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Lecture 16
Lecture 16
Lecture 16
Lecture 16
Lecture 16
Lecture 16
Lecture 16
Lecture 16
Lecture 16
Lecture 16
Lecture 16
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Lecture 16

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  • 1. THYROID DISORDERS Thyroid Structure The Thyroid has two lateral lobes joined by an isthmus. It comprises follicles which are spheres of single thyroid cells surrounded by basement membrane. These cells enclose colloid, a viscous gel that forms the storage site for thyroglobulin and thyroid hormones. There is about 100 days worth of thyroid hormone in storage. Scattered between the follicles are parafollicular cells or C cells which secrete calcitonin. The thyroid is a very vascular gland and if it becomes over-active, and the blood flow increases, a bruit may be heard. Thyroid Function Iodine is the most important prerequisite for thyroid hormone production. The normal sources for Iodine are water, especially seawater, iodinated salt and iodinated bread and kelp. Almost all the dietary Iodine is absorbed. Thyroglobulin is the precursor for all thyroid hormones and is the main protein in the follicular colloid. Inorganic iodine is actively transported into the thyroid follicle where it is oxidised and incorporated into thyroglobulin forming mono-iodo and di-iodothyronine which are coupled to form tetra-iodothyronine = thyroxine, T4 and tri-iodothyronine, T3. If a defect in the coupling of the mono and di form occurs there is a reduction in the formation of T3 and T4. This can arise as a result of inadequate iodine or a problem with the enzyme responsible for the coupling. In iodine deficiency there is a reduction in the formation of the di form and thus less T4 can be produced this is associated with a proportional increase in the level of T3 which can be considered an adaptive mechanism as T3 is more biologically active then T4. Drugs which are used to reduce the amount of thyroid hormone (thionamide drugs such as methimazole and propylthiouracil) have their effects both on iodination and coupling of the precursors. Thyroid hormone stimulation and excretion are controlled by internal and external factors. The external mechanism is mediated by Thyroid-stimulating hormone (TSH) which has a very short half-life. TSH is released from the anterior pituitary in response to thyrotrophin- releasing hormone (TRH) from the hypothalamus. TRH enhances the secretion of TSH by changing the set point of T3 inhibition of TSH secretion (T3 is the main inhibitor of TSH secretion in the anterior pituitary). TSH has a variety of effects on the thyroid and the net result is an increased thyroid hormone secretion. Thyroid hormone has a negative effect on TRH release. In hypothyroidism (due to primary thyroid disease) serum TSH levels are elevated. Autoregulation of the thyroid is responsible for the increased production of T3 compared with T4 when iodine availability is reduced. Circulating thyroid hormones are mostly bound to thyroxine binding globulin (TBG) and thyroxine binding prealbumin (TBPA) and only a small proportion circulates in the active form. Albumin has a low affinity for binding with thyroid hormones but as it is so plentiful in the plasma it actually binds a considerable amount (10% of T4 and 30% of T3). It is believed that it is only the free/unbound hormone which can enter cells and produce biological effects. Thus the bound hormone which comprises 99% of the total plasma thyroid hormone is acting as a reservoir. 1
  • 2. In the peripheral tissues T4 is predominantly de-iodinated to T3 which is primarily responsible for the metabolic effects. 30-40% of T4 is converted to T3 in the tissues, another 30% of T4 becomes reverse T3 (which may act as a counter hormone to reduce the activity of more active thyroid hormones) and the remaining 20-30% of T4 is excreted in the urine or faeces. Effects of Thyroid Hormones The main action of the hormone is regulation of the expression of specific enzymes including growth hormone and enzymes involved in key metabolic pathways which cause a significant effect on general cell metabolism by increasing the cellular mRNA synthesis. Thyroid hormones are very important in fetal development, particularly on the neural and skeletal systems. The maternal thyroid hormones do not cross the placenta in large enough quantities to maintain normal thyroid function in the fetus consequently fetal insufficiency of thyroid hormone produces cretinism comprising mental retardation and dwarfism. Thyroid hormones also increase basal metabolic rate = oxygen consumption at rest, in severe hyperthyroidism fever may develop, in hypothyroidism, hypothermia can occur. stimulate the cardiac muscle thus increasing the heart rate and contractility. in certain tissues, eg. myocardium and the eyelid muscles, thyroid hormone acts like catecholamines and these effects can be reversed by beta-adrenergic inhibition. For other thyroid effects, eg. increased oxygen consumption, the effect is not reversed by this form of