Andrew Gwynne has confirmed he is quitting as a Labour MP, triggering a by-election that could open a route back to Westminster for Greater Manchester mayor Andy Burnham and sharpen internal Labour tensions over the party’s direction and leadership.

Gwynne, a former Labour health minister, said in a social media post on Thursday that he has applied for one of the formal “offices of profit” used as a procedural device for MPs to vacate their seats in the House of Commons. His departure is expected to lead to a by-election in his Greater Manchester constituency.

In his statement, Gwynne cited serious health problems, including a deterioration in his mental health over the past year. He included a note from his GP which said he was suffering with poor mental health, is on “very high dose medication” and is unlikely to “return to his previous ‘normal’”.

Gwynne said he has “suffered significant ill-health over most of the 21 years” he has been an MP, and that this had been exacerbated by last year’s scandal in which he was found to have been part of a WhatsApp group sharing offensive messages.

“Over those years I haven’t got everything right, and I’ve certainly made mistakes, but I’ve always tried my very best and I have helped tens of thousands of constituents with their issues along the way,” he said. “Indeed, it’s been helping people that’s given me the greatest pleasure in these jobs.”

He added: “There will be a by-election soon, and I wish my successor, whoever it is, all the very best in representing what I consider to be the best constituency in the UK.”

The resignation prompted immediate speculation over whether Burnham, a former cabinet minister who now serves as Greater Manchester mayor, could seek selection as Labour’s candidate and return to Parliament. Burnham has been described by one Labour MP as a potential “local champion” for the seat, but any move could reignite briefing and counter-briefing over Labour’s ideological balance and the prime minister’s leadership.

Sir Keir Starmer sought to shut down leadership chatter as the rumours intensified. Speaking to Channel 4 News about the prospect of a leadership challenge, he said: “My message is to my entire party, and that is: That every minute we waste talking about anything other than the cost of living and stability in Europe and across the globe is a wasted minute.

“And I spend my time on the cost of living, the cost of living, the cost of living and doing what I need to do internationally to ensure that we have a stable and safe environment for everybody in this country.”

Labour MP Karl Turner, speaking on Thursday evening, said the party’s priority should be choosing a candidate who can win the by-election, warning Labour could face a difficult contest regardless of who stands.

“But what I do say is what the Labour Party needs to be concerned about is finding a candidate who can win a by-election seat, and with the way the polling is at the moment, it’s going to be a struggle for the Labour Party, no matter who the candidate is,” he said. “So if we’ve got the King of the North wanting to stand in that Greater Manchester region seat, then we ought to be supporting Andy Burnham as the candidate.”

Turner also pointed to the role of Labour’s National Executive Committee in setting selection rules and suggested the party could block Burnham by imposing an all-women shortlist or through other procedural decisions. He said he did not believe Burnham’s motivation was a “leadership contest” and criticised Downing Street advisers, arguing Labour should focus on delivering its manifesto and stop internal speculation. He said MPs were “brassed off” about leaks.

Opposition parties quickly signalled they will treat the contest as an opportunity to land a blow on the government. Reform MP Robert Jenrick said his party would take the by-election “very, very seriously” and claimed Reform is “really the official opposition in this country”.

“If you want to send a message to Keir Starmer and his failing government, then it is the only thing to do to back the Reform candidate in that by-election,” Jenrick said, while acknowledging it is “a historically Labour voting constituency”.

Gwynne’s decision to stand down follows his sacking from government and loss of the Labour whip in February last year, after reported sexist and offensive comments emerged from a WhatsApp chat involving local Labour councillors, party officials and another Labour MP, Oliver Ryan.

According to reports cited in Thursday’s political coverage, Gwynne made racist comments about Labour MP Diane Abbott and sexist remarks about then former deputy prime minister Angela Rayner. He was also reported to have said he hoped a pensioner would soon die after she asked a councillor about bin collections, and to have joked about a constituent being “mown down” by a truck.

Gwynne apologised when the comments came to light last year, saying he deeply regretted his “badly misjudged comments” and apologising for any offence caused. At the time he said: “I entirely understand the decisions the PM and the party have taken.”

He remains under investigation by Parliament’s independent standards commissioner for “actions causing significant damage to the reputation of the House as a whole, or of its Members generally”. Oliver Ryan had the Labour whip suspended when the controversy first emerged, but it was reinstated in September.

The timing of the by-election has not yet been confirmed, but it is expected to follow once the Commons formally processes Gwynne’s application to vacate his seat. The contest is likely to draw national attention, both as a test of Labour’s standing in a traditional heartland seat and as the party manages renewed internal focus on Andy Burnham’s political future.