"Isan" derives from the Pāli word for "northeast". The term "Isan" has been introduced by the Siamese government in 1900 to replace the old ethnic name for the administrative circle Monthon Lao Khao (capital: Ubon Ratchathani). Twelve years later, in 1912, Monthon Isan was divided up into the circles (monthon) of Roi-et and Ubon Ratchathani. At that time the term "Isan" was being transformed from a narrow administrative designation to a more general geographic term. Since c.1922 the so-called Northeastern region (phak isan) became a widely accepted designation for the whole of the Khorat plateau, comprising the territories of the former monthon of Isan (Roi-et, Ubon Ratchathani), Udon and Khorat. [...]In the map to the right I have marked the administrative circles (monthon, มณฑล) of the northeast in their layout of 1915. The two circles which made up the circle Isan until 1912 are the blue and pink to the southeast, encircled in red.
The split of the circle was announced in the Royal Gazette in April 1912, with Isan then still spelled อิสาน with a short I (instead of the long I it has today). And that spelling is consistent in all the announcements of that time, so the word Isan really changed spelling.
An interesting further reading is a blog posting on Isan’s Holy Men and Holy Waters.