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. 2021 Apr 6;17(1):54–77. doi: 10.1111/1749-4877.12533

Table 6.

List of evidences at different observation levels supporting the diagnosis of pituitary gigantism

Observation level List of evidences Description References
External morphology and morphometry Extremely length of long bones This is the main evidence suggesting the diagnosis of pituitary gigantism. It is due to an overstimulation of the chondroblasts present in the growth plates of long bones. Such condition is a typical effect of a great presence of growth hormone (GH) Kronenberg (2003); Rossellò‐Diez & Joyner (2015); Tritos & Klibanski (2016)
Slenderness index (SI = 0.066 in tibia and 0.074 in metatarsal bone) The length of long bones is very disproportionate with respect to the transverse diameter of diaphysis de Herder (2009); Melmed (2009)
Articular surfaces very short The size of the epiphyses of long bones do not follow the development of the diaphysis, so that the whole long bone appears disproportionate Killinger et al. (2012)
Bone fragility and fracture predisposition The risk of fractures is very increased because the bones lose robustness and become fragile. The causes of this condition are attributable to an excess of GH that induces bone demineralization and bone reabsorption Andreassen & Hoxlund (2001); Kužma et al. (2019)
Radiology Extreme thinning of the diaphyseal bone wall (and consequently medullary cavity enlargement) The thickness of the diaphyseal bone wall is the result of a process of enlargement of the medullary cavity due to reabsorption of subendosteal bone and a process of subperiosteal bone apposition. During the life, in physiological condition, these 2 processes are balanced and tend to gradually thicken the wall. In case of excess of GH, the enlargement of the medullary cavity prevails over the subperiosteal bone apposition, as confirmed by the growth zones delimited by LAGs Eugster & Pescovitz (1999); Schmidt et al. (2007); Mazziotti et al. (2018, 2019)
Bone radiotransparency One of the effects of the GH on bones is a process of reabsorption of bone tissue stimulating the activity of osteoclasts. In case of overactivity of GH, as in case of pituitary gigantism, this process can be vigorous leading to a lowering of radiopacity typical of bone tissue (radiotransparency), and formation of bone pores within the compact bone tissue (bone porosity) which can give rise to large cavities hundreds of μm long Ueland et al. (2002); Ueland (2005); Marotti et al. (2004); Dalle Carbonare et al. (2018)
Bone porosity
Histology Presence of wide cavities in diaphyseal bone wall
Secondary osteons almost circular Such information suggests that the bone tissue is subjected almost all to compression loads and not to mechanical stress in craniocaudal or mediolateral direction. It seems that the limb long bones were engaged in supporting the body weight than in participating in fast gaits Zedda et al. (2015, 2019, 2020)
Restricted growth zone between LAGs This suggests an unbalance between the elongation of long bones and enlargement of their diaphysis, in favor of the former. This is the histological base of the bone slenderness
Other indirect supports Absence of carnivores predators This condition allows the survival of individuals affected by pathologies restricting movements Palombo & Zedda (2016); Lyras et al. (2019)
Unique individual The number of LAGs is the same in the tibia and metatarsal bone suggesting that both bones belonged to a 6‐ to 7‐year‐ old deer