Endocrinology - Thyroid Flashcards

Question

What is reverse T3 (rT3)?

Answer 1

In peripheral tissues, T3 is converted into T4 (the more active form) by 5' iodinase or into rT3 by the liver. T3 is MORE biologically active than T4. rT3 is inactive.

Answer 2

The HPT axis controls thyroid hormone secretion. TRH is secreted by the hypothalamus and stimulates secretion of TSH by anterior pituitary. TSH increases both synthesis and secretion of thyroid hormones by follicular cells via an adenylate cyclase - cAMP mechanism. Chronic elevation of TSH causes hypertrophy of the thyroid gland. T3 down regulates TRH receptors in the anterior pituitary and therefore inhibits TSH secretion.

Answer 3

These are components of IgG fraction of plasma proteins and are antibodies to TSH receptors on the thyroid gland. These bind to TSH receptors and like TSH, stimulate the thyroid gland to secrete T3 and T4. These antibodies circulate in high concentrations in patients with Graves disease which is characterised by high levels of circulating thyroid hormones and accordingly low concentrations of TSH (because of negative feedback on the anterior pituitary).

Answer 4

Attainment of adult stature requires thyroid hormones. Thyroid hormones act synergistically with growth hormone and somatomedins to promote bone formation. Thyroid hormones stimulate bone maturation as a result of ossification and fusion of the growth plates. In thyroid hormone deficiency, the bone age is less than the chronologic age.

Answer 5

Hyperthyroidism causes hyperexcitability and irritability. | Hypothyroidism causes listlessness, slowed speech, somnolence, impaired memory and decreased mental capacity.

Answer 6

Maturation of the CNS requires thyroid hormone in the perinatal period. Thyroid hormone deficiency causes irreversible mental retardation. Because there is only a brief perinatal period where thyroid supplementation is helpful, screening for neonatal hypothyroidism is mandatory.

Answer 7

Thyroid hormone has many of the same actions as the sympathetic nervous system because it upregulates beta 1 adrenoceptors in the heart. Therefore, a useful adjunct for treating hyperthyroidism is treatment with beta blockers.

Answer 8

Oxygen consumption and basal metabolic rate are increased by thyroid hormone in all tissues EXCEPT the brain, gonads, and spleen. The resulting increase in heat production underlies the role of thyroid hormone in temperature regulation. Thyroid hormone also increases the activity of the Na+/K+ ATPase and consequently increases oxygen consumption of this pump.

Answer 9

Effects of thyroid function on cardiac output and ventilation are to ensure increased oxygen supply to tissues. Heart rate and stroke volume are increased. These effects combine to produce increased cardiac output. Excess thyroid hormone can cause high output cardiac failure. Ventilation rate is increased.

Answer 10

Overall metabolism is increased to meet the demand for substrate associated with the increased rate of oxygen consumption: - glucose absorption from the GIT is increased - glycogenolysis, gluconeogenesis, and glucose oxidation are increased - lipolysis is increased - protein synthesis and degradation are increased (the overall effect of thyroid hormone is catabolic)

Answer 11

Free concentrations are more useful as total amounts are affected by TBG. Total T4 and T3 are increased when TBG is increased and visa versa. TBG is increased in pregnancy, oestrogen therapy and hepatitis. TBG is decreased in nephrotic syndrome and malnutrition, drugs (androgens, corticosteroids, phenytoin) chronic liver disease and acromegaly.

Answer 12

Ask for T3, T4 and TSH. In hyperthyroidism, all will have reduced TSH (except for the rare phenomena of a TSH secreting pituitary adenoma). Most have a raised T4 but only 1% have raised T3.

Answer 13

As for only T4 and TSH. T3 does not add any extra information. TSH varies throughout the day: trough at 2pm; 30% higher during darkness, so during monitoring try to do at the same time.

Answer 14

In any systemic illness, TFTs may become deranged. The typical pattern is for everything to be low. The test should be repeated after recovery.

Answer 15

Increased TSH together with a normal T4 would suggest treated hypothyroidism or subclinical hypothyroidism.

Answer 16

Decreased TSH but normal T3 and T4.

Answer 17

Slow conversion of T4 to T3 which could be caused by deiodinase deficiency, euthyroid hyperthyroxinaemia or thyroid hormone antibody artifact.

Answer 18

This is the clinical effect of excess thyroid hormone, usually from gland hyperfunction. So strictly speaking, hyperthyroidism is a type of thyrotoxicosis but not all thyrotoxicosis is caused by hyperthyroidism.

