Thyroid disorders Flashcards
Explain the process of Thyroid Hormone Synthesis
1) Organification of iodide: Iodide → Iodine → condensed onto tyrosine residues → mono or di-iodinated tyrosine
2) Coupling reaction: 2 DIT molecules → T4
3) Release of the T3 and T4 from the thyroid gland
4) Major production of T3 occurs outside of the thyroid gland by peripheral conversion from T4
Explain the hypothalamo-pituitary-thyroid axis
Are primary or secondary disorders of thyroid gland more common?
Primary
Are thyroid diseases more common in women or men
Women
What are autoimmune thyroid disorders commonly associated with?
Other autoimmune diseases e.g. T1 DM, autoimmune adrenal insufficiency
Is T3 or T4 more more biologically active
T3
What is Hyperthyroidism?
Over-production of thyroid hormone by the thyroid gland
What is Thyrotoxicosis?
Abnormal and excessive quantity of thyroid hormone in the body
Most common cause of Hyperthyroidism?
List 4 other common causes of thyrotoxicosis
Graves’ Disease ☆
- Iatrogenic,
- Toxic adenoma,
- Toxic multinodular goitre
- Thyroiditis
- Iodide excess
What is Graves disease? Incl the pathophysiology
Autoimmune condition where TSH receptor antibodies cause a primary hyperthyroidism.
These TSH receptor antibodies (TSHRAb) mimic TSH and stimulate TSH receptors on the thyroid
What is subclinical hyperthyroidism?
Low levels of TSH but normal levels of T3 and T4
List 4 symptoms of hyperthyroidism
- Anxiety and irritability
- Weakness and fatigue
- Palpitations
- Sweating and heat intolerance
- Dyspnoea
- Frequent loose stools (hyperdefecation)
- Insomnia
- Poor concentration
- Menstrual abnormalities and sexual dysfunction
List 4 signs of hyperthyroidism
- Weight loss
- Proximal myopathy
- Tachycardia, arrythmias
- Warm, moist skin
- Tremor
- Eye conditions (stare, lid lag, lid retraction)
- Emotional lability
- Hyperactive deep tendon reflexes with shortened relaxation time
What is a Thyroid storm?
Exaggerated typical signs and symptoms, fever, jaundice, changes in neurologic function
Clinical features/presentation specific to Graves disease
- Diffuse goitre (without nodules)
- Graves eye disease
- Bilateral exophthalmos
- Pretibial myxoedema
Pathophysiology behind Graves’ Ophthalmopathy?
Antibodies to TSH receptor also target retroorbital tissues
- T-cell inflammatory infiltrate → fibroblast growth
- Severe: exposure keratopathy, diplopia, com-pressive optic neuropathy
Strong link with tobacco and seen in 50% of Graves Disease
Pathophysiology behind Graves’ Myxedema (thyroid dermopathy)
Activation of fibroblasts → increased hyaluronic acid and chondroitin sulfate
Asymmetric, raised, firm, pink-to-purple, brown plaques of nonpitting edema
Occurs In <5% of Graves disease
What is Thyroid acropachy?
List the 3 characteristic findings on imaging which comprise this
Rare complication of autoimmune thyroid disease
- Digital clubbing
- Soft tissue swelling of hands and feet
- Periosteal bone formation
Occurs in 0.1-1 % and almost always in patients with myxedema and ophthalmopathy
Laboratory findings indicative of primary hyperthyroidism?
Suppressed TSH (<0.05 uU/ml)
Elevated Free T4 and/or Free T3
Ddx in a patient with hyperthyroidism for the follow values of T3:T4
- T3:T4 > 20
- T3:T4 < 20
T3:T4 > 20:
- Graves’ Disease
- Toxic MN Goiter
T3:T4 < 20:
- Non-thyroid illness
- Thyroiditis
- Exogenous thyroxine
List 3 other investigations for hyperthyroidism
- Thyroid radioiodine uptake
- TSH receptor antibodies: Grave’s
- US thyroid: hypoechogenic in untreated diffuse toxic goitre
What would iodine uptake show on nuclear scintigraphy for the following:
- Toxic multinodular
- Graves
- De Quervain’s thyroiditis
- TMG: Patchy uptake
- Graves: diffuse, homogenous, increased uptake
- DQ thyroiditis: globally reduced uptake of iodine-131
List 4 complications of hyperthyroidism
- Atrial Fibrillation
- Osteoporosis
- Heart failure
- Thyroid Storm
List 4 treatments of thyrotoxicois?
