Endocrinology: Thyroid and Parathyroid Flashcards Preview

MRCS A: Systems > Endocrinology: Thyroid and Parathyroid > Flashcards

Flashcards in Endocrinology: Thyroid and Parathyroid Deck (60)
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1

Thyroid function in the foetus

1) Although T3 and T4 reach the foetal circulation from the mother, the foetus depends on its own thyroid gland for thyroid hormones.

2) Thyroid gland fully differentiated by 11 weeks gestation, but probably not until about 18 weeks that thyroid hormone production commences.

3) By 28 weeks free T4 values reach adult levels. Failure of thyroid gland development or hormone synthesis results in cretinism.

2

Cretinism

Gross mental retardation due to failure of brain development, and a failure of skeletal development leading to dwarfism.
Maternal TSH receptor stimulating antibodies may cross the placenta; this can lead to transient neonatal hyperthyroidism. Maternal TSH receptor blocking antibodies may likewise result in foetal hypothyroidism

3

Structure and function of thyroid gland

Spherical follicles of thyroid epithelial cells surrounding colloid (principally thyroglobulin) within a lumen. In addition, parafollicular or C-cells secrete calcitonin.

In each follicle, the epithelial cells are cuboidal when ‘resting’ and ‘columnar’ when under TSH stimulation

4

Thyroid follicular cells

• secrete thyroglobulin (Tg) and iodine into colloid

• absorb thyroglobulin from colloid

• secrete triiodothyronine (T3) and thyroxine (T4)
directly into the blood stream

5

Thyroid function: I and Na pump

Thyroid gland incorporates iodide into its cells from plasma by an active transport mechanism in which Iodine follows Na.

This ‘pump’ is influenced positively by TSH and TSH receptor antibodies (in Graves’ disease). Iodine can be blocked for example, digoxin.

6

Thyroid function: Within the follicular cell I

Iodide is quickly oxidised by thyroid peroxidase (TPO) and hydrogen peroxide and bound to thyroglobulin forming monoiodotyrosine (MIT) and diiodotyrosine (DIT)

Then transferred to the luminal colloid. MIT and DIT combine in a reaction catalysed by TPO, positively regulated by TSH to produce either triiodothyronine (T3) or thyroxine (T4) – all within the colloid.

7

Thyroid function: Within the follicular cell II

1) Under continued TSH control, colloid droplets are taken up by the thyroid cell via a process of endocytosis, lysosomes fuse with the droplets and proteolysis of thyroglobulin occurs.

2) In the plasma the hormones conjugate with thyroxine-binding globulin (TBG) produced by the liver that binds 70% of T3 and T4, to thyroxine-binding prealbumin, and to albumin.

3) Protein bound, T3 and T4 are inactive and thus are a ‘store’ of bound hormone allowing regulation of the levels of unbound active ‘free’ T3 and T4 available to the tissues.

8

Thyroid function: T3 and T4

Free T3 is the active hormone. Most T3 production (80%) is extrathyroidal from deiodination of T4. The half life of T3 is one day and of T4 is one week. Thus T4 appears to act as an immediately available source and regulator of T3 rather than as an hormone in its own right.

9

Control of thyroid function

1) Thyroid-stimulating hormone (TSH), from the anterior pituitary, has a stimulating effect on T3/T4 production.

2) Thyrotrophin-releasing hormone (TRH), which
is stored in the hypothalamus, stimulates TSH production and release.

3) Rising levels of T3/T4 (primarily a rising T3 concentration) have an inhibitory effect on the TRH/TSH axis.

10

Iodine and thyroid control

1) Thyroid autoantibodies may stimulate or inhibit thyroid function. TSH receptor antibodies may be stimulatory producing hyperthyroidism (Graves’ Disease) or have a blocking action producing hypothyroidism (atrophic thyroiditis).

4) Anti-TPO (thyroid peroxidase) autoantibodies are found in 90% of patients with Graves’ Disease and lymphocytic thyroiditis.

11

Mechanism of action of thyroid hormones

1) T3 and T4 have major effects on the growth, development and function of most tissues.

2) The main effects are seen on the cell membrane, on the mitochondria and on the cell nucleus.

3) At the cell membrane level there is increased uptake of amino acids when T3 stimulation occurs.

4) The effect on mitochondria is to increase
energy production.

5) T3 combines with T3 receptors within the nucleus, this causes increased or decreased mRNA expression with consequent effects on protein synthesis.

