The Man Who Couldn’t Stop Gaining Weight | A Medical Mystery

A previously healthy 21-year-old shows up with seven months of headaches and 30-plus pounds of weight gain he can’t explain. He’s eating the same and training more, and the scale climbs anyway. We hand the case to Dr. Austin Baraki cold and work it in real time: the exam, the labs, the MRI, and two diagnoses that turn a headache workup into the clearest proof we’ve got that body weight is set by the brain, not by character. This is the capstone of our weight series (willpower, calories, protein), and it ends on the drug that, this year, did something for these patients that nothing had done before.

Timestamps

00:00:00 Cold open: the man who couldn’t stop gaining weight
00:01:49 Meet the case (and the rules of the game)
00:02:36 The presentation: 21, headaches, unexplained weight gain
00:03:57 Austin’s one-liner and how a clinician builds a differential
00:05:10 Secondary headaches: what raises the red flag
00:13:12 The exam: vitals, and the eye findings that matter
00:14:37 The labs, one number at a time
00:16:08 Raised pressure and a visual-field clue (bitemporal hemianopia)
00:20:45 The MRI
00:21:54 First diagnosis: craniopharyngioma
00:25:32 The name: a tumor built from tooth tissue
00:25:50 Surgery, and what it costs
00:27:43 The new mystery: gaining weight faster than ever
00:33:41 Second diagnosis: acquired hypothalamic obesity
00:39:17 How your brain sets your weight: the POMC brake and the AgRP accelerator
00:42:07 What about leptin?
00:45:46 Monogenic vs common obesity
00:50:30 Why GLP-1 drugs still worked: the brainstem backdoor
00:52:11 Responders and non-responders
00:55:40 Setmelanotide: a drug for the broken circuit
00:56:53 TRANSCEND, and the new FDA approval
00:58:55 What it costs
01:01:32 Why we care about body fat at all: the garage
01:04:36 Flux: which fat is actually dangerous
01:09:15 Close

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1. Brijmohan A, et al. Acquired hypothalamic obesity following craniopharyngioma resection in a young adult [case report]. 2025. PMCID: PMC12268545; PMID: 40677794.

2. Miller JL, et al; TRANSCEND investigators. Setmelanotide in acquired hypothalamic obesity: a phase 3 randomized trial. N Engl J Med. 2026.

3. Rhythm Pharmaceuticals. FDA approves IMCIVREE (setmelanotide) for acquired hypothalamic obesity. News release. March 19, 2026.

4. US Food and Drug Administration. FDA approves first treatment for weight management for people with certain rare genetic conditions (setmelanotide). 2020.

5. Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997;387(6636):903-908.

6. Farooqi IS, Jebb SA, Langmack G, et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med. 1999;341(12):879-884.

7. Krude H, Biebermann H, Luck W, et al. Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet. 1998;19(2):155-157.

8. Farooqi IS, Keogh JM, Yeo GS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003;348(12):1085-1095.

9. Clément K, Vaisse C, Lahlou N, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature. 1998;392(6674):398-401.

10. Fabbrini E, Tamboli RA, Magkos F, et al. Surgical removal of omental fat does not improve insulin sensitivity and cardiovascular risk factors in obese adults. Gastroenterology. 2010;139(2):448-455.

11. Klein S, Fontana L, Young VL, et al. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med. 2004;350(25):2549-2557.

12. Guyenet SJ. The Hungry Brain: Outsmarting the Instincts That Make Us Overeat. Flatiron Books; 2017.

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