Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Multicenter Study
. 2015 Oct;22(5):745-57.
doi: 10.1530/ERC-15-0320. Epub 2015 Jul 17.

Clinical and Genetic Characterization of Pituitary Gigantism: An International Collaborative Study in 208 Patients

Free PMC article
Multicenter Study

Clinical and Genetic Characterization of Pituitary Gigantism: An International Collaborative Study in 208 Patients

Liliya Rostomyan et al. Endocr Relat Cancer. .
Free PMC article


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.

Keywords: X-linked acrogigantism (X-LAG) syndrome; aryl hydrocarbon receptor interacting protein gene; familial isolated pituitary adenoma (FIPA); gigantism; growth hormone; pituitary adenoma; somatotropinoma.

Conflict of interest statement

Declaration of interest: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.


Figure 1
Figure 1
Schematic representation of treatments used in the management of patients with pituitary gigantism. Numbers in parentheses indicate the number of patients. RadioThx =Radiotherapy, DA =Dopamine agonists, SSA = Somatostatin analogs, PegV = Pegvisomant. *2 patients had primary radiotherapy (1 controlled); 4 recently diagnosed patients awaiting treatment; **Follow up- 168 months [62;235]
Figure 2
Figure 2
Age and Z-scores for height of patients at last follow-up. Of the total population of 208 patients, 57 patients had an absolute height >200 cm at the last measurement (eight are still growing) and the tallest patient was 247 cm. Eleven that were controlled before the end of the liner growth had a height at the last follow-up of <+2SD (seven of these later had disease recurrence).
Figure 3
Figure 3
Genetic results in the study population. Numbers for each sector show the number of patients in the subgroup and its prevalence in the total group. AIP+ = AIP mutation affected; MAS = McCune-Albright Syndrome; X-LAG = X-linked acrogigantism syndrome; MEN1 = Multiple endocrine neoplasia type 1.
Figure 4
Figure 4
Comparisons of characteristics among genetically distinct groups of pituitary gigantism patients (genetically negative, AIP mutation positive (AIP+) and X-linked acrogigantism syndrome (X-LAG)), showing statistically distinct patterns of age at first symptoms (A), age at diagnosis (B) and no inter-group difference in terms of maximal tumor diameter at diagnosis (C). Panel D demonstrates the female and male predominance of X-LAG and AIP+ related gigantism cases; the genetically-negative group was also male-predominant although less markedly so than the AIPmut group.

Similar articles

  • AIP mutations and gigantism.
    Rostomyan L, Potorac I, Beckers P, Daly AF, Beckers A. Rostomyan L, et al. Ann Endocrinol (Paris). 2017 Jun;78(2):123-130. doi: 10.1016/j.ando.2017.04.012. Epub 2017 May 5. Ann Endocrinol (Paris). 2017. PMID: 28483363 Review.
  • Germline or somatic GPR101 duplication leads to X-linked acrogigantism: a clinico-pathological and genetic study.
    Iacovazzo D, Caswell R, Bunce B, Jose S, Yuan B, Hernández-Ramírez LC, Kapur S, Caimari F, Evanson J, Ferraù F, Dang MN, Gabrovska P, Larkin SJ, Ansorge O, Rodd C, Vance ML, Ramírez-Renteria C, Mercado M, Goldstone AP, Buchfelder M, Burren CP, Gurlek A, Dutta P, Choong CS, Cheetham T, Trivellin G, Stratakis CA, Lopes MB, Grossman AB, Trouillas J, Lupski JR, Ellard S, Sampson JR, Roncaroli F, Korbonits M. Iacovazzo D, et al. Acta Neuropathol Commun. 2016 Jun 1;4(1):56. doi: 10.1186/s40478-016-0328-1. Acta Neuropathol Commun. 2016. PMID: 27245663 Free PMC article.
  • X-linked acrogigantism syndrome: clinical profile and therapeutic responses.
    Beckers A, Lodish MB, Trivellin G, Rostomyan L, Lee M, Faucz FR, Yuan B, Choong CS, Caberg JH, Verrua E, Naves LA, Cheetham TD, Young J, Lysy PA, Petrossians P, Cotterill A, Shah NS, Metzger D, Castermans E, Ambrosio MR, Villa C, Strebkova N, Mazerkina N, Gaillard S, Barra GB, Casulari LA, Neggers SJ, Salvatori R, Jaffrain-Rea ML, Zacharin M, Santamaria BL, Zacharieva S, Lim EM, Mantovani G, Zatelli MC, Collins MT, Bonneville JF, Quezado M, Chittiboina P, Oldfield EH, Bours V, Liu P, W de Herder W, Pellegata N, Lupski JR, Daly AF, Stratakis CA. Beckers A, et al. Endocr Relat Cancer. 2015 Jun;22(3):353-67. doi: 10.1530/ERC-15-0038. Epub 2015 Feb 24. Endocr Relat Cancer. 2015. PMID: 25712922 Free PMC article.
  • [Overgrowth in children and in adults: novel clinical view, novel genes, novel phenotypes].
    Lebl J, Plachý L, Bláhová K, Elblová L, Fencl F, Koloušková S, Průhová Š. Lebl J, et al. Cas Lek Cesk. 2017 Fall;156(5):233-240. Cas Lek Cesk. 2017. PMID: 28992707 Czech.
  • Pituitary gigantism: Causes and clinical characteristics.
    Rostomyan L, Daly AF, Beckers A. Rostomyan L, et al. Ann Endocrinol (Paris). 2015 Dec;76(6):643-9. doi: 10.1016/j.ando.2015.10.002. Epub 2015 Nov 14. Ann Endocrinol (Paris). 2015. PMID: 26585365 Review.
See all similar articles

Cited by 33 articles

See all "Cited by" articles

Publication types


Supplementary concepts