THYROID AND THYROID DISEASE Flashcards
What are the arteries which supply the thyroid gland and where do they branch from?
Superior thyroid artery is a branch of the external carotid
Inferior thyroid artery is a branch of the thyrocervical trunk
Thyroid ima artery is small and not always present. Either a branch of the aorta or the brachiocephalic trunk.
In the thyroid, what substance fills the follicles?
Colloid
What is the role of the c-cells (the parafollicular cells) of the thyroid gland?
To make calcitonin
On histological examination, what would the thyroid follicles of someone with underactive thyroid disease look like?
Flattened follicular epithelial cells with increased colloid
On histological examination, what would the thyroid follicles of someone with overeractive thyroid disease look like?
Tall columnar epithelial cells with reduced colloid
What is congenital hypothyroidism?
Failure of the gland to develop as a result of a genetic mutation such as PAX8.
What is a thyroglossal cyst?
Failure of thyroglossal duct to atrophy after the thyroid has migrated.
What are the functions of thyroid hormone?
Increase basal metabolic rate
Regulate long bone growth (with GH)
Neural maturation
Cardiovascular - positively chronotropic and inotropic
Increase body’s sensitivity to catecholamines (eg adrenaline)
CNS - regulates alertness
What are the two forms of thyroid hormone that are made by the thyroid follicles?
Thyroxine (T4) and Tri-iodothyronine (T3)
Which form of thyroid hormone is most abundant in the blood?
T4 - 60-150 nmol/L
T3 - 1.2-2.9 nmol/L
But most of this is bound to proteins
What is the normal range of TSH in the blood?
0.3-4.5 mU/L
When we measure levels of thyroid hormone in the blood what are we actually measuring?
The amount of free T4 (9-22 pmol/L)
Which form of thyroid hormone is the most bioactive?
T3
What effect does thyroid hormone have on insulin?
It is antagnostic
How does thyroid hormone affect growth hormone releasing hormone?
It decreases the secretion of GHRH
What hormones do thyroid hormones have an effect on?
Insulin
Growth hormone releasing hormone
Adrenaline
Thyroid releasing hormone
In which part of the cell does thyroid hormone have its affect?
DNA - binds to TR response elements
Over which tracheal cartilages is the thyroid gland found?
Second and third
What attaches the thyroid gland to the trachea?
Pretracheal fascia
Does the thyroid gland move with the trachea and larynx during swallowing?
Yes, unless the tongue is protruded.
What are the veins that drain the thyroid gland?
Superior thyroid vein
Middle thyroid vein
Inferior thyroid vein
What are the four groups of nodes that drain the lymphatics from the thyroid gland?
Prelaryngeal
Pretracheal
Paratracheal
Deep cervical
How many days worth of thyroid hormone is normally stored in the thyroid gland?
100 days - this means it takes a long time for an acquired hypothyroidism to manifest as symptomatic.
What is the amino acid used to make thyroid hormone?
Tyrosine
What is the catalytic enzyme involved in the oxidation of iodide into iodine in the thyroid?
Thyroid peroxidase (TPO)
What is the catalytic enzyme involved in the binding of iodine to tyrosine in the thyroid?
Thyroid peroxidase (TPO)
Where is T4 converted into T3? What stimulates this conversion?
In the liver and kidney
Stimulated by TSH
Other than T3, what form can T4 be converted into?
Reverse T3 (rT3)
Is rT3 more or less biologically active than T4?
Less. rT3 has little or no biological activity.
How much iodine is need per day in the diet?
150 mg although only a fraction can actually be absorbed
Where is iodine excreted?
Kidney
What is the catalytic enzyme that is inhibited by thiacarbamide drugs (such as carbimazole)?
Thyroid peroxidase (TPO)
How is thyroid activity regulated?
Hypothalamus and anterior pituitary glands
What is the hormone released by the hypothalamus in the regulation of thyroid gland activity?
Thyrotrophin releasing hormone (TRH)
What is the role of TRH, release from the hypothalamus into the hypophyseal portal blood?
Stimulate the anterior pituitary to release TSH
What are the factors that might increase TRH (thyrotrophin relseasing hormone) release?
