- High incidence in the general population at any age
- High prevalence in women (2^4%)
- L & rsquo; thyroid hormone controls the & rsquo; metabolic activity of all regulating fabrics genes whose protein products are essential for cellular respiration
I/- physiological reminders :
Thyroid gland : endocrine gland in front of the trachea; below the larynx. It consists of two lobes connected by the & rsquo; isthmus. The thyroid tissue is organized in follicle
Role : synthesis, storage and secretion of thyroid hormones:
– T3 tri-iodothyronine.
– T4: levothyroxine.
Synthesis / storage and release of thyroid hormones :
The thyroid hormone synthesis involves several steps :
– Uptake of iodine : l & rsquo; dietary iodine is actively taken up by the thyroid
– Oxidation and fixation of iodine on the tyrosyl groups of thyroglobulin: provided by a thyroperoxidase (TPO).
– Coupling :
A mono-iodotyrosine residue (WITH) and a di-iodotyrosine residue(THIS) combine to form triiodothyronine T3, and two residues of di-iodotyrosine to form the tétrabdothyronine or thyroxine T4.T3 and T4 are fixed to the thyroglobulin.
– Storage : Thyroglobulin bringing T3, T4, MIT a DIT, is stored in the colloid in the light of thyroid follicle.
– Release : thyroglobulin passes from the follicular lumen to the apical portion of thyrocyte by endocytosis. Lysosomes containing catalytic enzymes release thyroid hormones by proteolysis of thyroglobulin .the hormones freed leave the thyrocyte at the basement membrane.
Distribution and Metabolism :
– T3 is metabolically more powerful than T4
– The free fraction of thyroid hormones is metabolized by the liver and excreted in the bile
Role of thyroid hormones :
The effects of thyroid hormones are very complex and are best known by the consequences of their disabilities. They act multilevel :
- height and weight growth :
A deficiency before birth gives an ossification defect but a child born with a normal size. Disabilities after birth causes failure to thrive development defect.
- Maturation of central nervous system :
The role of thyroid hormones is particularly important before birth and in 45 first days, because their disability is the & rsquo; origin of cretinism (irreversible mental retardation). The myelin protein (important constituent of myelin) is produced by a gene regulated by thyroid hormones during development.
- Basal metabolism and thermogenesis :
Thyroid hormones increase the basal metabolism and consumption & rsquo; oxygen to the heart, skeletal muscle, liver, kidneys, but not in the brain, spleen and gonad. The l & rsquo mechanism; calorigenic action of thyroid hormones remains unclear.
- Heart : They increase the speed and especially the cardiac rhythm.
- striated muscle :
L & rsquo; Hyperthyroidism causes muscle wasting and & rsquo; hypothyroidism slower contraction.
- Adipose tissue :
They increase the sensitivity of fat cells to the & rsquo; lipolytic effect of various hormones, particularly catecholamines. They stimulate the catabolism of cholesterol into bile acids and & rsquo; cholesterol is a characteristic sign of & rsquo; hypothyroidism.
– The synthesis is regulated by thyrotropin pituitary (TSH) itself controlled by thyrotropin releasing hormone (MARKET) hypothalamic
– Thyroid hormones exert Feed Back on the secretion of TSH and TRH.
normal values :
TSH : 0.4 at 4 Hare / l
II/- the hypothyroidism :
- L & rsquo; hypothyroidism is a thyroid hormone secretion deficiency = Inability of the thyroid to produce enough & rsquo; hormones to fill the metabolic needs.
