'Internal server error 500' error message in Portal for ArcGIS

[JuhaHaanpera]

Hello hello,

The Portal for ArcGIS occasionally gives end users an 'Internal server error 500' error message, the root cause of which we have been hunting for a long time with ArcGIS Monitor, among other things, and searching the server logs without success. Have others encountered the 'Internal server error 500' error and how have you fixed the problem?

Our ArcGIS Enterprise environment, which runs on version 10.81, consists of a separate IIS Webadaptor Windows server on the DMZ, a Portal, and three robust GIS servers, and an MS SQL Geodatabase server. Attached is a simplified topology image of the Enterprise environment. The portal has hundreds of simultaneous end users on the browser and Field Maps from the public Internet, as well as twenty ArcGIS Pro users in the office network. Where else could we try to find the cause of the fault? 
I have run all the patches with the Esri Updater tool and all the updates provided by Microsoft are automatically installed on the servers.

Thanks in advance for the tips.

B.r. Juha

[DamonNelton]

Looks like its been awhile but any updates on the root cause?? We recently upgraded from 11.0 to 11.2 Enterprise with a similarly diverse deployment (several Machines) and are getting the same experience as this thread first explained. - Thanks Damon