THYROID%20DISORDERS

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THYROID DISORDERS

• Abdelaziz Elamin. MD, PhD, FRCPCH
• Professor of Child Health
• Consultant Pediatric Endocrinologist
• Sultan Qaboos University, Oman

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HYPOTHYROIDISM-EPIDEMIOLOGY

• Neonatal screening reveals incidence that varies
  between 1-5/1000 live births
• The most common cause of preventable mental
  retardation in children
• Both acquired congenital forms are linked to
  iodine deficiency
• Diagnosis is easy early treatment is beneficial

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ETIOLOGY

• CONGENITAL
• Hypoplasia mal-descent
• Familial enzyme defects
• Iodine deficiency (endemic cretinism)
• Intake of goitrogens during pregnancy
• Pituitary defects
• Idiopathic

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ETIOLOGY /2

• ACQUIRED
• Iodine deficiency
• Auto-immune thyroiditis
• Thyroidectomy or RAI therapy
• TSH or TRH deficiency
• Medications (iodide Cobalt)
• Idiopathic

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KILPATRIK GRADING OF GOITRE

• Grade 0 Not visible neck extended Not
  palpable
• Grade 1 Not visible, but palpable
• Grade 2 Visible only when neck is
  extended on swallowing,
• Grade 3 Visible in all positions
• Grade 4 Large goiter

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THYROID GLAND

• Derived from pharyngeal endoderm at 4/40
• Migrate from base of the tongue to cover the 23
  tracheal rings.
• Blood supply from ext. carotid subclavian and
  blood flow is twice renal blood flow/g tissue.
• Starts producing thyroxin at 14/40.

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OVERVIEW (2)

• Maternal fetal glands are independent with
  little transplacental transfer of T4.
• TSH doesnt cross the placenta.
• Fetal brain converts T4 to T3 efficiently.
• Average intake of iodine is 500 mg/day. 70 of
  this is trapped by the gland against a
  concentration gradient up to 6001

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THYROID HORMONES

• Iodine tyrosine form both T3 T4 under TSH
  stimulation. However, 10 of T4 production is
  autonomous and is present in patients with
  central hypothyroidism.
• When released into circulation T4 binds to
• Globulin TBG 75
• Prealbumin TBPA 20
• Albumin TBA 5

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THYROID HORMONES (2)

• Less than 1 of T4 T3 is free in plasma.
• T4 is deiodinated in the tissues to either T3
  (active) or reverse T3 (inactive).
• At birth T4 level approximates maternal level but
  increases rapidly during the first week of life.
• High TSH in the first 5 days of life can give
  false positive neonatal screening

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TSH

• Is a Glico-protein with Molecular Wt of 28000
• Secreted by the anterior pituitary under
  influence of TRH
• It stimulates iodine trapping, oxidation,
  organification, coupling and proteolysis of T4
  T3
• It also has trophic effect on thyroid gland

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TSH (2)

• T4 T3 are feed-back regulators of TSH
• TSH is stimulated by a-adrenergic agonists
• TSH secretion is inhibited by
• Dopamine
• Bromocreptine
• Somatostatin
• Corticosteroids

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THYROID HORMONES (3)

• Conversion of T4 to T3 is decreased by
• Acute chronic illnesses
• b-adrenergic receptor blockers
• Starvation severe PEM
• Corticosteroids
• Propylthiouracil
• High iodine intake (Wolff-Chaikoff effect)

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THYROXINE (T4)

• Total T4 level is decreased in
• Premature infants
• Hypopituitarism
• Nephrotic syndrome
• Liver cirrhosis
• PEM
• Protein losing entropathy

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THYROXINE (2)

• Total T4 is decreased when the following drugs
  are used
• Steroids
• Phenytoin
• Salicylates
• Sulfonamides
• Testosterone
• Maternal TBII

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THYROXINE (3)

• Total T4 is increased with
• Acute thyroiditis
• Acute hepatitis
• Estrogen therapy
• Clofibrate
• iodides
• Pregnancy
• Maternal TSI

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FUNCTIONS OF THYROXINE

• Thyroid hormones are essential for
• Linear growth pubertal development
• Normal brain development function
• Energy production
• Calcium mobilization from bone
• Increasing sensitivity of b-adrenergic receptors
  to catecholeamines

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CLINICAL FEATURES

• Gestational age gt 42 weeks
• Birth weight gt 4 kg
• Open posterior fontanel
• Nasal stuffiness discharge
• Macroglossia
• Constipation abdominal distension
• Feeding problems vomiting

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CLINICAL FEATURES (2)

• Non pitting edema of lower limbs feet
• Coarse features
• Umbilical hernia
• Hoarseness of voice
• Anemia
• Decreased physical activity
• Prolonged (gt2/52) neonatal jaundice

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CLINICAL FEATURES (3)

• Dry, pale mottled skin
• Low hair line dry, scanty hair
• Hypothermia peripheral cyanosis
• Hypercarotenemia
• Growth failure
• Retarded bone age
• Stumpy fingers broad hands

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CLINICAL FEATURES (5)