inhibition. The exact relationship between thyroid hormones and catecholamines has yet to be clearly defined. important in the normal hypercapnic and hypoxic drive of the respiratory centre, so that in severe hypothyroidism there is hypoventilation with hypoxia and hypercapnia. increase erythropoiesis, increase the metabolism of hormones and drugs, including cortisol, prolactin, insulin, parathyroid hormone, there is also an alteration to LH and FSH secretion which can result in anovulation and menstrual changes in hypothyroidism. increase bone formation and resorption and increase the rate of muscle relaxation. DISORDERS OF THE THYROID Are relatively common effecting 5% of the population particularly women. The common complaints related to the thyroid are, enlargement = goitre, symptoms of hypothyroidism, symptoms of hyperthyroidism, complications of a form of hyperthyroidism, Graves disease, such as exophthalmos or thyroid dermopathy ( thickening of the skin over the lower limbs). SIMPLE OR NONTOXIC GOITRE 2
  • 3. The thyroid may become enlarged either diffusely or in a multinodular form and the patient is euthyroid. Aetiology Possibly suboptimal dietary iodine, minor degrees of disorders in hormone formation, goitrogens such as lithium carbonate (used to treat bipolar disorders) and some chemicals found in vegetables eg, thioglucosides in cabbage, pregnancy and ingestion of the oral contraceptive pill or low grade Hashimoto’s thyroiditis. Pathology Areas of diffuse hyperplasia are replaced by focal hyperplasia with necrosis and fibrosis and further areas of focal necrosis develop. Initially the hyperplasia is TSH dependent but it gradually becomes autonomous. Clinical Features Simple diffuse goitre often presents in young women between the ages of 15-25, particularly when they are pregnant. The goitre is soft and symmetrical and apart from its visible enlargement the only other symptom is a tight sensation in the neck on swallowing. There is no tenderness or bruit. The levels of T3, T4 and TSH are all normal (euthyroid) and no thyroid antibodies are detected. Treatment is not necessary and the goitre regresses. There is a chance that the hyperplasia will sporadically recur with the result that a multinodular gland can develop. SIMPLE MULTINODULAR GOITRE Results from the gradual enlargement of the gland over years. There may be haemorrhage into a nodule which produces pain and swelling. The goitre can become very large and can spread retrosternally to cause mediastinal compression with stridor, dysphagia and obstruction of the superior vena cava. Hoarseness can follow compression of the recurrent laryngeal nerve. Usually T3, T4 and TSH are all within normal limits but there can in 25% of patients be a subclinical hyperthyroidism and the T3 and T4 are at the upper range of normal and the TSH is undetectable. Treatment is annual review if the goitre is not too large. Partial thyroidectomy may be necessary if it is causing compression. Unfortunately there is a high incidence of recurrence of the goitre 15-20 years later. HYPOTHYROIDISM Is the clinical syndrome resulting from a deficiency of thyroid hormones and the consequent slowing down of metabolic pathways. If it occurs in utero or childhood it can reduce growth and development and can cause mental retardation. If it develops in adulthood it produces a general slowing and the deposition of glycosaminoglycans in intracellular spaces a process called myxoedema . Aetiology and Classification Primary = due to Thyroid Failure 3
  • 4. Prevalence = 10/1000 rising to 50/1000 if subclinical cases are included = nT4 with elevated TSH Hashimoto’s thyroiditis with a goitre or as the end stage of either Hashimoto’s or Graves disease, so-called spontaneous atrophic, following surgical removal of the thyroid for hyperthyroidism or after use of radioactive Iodine as treatment for Graves disease, these are the commonest causes in areas which are not Iodine deficient and they account for 90% of cases. Lithium carbonate acts to prevent the release of thyroid hormones, usually administration of this drug merely produces a raised TSH but in patients with an underlying autoimmune thyroiditis this can precipitate goitre and hypothyroidism. Secondary = due to pituitary TSH deficiency Prevalence = rare pituitary adenoma, pituitary ablative therapy. Tertiary = hypothalamic deficiency of TRH. hypothalamic dysfunction which is rare. It is also possible for the peripheral tissues to develop a resistance to the effects of thyroid hormone. CRETINISM Is uncommon but important because prompt replacement of thyroid hormone can prevent the development of serious consequences. Aetiology Thyroid agenesis failure of thyroid hormone synthesis due to severe iodine deficiency is rare, it also can be due to an autosomal recessive enzyme deficiency of which several types are known (enzyme deficiencies causing failure of any of the steps in thyroid hormone synthesis have been identified). Pathology Depends on the cause, for example there can be a failure of the gland to develop or if there is a failure of thyroid hormone synthesis the gland becomes enlarged due to hyperplasia owing to the increased stimulation by TSH due to reduced negative feedback. Clinical Features Include respiratory difficulty, lethargy, somnolence, hypothermia, cyanosis, persistent neonatal, jaundice, poor feeding, hoarse cry, large protruding tongue, umbilical hernia, muscle weakness, hypotonia and marked retardation of bone maturation. It is normal for all full-term babies weighing over 2.5 kg to have proximal tibial epiphyses and distal femoral epiphyses and these are absent in hypothyroidism. Early diagnosis is important to prevent the development of mental retardation. 4
