Differential diagnosis and complications of Childhood obesity

Endocrine diseases, congenital and acquired hypothalamic defects, genetic syndromes, and use of drugs affecting appetite should be considered during assessment of paediatric patients with obesity (figure 2).

Clinical history and examination should guide differential diagnosis. Onset of obesity during early infancy raises suspicion of function-changing genetic mutations affecting the leptin signalling pathway, but these disorders are very rare, with the most common, melanocortin-4-receptor defects, affecting less than 5% of children with early-onset obesity.⁵⁶

During assessment of new-onset excessive weight gain, potential side-effects from a recently initiated drug should be taken into consideration, because weight gain can be associated with administration of insulin or insulin secretagogues, glucocorticoids, hormonal contraceptives (eg, depot medroxyprogesterone acetate), psychotropic drugs (including atypical antipsychotics [eg, clozapine, olanzapine, risperidone], mood stabilisers [eg, lithium], tricyclic antidepressants [eg, amitriptyline, imipramine, and nortriptyline], and anticonvulsants [eg, valproic acid, gabapentin, and carbamazepine]), antihypertensive drugs (eg, propranolol and clonidine), and antihistamines.⁶⁵ In patients with decreased growth velocity despite continued weight gain, an endocrinopathy should be considered; measurement of thyroidstimulating hormone and free thyroxine and referral to a paediatric endocrinologist are recommended.

Almost all patients, however, do not have any of these identifiable disorders. All patients, irrespective of cause of obesity, should be assessed for modifiable lifestyle factors, including physical activity and diet, and screened for complications of obesity, including measurement of lipid and glucose concentrations after overnight fasting, and alanine aminotransferase. If fasting glucose concentration is 5.6 - 6.9 mmol/L, an oral glucose tolerance test is recommended. Screening for vitamin D and iron deficiency should also be considered.

Figure 1A simplified model of the leptin signalling pathway
Lines with arrowheads show stimulatory action. Lines with perpendicular endblocks show inhibitory action. AgRP=agouti-related protein. BDNF=brain-derived neurotrophic factor. CART=cocaine-amphetamine related transcript. CPE=carboxypeptidase E. CRH=corticotropin-releasing hormone. GABA=gamma amino butyric acid.

GI=gastrointestinal. IR=insulin receptor. LR=leptin receptor. MCH=melanin-concentrating hormone. MSH=melanocyte-stimulating hormone. NPY=neuropeptide Y.
PC1=prohormone convertase 1. POMC=pro-opiomelanocortin. PYY=peptide YY. TRH=thyrotropin-releasing hormone. TrkB=tropomyosin receptor kinase B.