• Skeletal abnormalities
• Infantile proportions
• Hip knee flexion
• Exaggerated lumbar lordosis
• Delayed teeth eruption
• Under developed mandible
• Delayed closure of anterior fontanel

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OCCASIONAL FEATURES

• Overt obesity
• Myopathy rheumatic pains
• Speech disorder
• Impaired night vision
• Sleep apnea (central obstructive)
• Anasarca
• Achlorhydria low intrinsic factor

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OCCASIONAL FEATURES (2)

• Decreased bone turnover
• Decreased VIII, IX platelets adhesion
• Decreased GFR hyponatremia
• Hypertension
• Increased levels of CK, LDH AST
• Abnormal EEG high CSF protein
• Psychiatric manifestations

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ASSOCIATIONS

• Autoimmune diseases (Diabetes Mellitus)
• Cardiomyopathy CHD
• Galactorrhoea
• Muscular dystrophy pseudohypertrophy
  (Kocher-Debre-Semelaigne)

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GOITROGENS

• DRUGS
• Anti-thyroid
• Cough medicines
• Sulfonamides
• Lithium
• Phenylbutazone
• PAS
• Oral hypoglycemic agents

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GOITROGENS

• FOOD
• Soybeans
• Millet
• Cassava
• Cabbage

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CLINICAL FEATURES (4)

• Neurological manifestations
• Hypotonia later spasticity
• Lethargy
• Ataxia
• Deafness Mutism
• Mental retardation
• Slow relaxation of deep tendon jerks

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CONGENITAL HYPOTHYRODISM

• Primary thyroid defect usually associated with
  goiter.
• Secondary to hypothalamic or pituitary lesions
  not associated with goiter.
• 2 distinct types of presentation
• Neurological with MR-deafness ataxia
• Myxodematous with dwarfism dysmorphism

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DIAGNOSIS

• Early detection by neonatal screening
• High index of suspicion in all infants with
  increased risk
• Overt clinical presentation
• Confirm diagnosis by appropriate lab and
  radiological tests

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LABROTARY FINDINGS

• Low (T4, RI uptake T3 resin uptake)
• High TSH in primary hypothyroidism
• High serum cholesterol carotene levels
• Anaemia (normo, micro or macrocytic)
• High urinary creatinine/hydroxyproline ratio
• CXR cardiomegaly
• ECG low voltage bradycardia

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IMAGING TESTS

• X-ray films can show
• Delayed bone age or epiphyseal dysgenesis
• Anterior peaking of vertebrae
• Coxavara coxa plana
• Thyroid radio-isotope scan
• Thyroid ultrasound
• CT or MRI

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TREATMENT (2)

• L-Thyroxin is the drug of choice. Start with
  small dose to avoid cardiac strain.
• Dose is 10 mg/kg/day in infancy. In older
  children start with 25 mg/day and increase by 25
  mg every 2 weeks till required dose.
• Monitor clinical progress hormones level

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TREATMENT

• Life-long replacement therapy
• 5 types of preparations are available
• L-thyroxin (T4)
• Triiodothyronine (T3)
• Synthetic mixture T4/T3 in 41 ratio
• Desiccated thyroid (38mg T4 9mg T3/grain)
• Thyroglobulin (36mg T4 12mg T3/grain)

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THYROID FUNCTION TESTS

• 1. Peripheral effects
• BMR
• Deep Tendon Reflex
• Cardiovascular indices (pulse, BP, LV function
  tests)
• Serum parameters (high cholesterol, CK, AST, LDH
  carcino-embryonic antigen)

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THYROID FUNCTION TESTS (2)

• 2. Thyroid gland economy
• Radio iodine uptake
• Perchlorate discharge test (ve in Pendred
  syndrome autoimmune thyroiditis)
• TSH level
• TRH stimulation tests
• Thyroid scan

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THYROID FUNCTION TESTS (3)

• 3. Tests for thyroid hormone
• Total free T4 T3
• Reverse T3 level
• T3 Resin Uptake
• T3RU x total T4 Thyroid Hormone Binding Index
  (formerly Free Thyroxin Index)

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THYROID FUNCTION TESTS (4)

• Special Tests
• Thyroglobulin level
• Thyroid Stimulating Immunoglobulin
• Thyroid antibodies
• Thyroid radio-isotope scan
• Thyroid ultrasound
• CT MRI
• Thyroid biopsy

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PROGNOSIS

• Depends on
• Early diagnosis
• Proper diabetes education
• Strict diabetic control
• Careful monitoring
• Compliance

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MYXOEDMATOUS COMA

• Impaired sensorium, hypoventilation bradycardia,
  hypotension hypothermia
• Precipitated by
• Infections
• Trauma (including surgery)
• Exposure to cold
• Cardio-vascular problems
• Drugs

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PROGNOSIS

• Is good for linear growth physical features
  even if treatment is delayed, but for mental and
  intellectual development early treatment is
  crucial.
• Sometimes early treatment may fail to prevent
  mental subnormality due to severe intra-uterine
  deficiency of thyroid hormones