Unlocking the Genetic Secrets of Acromegaly: Exploring the Role of Genetics in a Rare Disorder

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The authors present a review of pituitary adenomas and the genetic contributions of various situations.  The review is well-written, but could use a bit of restructuring by defining different scenarios.  Namely, isolated, sporadic, somatic and syndromic.

There is some overlap between these situations and therefore some repetition is seen. 

For clarity, the authors could consider encompassing sporadic cases (which are de novo cases of germline etiology) into the isolated and syndromic.  Sporadic GNAS could also be encompassed in the syndromic McCune Albright discussion along with mosaicism.  This type of reorganization should have a preamble on the definitions of these different states to provide the reader context of the complexities of these genetic concepts.

Comments on the Quality of English Language

moderate english editing.  For example:

Lots of uncertain significance

Clinical particularities:

Treatment particularities:

do not seem like scientific phrases consider using different words (Clinical features etc).

Author Response

Please see attachment. 

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

The review entitled “Unlocking the Genetic Secrets of Acromegaly: Exploring the Role of Genetics in a Rare Disorder” is an interesting updated review about the genetics of acromegaly. However, it needs more clarity on the literature survey and presentation of the content to make it more reader-friendly. Authors have tried and narrated the science of genetics and acromegaly in a textual way, which is a rare endocrine disorder characterised by excessive growth hormone production in adulthood. It is caused by certain pituitary neuroendocrine tumours with a hereditary predisposition. These tumours are classified into syndromic tumours and familial isolated pituitary adenomas. Both involve germline mutations, highlighting the need for genetic testing. Somatic mutations also contribute to acromegaly. Despite multiple treatment options, diagnosis often occurs after years, making early detection crucial for preventing complications and improving quality of life.

The revised and intriguing overview of acromegaly's genetic causes is noteworthy. More clarification on the literature survey and content presentation towards reader friendliness would help, though. The study excludes many recent findings.

Authors should narrate the genetic factors of acromegaly in a more illustrated way rather than only in running text.

Many statements like “Benefits of genetic testing: Currently, there is not sufficient evidence to justify testing the GIPR expression. However, we believe that the persistent paradoxical GH response could make it challenging to differentiate between a genuinely high GH level requiring further intervention (such as medication, a second surgery, or radiotherapy) and a GH  level that appears elevated solely due to the glucose load, possibly accompanied by a normal IGF-1 level. Knowing the higher GIPR expression in such situations could help guide 368 the management.” are not supported by appropriate citations. Specially “GH  level that appears elevated solely due to the glucose load” should be supported  with appropriate citations.

Authors should be cautious about statements without appropriate citations.

Authors should prepare an overall self explanatory illustration as a unique work for the review to reveal the molecular mechanisms underlying acromegaly.

Genes and genetic factors associated with multiple clinical particularities should be discussed thoroughly.

Comments on the Quality of English Language

Moderate editing of English language required

Author Response

Please see attachment.

Author Response File: Author Response.pdf

Round 2

Reviewer 2 Report

Comments and Suggestions for Authors

Revised MS can be considered 

Comments on the Quality of English Language

Minor editing of English language required.