Unintentional weight gain - red flag symptoms

Recognising red flags in cases of unintentional weight gain, with advice on questions to ask, how to examine a patient and when to refer.

Red flags

  • Rapid onset
  • Recurrent hypoglycaemia
  • Headache
  • Uncontrollable hunger
  • Shortness of breath
  • Abdominal pain
  • Hair or skin change
  • Constipation or cold intolerance
  • Menstrual disturbance
  • Mood disturbance


Ask the patient about:

  • Onset - has it been sudden or gradual?
  • Amount of weight gain
  • Distribution – central or peripheral?
  • Palpitations or shortness of breath
  • Hair (thinning, hirsutism) and skin (acne, bruising) changes
  • Menstrual disturbance
  • Constipation or cold intolerance
  • Mood disturbance
  • Family history of obesity
  • Current medications
  • Lifestyle habits

The patient may be unaware of weight gain so previous weight data can frame the consultation and your concerns.

Causes of weight gain
  • Lifestyle factors such as diet, exercise, and alcohol
  • Cushing’s syndrome
  • Insulinoma
  • Hypothyroidism
  • Polycystic ovary syndrome (PCOS)
  • Pregnancy
  • Genetic causes such as Prader-Willi syndrome
  • Drug effects
  • Organ failure
  • Mental health problems such as depression

Possible causes

Cushing’s syndrome
Hypertension, glucose intolerance and hypokalaemia suggest this diagnosis. Reconsider a diagnosis of PCOS. Pituitary and adrenal tumours are five times more frequent in women than men.1 Iatrogenic corticosteroids and ectopic paraneoplastic adrenocorticotropic hormone (ACTH) syndrome (such as lung cancer) are other causes.

Explore the family history of thyroid or autoimmune disease. Myxoedema coma is a life-threatening state of decompensation because of systemic stress (infection/trauma) or discontinuation in thyroxine supplementation, and its mortality rate is 25-60%. Be alert to altered consciousness, hypothermia, hypoglycaemia and bradycardia.

Palpitations, tremor, drowsiness, hunger or weakness may suggest hypoglycaemia and an underlying pancreatic neuroendocrine tumour. Symptoms exacerbate during fasting or exercise. Incidence is estimated at 4 per million individuals per year.2 Patients eat to avoid symptoms so 20-40% experience weight gain. Hypoglycaemia during a supervised 72-hour fast with raised serum insulin and C-peptide levels is consistent with insulinoma.

Weight gain may be an effect of:

  • Antipsychotics
  • Tricyclic antidepressants
  • SSRIs
  • Mood stabilisers
  • Beta-blockers
  • Corticosteroids
  • Diabetic medication
  • The contraceptive injection.

Mental health
Identify poor sleep, social isolation, stress, depression or alcohol misuse.

Organ failure
Progressive cardiac, liver or renal disease can cause fluid retention. Ask about poor appetite, pruritus, orthopnoea, stool/urine colour changes and peripheral swelling.

Glucose intolerance, insulin resistance and hyperandrogenaemia contribute to weight gain in PCOS. Exclude pregnancy in those with oligomenorrhoea.

Genetic disease
Prader-Willi syndrome has an estimated incidence of 1 in 15,000 births.3 Poor feeding is followed by hyperphagia (excessive overeating).


Look for signs of Cushing’s syndrome such as ‘moon-like’ facies and a dorsal neck fat pad. Look for acne, skin coarseness, hair thinning and hirsutism. Assess for abdominal striae, bruises and stigmata of chronic liver disease.

Measure temperature, pulse and blood pressure. Examine for a goitre. Assess for cardiomegaly, cardiac murmurs, pulmonary oedema and pleural effusions. Palpate the abdomen for organomegaly and percuss for shifting dullness of ascites. Palpate for any bilateral pitting oedema.

In children, look for almond shaped eyes, narrow forehead, thin upper lip and short stature indicative of Prader-Willi syndrome. Assess for hypotonia and consider hypogonadism and behavioural difficulties.


Investigations should be guided by history and clinical suspicion but may include:

  • Blood tests: FBC, U&E, LFT, TFT, glucose, serum insulin, brain natriuretic peptide, free androgen index (PCOS), or refer for overnight dexamethasone test and ACTH level.
  • Urine tests: dipstick, 24-hour urine cortisol.
  • Pregnancy test.
  • Abdominal/pelvic ultrasound.
  • Echocardiogram
  • CT/MRI
  • Depression/alcohol questionnaire e.g. PHQ-9/AUDIT-C.

When to refer

Refer suspected Cushing’s syndrome and insulinoma to endocrine teams for diagnosis and potential tumour localisation. Rapid access heart failure clinics and outpatient renal/liver teams may be necessary. Refer to paediatrics if Prader-Willi syndrome is suspected. Psychiatry and dietitian teams may also be needed.

  • Dr Rupesh Amin is a GP in London

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  1. Lahera Vargas M, da Costa CV. Prevalence, etiology and clinical findings of Cushing's syndrome. Endocrinol Nutr. 2009;56(1):32-9
  2. Okabayashi T, Shima Y, Sumiyoshi T et al. Diagnosis and management of insulinoma. World J Gastroenterol 2013;19(6):829-37
  3. Hurren BJ, Flack NA. Prader-Willi syndrome: A spectrum of anatomical and clinical features. Clin Anat 2016; Online first

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