12

Effects of thyroid hormone

These are widespread and include energy and heat production, an overall catabolic effect – particularly on glucose and fat metabolism, cardiovascular and adrenergic effects, effects on production of other hormones, effects
on bone, foetal development and growth.

13

Effects of thyroid hormone: heat production

Heat production is brought about by the T3 effect
on mitochondria: there is increased O2 uptake by the mitochondria with production of ATP in most tissues, although not in the brain.

Thyroid hormone is responsible for the increase in basal metabolic rate (BMR) that occurs in hyperthyroidism, and consequently the heat intolerance described by patients.

.

14

Effects of thyroid hormone: Catabolic effects

Thyroid hormones stimulate glycogenolysis in the liver, an increase in insulin breakdown and a rise in glucose absorption from the gut.

Hyperthyroidism is associated with insulin resistance and glucose intolerance, diabetes may be ‘unmasked’ or, its control in a patient with established diabetes may be more difficult.

15

Effects of thyroid hormone: Cardiovascular and adrenergic effects

The number of alpha adrenergic receptors in cardiac muscle increase

Consequently thyroid hormones have a positive inotropic effect. In patients with thyrotoxicosis, the cardiac output and heart rate increase. Alpha adrenergic receptor activity also increases in other tissues, including skeletal muscle.

The management of the tachycardia and dysrhythmia associated with thyrotoxicosis logically includes a-adrenergic receptor blocker such as propranolol or metoprolol.

In hypothyroidism cardiac output is reduced; pericardial effusions may occur.

16

Effects of thyroid hormone: Effects on bone

T3 and T4 increase metabolic activity in bone, there
is increased bone resorption and bone formation.
The catabolic effect is predominant in thyrotoxicosis
which results in a net reduction in bone density.
Hypercalcaemia (rarely severe) and hypercalciuria
can occur in thyrotoxicosis, PTH levels will be normal or low.

17

Effects of thyroid hormone: Gastrointestinal effects

Weight loss and diarrhoea are common symptoms
reported by patients with hyperthyroidism. Constipation, loss of appetite and weight gain are frequent symptoms in hypothyroidism.

18

Investigation of thyroid function

Low TSH and high fT4 and /or fT3 will ordinarily indicate thyrotoxicosis.

High TSH with low thyroid hormone indicate a hypothyroid state.

In pregnancy there is a rise in TBG with a consequent rise in total T3 and T4 levels: however, the free T3 and T4 levels are little changed.

In very early pregnancy the free T3 and T4 levels may increase due to the effects of hCG. The thyroid gland often increases in size during pregnancy. Post-partum thyroid dysfunction is common (15%).

19

Thyroid and paediatrics

In children, free T4 levels reach the normal adult range by the end of the first year. Free T3 levels remain high in childhood and early adolescence. In sick patients with non thyroidal illness, a transient rise in TSH and low free T4 and free T3 is often seen. With recovery from the illness, thyroid function tests return to normal.

20

Thyroid antibodies

Thyroid autoantibody status should also be determined. In patients with Graves’ disease TPO antibodies are positive in approximately 80% of patients. Approximately 90% of patients with Hashimoto’s disease have positive TPO antibodies. It should be remembered that in itself positive antibody status does not constitute a diagnosis of thyroid disorder as at least a third of the normal population will have a positive antibody titre.

21

Thyroid tumour markers

Thyroglobulin in patients with differentiated (papillary or follicular) thyroid who have undergone complete eradication of thyroid tissue by the combination of surgery and postoperative radioactive iodine therapy.

A rise in thyroglobulin levels indicates persistent or recurrent disease.

Calcitonin is measured in patients with medullary thyroid cancer (MTC) (a tumour that arises from thyroid C cells).

Calcitonin levels are also measured in patients who have undergone surgery for MTC; a raised or increasing level of calcitonin indicates residual or recurrent disease.

22

Thyroid pathology investigation

1) FNA distinguishes solid from cystic thyroid enlargement.

2) Ultrasound of the thyroid is very sensitive at detecting abnormal thyroid tissue but not specific, and rarely contributes to the diagnosis of thyroid swellings. Useful for targeted FNA and reduces the number of unsatisfactory needle aspirates.

2) Thyroid CT and MRI can delineate the extent of thyroid enlargement in the neck and chest as well as the encroachment/invasion of adjacent structures in benign and malignant disease.