Low thyroid hormone levels
Cold
Pregnancy (oestrogens acting on anterior pituitary)
What acts directly on the thyroid gland to increase release of thyroid hormone?
TSH
Adrenaline
What will inhibit the release of TSH?
Raised serum thyroid hormones Somatostatin Glucocorticoids Chronic illness Heat High levels of iodine in serum
What are the half lives of T3 and T4?
T3 - 1 day
T4 - 7 days
What is the role of rT3 (reverse T3)?
To conserve energy by blocking the binding site of T3. This happens in periods of illness or when energy stores are low.
What is the prevalence of hyperthyroidism in women?
1 in 50
What is the prevalence of hyperthyroidism in men?
1 in 500
What are the classic symptoms associated with general hyperthyroidism (as opposed to Graves’)? (Name at least 7)
Weight loss (although paradoxical weight gain in 10-30%) Poor toleration of warm weather Sweating Anxiety Restlessness Fatigue Hair loss Reduced libido
Goitre
Palpitations
Diarrhoea
Tremor
Infertility
Menorrhagia
Osteoporosis
What do we call an acute exacerbation of symptoms associated with thyrotoxicosis?
Thyrotoxic storm
On examination, what are the signs that might be seen in a patient with hyperthyroidism?
Restlessness Tachycardia Atrial fibrillation Tremor Hypereflxia Sweating
What are the signs and symptoms specifically associated with Graves’ disease?
Exophthalmos Excess lid retraction Lid lag Pretibial myxoedema Bruit in the goitre
What are the main causes of hyperthyroidism?
Graves’ disease - most common
Toxic multinodular goitre
Toxic adenoma
What are the precipitating factors of a thyrotoxic storm?
Recent thyroid surgery
Infection
MI
Resistance to therapy
What are the clinical features and complications of a thyrotoxic crisis?
High fever (often above 40˚) Sweating Confusion Tachycardia AF Vomiting Diarrhoea Agitation Heart failure MI
How should someone suffering a thyrotoxic storm be managed?
Beta blockers Anti-thyroid agents - thionamide, propylthiouracil, methimazole Potassium iodide Fluids Oxygen Paracetamol
How is a diagnosis of a thyrotoxic storm confirmed?
Technetium scan
What investigations would you order for someone with suspected hyperthyroidism?
Blood tests - TSH, T3 and T4
ECG
Autoantibody screen - ELISA (enzyme-linked immunosorbent assay)
Radioisotope scanning
Why might radioisotope scanning be useful in someone with suspected hyperthyroidism?
To show the size of the thyroid and to look for any abnormal ‘hot’ areas such as a toxic adenoma.
What is the medical management of hyperthyroidism?
Beta-blocker
Carbimazole - inhibits TPO, sometimes used in conjunction with thyroxine to prevent iatrogenic hypothyroidism.
What are the non-medical management options for someone with hyperthyroidism?
Radioiodine - slow response, may require adjunct carbimazole
Partial thyroidectomy
What are the antibodies that might be detected on an autoantibody screen in someone with Graves’ disease?
Present in Graves’ and Hashimoto’s:
Thyroglobulin antibody (TgAb)
Thyroid peroxidase antibody (TPOAb)
Specific to Graves’:
Thyroid receptor antibody (TRAb)
Thyroid-stimulating hormone receptor antibody (TSH-RAb)
How is Graves’ disease treated?
Same as other causes of hyperthyroidism, although eye disease will only respond to non-medical management.
What is thyroid hormone resistance syndrome?
Rare condition which occurs as a result of mutation of thyroid receptor genes. Normally compensated for by raised T3 and T4 but can present as congenital hypothyroidism.
What is the term used to describe symptomatic hypothyroidism?
Myxoedema
What is the prevalence of myxoedema in men and women?
Men 1 in 500
Women 1 in 100
What are the main features of hypothyroidism?
Coarse and thin hair Mental slowing Tiredness Pale puffy face Weight gain/obesity Intolerance to cold Goitre
What are the less common features of hypothyroidism?
Loss of outer third of eyebrow Psychosis Deafness Hoarse voice Bradycardia Muscle weakness Constipation Carpel tunnel syndrome Cold peripheries Chronic oedema Slow relaxing reflexes
What stage of life is hypothyroidism most damaging? Why?
