Malattia di Graves e Deficienza di GH

Growth Hormone in Pediatrics: Indications and Specificities in Children

• Short Stature Definition: Stature below -2 standard deviations (SD) compared to the general population, normalized by gender and chronological age.

• Auxological Evaluation (Children <2 years old): Measured using length, Weight, Sitting height, Span/height, Height velocity, and Head circumference.

• Auxological Evaluation (Children >2 years old): Measured using Height, Weight, Sitting height, Span/height, Height velocity, and Head circumference.

• Familiar Target: Methods to estimate the expected height of a child, accounting for the parents' height to predict potential growth.

Physiological Conditions Contributing to Short Stature

• Familiar short stature: A condition where short stature runs in families.

• Constitutional delay of growth and puberty: A common cause of short stature, characterized by a delay in the timing of puberty and growth.

• Intrauterine growth retardation: A condition where a child's growth is impaired during pregnancy.

• Systemic diseases: Various illnesses that can affect growth and development.

• Causes of malabsorption: Conditions that impair the absorption of nutrients.

• Genetic syndromes: Conditions associated with specific genetic mutations, that may cause short stature.

• Congenital defects of metabolism: Congenital problems in metabolic pathways responsible for growth.

Endocrinological Conditions Contributing to Short Stature

• GH deficiency: A deficiency in growth hormone production.

• Hypothyroidism: A condition with insufficient production of thyroid hormone.

• Untreated precocious puberty: An early onset of puberty.

• Untreated congenital adrenogenital syndromes: A condition of impaired adrenal gland function.

First Level Assessment for Short Stature

• Blood tests: Full blood count, tTG-reflex, TSH-reflex, general biochemistry (kidney function), urine examination, and IGF-I (particularly important in low body weight children <4 years)

• Radiological examination: Non-dominant hand-wrist X-ray to assess bone age.

Bone Age Reading Methods

• Atlas of Greulich and Pyle

• Tanner-Whitehouse II and III

• FELS

Assessment for Short Stature

• Assessment can include the progression level of metaphyseal welding and the morphology of the skeleton (in order to exclude skeletal dysplasia)

Recombinant Growth Hormone Administration

• Indications: Demonstrated GH deficiency, Turner syndrome,, SGA without catch-up growth (Silver-Russell),, Haploinsufficiency of the SHOX gene, Prader-Willi syndrome, Chronic renal failure, Noonan syndrome.

GH Deficiency: Etiology

• Primary causes (83.5%): Idiopathic GH deficiency, dysembryogenic anomalies, septo-optic dysplasia, midline abnormalities, cleft palate, known genetic mutations (PROP-1, POUF-1, etc.)

• Secondary causes (16.5%): Head trauma, neoplasms (craniopharyngiomas, dysgerminomas, Langherans cell histiocytosis), Nervous system infections, radiation, hydrocephalus.

GH Deficiency: Physiology of Serum Levels

• Graph displays levels over a 24-hour period, showing changes and usual patterns across different ages (7, 13, 20, and 30).

GH Deficiency: Diagnosis

• Auxological/Radiological Criteria: Stature ≤ -3 SD or Stature ≤-2 SD and growth rate/year <-1.0 SD for age and sex assessed for at least 6 months or a reduction in stature of 0.5 SD/yr. Additional measures based on the genetic target and growth rate are also used.

• Biochemical Criteria: GH peak <8 ng/mL in two different stimulation tests.

GH Deficiency: Clinical Data in the Newborn

• Normal or subnormal height and birth weight.

• Micropenis.

• Hypoglycemic episodes.

• Protracted jaundice.

• Dysembryogenetic anomalies of the midline of the face.

Treatment of GH Deficiency

• rhGH treatment: Subcutaneous administration in the evening before bed, daily administration, potentially with 7/7 days, 6/7 days, or 5/7 days dosing. Compliance is a crucial factor, and treatment doses are modulated based on the statural response and IGF-1 values. Catch-up growth, maintenance during puberty, and continued into adulthood are expected outcomes.

• Long-term Side effects: Risk of secondary cancers (bone, colon, prostate) has been observed in studies, but overall risk is minimized by careful followup observation over time and adjusting dosage based on progress.

Thyroid Disorders in Pediatrics

• Anatomy: The thyroid is located in the anterior median region of the neck and consists of two lateral lobes connected by a median isthmus, lying on the ventral surface of the larynx and the first two tracheal rings within the perithyroid fibrous sheath. This area has specific characteristics of follicle epithelial cells surrounded by a colloid.

• Physiology: The hypothalamic-pituitary-thyroid axis regulates thyroid hormone levels.

• Effects of thyroid hormones: Growth promotion, stimulation of fat and carbohydrate metabolism, increased basal metabolism, effects on the cardiovascular system, increased gastrointestinal motility, and CNS performance and muscle contraction.

• Congenital Hypothyroidism: High incidence (1:3,000-4,000 live births), with more females affected.

  • Retesting: important in preterm infants, low birth weight (LBW) infants, very low birth weight (VLBW) infants, twins, infants of mothers with hypothyroidism, hospitalized in a paediatric intensive care unit (PICU).
  • Causes: Transient: hypothyroidal mother in pregnancy, iodine deficiency, isolated and transient TSH deficiency in offspring of mothers with Graves' disease, transient (preterm) infant hyperthyroxinemia; Permanent: thyroid dysgenesis, Endemic iodine deficiency, Defects of thyroid hormonogenesis, Central hypothyroidism (congenital TSH deficiency.)
  • Morphology: Ectopia (48%), Agenesis (31%), Hypoplasia (5%), Hyperplasia (6%), Normal (10%).
  • Clinical findings: Coarse appearance, persistence of lanugo, umbilical hernia, goiter, macroglossia, hoarse cry, prolonged jaundice, distended abdomen, floppiness, hypersomnia and difficult sucking, noisy breathing.
  • Later Clinical findings: Constipation, tendency to hypothermia, poor weight gain, poor height gain, delay in psycho-motor development, hoarse voice, bradylalia, and delayed bone age.
  • Treatment: L-thyroxine doses based on age. Follow-up of TSH and FT4 to monitor progress.

