Lipodystrophy
A group of conditions characterised by abnormal body fat distribution or loss. HIV-associated lipodystrophy (excess visceral fat with peripheral fat loss) is the approved indication for tesamorelin, the only GHRH analogue currently approved. Injection-site lipodystrophy can also occur with repeated subcutaneous injections.
Technical Context
HIV-associated lipodystrophy subtypes: lipoatrophy (loss of peripheral subcutaneous fat — face, limbs, buttocks; caused primarily by older NRTIs like stavudine and zidovudine), lipohypertrophy (accumulation of visceral fat — central abdomen, dorsocervical fat pad/buffalo hump; multifactorial — HIV infection itself, protease inhibitors, NRTIs), and mixed pattern (both features). Tesamorelin mechanism: GHRH analogue → pituitary GH release → GH acts on visceral adipose tissue → stimulates lipolysis (via hormone-sensitive lipase activation) and inhibits lipogenesis → reduced visceral fat. TERAHEART and TERASTRA Phase III trials showed ~15-18% reduction in trunk fat vs placebo at 26 weeks. Effect is maintained with continued treatment but reverses upon discontinuation (visceral fat returns to baseline within months). Side effect profile includes: arthralgia, injection site reactions, and potential IGF-1 elevation requiring monitoring.