Excessive appetite

Excessive appetite is an increase in hunger or food intake beyond the body's energy needs. Polyphagia is the symptom of increased hunger. Hyperphagia is the behaviour of eating in excess, which may be driven by hunger that does not settle after eating. The main clinical questions are whether weight is rising or falling, whether the eating is episodic with loss of control, and whether a medical, drug or hypothalamic cause exists.

Clinical relevance. Polyphagia with weight loss is a classic feature of uncontrolled diabetes mellitus, hyperthyroidism and malabsorption. Polyphagia with weight gain suggests drug effect, Cushing syndrome, hypothalamic disease, hypothyroidism with mood disorder, insufficient sleep or an eating disorder. Hyperphagia in a child is a feature of Prader-Willi syndrome and hypothalamic injury.

Physiology. Arcuate nucleus neurones integrate signals from ghrelin (raises hunger before meals), leptin and insulin (long term energy stores), and gut peptides (cholecystokinin, peptide YY, glucagon like peptide 1) that signal satiety. Reward circuits and stress hormones modify eating beyond need.

Classification.

• Appetite driven by energy loss: diabetes mellitus (glucosuria), hyperthyroidism, malabsorption, pregnancy, lactation, intense exercise, growth, recovery from illness.
• Appetite driven by hypoglycaemia: insulinoma, reactive hypoglycaemia, post gastric surgery, insulin or sulphonylurea excess.
• Central dysregulation: hypothalamic disease, drugs, sleep deprivation, Prader-Willi syndrome, Kleine-Levin syndrome, frontotemporal dementia.
• Behavioural and psychiatric: binge eating disorder, bulimia nervosa, night eating syndrome, atypical depression, premenstrual change, stress and emotional eating.

Binge eating. An episode of eating, within a discrete period, a clearly larger amount than most people would eat, with a sense of loss of control. Binge eating disorder requires episodes on average at least once weekly for 3 months with distress, eating rapidly, until uncomfortably full, when not hungry or alone from embarrassment, and without regular compensatory behaviour. Bulimia nervosa adds compensatory behaviour (vomiting, laxatives, fasting, excessive exercise).

History.

• Pattern: constant hunger, hunger soon after meals, episodic binges with loss of control, night eating, cravings, food seeking, hoarding.
• Weight trend: loss, gain or stable. Dates of onset in relation to drugs, illness, stress, sleep change, smoking cessation, pregnancy or menstrual cycle.
• Symptoms of diabetes (polyuria, thirst, blurred vision), hyperthyroidism (tremor, palpitations, heat intolerance, diarrhoea), malabsorption (steatorrhoea, bloating), hypoglycaemia (sweating, shakiness, confusion before meals), Cushing syndrome (bruising, striae, weakness), hypothalamic disease (headache, visual loss, polyuria, temperature disturbance, sleep change).
• Mood and mental state: depression, hypersomnia, anxiety, mania, trauma, body image concerns, purging, laxative or diuretic misuse, excessive exercise.
• Drugs: corticosteroids, antipsychotics (olanzapine, clozapine), mirtazapine, paroxetine, valproate, lithium, gabapentin, antihistamines (cyproheptadine), benzodiazepines, insulin, sulphonylureas, cannabis, progestins; recent drug withdrawal (stimulants, nicotine).
• Sleep duration and quality. Alcohol use.
• Neurological and cognitive change: new hyperorality, food fixations, personality change, seizures.
• Children: early onset obesity, developmental delay, hypotonia in infancy, family history.

Examination.

• Weight, height, body mass index, waist circumference, blood pressure, pulse, temperature.
• Hydration, tremor, goitre, eye signs, skin (striae, bruising, acanthosis nigricans), hair, dentition (enamel erosion), parotid enlargement, Russell sign, features of hypothyroidism.
• Cushingoid features, hirsutism, proximal weakness.
• Visual fields and cranial nerves. Cognitive and frontal lobe assessment.
• Capillary glucose at the time of symptoms.
• Dysmorphic features in children (almond shaped eyes, small hands and feet in Prader-Willi syndrome).

Red flags.

• Weight loss despite increased appetite.
• Polyuria, polydipsia, ketones or vomiting.
• Neuroglycopenic symptoms, glucose under 3.0 mmol/L.
• Headache, visual field loss, polyuria, temperature instability, hypogonadism.
• Purging, laxative misuse, dizziness, palpitations, low potassium.
• Behavioural change or hyperorality in a person over 45.
• Early childhood hyperphagia with rapid weight gain.
• Suicidal thoughts.