- The primary deficit is said in the case of & rsquo; achievement of the thyroid gland (elevated TSH)
- The deficit is called secondary if TSH deficiency related to a pituitary or hypothalamic damage (normal or low TSH)
Clinical signs :
Asthenia – Weight gain – bradycardia – Hypothermia – dryness Constipation – Myalgie ; Muscle cramps – Arthralgie – Hair loss
• Not treated, l & rsquo; hypothyroidism has significant deleterious effects on cardiovascular health, neurological function, reproduction and fetal development
Consequences if not support for hypothyroidism :
—> cardiovascular : Decreased cardiac output
—> neurological Slowdown of intellectual functions, psychiatric disorders, cerebral hypoxia
- Impairment of Fertility
- Increased risk of & rsquo; spontaneous abortion and d & rsquo; premature delivery
- Impaired development of the newborn
—> Coma myxœdémateux : Hypotension grave + multi-organ failure
Diagnosis hypo-thyroïdies :
- TSH = sensitive measuring thyroid function
- Measurement of d & rsquo rates; thyroid antibodies
III/- hyperthyroidism :
Overactive thyroid gland with increased secretion of thyroid hormones -> Thyrotoxicose
Different forms and their etiologies :
anti TSH receptor antibody
|Thyrotoxicosis ophthalmopathy goiter diffuse homogeneous|
|toxic adenoma||Benign tumor secreting||thyrotoxicosis isolated nodule|
|Goitre multi- toxic nodular||secreting benign tumors||Big goiter thyrotoxicosis heterogeneous multiple nodules|
|Surcharge iodée||Iatrogène (Amiodarone, products of iodinated contrast, antiseptic
|Thyrotoxicose Goitre variable|
typical form of thyrotoxicosis :
general signs: Weightloss, skin temperature with high Sweating and polydipsia cardiovascular Signs: palpitations and tachycardia rest (chronotropic and inotropic effects positive)
neuromuscular signs: mainly muscle intense fatigue, tremors, Nervousness, agitation, sleeping troubles
Complications are often heart (rhythm disorders and heart failure) with alteration of the & rsquo; condition (weakness and significant weight loss)
positive diagnosis :
TSH and free T4
IV/- Treatment of thyroid dysfunction :
A / Treatment of hypothyroidism :
- levothyroxine (The T4) is the replacement therapy of choice for hypothyroidism Y. It is indicated for the primary or secondary hypothyroidism and in all situations where Your wishes to brake TSH.
- La liothyronine (L-T3) is also marketed; faster action; low half-life; generally used in the case of emergencies
Strategy and therapeutic optimization :
The doses are adapted to the patient's response (symptom control) and assay results TSH
All the 6 at 8 week s & rsquo; requires clinical assessment and biochemical
+ The doses were increased in increments of 12,5 normalization of TSH levels and reversal of signs and symptoms
Rate of target TSH 0,45-4,12mUI / L
+ 1 daily intake, morning fasting (long half-life)
+ Distance from any power (at least 20 at 30 minutes before breakfast).
B / Treatment of hyperthyroidism :
Basic treatment :
- To reduce the & rsquo; activity of the & rsquo; thyroid hormone, the ANTITHYROl'DIENS used
- The treatments are designed to limit the amount of & rsquo; thyroid hormones born the gland can produce
- The therapeutic aims:
A directly decrease the synthesis Block ionic transport
L & rsquo; use of physiological mechanisms regulating partial thyroid Destruction
a- Uptake inhibitor d & rsquo; iodine :
- Some anions compete with the & rsquo; iodine to its carrier
- Reduce the & rsquo; available iodine for the synthesis of & rsquo; hormones
- Leurutilisation is limited : risk & rsquo; aplasia
b- Inhibitor & rsquo; incorporation : halide
• L & rsquo; radioiodine 131l¯; Emission of toxic β radiation for the cell
+ Capturé sans distinction avec 127L by the symporter Na + / I-
+ Results in local and specific destruction of the cell c.
c- Inhibitors of & rsquo; incorporation : represented by :
- Derivatives mercaptoimidazole : Thiamazole Carbimazole
- thiouracil derivatives: Benzylthiouracile Propylthiouracile
Mechanism & rsquo; Action :
Inhibiting the formation of thyroid hormone by :
– Interference with the & rsquo; iodine incorporation on tyrosyl residues of thyroglobulin
– Inhibiting the assembly of iodotyrosyl in thyronines
– Inhibition of peroxidase
L & rsquo; clinical effect takes a long time (weeks) to appear
Indications : All forms of hyperthyroidism
Side effects :
– neutropenia / agranulocytose, dangerous, reversible.
– Rush skin
– icterus (liver injury)
– Joint pain
therapeutic strategies :
– Amiodarone is an anti-arrhythmic agent that contains more 35% d & rsquo; iodine in its structure. It has the particularity to induce different effects on thyroid function including decreased conversion of T4 to T3 and the occurrence of & rsquo; hypothyroidism. It can also be responsible for two types of hyperthyroidism, which can take the form of & rsquo; hyperthyroidism with iodine load or d & rsquo; a painless thyroiditis.
– It uses non-cardioselective beta-blockers for symptomatic treatment of hyperthyroidism because & rsquo; it was found in the hyperthyroidism overexpress receptor beta.
Cours du Dr BRIK-BOUGHELLOUT – Faculty of Constantine