Overview
Definition:
Obesity in children is defined as a body mass index (BMI) at or above the 95th percentile for age and sex
While multifactorial, endocrine disorders can contribute, often as rare but significant causes
This article focuses on the pediatric presentations of Cushing syndrome and hypothyroidism as endocrine etiologies for obesity.
Epidemiology:
While most childhood obesity is polygenic and related to lifestyle, endocrine causes account for a smaller but significant proportion
Cushing syndrome is rare in children, with an incidence of approximately 2-3 per million per year
Primary hypothyroidism is one of the most common endocrine disorders in children, with prevalence varying by screening programs and iodine sufficiency, affecting 1 in 2000 to 1 in 4000 neonates, and with acquired forms also contributing to obesity.
Clinical Significance:
Identifying endocrine causes of obesity is crucial as they often require specific medical or surgical management and can have serious long-term health implications if untreated
Early diagnosis and intervention can improve outcomes and prevent complications such as growth failure, metabolic derangements, and cardiovascular disease
This is particularly important for DNB and NEET SS aspirants to differentiate from more common causes.
Clinical Presentation
Symptoms:
For Cushing syndrome: Rapid weight gain, often with central distribution (truncal obesity, moon face, buffalo hump)
Poor linear growth despite weight gain
Fatigue and weakness
Irritability or emotional lability
Recurrent infections
For hypothyroidism: Weight gain despite normal or decreased appetite
Sluggishness, lethargy, and fatigue
Cold intolerance
Constipation
Delayed puberty or menarche
Dry skin and hair loss
Developmental delay in infants.
Signs:
For Cushing syndrome: Characteristic central obesity, moon face, buffalo hump, thin skin with easy bruising, striae (often purple), hypertension, hirsutism, acne, muscle weakness, delayed linear growth
For hypothyroidism: Short stature or poor growth velocity, coarse facial features, periorbital edema, delayed reflexes, goiter (in some cases), bradycardia, hypothermia, abdominal distension.
Diagnostic Criteria:
Diagnosis relies on a combination of biochemical tests to confirm hypercortisolism or hypothyroidism, followed by specific tests to identify the underlying cause
For Cushing syndrome: Elevated urinary free cortisol, abnormal dexamethasone suppression test results, elevated midnight salivary cortisol
For hypothyroidism: Elevated TSH (Thyroid Stimulating Hormone) and low free T4 (Thyroxine) levels.
Diagnostic Approach
History Taking:
Detailed history of weight gain pattern and distribution
Growth charts are essential to track height and weight velocity
Assess for symptoms suggestive of Cushing syndrome (e.g., rapid weight gain, behavioral changes, poor growth, skin changes) or hypothyroidism (e.g., lethargy, cold intolerance, constipation, developmental concerns)
Inquire about family history of endocrine disorders or obesity
Review medications that might induce Cushingoid features.
Physical Examination:
Measure height, weight, and calculate BMI
Plot on age- and sex-specific growth charts
Assess for dysmorphic features
Examine skin for striae, bruising, thinning, hirsutism, and acne
Evaluate for central obesity, moon facies, and buffalo hump
Assess muscle strength and reflexes
For suspected hypothyroidism, examine the thyroid gland for goiter and assess reflexes.
Investigations:
For suspected Cushing syndrome: Initial screening includes 24-hour urinary free cortisol (UFC) and low-dose (1 mg) overnight dexamethasone suppression test (DST)
If abnormal, further testing may include midnight salivary cortisol, repeat DST with higher doses, and ACTH (Adrenocorticotropic Hormone) levels to differentiate ACTH-dependent from ACTH-independent Cushing syndrome
Imaging (MRI of pituitary or CT of adrenals) may be indicated
For suspected hypothyroidism: TSH and free T4 are the primary tests
If TSH is elevated and free T4 is low, consider thyroid autoantibodies (anti-TPO, anti-thyroglobulin) to assess for autoimmune thyroiditis and thyroid ultrasound if indicated
Consider thyroxine-binding globulin (TBG) levels if free T4 is borderline.
Differential Diagnosis:
For Cushing syndrome: Exogenous corticosteroid use (most common cause of Cushingoid appearance), pseudocushing states (obesity, depression, alcoholism), constitutional delay of puberty with obesity
For hypothyroidism: Constitutional delay of growth with obesity, other causes of short stature, central hypothyroidism (secondary/tertiary, where TSH may be normal or low)
Other causes of weight gain like genetic obesity syndromes, hypothalamic obesity (e.g., after craniopharyngioma treatment), and dietary factors.
Management
Initial Management:
The primary goal is to address the underlying endocrine cause
For Cushing syndrome, this involves reducing or normalizing cortisol levels
For hypothyroidism, this involves restoring euthyroid state
Nutritional counseling and lifestyle modifications are supportive but not curative for these endocrine causes.
