Complete the following steps to troubleshoot this issue:

1. Add TCP profile with "Keep-alive probes". For more information refer to CTX200901 - Microsoft Exchange 2010 Load Balanced on NetScaler Faces Intermittent Outlook RPC Disconnections.
   Connection idle time before sending probe (secs): 30
   Keep-alive probe internal (secs): 20

   

2. Verify the Persistence method and make sure that it is configured properly based on the Exchange services being used.
   Misconfigured Persistence can cause Outlook clients to bounce and prompt for password. It is recommended to use persistence type Cookieinsert with 0 (indefinite) timeout and as backup use sourceIP persistence for OWA and sourceIP persistence for RPC Client Access Service (CAS) server with timeout value of 9000 seconds.

   Refer to the article CTX135107 - Persistency Issues When Using Exchange 2010 AppExpert Templates on NetScaler if Exchange configuration on NetScaler is done using AppExpert template.

3. It is a known limitation of Outlook client that, if load balanced and the connection goes to another CAS server (because of some reason) the only workaround is to restart the Outlook client. So configure Persistence properly.

4. When Surge Protection is enabled, to protect the servers, the NetScaler will queue connections past a limit to try and limit how many open connections a server has to deal with at a time.
   The Surge Protection feature does not work well with Exchange and it is recommended to disable it as part of the standard configuration for Exchange.
   If servers are not overloaded, you should disable Surge Protection in the NetScaler and verify the behavior. With Surge Protection turned OFF, NetScaler does not queue any User Connections (even if the back end servers are overloaded) and will push all the traffic to the back end servers directly; with that it is up to the back end severs to handle that traffic.

   To learn more about Surge protection refer to Citrix Documentation - Setting Thresholds for Surge Protection

Additional Resources

CTX201899 - HTTP Error 500 While Accessing Microsoft Exchange 2013 Through NetScaler Appliance

CTX135875 - Troubleshooting Steps for AAA Issues on Exchange OWA Through NetScaler