Acromegaly in Carney complex复制标题

卡尼复合体的肢端肥大症

In this paper, we report, to the best of our knowledge, a new PRKAR1A mutation, responsible for a 4-nucleotide deletion in exon 2 (c.80_83del, p.(Ile27Lysfs*101) in a patient with CNC revealed by atrial myxoma, spotty skin pigmentation, cutaneous myxomas and acromegaly due to a GH-secreting microadenoma. In CNC, it seems that acromegaly is more frequently due to a microadenoma as compared to sporadic acromegaly. This observation could be however the consequence of a systematic hormonal and/or imaging assessment as soon as the diagnosis of CNC is done or suspected. Another hypothesis could be that only a subset of somatotroph cells will exhibit loss of heterozygosity (LOH) at 17q22-24, consistent with the Knudson two-hit model of hereditary tumorigenesis of this syndrome, and therefore will result in an adenoma of small size. Another matter of the discussion is related to the rarity of “true” acromegaly in CNC (10%) contrasting with up to 70% of patients who will have subtle abnormalities of the GH axis. This is likely due to a certain degree of somatotroph hyperplasia which suggests, from a pathophysiological point of view, that PRKAR1A mutations may lead to GH hyperplasia, which in turn may sometimes result, albeit not systematically, to the development of a GH-secreting microadenoma or macroadenoma. This observation is further supported by the development of GH hyperplasia in patients with MAS, a pathology in which a sustained activation of the cAMP signaling pathway occurs as well. Unlike FIPA or the so-called X-linked acrogigantism (X-LAG) syndrome, CNC-related acromegaly does not seem to be correlated with higher concentrations of GH and/or IGF-1 as compared with non-syndromic acromegaly. On the contrary, it even appears that a higher proportion of microadenomas are likely to be found presumably due to an active screening in the population of patients with clinical patterns of CNC. However, it could not be entirely ruled out that CNC may predispose to mild forms of acromegaly, which will be diagnosed at a later stage of the disease as compared to other CNC symptoms. This is particularly highlighted in the cases from the literature by a very low proportion of patients for who acromegaly was the inaugural lesion of the syndrome.

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