- Antithyroid medications: Carbimazole and Propylthiouracil
- β- blockers for symptom control (Propranolol preferred)
- Radioactive iodine
- Surgery
List 2 dangers/ side effects of Antithyroid medications
Carbimazole and Propylthiouracil can cause Agranulocytosis, and or hepatotoxicity (PTU)
What is hypothyroidism?
Inadequate output of thyroid hormones by the thyroid gland
List 4 populations at risk of hypothyroidism
- Women
- History of Graves disease or postpartum thyroid dysfunction
- Elderly
- Other autoimmune disease
- Family history of thyroid disease, pernicious anemia, type I DM
Is primary or secondary hypothyroidism more common?
What is the difference between these
1o → Thyroid gland insufficiency (more common)
2o → Pituitary pathology
What defines subclinical hypothyroidism?
Normal free T4 concentration in the presence of an elevated TSH concentration
What is the treatment of choice for hypothyroidism?
Levothyroxine (needs to be titrated)
List 4 causes of Hypothyroidism
- Hashimoto’s thyroiditis
- Thyroiditis
- Congenital hypothyroidism
- Drug induced
- Post radiation
- Thyroid surgery
List 4 clinical features of hypothyroidism
- Weight gain
- Fatigue
- Dry skin
- Coarse hair and hair loss
- Fluid retention (oedema, pleural effusions, ascites)
- Heavy or irregular periods
- Constipation
What is a Myxedema coma?
How does it present?
Medical emergency - end stage of untreated/insufficiently treated hypothyroidism
Presents with:
- hypothermic
- hypotensive
- hypoventilation
- bradycardic
- Impaired sensorium
What is cretinism and why does it occur?
List 3 clinical features
Lack of thyroxine from birth or before birth (severe and irreparable)
From lack of thyroid gland or lack of iodine in mother
- Mental defects
- Stunted growth
- Reduced growth and function of many organs
Typical clinical picture of a Myxedema Coma?
- Elderly obese female
- Becoming increasingly withdrawn, lethargic, sleepy and confused
- Slips into a coma
List 4 physical findings of Myxedema Coma
- Comatose or semi comatose
- Hypothyroid features: dry coarse skin, hoarse voice, thin dry hair
- Delayed reflex relaxation time
- Hypothermia
- Pericardial, pleural effusions, ascites
Typical history of a Myxedema Coma?
- Previous thyroid surgery
- Radioiodine
- Default thyroid hormone therapy
List 4 things which may precipitate a Myxedematous Coma
- Infections
- Trauma (incl surgery)
- Exposure to cold
- CVS problems
- Drugs
Management of Myxedema?
- ICU admission - ventilatory support and IV meds
- Parenteral thyroxine
- Electrolytes - water restriction for hyponatremia, avoid fluid overload
- Avoid sedation
- Glucocorticoids - Hydrocortisone
List 4 factors which may reduce levothyroxine effectiveness
- Malabsorption Syndromes ie. celiac disease
- Drugs that ↑ clearance ie. rifampin
- Factors that ↓ T4 to T3 clearance ie. amiodarone
- ↓absorption ie. ferrous sulfate
- Other Mechanisms ie. sertraline
What is Hashimoto’s Thyroiditis?
Autoimmune inflammation of the thyroid gland.
Initially it causes a goitre after which there is atrophy of the thyroid gland.
List 2 antibodies which are associated with Hashimoto’s Thyroiditis
- antithyroid peroxidase (anti-TPO) antibodies
- antithyroglobulin antibodies
a) What is the most common cause of hypothyroidism in the developed word
b) What is the most common cause of hypothyroidism in the developing world
a) Hashimoto’s Thyroiditis
b) Iodine Deficiency
All treatments for hyperthyroidism have potential to cause hypothyroidism, list 4 of these
- Carbimazole
- Propylthiouracil
- Radioactive iodine
- Thyroid surgery
List 2 other medications which can cause hyperthyroidism
- Lithium - inhibits production of thyroid hormones in the gland, can cause a goitre and hypothyroidism
- Amiodarone - interferes with thyroid hormone production and metabolism, can cause both hypothyroidism and thyrotoxicosis
What findings on a thyroid function test would be indicative of a primary vs secondary cause of hypothyroidism?
1o → low T3 & T4, high TSH
2o → low TSH, low T3 & T4
What is secondary hypothyroidism?
Where the pituitary gland is failing to produce enough TSH.
Often associated with a lack of other pituitary hormones ie. ACTH - known as ‘hypopituitarism’
List 4 causes of secondary hypothyroidism
- Tumours
- Infection
- Vascular (e.g. Sheehan Syndrome)
- Radiation
What is Sheehan Syndrome?
Hypopituitarism caused by ischemic necrosis due to blood loss and hypovolemic shock during and after childbirth
Also known as postpartum pituitary gland necrosis
