Hypothyroidism THYROID DISORDERS Abdelaziz Elamin

Document Sample
Hypothyroidism THYROID DISORDERS Abdelaziz Elamin Powered By Docstoc
					THYROID DISORDERS
  Abdelaziz Elamin. MD, PhD, FRCPCH
  Professor of Child Health
  Consultant Pediatric Endocrinologist
  Sultan Qaboos University, Oman
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
           ETIOLOGY
• CONGENITAL
 Hypoplasia & mal-descent
 Familial enzyme defects
 Iodine deficiency (endemic cretinism)
 Intake of goitrogens during pregnancy
 Pituitary defects
 Idiopathic
         ETIOLOGY /2

• ACQUIRED
 Iodine deficiency
 Auto-immune thyroiditis
 Thyroidectomy or RAI therapy
 TSH or TRH deficiency
 Medications (iodide & Cobalt)
 Idiopathic
 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
        THYROID GLAND
• Derived from pharyngeal endoderm at
  4/40
• Migrate from base of the tongue to
  cover the 2&3 tracheal rings.
• Blood supply from ext. carotid &
  subclavian and blood flow is twice renal
  blood flow/g tissue.
• Starts producing thyroxin at 14/40.
           OVERVIEW (2)

• Maternal & fetal glands are independent
  with little transplacental transfer of T4.
• TSH doesn’t 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 600:1
    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%
  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
                 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
             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
    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)
       THYROXINE (T4)
 Total T4 level is decreased in:
  Premature infants
  Hypopituitarism
  Nephrotic syndrome
  Liver cirrhosis
  PEM
  Protein losing entropathy
        THYROXINE (2)
 Total T4 is decreased when the
 following drugs are used:
 Steroids
 Phenytoin
 Salicylates
 Sulfonamides
 Testosterone
 Maternal TBII
        THYROXINE (3)
 Total T4 is increased with:
  Acute thyroiditis
  Acute hepatitis
  Estrogen therapy
  Clofibrate
  iodides
  Pregnancy
  Maternal TSI
 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
    CLINICAL FEATURES
Gestational age > 42 weeks
Birth weight > 4 kg
Open posterior fontanel
Nasal stuffiness & discharge
Macroglossia
Constipation & abdominal distension
Feeding problems & vomiting
     CLINICAL FEATURES (2)
•   Non pitting edema of lower limbs & feet
•   Coarse features
•   Umbilical hernia
•   Hoarseness of voice
•   Anemia
•   Decreased physical activity
•   Prolonged (>2/52) neonatal jaundice
     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
  CLINICAL FEATURES (5)
• Skeletal abnormalities:
  Infantile proportions
  Hip & knee flexion
  Exaggerated lumbar lordosis
  Delayed teeth eruption
  Under developed mandible
  Delayed closure of anterior fontanel
      OCCASIONAL FEATURES

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

•   Autoimmune diseases (Diabetes Mellitus)
•   Cardiomyopathy & CHD
•   Galactorrhoea
•   Muscular dystrophy + pseudohypertrophy
    (Kocher-Debre-Semelaigne)
          GOITROGENS
• DRUGS
 Anti-thyroid
 Cough medicines
 Sulfonamides
 Lithium
 Phenylbutazone
 PAS
 Oral hypoglycemic agents
         GOITROGENS

 FOOD
 Soybeans
 Millet
 Cassava
 Cabbage
  CLINICAL FEATURES (4)
 Neurological manifestations
  Hypotonia & later spasticity
  Lethargy
  Ataxia
  Deafness + Mutism
  Mental retardation
  Slow relaxation of deep tendon jerks
 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
             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
    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
        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
           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
            TREATMENT

 Life-long replacement therapy
 5 types of preparations are available:
  L-thyroxin (T4)
  Triiodothyronine (T3)
  Synthetic mixture T4/T3 in 4:1 ratio
  Desiccated thyroid (38mg T4 & 9mg T3/grain)
  Thyroglobulin (36mg T4 & 12mg T3/grain)
 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)
 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
 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)
 THYROID FUNCTION TESTS (4)
 Special Tests:
  Thyroglobulin level
  Thyroid Stimulating Immunoglobulin
  Thyroid antibodies
  Thyroid radio-isotope scan
  Thyroid ultrasound
  CT & MRI
  Thyroid biopsy
          PROGNOSIS
Depends on:
 Early diagnosis
 Proper diabetes education
 Strict diabetic control
 Careful monitoring
 Compliance
  MYXOEDMATOUS COMA
 Impaired sensorium, hypoventilation
 bradycardia, hypotension & hypothermia
 Precipitated by:
      Infections
      Trauma (including surgery)
      Exposure to cold
      Cardio-vascular problems
      Drugs
           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