Metabolic and endocrine. Diabetes mellitus (uncontrolled), hyperthyroidism, hypoglycaemia (insulinoma, reactive hypoglycaemia, post bariatric hypoglycaemia, insulin or sulphonylurea excess), Cushing syndrome, hypothyroidism with associated mood change, growth hormone deficiency, polycystic ovary syndrome, phaeochromocytoma, glucagonoma, acromegaly.

Gastrointestinal. Malabsorption (coeliac disease, pancreatic insufficiency, short bowel, giardiasis), helminth infestation (hookworm, tapeworm), post gastric surgery dumping.

Physiological. Pregnancy, lactation, adolescent growth, premenstrual phase, intense physical training, recovery after illness or starvation, high altitude, cold exposure, smoking cessation, sleep deprivation.

Drugs and substances. Corticosteroids, olanzapine, clozapine, risperidone, mirtazapine, tricyclics, paroxetine, valproate, lithium, gabapentin, cyproheptadine, benzodiazepines, insulin, sulphonylureas, medroxyprogesterone, cannabis, alcohol withdrawal and recovery from stimulant use.

Neurological. Hypothalamic lesions (craniopharyngioma, tumour, trauma, surgery, radiation, inflammation, infiltrative disease), frontotemporal dementia (hyperorality), Klüver-Bucy syndrome, Kleine-Levin syndrome, temporal lobe epilepsy, stroke, Parkinson disease treatment.

Psychiatric and behavioural. Binge eating disorder, bulimia nervosa, night eating syndrome, atypical depression, bipolar disorder (depressive and manic phases), anxiety, post traumatic stress disorder, emotional eating, seasonal affective disorder.

Genetic. Prader-Willi syndrome, Bardet-Biedl syndrome, melanocortin 4 receptor deficiency, leptin deficiency, Alström syndrome.

1. Establish the weight trajectory, the pattern of eating, and the drug and sleep history. Measure capillary glucose.
2. First line tests: HbA1c and fasting glucose, full blood count, urea, creatinine and electrolytes (potassium and bicarbonate low in purging), liver function tests, thyroid stimulating hormone, tissue transglutaminase IgA with total IgA, urinalysis (glucose, ketones), pregnancy test.
3. Diabetes mellitus: HbA1c 48 mmol/mol (6.5%) or more, fasting glucose 7.0 mmol/L or more, or random glucose 11.1 mmol/L or more with symptoms.
4. Hyperthyroidism: suppressed thyroid stimulating hormone with raised free thyroxine or triiodothyronine; antibodies and uptake scan by specialists.
5. Hypoglycaemia: document Whipple triad (symptoms, plasma glucose under 3.0 mmol/L, relief with glucose). Supervised fast of up to 72 hours when insulinoma is suspected; a diagnosis is supported by glucose under 3.0 mmol/L (55 mg/dL) with insulin 3 microunits/mL or more, C peptide 0.6 ng/mL or more, proinsulin 5 pmol/L or more, beta hydroxybutyrate 2.7 mmol/L or less, and a negative sulphonylurea screen. Then CT, MRI or endoscopic ultrasound.
6. Cushing syndrome screening if features exist: 1 mg overnight dexamethasone suppression test (08:00 cortisol under 50 nmol/L excludes), or late night salivary cortisol on 2 occasions, or 24 hour urinary free cortisol on 2 collections.
7. Hypothalamic disease: MRI of the brain with pituitary and hypothalamic sequences, visual fields, prolactin, LH, FSH, testosterone or oestradiol, IGF-1, 08:00 cortisol, thyroid function, and osmolality studies when polyuria is present.
8. Stool microscopy or antigen tests for Giardia and helminths in endemic settings, faecal elastase (under 200 microgram/g suggests exocrine pancreatic insufficiency).
9. Eating disorders: structured screening (SCOFF questions; 2 or more positive answers suggest a disorder), weight and body mass index, electrolytes (potassium, phosphate, magnesium), ECG for QT interval, bone density when chronic.
10. Genetic testing (methylation analysis for Prader-Willi syndrome) in children with hyperphagia and obesity from early life. Cognitive and neuroimaging assessment for suspected frontotemporal dementia.

Limits. Diagnosis of binge eating disorder rests on history; laboratory tests are normal. Screening tests for Cushing syndrome have false positives in obesity, depression, alcohol use and oestrogen therapy. Fasting tests need monitoring in hospital.

