65  Basics

65.1 Introduction

Endocrinology is the study of hormones and the glands that produce them. In children, the endocrine system governs critical processes such as growth, puberty, metabolism, and stress response. Pediatric endocrinology focuses on disorders affecting hormone production, secretion, and action during the developmental years.

Unlike adults, endocrine disorders in children often present with growth disturbances, delayed or precocious puberty, or developmental abnormalities, rather than classical systemic symptoms. A strong understanding of endocrine physiology, growth assessment, and hormonal feedback mechanisms is essential for early recognition and management.

This essay outlines the anatomy and physiology of the endocrine system, key hormones, principles of endocrine function testing, and an overview of common endocrine disorders in children.

65.2 Anatomy and Physiology of the Endocrine System

The endocrine system consists of specialized glands that secrete hormones directly into the bloodstream to act on distant target organs. These hormones regulate metabolism, electrolyte balance, growth, and reproduction.

65.2.1 Major Endocrine Glands in Children

Gland Major Hormones Primary Functions
Hypothalamus CRH, TRH, GHRH, GnRH Regulates pituitary secretion
Pituitary GH, ACTH, TSH, LH, FSH, Prolactin Growth, metabolism, reproduction
Thyroid T3, T4, Calcitonin Metabolism, growth, brain development
Parathyroid PTH Calcium and phosphate balance
Adrenal Cortisol, Aldosterone, Androgens Stress response, electrolyte control
Pancreas Insulin, Glucagon Blood glucose regulation
Gonads Oestrogen, Testosterone Pubertal development
Pineal Melatonin Circadian rhythm

These glands communicate through a hierarchy known as the hypothalamic–pituitary–target gland axis.

65.3 The Hypothalamic–Pituitary Axis

The hypothalamus integrates neural and hormonal signals to regulate endocrine function. It secretes releasing or inhibiting hormones into the hypophyseal portal system that act on the pituitary gland.

The pituitary, often termed the “master gland,” releases trophic hormones that stimulate target organs such as the thyroid, adrenal glands, and gonads.

65.3.0.1 Example of Hormonal Axes

Axis Hypothalamic Hormone Pituitary Hormone Target Organ Target Hormone
Thyroid TRH TSH Thyroid gland T3, T4
Adrenal CRH ACTH Adrenal cortex Cortisol
Gonadal GnRH LH, FSH Ovaries/Testes Oestrogen, Testosterone
Growth GHRH GH Liver IGF-1

Feedback loops maintain hormone balance: elevated target hormones inhibit hypothalamic and pituitary secretion, preventing overproduction.

65.4 Principles of Hormone Action

Hormones exert their effects through specific receptors located either on the cell membrane (peptide hormones) or within the cell (steroid and thyroid hormones).

65.4.1 Types of Hormones

Type Examples Mechanism of Action
Peptide hormones GH, insulin, ACTH Bind to cell-surface receptors → activate second messengers
Steroid hormones Cortisol, oestrogen, testosterone Enter cells → bind nuclear receptors → modulate gene transcription
Amine hormones T3, T4, catecholamines Derived from tyrosine → act on nuclear or membrane receptors

Because of these mechanisms, hormone effects may be rapid (e.g., insulin, catecholamines) or delayed but sustained (e.g., thyroid or steroid hormones).

65.5 Growth and Development: A Central Theme

Growth is the most visible reflection of endocrine health in children. It results from the interplay between genetics, nutrition, and hormones—particularly growth hormone (GH), thyroid hormones, cortisol, sex steroids, and insulin.

65.5.1 Growth Hormone Axis

  • GH is secreted by the anterior pituitary in a pulsatile fashion.
  • Stimulated by GHRH and inhibited by somatostatin.
  • Acts on the liver to produce Insulin-like Growth Factor-1 (IGF-1), which mediates bone and tissue growth.

Deficiency of GH leads to short stature with normal body proportions, while excess GH (rare in children) causes gigantism.

65.6 Assessment of Endocrine Function in Children

Because hormone levels fluctuate with time of day, age, and physiological state, interpretation of results must be age-appropriate.

