long-term follow-up. Final height was
greater in younger onset patients, with larger tumors and higher GH
levels. Later disease control was associated with a greater difference
from mid-parental height (r=0.23, P=0.02). AIP mutations occurred in
29%; microduplication at Xq26.3 - X-linked acrogigantism (X-LAG) -
occurred in two familial isolated pituitary adenoma kindreds and in ten
sporadic patients. Tumor size was not different in X-LAG, AIP mutated
and genetically negative patient groups. AIP-mutated and X-LAG patients
were significantly younger at onset and diagnosis, but disease control
was worse in genetically negative cases. Pituitary gigantism patients
are characterized by male predominance and large tumors that are
difficult to control. Treatment delay increases final height and symptom
burden. AIP mutations and X-LAG explain many cases, but no genetic
etiology is seen in > 50% of cases.