General measures. Regular meal structure (three meals and two or three planned snacks, no long fasts), protein and fibre rich foods, adequate sleep of 7 to 9 hours, limiting alcohol, reducing availability of trigger foods, and a food and mood diary. Avoid labelling the patient as lacking willpower.

Cause directed treatment.

• Diabetes mellitus: correct hyperglycaemia. Metformin 500 mg orally once daily with the evening meal, increased by 500 mg weekly to 1 g twice daily (reduce when eGFR is 30 to 45 mL/min; stop under 30 mL/min), with insulin for ketosis or marked hyperglycaemia. Specialist directed.
• Hyperthyroidism: carbimazole 20 to 40 mg orally once daily initially (maximum 60 mg daily), checking full blood count and liver function, with propranolol 10 to 40 mg orally three times daily for symptoms.
• Hypothyroidism: levothyroxine 1.6 micrograms/kg orally once daily on an empty stomach (start 25 micrograms daily in older adults or coronary disease and increase every 4 to 6 weeks).
• Hypoglycaemia: oral glucose 15 to 20 g for conscious patients, glucose 10% 150 to 200 mL intravenously or glucagon 1 mg intramuscularly for severe episodes. Insulinoma needs surgical resection; diazoxide (usual range 3 to 8 mg/kg daily in two to three divided doses) controls symptoms before surgery, with monitoring for fluid retention.
• Cushing syndrome: endocrinology review; stop avoidable glucocorticoids slowly.
• Drug induced hyperphagia: review need, dose and alternatives (for example aripiprazole rather than olanzapine; bupropion rather than paroxetine), and add metformin 500 mg twice daily increasing to 1 g twice daily for antipsychotic weight gain.
• Binge eating disorder: supervised self help or cognitive behavioural therapy first. Lisdexamfetamine 30 mg orally each morning, increased by 20 mg weekly to 50 to 70 mg (maximum 70 mg), under specialist direction; avoid in cardiovascular disease, uncontrolled hypertension, anxiety, substance misuse or mania; monitor blood pressure and pulse. Selective serotonin reuptake inhibitors give modest benefit.
• Bulimia nervosa: cognitive behavioural therapy and fluoxetine 60 mg orally once daily (start 20 mg and increase over 1 to 2 weeks). Correct electrolytes; avoid rapid refeeding in severely malnourished patients.
• Night eating syndrome: sleep regulation, cognitive behavioural therapy, sertraline 50 mg orally daily, increased as needed to 100 to 200 mg.
• Atypical depression, bipolar disorder and anxiety: treat the mood disorder.
• Prader-Willi syndrome: specialist multidisciplinary care, strict control of food access, growth hormone and sex hormone therapy where indicated.
• Hypothalamic obesity: specialist endocrine care, structured diet and activity, and treatment of other pituitary deficiencies.
• Frontotemporal dementia: structured environment, food access control, and specialist care.
• Helminths: albendazole 400 mg orally once, repeated after 2 weeks if needed. Giardiasis: tinidazole 2 g orally once, or metronidazole 400 mg orally three times daily for 5 days.

Monitoring. Weight every 2 to 4 weeks, glucose and HbA1c at 3 months, thyroid function at 6 to 8 weeks after starting treatment, mood and eating diary at each visit, and electrolytes when purging is present.

Referral and escalation. Eating disorder services for binge eating disorder, bulimia nervosa or night eating syndrome that does not respond to first line care. Endocrinology for suspected Cushing syndrome, hypothalamic disease or insulinoma. Paediatric endocrinology and genetics for childhood hyperphagia. Neurology or old age psychiatry for suspected frontotemporal dementia.

Admission. Diabetic ketoacidosis, severe hypoglycaemia, electrolyte disturbance with purging (potassium under 3.0 mmol/L or QT prolongation), suicidal risk, or need for monitored fasting.

Safety netting. Return for vomiting, collapse, palpitations, confusion, severe thirst and polyuria, weight loss despite eating, or worsening mood.

Special groups. Pregnancy: increased appetite is expected; screen for gestational diabetes at 24 to 28 weeks. Children: hyperphagia needs growth assessment, thyroid function, cortisol, MRI and genetic review. Older adults: consider dementia, diabetes and drugs. HIV: antiretroviral therapy (especially integrase inhibitors) and steroids increase appetite and weight.