65.6.1 Clinical Assessment

  1. Detailed history
    • Growth pattern, family history of endocrine disorders.
    • Pubertal changes, appetite, and energy levels.
  2. Physical examination
    • Height and weight plotted on growth charts.
    • Pubertal staging (Tanner).
    • Dysmorphic features, goitre, pigmentation, or obesity.

65.6.2 Laboratory Evaluation

  • Basal hormone levels: measured at specific times (e.g., morning cortisol).
  • Dynamic tests:
    • Stimulation tests (for suspected deficiency): e.g., GH stimulation, ACTH stimulation.
    • Suppression tests (for suspected excess): e.g., dexamethasone suppression test.
  • Imaging: MRI of hypothalamic-pituitary region, thyroid ultrasound, or adrenal CT where indicated.
  • Genetic testing: for congenital or syndromic causes.

65.7 Common Endocrine Disorders in Children

65.7.1 Disorders of Growth and Pituitary Function

65.7.2 Growth Hormone Deficiency (GHD)

  • Causes: congenital pituitary hypoplasia, tumours, trauma, or idiopathic.
  • Features: short stature, delayed bone age, infantile face, hypoglycaemia.
  • Diagnosis: low IGF-1, failed GH stimulation.
  • Treatment: recombinant GH therapy.

65.7.3 Growth Hormone Excess

  • Usually from a pituitary adenoma.
  • Causes excessive linear growth (gigantism) or acromegalic features.
  • Managed surgically or with somatostatin analogues.

65.8 Thyroid Disorders

65.8.1 Congenital Hypothyroidism

  • Caused by thyroid dysgenesis or dyshormonogenesis.
  • Features: prolonged neonatal jaundice, macroglossia, hypotonia, umbilical hernia.
  • Early detection via newborn screening.
  • Treatment: lifelong levothyroxine replacement.

65.8.2 Juvenile Hypothyroidism

  • Often autoimmune (Hashimoto’s thyroiditis).
  • Features: growth retardation, fatigue, dry skin, constipation.
  • Managed with thyroid hormone replacement.

65.8.3 Hyperthyroidism

  • Most commonly Graves’ disease (autoimmune).
  • Presents with weight loss, tachycardia, goitre, tremor.
  • Treatment includes antithyroid drugs (carbimazole), beta-blockers, or surgery.

65.9 Adrenal Disorders

65.9.1 Congenital Adrenal Hyperplasia (CAH)

  • Autosomal recessive enzyme defect (most often 21-hydroxylase deficiency).
  • Features: ambiguous genitalia in females, dehydration, salt wasting.
  • Diagnosis: elevated 17-hydroxyprogesterone.
  • Treatment: hydrocortisone and fludrocortisone replacement.

65.9.2 Adrenal Insufficiency (Addison’s Disease)

  • Causes: autoimmune, infections (TB), or congenital defects.
  • Features: fatigue, hyperpigmentation, hypotension, salt craving.
  • Treatment: hydrocortisone and mineralocorticoid replacement.

65.9.3 Cushing Syndrome

  • From prolonged steroid therapy or adrenal tumour.
  • Features: obesity, moon facies, striae, growth retardation.
  • Managed by reducing steroid dose or surgical excision of the tumour.

65.10 Disorders of Puberty

65.10.1 Precocious Puberty

  • Onset of secondary sexual characteristics before 8 years in girls, 9 years in boys.
  • May be central (early activation of HPG axis) or peripheral (excess sex steroids).
  • Requires MRI brain and hormonal evaluation.
  • Managed with GnRH analogues for central forms.

65.10.2 Delayed Puberty

  • Absence of pubertal changes beyond 13 years (girls) or 14 years (boys).
  • May result from constitutional delay, hypogonadism, or chronic illness.
  • Treatment involves reassurance or sex steroid replacement when indicated.

65.11 Disorders of Glucose Metabolism

65.11.1 Type 1 Diabetes Mellitus (T1DM)

  • Autoimmune destruction of pancreatic beta cells.
  • Commonest endocrine disorder in children.
  • Symptoms: polyuria, polydipsia, weight loss, fatigue.
  • Complication: diabetic ketoacidosis (DKA).
  • Management: insulin therapy, dietary regulation, self-monitoring.

65.11.2 Type 2 Diabetes Mellitus (T2DM)

  • Increasingly seen in obese adolescents.
  • Features: obesity, acanthosis nigricans, mild hyperglycaemia.
  • Managed by lifestyle changes, metformin, and sometimes insulin.