23

Hypothyroidism

1) Caused by a deficiency of or resistance to thyroid hormone.

2) Primary hypothyroidism is the cause of 95% of adult cases; Hashimoto’s disease (chronic lymphocytic thyroiditis) is responsible for 70% of these.

3) Patients with hypothyroidism sometimes present with a goitre to surgeons. The combination of abnormal thyroid function tests, positive TPO autoantibodies and sometimes aspiration cytology is sufficient to confirm the diagnosis.

24

Myxoedema

1) Myxoedema, the end result of severe long
standing hypothyroidism, is associated with marked
symptoms and signs, characteristic skin changes and in extreme cases, confusion and coma associated with a very high mortality.

2) The patient has profound hypothermia, and may demonstrate hypoglycaemia, water retention, and hypoventilation.

3) In generalised myxoedema there is accumulation of glycosaminoglycans within soft tissues, and facial and cutaneous oedema (containing mucopolysaccarides, hyaluronic acid and chondroitin sulphate).

25

Hypothyroidism treatment

1) Lifelong thyroxine is the treatment of choice and in most cases is associated with a reduction in size of the goitre as TSH levels fall.

2) Thyroid lymphoma is more common in patients with lymphocytic thyroiditis. A nodule or continued enlargement of the thyroid in a patient with Hashimoto’s disease despite thyroxine treatment must be viewed with suspicion and aggressively investigated.

3) The surgeon should be aware of the many manifestations of hypothyroidism. Some patients will be asymptomatic despite significant degrees of biochemical dysfunction.

4) The patient who presents with constipation without an obvious mechanical cause requires thyroid function tests. Other risk groups the surgeon should consider are individuals who have previously undergone thyroid surgery who may become hypothyroid as a delayed consequence of surgery or, as a result of failure to take thyroxine medication.

26

Hyperthyroidism

1) This is defined as thyroid over-activity with a sustained increase in production of thyroid hormones. Thyrotoxicosis is the clinical syndrome that results from an increase in the serum concentration of thyroid hormones.

2) The commonest cause of thyrotoxocosis is Graves’ disease (60%), an autoimmune condition
in which TSH receptor antibodies are present which
stimulate thyroid cell activity and growth.

3) Other common causes of hyperthyroidism include toxic multinodular goitre and toxic adenoma. The clinical features of thyrotoxicosis include diffuse or nodular thyroid enlargement, and systemic manifestations of raised blood thyroid hormone levels.


27

Graves Disease

1) In Graves’ disease, eye signs (thyroid associated opthalmopathy: TAO) occur that may be clinically inapparent but are evident on screening in up to 90% of patients. Signs of TAO, unilateral in 10% of cases, include lid retraction, lid lag and proptosis.

2) Less than 10% of patients will develop severe eye changes that include diplopia, opthalmoplegia and sight loss. The histological findings in the soft tissues within the orbit in TAO include oedema, lymphocyte infiltration, glycosaminoglycan deposition and inflammatory changes in the extra ocular muscles with fibrosis.

3) The aetiology of TAO is unclear, predisposing
factors include male sex and smoking, immunogenetic factors have little if any effect.

4) Radioiodine leads to a worsening of eye disease in some patients. Patients with Graves’ disease may develop pretibial myxoedema (thyroid associated dermopathy) and thyroid acropachy.

28

Treatment options for Graves’ disease

• Antithyroid drugs
• Radio-iodine treatment
• Surgery

29

Antithyroid drugs: The thionamides

The thionamides –carbimazole and propylthiouracil (PTU) are most commonly used.

1) They block thyroid peroxidase activity (inhibition of
iodine organifi cation and iodotyrosyl coupling); in
addition PTU inhibits deiodination.

2) Thionamides also have an immunomodulatory effect on the disease process, probably as a result of a direct action on thyroid cells.

3) They control thyroid hormone production
as long as they are continued and are used as primary treatment in Graves’disease. They can be given either to partially reduce thyroid hormone production to achieve a euthyroid state (titration regimen) or at a high dose to render the patient hypothyroid; thyroxine is then introduced (block and replace regimen).

30

Antithyroid drugs: The thionamides

1) Patients remain on treatment for a variable period of time – at least six months, sometimes a year or more, medication is then discontinued.

2) Approximately 40% of patients with Graves’ have a sustained remission after antithyroid drug treatment. A higher chance of relapse can be predicted in patients with large goitre, severe hyperthyroidism and a long duration of symptoms.