From birth to puberty thyroid hormones are essential for normal development of the CNS. Deficiency can cause cretinism (irreversible mental retardation).
What screens are done to avoid the development of cretinism?
TSH levels are checked in all newborns. Levels will be raised in those with a dysfunctioning thyroid gland.
If the blood tests of a patient with signs and symptoms of hypothyroidism show low levels of T3, T4 and TSH, where is the likely source of the myxoedema?
Lesion in the pituitary gland or hypothalamus.
What is Hashimoto’s thyroiditis?
Hashimoto’s thyroiditis is an autoimmune disease in which the thyroid gland is attacked by a variety of cell- and antibody-mediated immune processes, causing primary hypothyroidism. It was the first disease to be recognized as an autoimmune disease.
What is the gene most strongly implicated in Hashimoto’s disease?
HLA-DR5
How is hypothyroidism treated?
Levothyroxine
What do we monitor in someone with hypothyroidism currently on Levothyroxine?
TSH levels
What are the causes of hypothyroidism?
Congenital hypothyroidism Over treatment of hyperthyroidism Hashimoto's thyroiditis Primary atrophic hypothyroidism De Quervain's (subacute) thyroiditis Iodine deficiency Dyshormogenesis
What are the autoantibodies associated with Hashimoto’s thyroiditis?
Present in Graves’ and Hashimoto’s:
Thyroglobulin antibody (TgAb)
Thyroid peroxidase antibody (TPOAb)
Present in Hashimoto’s:
Antibodies against rough endoplasmic reticulum (microsomal antibodies)
What might be seen in early Hashimoto’s thyroiditis?
A hyperthyroid picture as early destruction of the thyroid gland leads to release of thyroglobulin colloid.
What is De Quervain’s thyroiditis?
Inflammation of the thyroid gland caused by a virus (often Coxsackie virus, mumps or adenoviruses). More common in young or middle-aged women. Immune reaction against thyroglobulin release causes formation of granulomas.
Why do hyperthyroid patients get a goitre?
Excessive TSH stimulation leads to hypertrophy.
How would you describe a goitre associated with iodine deficiency hypothyroidism?
Diffusely enlarged and smooth
How would you describe a goitre associated with Graves’ disease?
Diffusely enlarged and smooth. Very vascular to the extent that a bruit can be heard with a stethoscope.
What might a multinodular central neck goitre be indicative of?
Hyperplasia
What proportion of women are found to have a thyroid lump?
5%
What proportion of thyroid lumps are benign?
80%
What investigations would you order for someone who presents with a thyroid lump?
Fine needle aspirate
Thyroid function tests
Will fine needle aspirate be enough to distinguish between a thyroid follicular adenoma and a thyroid follicular carcinoma?
No. You need to do thyroid function tests. A low TSH indicates adenoma as it is producing thyroid hormone. Carcinomas do not tend to produce active hormone.
What are the causes of a thyroid lump?
Thyroid cyst
Nodule of multinodular goitre
Follicular adenoma
Malignancy
What are the five types of malignancy that can arise in the thyroid gland? Which cells does each type affect?
Papillary - Follicle cells Follicular - Follicle cells Medullary - Parafollicular cells Malignant lymphoma - lymphatics Anaplastic - Follicle cells
What hormones do malignancies of the parafollicular cells tend to secrete?
Calcitonin
ACTH - Cushings
5-Hydroxytryptamine (5HT/serotonin) - Carcinoid
What is the mutation associated with papillary thyroid cancer as well as medullary thyroid carcinoma?
RET proto-oncogene - transmembrane receptor with tyrosine kinase
What is the mutation most commonly associated with follicular thyroid cancer?
RAS proto-oncogene
What is the mainstay of treatment for thyroid cancer?
Surgery
Radioactive-iodine
Which thyroid cancer is most associated with p53 mutation?
Anaplastic thyroid cancer
What are the two medical emergencies associated with thyroid gland?
Thyrotoxic storm
Myxoedema coma
What are the precipitates of myxoedema coma?
Infection
Stroke
MI
Trauma
What are the signs and symptoms of a myxoedema coma?
Hypothermia Hyporeflexia Hypoglycaemia Bradycardia Coma Seizures