• Acquired Hypothyroidism: Acquired after the neonatal period. Intellectual prognosis is normal.

  • Causes: Hashimoto's thyroiditis, Iodine deficiency, Subacute thyroiditis, Resistance to thyroid hormones, TSH-deficient hypothyroidism, Iatrogenic, Cystinosis.
  • Clinical findings: Reduced height velocity, weight gain, asthenia/sleepiness, constipation, cold intolerance, goiter, subcutaneous edema, bradycardia, pubertal delay/menses irregularities.
  • Lab Findings: elevated TSH, lowered FT4 (primary); Lowered TSH, with lowered FT4(central hypothyroidism)

• Hashimoto's Thyroiditis:

  • Epidemiology: Most common autoimmune thyroid disease in children and adolescents, with females more commonly affected.
  • Causes: Organ-specific autoimmune disorder with immune-mediated destruction of the thyroid and lymph cell infiltration, resulting in follicle destruction.. Also associated familial predisposition.
  • Clinical findings: Variable clinical course, potentially with euthyroidism, hyperthyroidism, overt hypothyroidism and subclinical hypothyroidism.
  • Lab findings: FT4 and FT3 are low or normal, TSH is elevated or normal. Anti-thyroglobulin, Anti-thyroid peroxidase antibodies.
  • Thyroid ultrasound: Evidence of inhomogeneous parenchyma with hypoechoicity, hyperechoic septa (fibrosis), thickened isthmus, increased vascularization, pseudonodules.
  • Therapy: Replacement therapy with L-thyroxine.

• Graves' Disease:

  • Epidemiology: A rare but autoimmune cause of hyperthyroidism.
  • Causes: Autoimmune etiology mainly due to antibodies activating the TSH receptor (TRAb).
  • Clinical findings: Goiter, Tachycardia, palpitations, arterial hypertension, behavior disorders, reduced school performance, ophthalmopathy(exophthalmos), tremors, increased appetite, weight loss, frequent stools.
  • Lab findings: FT3 and FT4 are elevated, TSH is typically very low. Elevated Anti-TSH receptor. Negative or positive antithyroid antibodies (e.g., anti-thyroglobulin, anti-thyroperoxidase).
  • Ultrasound: Enlarged thyroid gland with increased size, exhibiting a finely inhomogeneous, predominantly hypo-reflective structure, with blood overflow.
  • Neuro-ophthalmological visit: important, due to ocular manifestations.
  • Therapy: Methimazole, Propylthiouracil, Radio metabolic therapy, total thyroidectomy.

• Thyroid Nodules:

  • Indications of malignancy: hypoechoic nodule, diameter >1 cm, uneven margins, diffuse "spray" microcalcifications, marked intranodal vascularization (using Doppler ultrasound), satellite lymph node lacking a typical oval shape.
  • ACR TI-RADS Classification (to assess the risk)

Obesity in Pediatrics

• Epidemiology: Historic changes in perceptions; obesity has become a significant health concern in industrialized countries, with prevalence increasing over the past 10-15 years. Changes in prevalence related to age, gender, geography, socio-economic status, family history of obesity, and family education.

• Diagnostic Criteria: BMI (Body Mass Index) is the recommended parameter (weight [kg] / height²[m²]). Weight excess is measured relative to ideal weight (IW).

• Diagnostic Criteria: BMI in children and BMI in adults.

  • Obesity is diagnosed in different ways in children and adults.

• Etiopathogenesis: Multifactorial. Environmental factors (sedentary lifestyle, excessive nutrition) and genetic factors (40-50% contribution). Monogenic forms and Syndromic forms are also possible.

• Environmental factors: Inadequate nutrition habits (simple sugars diet, excessive processed foods, skipping breakfast), limited physical activity in favor of TV, computer, video games, sedentary activities, educational issues (food reward, little time dedicated for children, limited opportunity for sports, parental separation).

• Complications: Orthopedic (flat-valgus foot, valgus knee, hyperlordosis, scoliosis, femoral head epiphysiolysis), Neurologic (pseudotumor cerebri), Respiratory (dyspnea, OSAS), Gastrointestinal (fatty liver [25%], transaminase elevations [10%], cholelithiasis, hiatal hernia), Dermatologic (atrophic or rubrous striae, intertrigo, acne, eczema, acanthosis nigricans). Other potential complications in adolescents: Cardiocirculatory (metabolic risk factors associated w/ arterial HT, predictive of atheromatous diseases), Psychological aspects (increased risk of psychological or psychiatric problems, reduced self-esteem, anger).

• Clinical Approach: The clinical approach involves a thorough history (family history of obesity, type 2 diabetes, endocrinopathies, dyslipidemia, hypertension, psychological or social history, depression, eating disorders; diet; medication history) and examinations (physical assessment with weight, height, BMI, blood pressure plicometry, and additional evaluation of various organ systems; and blood tests to evaluate lipid profile, glycemia levels, insulin, glycosylated Hb, liver profile, thyroid function and uric acid levels; and OGTT for high-risk groups.)

• Treatment: Family approach to problem management, increasing physical activity through structured workouts, implementation of a healthy diet, and appropriate medications (GLP-1 inhibitors, metformin).