HYPERTHYROIDISM Flashcards
Anatomy and biochemistry of the thyroid gland
Weighs15 – 25gm in adult life, larger in Africans than in Caucasians ;
Rarely absent, the thyroid gland may be lingual, retrosternal or have agenesis of one or both lobes
Produces triiodothyronine (T3) & thyroxine T4 by actively trapping
99% of T3 & T4 exist bound to thyroid binding (TBG)..
Discuss the thyroid hormone
synthesized by follicular epithelial cells of the thyroid
Requires availability of iodine
Small amounts secreted continuously into blood
Almost entirely bound to plasma proteins (60% TBG)
Small % remaining free (unbound)
T4 secreted in greater amounts than T3
T3 more biologically potent than T4
Most T3 derived from extrathyroidal conversion of T4 by 5’ monodeiodinase type 1 in peripheral tissues
Thyroid hormones synthesis
Synthesis of thyroid hormone requires iodine.
Dietary inorganic iodide is transported into the gland by an iodide transporter, converted to iodine.
Bound to thyroglobulin by the enzyme thyroid peroxidase through a process called organification leading to formation of monoiodotyrosine (MIT) and diiodotyrosine (DIT).
MIT and DIT are coupled to form T3 and T4; these are then stored with thyroglobulin in the thyroid’s follicular lumen. The thyroid contains a large supply of its preformed hormones.
FACTORS AFFECTING FUNCTION OF HYPOTHALAMIC-PITUITARY-THYROID AXIS
Physiologic
Age, pregnancy, stress, temperature, genetics
Pathologic
Hyper- or hypothyroidism, systemic illness, surgery, starvation, pharmacologic
May produce alterations in serum concentration of thyroid hormones
Thyrotoxicosis
Clinical syndrome resulting from exposure of body tissues to excess circulating levels of thyroid hormones
More common causes:
Graves disease
Toxic multinodular goitre
Subacute thyroiditis
Post partum thyroiditis
Thyroid adenomas
Causes of thyrotoxicosis
Less common:
Iodine induced: Iodide xs (Jodbasedow syndrome), amiodarone, radiographic contrast agents
Amiodarone induced (injury with leakage of T4 & T3)
Factitious thyrotoxicosis / surreptitious ingestion of thyroid hormone
Uncommon forms:
trophoblastic tumors (HCG mediated)
TSH producing pituitary adenoma
pituitary resistance to TSH
functioning follicular carcinoma
struma ovarii,
What is hyperthyroidism?
Hyperthyroidism is a set of disorders that involve excess synthesis and secretion of thyroid hormones by the thyroid gland, which leads to the hypermetabolic condition of thyrotoxicosis.
Causes of hyperthyroidism
The most common cause is Diffuse toxic goiter (Graves’ disease)
Toxic multinodular goiter (Plummer disease).
Toxic adenoma.
What is Graves’ disease?
The most common cause of thyrotoxicosis is Graves disease (50-60% of cases).
Graves disease is an organ-specific autoimmune disorder.
Acirculating autoantibody against the thyrotropin receptor provides continuous stimulation of the thyroid gland.
What is graves disease Characterized by?
Diffuse goiter
Infiltrative ophthalmopathy/orbitopathy
Occasionally infiltrative dermopathy
pretibial myxedema
Epidemiology of Graves’ disease
Most frequently seen in young females
but not uncommon in any age group or population
F:M ratio reported as approximately 5-10:1
Peak incidence: 20-40yrs
GRAVES DISEASE - ASSOCIATION WITH OTHER AUTOIMMUNE DISEASES
Addisons disease
Type 1 DM
Vitiligo
Myasthenia gravis
SLE
RA
Pernicious anemia
GRAVES’ OPHTHALMOPATHY
It involves an antibody reaction against the TSH receptor that results in activation of T cells against tissues in the retro-orbital space that share antigenic epitopes with thyroid follicular cells.
These immune processes lead to an active phase of inflammation.
Lymphocyte infiltration of the orbital tissue and release of cytokines that stimulate orbital fibroblasts to multiply and produce mucopolysaccharides (glycosaminoglycans), which absorb water.
The extraocular muscles thicken and the adipose and connective tissue of the retro-orbit increase in volume.
What is Lid lag and lid retraction?
Lid lag and lid retraction may be present irrespective of the aetiology of the thyrotoxicosis
Lid retraction-with eyes directed horizontally forwards without staring, a band of white sclera is seen above the iris
Lid lag-failure of the lid to accompany the globe descent on downward gaze
Clinical features
Weight loss despite an increased appetite
Rapid or irregular heartbeat
Nervousness, irritability, trouble sleeping, fatigue
Tremor, muscle weakness
Sweating or heat intolerance
Hyperdefecation
Goiter
Eye symptoms
Signs
Restlessness
Fine tremor
Warm, moist skin
Fine silky hair ± alopecia
hyperhidrosis
Sweaty palms
Palmar erythema
Onycholysis
Goitre
Eye signs - lid lag, lid retraction
Exophthalmos (Graves disease)
Thyroid bruits
Tachycardia
Atrial fibrillation
High output heart failure
Increased pulse pressure
Pretibial myxedema (Graves disease)
Proximal myopathy
Hyperreflexia
Evidence of weight loss
Other mental state changes
Irritability, anxiety, emotional lability, depression, other psychiatric reactions
Investigations
Thyroid function test: TSH, FT3, FT4
Anti TPO antibody
Anti TSH receptor antibody
ECG
LFT
Neck ultrasound scan, CT, MRI
Full blood count
Electrolyte, urea and creatinine
Serum ca, Phosphate
Treatment
Propylthiouracil
Methimazole
B-blockers e.g propranolol
For those with asthma ; verapamil and diltiazen can be used.
Iodides, Ipodate (iodinated radio contrast agent)
Inhibit thyroid hormone synthesis and secretion
Useful in lowering T3 & T4 concentration
Can be used to quickly prepare patients for surgery, when there is insufficient time to give thionamides
Useful in combination treatment of thyroid storm.
The antithyroid drug dose should be titrated every 4 weeks until thyroid functions normalize.
Graves disease go into a remission after treatment for 12-18 months, and the drug can be discontinued.
Recurrence of hyperthyroidism in 50% within the following year.
Toxic multinodular goiterand toxic adenoma are permanent conditions and will not go into remission.
Radiotherapy: RAI- ¹³¹I
Surgery
Lobectomy or lobectomy plus isthmusectomy to treat a toxic adenoma.
Subtotal or total thyroidectomy
INDICATIONS FOR THYROIDECTOMY
Indicated in
those with very large goiters
Where there is possibility of malignancy
Severe or advancing ophthalmopathy
patient who relapses after medical therapy
Pregnant patient on drugs whose disease is hard to control
those with severe reactions to antithyroid drugs
patients who have refused I 131 therapy
woman wishing to achieve a pregnancy in the near future
Make euthyroid before surgery to avoid the risk of thyroid storm post-op
COMPLICATIONS OF HYPERTHYROIDISM
Thyroid storm
Thyrotoxic heart disease
Erectile dysfunction
Infertility
Psychosis