Medical Management:
For Cushing syndrome: Medical therapy is often used when surgery is not feasible or as a bridge to surgery
Medications include ketoconazole, metyrapone, or osilodrostat to inhibit cortisol synthesis
Mifepristone can block the effects of cortisol
For hypothyroidism: Lifelong thyroid hormone replacement therapy with levothyroxine is standard
Dosage is individualized based on age, weight, and TSH/free T4 levels
Typical starting dose for congenital hypothyroidism is 10-15 mcg/kg/day
for acquired hypothyroidism, it can range from 1-5 mcg/kg/day.
Surgical Management:
For Cushing syndrome: The primary treatment for ACTH-dependent Cushing disease (pituitary adenoma) is transsphenoidal surgery
Adrenalectomy is indicated for adrenal adenomas or carcinomas
For ACTH-independent Cushing syndrome, surgical removal of the affected adrenal gland(s) is the treatment
For hypothyroidism: Surgery is generally not indicated for primary hypothyroidism unless there is a symptomatic goiter or malignancy.
Supportive Care:
Close monitoring of growth, metabolic parameters (glucose, lipids), blood pressure, and bone health is essential
Nutritional support and physical therapy may be required to address muscle weakness
Psychological support for both the child and family is important given the significant impact of these conditions
Regular follow-up with an endocrinologist is critical.
Complications
Early Complications:
For Cushing syndrome: Adrenal crisis following bilateral adrenalectomy or abrupt cessation of steroids
Infections
Wound complications after surgery
Poor wound healing
For hypothyroidism: Myxedema coma (rare, severe)
Hypoglycemia
Respiratory compromise.
Late Complications:
For Cushing syndrome: Stunted growth, osteoporosis, impaired glucose tolerance or diabetes mellitus, hypertension, increased risk of cardiovascular disease, infertility
For hypothyroidism: Irreversible cognitive impairment (if untreated in infancy), persistent short stature, delayed puberty, infertility, metabolic syndrome, increased risk of cardiovascular disease.
Prevention Strategies:
Early diagnosis and prompt, appropriate management of the underlying endocrine disorder are key to preventing complications
Careful titration of thyroid hormone replacement in hypothyroidism minimizes long-term sequelae
Monitoring for comorbidities like hypertension and diabetes in Cushing syndrome is crucial
Regular follow-up allows for timely detection and management of emergent issues.
Prognosis
Factors Affecting Prognosis:
For Cushing syndrome: Depends on the etiology (pituitary vs
adrenal), success of surgical treatment, and timely control of hypercortisolism
Early diagnosis and treatment lead to better outcomes
For hypothyroidism: Excellent prognosis with early diagnosis and consistent thyroid hormone replacement, especially if treated from infancy
Long-term outcomes are influenced by the duration and severity of untreated hypothyroidism.
Outcomes:
For Cushing syndrome: Successful treatment can lead to normalization of weight, growth, and metabolic parameters, though residual effects like linear growth impairment may persist
For hypothyroidism: With adequate treatment, children can achieve normal growth, development, and pubertal maturation
Cognitive function is generally preserved if treatment is initiated early.
Follow Up:
Children with Cushing syndrome require long-term monitoring for recurrence of hypercortisolism, growth, metabolic parameters, bone density, and psychological well-being
Follow-up for hypothyroidism includes regular monitoring of TSH and free T4 levels to ensure optimal thyroid hormone replacement, growth assessment, and monitoring for potential complications like autoimmune comorbidities.
Key Points
Exam Focus:
Differentiate between constitutional obesity and endocrine causes
Recognize characteristic features of pediatric Cushing syndrome and hypothyroidism
Understand first-line investigations for each condition
Know the role of surgery and medical management for Cushing syndrome and hormone replacement for hypothyroidism
DNB/NEET SS examiners often test management nuances and diagnostic workup.
Clinical Pearls:
Always plot growth on standardized charts for pediatric obesity
poor linear growth with weight gain is a red flag for endocrine causes
Consider Cushing syndrome in a child with rapid weight gain, moon face, purple striae, and poor growth
Suspect hypothyroidism in a lethargic, constipated child with weight gain and dry skin
ACTH levels are key in differentiating Cushing syndrome etiologies.
Common Mistakes:
Attributing all childhood obesity to diet/lifestyle without considering underlying endocrine pathology
Delaying diagnostic workup in suspected cases
Incorrect interpretation of screening tests (e.g., not repeating abnormal tests)
Inadequate dosing or monitoring of thyroid hormone replacement therapy
Inappropriate management of adrenal insufficiency post-adrenalectomy for Cushing syndrome.