Answer 19

``` Diarrhoea Weight loss Increased appetite Over active Sweats Heat intolerance Palpitations Tremor Psychosis is rare Chorea ```

Answer 20

Pulse is fast/ irregular (i.e. AF or SVT) Warm moist skin Fine tremor Palmar erythema Thin hair Lid lag (eye lids lag behind eyes descent as patient watches your finger descend slowly) Lid retraction (= exposure of sclera above the eye causing "staring") There may be goitre, thyroid nodules or bruit depending on the cause

Answer 21

Grave's disease is one of the causes of thyrotoxicosis and has certain signs associated with it. These include: 1) Eye disease - exophthalmos, ophthalmoplegia - exophthalmos is the appearance of protruding eyes 2) Pretibial myxoedema - oedematous swellings just above the lateral malleoli (the term myxoedema is confusing here) 3) Thyroid acropatchy - extreme manifestation with clubbing, painful finger and toe swelling and periosteal reaction in limb bones

Answer 22

TSH is suppressed (due to the negative feedback from high levels of thyroid hormones). T4 and T3 are both elevated. There may be a mild normocytic anaemia, mild neutropaenia (in Grave's), raised ESR, high Ca++ and elevated LFT. Also check thyroid autoantibodies. An isotope scan should be performed if the cause is unclear, to detect nodular disease or subacute thryoiditis. If ophthalmopathy test visual fields, acuity and eye movements.

Answer 23

Common - Graves disease, toxic multinodular goitre Less common - toxic adenoma, drug induced (e.g. amiodarone, inappropriate treatment with levothyroxine), ectopic thyroid tissue, others Rare - struma ovarii, metastatic follicular thyroid carcinoma

Answer 24

This accounts for 2/3 of all hyperthyroidism and is more common in females. Typical age of onset is 40-60years (younger if maternal family history). It is caused by circulating IgG autoantibodies binding to an activating the GPCR thyrotopin (TSH) receptors which cause smooth thyroid enlargement and increased hormone production (esp. T3). They also react with orbital antigens producing thyroid eye disease. Triggers can include stress, infection or childbirth. It is associated with other autoimmune diseases such as vitiligo, type 1 DM and Addison's disease.

Answer 25

This is most commonly seen in the elderly and in iodine deficient areas. There are nodules that secrete thyroid hormones. Surgery is indicated for compression symptoms from the enlarged thyroid (i.e. dysphagia or dyspnoea).

Answer 26

This is a less common cause of thyrotoxicosis. There is a solitary nodule on the thyroid producing T3 and T4. On isotope scan the nodule is "hot" and the rest of the gland is suppressed.

Answer 27

This is rare and only occurs in metastatic follicular thyroid carcinoma or struma ovarii (ovarian teratoma with thyroid tissue).

Answer 28

1) Subacute de Quervain's thyroiditis - self limiting post viral with painful goitre, raised temperature and raised or normal ESR. There is low uptake on the isotope scan and it is treated with NSAIDs 2) Drugs - amiodarone and lithium (but hypothyroidism is more common) 3) Post partum 4) TB (rare)

Answer 29

1) Beta blockers (e.g. propranolol) for rapid control of symptoms 2) Anti-thyroid medication - 2 strategies are equally effective: (i) Titration - e.g. carbimazole 20-40mg/24h PO for 4wks reducing according got TFTs every 1-2 months (ii) Block - replace - give carbimazole + thyroxine simultaneously (less risk of iatrogenic hypothyroidism) In Graves remain on either regimen for 12-18 months then withdraw. 50% will repalse requiring radioiodine or surgery.

Answer 30

The main adverse side effect is agranulocytosis (reduced neutrophils, can lead to dangerous sepsis). Warm patients to stop and get an urgen FBC if signs of infection (e.g. fever, rigors, sore throat/ mouth ulcers).

Answer 31

It may be used as first line therapy (especially for toxic nodular goitre) or following ATD (anti-thyroid drug) failure. Most become hypothyroid post treatment. There is no evidence for increased cancer, birth defects or infertility in women. Contraindications include pregnancy and lactation. There is a risk in active hyperthyroidism of thyroid storm so caution patients about this.

Answer 32

Surgery is normally reserved for those with relapsing thyrotoxicosis who decline or are not suitable for RAI or if there is significant compressive symptoms. Potential complications include damage to recurrent laryngeal nerve (hoarse voice) and hypoparathyroidism. Patients may become hypothyroid.

Answer 33

Heart failure (thyrotoxic cardiomyopathy, increased in elderly) angina, AF, osteoporosis, ophthalmopathy, gynaecomastia, thyroid storm. AF in thyrotoxicosis responds poorly to warfarin and usually higher doses are needed. It is important to anticoagulate patients.

Answer 34

Diffuse goitres: - Physiological (especially in girls around the time of puberty or during pregnancy) - Grave's disease - Hashimotos thyroiditis - Subacute (de Quervain's) thyroiditis (painful) Nodular: - Multinodular goitre - Adenoma - Carcinoma

Answer 35

Goiter is enlargement of the thyroid. It may be diffuse or multinodular. Enlargement of the thyroid is usually related to a defect in the synthesis of thyroid hormones, evoking a compensatory hyperplasia of thyroid cells. The inefficient synthesis of thyroid hormones results in accumulation of colloid inside the follicles (colloid goiter). Irregular proliferation of thyroid cells coupled with degenerative changes that evoke hemorrhage, fibrosis, and calcification will cause transformation of simple colloid goiters into nodular goiter.

Answer 36

A simple goitre is a diffuse enlargement of the thyroid gland due to an absolute or relative deficiency of iodine or to goirtrogenic agents. There are 3 main subtypes of simple goitre - endemic, sporadic and physiological. Sporadic goiter, the most common form of thyroid enlargement in the United States, is a disease that usually affects young women. Although it may be related to the ingestion of goitrogens, such as Brussels sprouts, cabbage, or cauliflower, in most instances the cause remains undetermined. Thyroid enlargement represents a “cosmetic defect” but is not accompanied by hypo- or hyperthyroidism. Endemic goiter is a term used to denote thyroid enlargement found in more than 10% of the population. It is always related to iodine deficiency, and it occurs typically in mountainous areas of underdeveloped countries. The symptoms of the disease are related to the mass effect of the enlarged thyroid gland. In all cases of simple goitre, the gland is more vascular and diffusely enlarged with hyperplasia (increased number of acini, tall columnar epithelium and some colloid deficiency).

Answer 37

Hypothyroidism or myxoedema is the clinical effect of thyroid hormone lack. It is common and if treated has an excellent prognosis. But if untreated it can be disastrous with heart disease and dementia.

Answer 38