65.11.3 Parathyroid and Calcium Disorders

  • Hypocalcaemia due to hypoparathyroidism, vitamin D deficiency, or pseudohypoparathyroidism → tetany, seizures, Chvostek and Trousseau signs.
  • Hypercalcaemia due to hyperparathyroidism or malignancy → polyuria, vomiting, bone pain.
  • Management focuses on correcting calcium and vitamin D levels.

65.12 Diagnostic Principles in Pediatric Endocrinology

Because hormone secretion in children changes with age and puberty, interpretation requires age-specific reference ranges. For example: - Neonates have higher cortisol and thyroid hormone levels. - GH secretion is pulsatile; random measurements are unreliable. - Pubertal staging is crucial for evaluating gonadal hormones.

Dynamic testing remains a cornerstone of diagnosis:

  • Stimulation tests (GH, ACTH, GnRH) evaluate deficiency.

  • Suppression tests (dexamethasone, glucose tolerance) assess hormone excess.

In addition, imaging helps detect structural lesions, and genetic testing confirms syndromic causes such as Prader–Willi, Turner, or Kallmann syndromes.

65.13 Principles of Management

65.13.1 Hormone Replacement

  • Use physiological doses to mimic normal secretion (e.g., hydrocortisone 3 times daily rather than dexamethasone).
  • Regular adjustment according to growth and puberty.

65.13.2 Suppression of Hormone Excess

  • Antithyroid drugs, glucocorticoid therapy for CAH, or GnRH analogues for precocious puberty.

65.13.3 Treatment of Underlying Causes

  • Surgery for tumours, antibiotics for infections, or withdrawal of exogenous steroids.

65.13.4 Long-Term Follow-Up

  • Regular growth and pubertal assessment.
  • Monitoring for treatment side effects (e.g., growth suppression from steroids).
  • Transition planning for adult endocrinology care.

65.14 Growth Monitoring and Interpretation

Growth assessment is central to paediatric endocrinology.
Essential tools include:

  • Growth charts: plot height, weight, BMI, and head circumference.
  • Mid-parental height: predicts target range.
  • Growth velocity: <4 cm/year after age 4 suggests pathology.
  • Bone age: X-ray of left hand/wrist compared with standards (Greulich–Pyle).

Discrepancy between bone age and chronological age helps differentiate constitutional delay from endocrine causes of short stature.

65.15 Psychosocial Aspects

Endocrine disorders can profoundly affect self-esteem, body image, and school performance.
Children with delayed puberty or short stature may face bullying or anxiety, while those with obesity or hirsutism may experience social withdrawal.

Management should include:

  • Psychological counselling.
  • Support groups and family education.
  • Encouragement of normal participation in school and sports.

65.16 Summary Table

Domain Common Disorders Key Hormones Typical Features
Growth GH deficiency/excess GH, IGF-1 Short/tall stature
Thyroid Hypo-/hyperthyroidism T4, TSH Growth delay, goitre
Adrenal CAH, Addison’s, Cushing’s Cortisol, Aldosterone Virilisation, fatigue, obesity
Puberty Precocious, delayed LH, FSH, sex steroids Early/late sexual changes
Glucose T1DM, T2DM Insulin, glucagon Polyuria, weight change
Calcium Hypo-/hyperparathyroidism PTH, Vit D Tetany, bone pain

65.17 Key Takeaways

  • Pediatric endocrinology deals with hormonal disorders affecting growth, metabolism, and development.
  • Early recognition is crucial to prevent irreversible effects on growth and neurodevelopment.
  • Growth failure, pubertal delay, or unexplained obesity should prompt endocrine evaluation.
  • Lifelong follow-up, family education, and psychosocial support are integral to successful management.

65.18 Suggested Reading

  1. Nelson Textbook of Pediatrics, 22nd Edition.
  2. Sperling M. A., Pediatric Endocrinology, 5th Edition.
  3. Brook CGD, Clayton PE. Clinical Pediatric Endocrinology, 7th Edition.
  4. WHO. Handbook on Pediatric Endocrine Disorders for Low-Resource Settings, 2021.
  5. ESPE Clinical Practice Guidelines, 2023.