Thyroid diseases

Kussia (MD)
 Basic science - physiology
o The thyroid gland is located immediately below the
larynx on each side of trachea( inferior to cricoid
cartilage).
o Butterfly shaped with two lobes
o Involved in production, storage, and release of thyroid
hormone
o Thyroid secretion is controlled primarily by thyroid
stimulating hormone (TSH) secreted by anterior
pituitary and thyrotropin releasing hormone(TRH)
secreted by hypothalamus.
 Basic science - physiology
• Primary function of the thyroid gland is the
secretion of thyroid hormones
– T4 is primary released hormone
– T3 at least 4 times more active
– T4 is converted to T3 peripherally
• Production of thyroid hormones is regulated
in normal gland by thyroid stimulating
hormone (TSH) from the anterior pituitary
• T4 and T3 act as negative feedback to the
release of TSH
• TSH is stimulated by thyroid releasing
hormone (TRH) of the hypothalamus
– TRH is believed to be continually secreted
– Pituitary gland is more sensitive to negative
feedback of T4 and T3 than TRH
Hypothalamic Pituitary Axis
 Thyroid hormone synthesis
o Only 1/5th of the circulating iodides is
absorbed by thyroid cells for hormone
production.
o Transfer of iodides to the interior of the cells is
called iodide trapping.
o Oxidation of iodides to iodines by peroxidase.
o Binding of iodine to tyrosine in the
thyroglobulin is called iodinification.
• Tyrosine +iodine → monoiodotyrosine
• Monoiodotyrosine +
monoiodotyrosine→diiodotyrosine
• Diiodotyrosine +
monoiodotyrosine→triiodotyronine(T3)
• Diiodotyrosine + diiodotyrosine
→thyroxine(T4)
 Thyroid Hormones

Thyroxine ((T4) & 3,5,3-triiodothyronine (T3)

 Lipid soluble
• Thyroid hormone is stored in the thyroglobulin
in sufficient amount for 2-3 months.
• Thyroid hormones are cleaved from
thyroglobulin and released in to circulation.
• Thyroid hormones are bound to plasma
proteins and slowly released to tissues.
• Thyroid hormones bound to intracellular
proteins(nuclear receptor)
 Effects of Thyroid Hormone
• Fetal brain and skeletal maturation
 Increase in basal metabolic rate
 Inotropic and chronotropic effects on heart
• Increases sensitivity to catecholamines
• Stimulates gut motility
• Increase bone turnover
• Promotes glucose up take, decrease in serum
cholesterol
• They affect the function of virtually every organ
system.
When the Thyroid Doesn’t Work

Hyperthyroidism Hypothyroidism
• Too Much Thyroid • Too Little Thyroid
Hormone Hormone
• Metabolism Speeds • Metabolism Slows
Up Down
 Hypothyroidism
• Hypothyroidism results from deficient
production of thyroid hormone or a defect in
thyroid hormone receptor activity.
• Central –hypothalamus/pituitary
• TSH deficiency
• RH deficiency/unresponsiveness
• Primary –thyroid disease
• Congenital/acquired
 Congenital hypothyroidism
o Occurs 1/4,000 live births (USA)
o Causes include
o Thyroid dysgenesis
(aplasia,hypoplasia ,ectopic thyroid)
 Accounts 80-85% of congenital
hypothyroidism
o Defective synthesis of thyroid hormone
o Defect of iodide transport
• Thyroid perioxidase defect of organification
• Defect of thyroglobulin synthesis
• Defect in thyroid hormone transport
• Radioiodine administration
• Thyrotropin deficiency
• Thyroid hormone unresponsiveness
Iodine deficiency
 Clinical Manifestations
o Most are asymptomatic at birth
o Feeding difficulties, sluggishness
o Protruding tongue ,hypertelorism, eye lid edema, short
neck, depressed nasal bridge, hair line down at fore head
o Slow crying ,subnormal temperature
o Respiratory difficulties ,noisy respirations
o Cool and dry skin
o Edema of genitalia and extremities
o jaundice
Congenital hypothyroidism
• Wild anterior fontanel, normal or increased
head circumference
• Slow pulse, Cardiomegaly and pericardial
effusion
• 10% associated with congenital anomalies
especially cardiac
• Mental and growth retardation if not early
detected and treated
 Investigation
o T3 &T4
o TSH
o Thyroid scanning
o Thyroid ultra sound
o Thyroglobulin level
o Bone radiography
 Treatment
o Levothyroxine 10-15 microgram/kg
o Prognosis is excellent with early diagnosis and
appropriate treatment
o Mental and physical retardation if treatment
delayed or not treated
 Acquired hypothyroidism
• Hypothyroidism affects 1/333 school aged
children, most of which are subclinical
• Causes include:
• Autoimmune thyroidits
• Thyroidectomy,antithyroid drugs
• Head and neck irradiation
• Langerhancell histocytosis
• Hypothalamic pituitary disease
 Clinical manifestation

• Growth deceleration
• Goiter
• Myxedema
• Delayed puberty or precocious puberty
• Cold intolerance, decreased energy
• Increased need for sleep
• Menstrual abnormalities in females
• School performance is usually not affected
 Diagnosis and treatment
• Clinical evaluation
• TSH and T4,T3
• Response for thyroxine replacement is
satisfactory but expected adult height may not
be achieved.
 Hyperthyroidism
• Hyperthyroidism results from excessive secretion of
thyroid hormone
• Causes of hyperthyroidism include :
• Graves disease
• Neonatal Graves disease
• Thyrotropin-secreting tumor
• Toxic multinodular goiter
• Toxic solitary adenoma
• Subacute thyroiditis
 Graves Disease
• Most common cause of hyperthyroidsm in children
• Prevalence 1: 5000 of children (USA)
• 5 : 1 female to male ratio
• Peak incidence 11- 15 years
• Results from autoantibodies to the (TSH) receptor
(TSHR-Ab) that activate the receptor, there by
stimulating thyroid hormone synthesis and secretion as
well as thyroid growth (causing a diffuse goiter).
• TSH receptors have been identified in retro-orbital
adipocytes and might represent a target for antibodies
 Clinical Manifestation
• The clinical course in children is highly variable
• Symptoms develop gradually in children
• Emotional disturbances accompanied by
motor hyperactivity
• Restless, sleepless
• Tremor of the fingers
• voracious appetite combined with loss of or
no increase in weight
• Acceleration in growth velocity.
• Heat intolerance, increased sweating ,
Palpitation , weakness
• Sinus tachycardia, Warm, moist skin
• High-output heart failure
• Diffuse goiter
• Exophthalmos
• May be associated with other autoimmune diseases
Graves disease
 Thyroid crisis, or thyroid storm
• An acute onset, hyperthermia, severe
tachycardia, heart failure, and restlessness.
• Rapid progression to delirium, coma, and
death
• Precipitated by infection, surgery
Investigation
• T3,T4
• TSH
• Anti thyroid antibodies

TREATMENT
• Antithyroid drugs(PTU and methimazole)
• β-adrenergic blocking agent (Propranol)
• radioiodine
• Surgery