``` Tired Sleepy Lethargic Decreased mood Cold Weight gain Constipation Menorrhagia Memory/ cognitive decline ```

Answer 39

This can be remembered using the aid memoire "bRADYCARDIC" (which is also what hypothyroid can cause!) ``` Reflexes relax slowly Ataxia (cerebellar) Dry/ thin hair/skin Yawning/ drowsy/ coma Cold hands Ascites +/- non pitting oedema +/- pericardial or pleural effusion Round puffy face Defeated demenour Immobile +/- ileus CCF ``` Don't forget neuropathy, myopathy and goitre can also be present.

Answer 40

Have a low threshold for requesting TFTs. Results typically show: - raised TSH (i.e. >4mU/L) - reduced T4 - raised cholesterol and triglyceride - macrocytosis

Answer 41

1) Primary atrophic hypothyroidism - more common in females and characterised by diffuse lymphocytic infiltration of the thyroid leading to atrophy and hence no goitre 2) Hashimoto's thyroiditis - goitre due to lymphocytic and plasma cell infiltration. Commoner in women aged 60-70 years. May be hypothyroid or euthyroid; rarely there can be an initial period of thyrotoxicosis ("Hashitoxicosis"). Autoantibody titres are very high

Answer 42

Hypothyroidism may be related to three sets of causes: 1) Structural defect (lack of thyroid cells) 2) Functional defect in the synthesis of thyroid hormones 3) Extrathyroid tissue (hypothalamic or pituitary lesion) For an extended list of possible causes of hypothyroidism use the mnemonic "ADD IODINE" Autoimmune diseases (e.g. Hashimotos, Riedels thyroiditis) Developmental (agenesis of the thyroid) Dietary (goitrogens in foods such as brassica spp) Iodine deficiency (most common cause worldwide) Oncologic disease (destruction of the thyroid by cancer) Drugs (propylthiouracil, methimazole and lithium) Iatrogenic interventions (radiation therapy, surgical thyroidectomy) Nonthyroidal defects (TBG deficiency) Endocrine disease (pituitary deficiency and hypothalamic disorders)

Answer 43

This occurs when the disease is not due to the thyroid gland but other endocrine organs. In this case, there is not enough TSH to stimulate thyroid hormone production (i.e. hypopituitarism) but this is rare.

Answer 44

Cretinism is a term used for hypothyroidism in infancy and childhood. Previously, it was endemic in iodine deficient areas. Today it is very rare in the western world, and is most commonly caused by agenesis of the thyroid or inborn errors of metabolism and thyroid hormone synthesis.

