Basically, amongst usual reading of jōyō kanji :
to distinguish between KU and KUU : except for 空 which has reading KUU, it is KU and never KUU.
There is also 宮 which amongst various readings is often read GUU (神宮 じんぐう) and most exceptionally KUU, in the name of the two shrines in Ise as far as I know of a concrete use : 内宮 (ないくう) ,外宮(げくう)
to distinguish between KYU and KYUU : it is KYUU, never KYU.
I don’t know if there is a topic for this sort of tips (i would be interested by a link!) , so I’ve created a separate topic to share this little fact.
I strongly recommend Heisig Remembering the kanji vol.2 to know when a reading is unique amongst usual kanji , if a component always give its pronunciation to composite kanji or if only around half the time or if there is no regularity, etc.