Session: OR20-Genetics of Growth
Bench to Bedside
Room 122 (Moscone Center)
Aim: To characterize comprehensively a large series of patients (pts) with pituitary gigantism. Standard case report forms were used with height assessments related to local country norms.
Results: 199 pts were recruited and 158 (129 male) had GH-excess and abnormal growth velocity for age or final height > 2SD over local norms Median age at diagnosis was significantly lower in females vs. males (16.5yr vs. [10.5;26.5] 23yr [19;29], p=0.006). Median delay in diagnosis was 5yr [2;10]. 96% had acromegalic changes at time of diagnosis. Macroadenomas occurred in 84% with extrasellar extension in 77% and invasion in 54%. >3 distinct treatment types were used in 40% of cases; in these only 43% had disease control. Hypopituitarism rose from 24% at baseline to 69% at last follow-up. 134 patients had stopped growing at age of 20yr. The difference from calculated target height was greater in those with control of GH-excess after 20 yr of age than before 20 yr of age (10.9% over MPH [8.4;15] vs 7.9% over MPH [5.9;10.3], p=0.012). Genetic/inherited features were seen in 34% at presentation and included syndromes like FIPA, McCune-Albright, Carney complex, and familial pituitary hyperplasia. Germline mutations in the AIP gene (AIPmut) were found in 52.9% (27/52) of those tested. There were no differences between AIPmut positve and negative pts with gigantism regarding tumor size. AIPmut positive pts had a significantly younger age at first symptoms (p=0.02) and diagnosis (p=0.047) than AIPmut negative pts. Median height Z-scores were +3.5SD [2.7;4.7] and +3SD [2.5;4.3] in AIPmut positive and negative groups, respectively. At last follow-up in the height Z-scores of AIPmut positive pts was positively correlated with age at diagnosis (r=0.31, p=0.048). While median follow up did not differ between the groups (7.4yrs. [2;16] vs. 8yrs [4;17], p=0.4), disease control was more frequent in the AIPmut negative group (p=0.039) despite less use of multimodal treatment in AIPmut negative pts.
Conclusions: Pituitary gigantism pts have characteristic features of male predominance and larger tumors that are difficult to control. Treatment delay may increase the harm from GH-excess, particularly on excess stature. Syndromic or genetic features occurred in 1/3 of pts; AIPmut are common. Improved recognition and early diagnosis may help to decrease excessive height.
Nothing to Disclose: LR, AFD, AL, ALL, EN, AM, LAN, DK, IMH, SF, CJ, MS, MO, ES, MT, II, MZ, JYB, EM, RS, SL, DMM, AIM, KV, JD, EN, RSA, DLM, JOJ, TE, DF, GKS, PB, LA, AC, VP, AB, TB, VR, SM, FB, SJN, MLJ, CAS, PC, SZ, PP, NS, AB
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