Answer 45

Hypothyroidism in infancy or early childhood retards somatic growth and affects the development of the central nervous system. These children have short stature and are mentally retarded. Their faces have course features with protruding tongues.

Answer 46

Myxoedema is the term used to denote oedema of the skin and internal organs due to the accumulation of hygroscopic glycosaminoglycans that typically occurs in hypothyroidism of the adult. By inference, the term myxoedema has become synonymous with hypothyroidism.

Answer 47

Autoimmune causes of hypothyroidism is seen with other autoimmune diseases (e.g. type 1 DM, Addisons and PA). Turners and Downs syndrome are also associated with hypothyroid as is cystic fibrosis, primary biliary cirrhosis and ovarian hyperstimulation. POEMS syndrome - polyneuropathy, organomegaly, endocrinopathy, m protein band (plasmacytoma) and skin pigmentation/ tethering.

Answer 48

Eclampsia, anaemia, prematurity and decreased birthweight.

Answer 49

Levothyroxine is first line - 50-100micrograms/ 24h PO, review at 12 wks. Thyroxine has a half life of 7d, so wait 4wks before checking TSH to see if a dose change is needed. Enzyme inducers increase metabolism of levothyroxine.

Answer 50

Start levothyroxine at a lower dose (e.g. 25 micrograms) and increase the dose by 25 every 4wks according to TSH. Be cautious as thyroxine may precipitate angina or MI.

Answer 51

Amiodarone is an iodine rich drug and is structurally like T4. 2% of uses will get significant thyroid problems from it - this can be hyper or hypo thyroidism. Hypothyroidism is caused by toxicity from iodine excess (which reduces T4 release by the Wolff-Chaikoff effect). Hyperthyroidism/ thyrotoxicosis may be caused by a destructive thyroiditis causing hormone release from damaged thyroid follicular cells. Thyroidectomy may be needed if amiodarone cannot be stopped.

Answer 52

Thyroiditis, inflammation of the thyroid, most often has an autoimmune pathogenesis. Simple chronic lymphocytic thyroiditis is usually subclinical and is diagnosed histologically as an incidental finding on autopsy. Like all other thyroid diseases, it occurs more commonly in females than males. The most common form of thyroiditis associated with clinical symptoms is Hashimoto's thyroiditis which leads to hypothyroidism. Infectious thyroiditis is rare.

Answer 53

Hashimoto thyroiditis is an autoimmune disease causing progressive loss of thyroid tissue, which is replaced by lymphoid cells. Both T and B cells play a pathogenic role in the destruction of thyroid follicles. The disease is often associated with other autoimmune diseases and is 10 to 20 times more common in women than in men. A familial and HLA (human leukocyte antigen)-related clustering of cases suggests a genetic predisposition.

Answer 54

Almost all patients with Hashimoto thyroiditis have antibodies to thyroglobulin and thyroid peroxidase (an enzyme located in the microvilli on the apical, or inner, cell membrane of thyroid follicular cells). However, these antibodies are nonspecific signs of thyroid injury and occur in other thyroid disorders as well. Antibodies to the TSH receptor, like those in Graves disease, are also found. However, in Hashimoto disease anti-TSH antibodies do not stimulate thyroid cells but rather have a blocking effect, which accounts for the hypothyroidism in most cases.

Answer 55

The cause and the pathogenesis of Hashimoto thyroiditis are not known. It is an autoimmune disease in which the loss of suppressor T-cell activity leads to overproduction of antibodies to thyroid antigens and an unregulated function of T cytotoxic cells, which destroy the thyroid follicles and cause hypothyroidism. Antithyroglobulin antibodies are found in serum and are useful for the diagnosis of this disease.

Answer 56

The thyroid is diffusely enlarged in most cases. Histologically the parenchyma is infiltrated with lymphocytes and plasma cells replacing thyroid follicles. Lymphocytes may form germinal centers reminiscent of those normally found in lymph nodes. The remaining thyroid follicles vary in size and shape and are typically lined by cuboidal cells that have eosinophilic granular cytoplasm. These cells, known as oncocytes or Hürthle cells, contain numerous mitochondria in their cytoplasm but are inefficient producers of thyroxine.

Answer 57

Like many other autoimmune disorders, Hashimoto thyroiditis is associated with an increased incidence of B-cell lymphoma, which usually presents as a low-grade lymphoma limited to the thyroid. Papillary carcinoma, a low-grade epithelial malignant tumor of the thyroid, also occurs more often in thyroids affected by Hashimoto disease.

Answer 58

This should be suspected in cases where the TSH is >4mU/L with a normal T4 and T3 and no obvious symptoms. It is common, 10% of over 55s have an increased risk of raised TSH.

Answer 59

1) Confirm that the raised TSH is persistent (recheck in 2-4 months) 2) Recheck history - if any non-specific features (e.g. depression) discuss benefits of treating with the patient 3) Have a low threshold for treating - treat if (i) TSH>10mU/L, or (ii) if positive thyroid antibodies or (iii) past (treated) Grave's disease

Answer 60

Note this is a different condition to subacute (de Quervain's) thyroiditis. Subclinical hyperthyroidism can be considered when TSH is low but there is normal T4 and T3. This is a serious condition, as there is a 41% increase in relative mortality from all causes versus euthyroid control subjects - e.g. from AF or osteoporosis Options for treatment are carbimazole or propylthiouracil. But treatment should not be started until there is confirmation that the TSH is suppressed.

Answer 61

Most thyroid adenomas present as well-encapsulated nodules, measuring, on average, 3 to 10 cm in diameter. These benign tumors represent clonal proliferation of follicular cells resembling adult or embryonic or fetal thyroid cells. Several histologic variants have been identified. Histologic subclassification of adenomas is of no clinical significance. Well-differentiated follicular carcinomas may be composed of cells that are indistinguishable from those in adenomas, and in such cases the diagnosis of malignancy is established by demonstrating penetration of tumor cells through the capsule or invasion of blood vessels.

Answer 62

Most adenomas do not take up radioactive iodine and present as cold nodules on thyroid radionucleotide scans. Radioactive iodine scans cannot distinguish benign nonfunctioning adenomas from thyroid carcinomas, which also present as cold nodules. Approximately 10% of solitary cold nodules are carcinomas. Approximately 5% of thyroid adenomas present as hot nodules. Hot nodules are almost never malignant.

Answer 63

Thyroid carcinomas are rare and account for only 1.5% of all malignant tumors of internal organs. It is worth remembering that: ▪ Most tumors (80%) are low-grade papillary carcinomas. ▪ Most tumors arise in middle-aged adults. ▪ Women are more often affected than men, except for the rare tumors of children and the elderly, which show no sex predilection.

Answer 64

Risk factors for thyroid cancer include: ▪ Ionizing radiation ▪ Autoimmune thyroid diseases ▪ Iodine deficiency ▪ Genetic factors The incidence of thyroid cancer is increased in people who were exposed to ionizing radiation during childhood. Increased incidence has been noticed in men and women treated by x-rays for acne during puberty and those who survived the atomic blast in Japan during World War II or the Chernobyl nuclear plant accident in Ukraine in 1986. Hashimoto thyroiditis is associated with an increased incidence of thyroid epithelial tumors and lymphomas. Endemic goiter in iodine-deficient areas of the world is associated with an increased incidence of follicular carcinoma. Medullary carcinoma shows familial clustering, and in some cases it is one of the tumors of the syndrome of multiple endocrine neoplasia (MEN-2). Such tumors show rearrangement of chromosome 10 containing the RET protooncogene. The RET oncogene is mutated in approximately 95% of patients with MEN-2. The RET oncogene also plays a role in the pathogenesis of some papillary carcinomas.

Answer 65

``` Papillary carcinoma (70%) Follicular carcinoma (15%) Medullary carcinoma (5%) Undifferentiated (anaplastic) carcinoma (2%–3%) ```

Answer 66

- It is the most common malignant tumor of the thyroid - It affects women more often than men - It may occur in early adulthood and throughout adult life (20–60 years of age) - It has a good prognosis in most instances (10-year survival >90%), but some tumors in older patients have a less favourable prognosis

Answer 67

Most tumours present as small nodules with sharp margins, but larger tumours may not have a distinct capsule. Microscopically, the tumour is composed of cuboidal cells lining the fibrovascular papillae. Foci of calcification called psammoma bodies are common. Tumour cell nuclei contain cytoplasmic inclusions or appear "empty" and are described as "Orphan Annie eyes". These nuclear features are important for making fine needle aspiration biopsy diagnosis of papillary carcinoma and in tumours that do not form obvious papillae.

Answer 68

These tumours have a tendency to invade lymphatics and metastasize early to ipsilateral lymph nodes on the neck. This local spread does not worsen as the disease progresses, which is usually excellent. Less favourable variants are tumours that invade the blood vessels. Papillary carcinoma in the elderly has a less favourable prognosis.

Endocrinology - Thyroid Flashcards

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