  • 5. The diagnosis is made on the findings of a low T4 (<6 microg/dL ) or a serum TSH of greater than 30 microU/mL. Treatment is via replacement of thyroid hormone in the form of levothyroxine and has a good result thus mental retardation is prevented to a large extent. HASHIMOTO’S THYROIDITIS Probably the most common cause of goitrous hypothyroidism. It effects females ten times more often than males and predominantly occurs in middle age. It is more likely to be associated with a goitre in younger patients. Aetiology Is believed to be caused by an auto-immune reaction to the thyroid but the precise mechanism is not clear. It is possible to find Ig G autoantibodies to thyroglobulin, anti- microsomal antibodies and another directed against a component of colloid other than thyroglobulin, in the serum of those with the disorder. The levels of these antibodies do not correlate with the severity of the disease and their exact relationship to the destruction of thyroid tissue is not clear, but they are helpful in making the diagnosis of Hashimoto’s. Pathology In the early stages the gland is enlarged but as the process continues the thyroid shrinks until it ultimately becomes markedly atrophic. Microscopically there is destruction of the thyroid follicle with considerable infiltration by lymphocytes and progressive fibrosis. Clinical Features The commonest presentation is a gradually enlarging thyroid. Thyroid function is variable and thyroid hormone levels maybe normal or mildly hypothyroid. If untreated hypothyroidism will develop. The clinical features of hypothyroidism are due both to the widespread effects of the hormones and specifically to the accumulation of hydrophilic substances known as glycosaminoglycans in the skin, heart muscle and striated muscle especially. This accumulation occurs because of decreased breakdown of the substances not excessive synthesis. It is responsible for the low-pitched voice, poor hearing, slurred speech (due to an enlarged tongue) and compression of the median nerve. Infiltration of the dermis results in non-pitting oedema called myxoedema which is most noticeable in the skin of the hands, feet and eyelids. This causes a periorbital puffiness and when combined with a facial pallor, due to vasoconstriction and anaemia, is most characteristic of the disorder. Most patients do not have such an obvious facies and instead present with tiredness, somnolence, cold intolerance, weight gain, depression and carpal tunnel syndrome. Other possible clinical features are goitre, bradycardia, angina (coronary artery disease is more common in hypothyroidism although it is not clear whether the decreased function of the thyroid is causative), hypertension, xanthelasma, aches, pains and muscle stiffness, macrocytosis (there are several mechanisms which interfere in normal blood cell formation these are impaired haemoglobin synthesis, menorrhagia producing iron- deficiency anaemia, folate deficiency due to impaired intestinal absorption and pernicious anaemia as part of a spectrum of auto-immune disease), dry flaky skin and hair, alopecia, vitiligo, menorrhagia, infertility, constipation and pericardial effusion. There are a large 5
  • 6. number of patients who are asymptomatic and in whom thyroid replacement provides little benefit. Investigations High levels of antibodies are diagnostic, moderate levels of the same Antibodies may occur in Graves’ disease, multinodular goitre and thyroid neoplasms. There are low T4, low free thyroxine index and elevated TSH. The T3 level is variable. Management Thyroid replacement therapy maintains a euthyroid state. Taken as a daily tablet, there is improvement within 2-3 weeks but the skin changes and pericardial effusions may take months to resolve. Complications Approximately 5% of patients with Hashimoto’s disease develop a malignant neoplasm of the thyroid. As hypothyroidism occurs commonly in the elderly it often coexists with coronary artery disease. Although hyperlipidemia is associated with reduced function of the thyroid it probably does not increase the risk of C.A.D. In the older person with the two disorders the low levels of circulating thyroid hormone protect against increasing cardiac demands thus also protecting from cardiac ischaemia. Thus treatment to increase the thyroid levels must be introduced gradually to avoid precipitation of angina or myocardial infarction. THYROTOXICOSIS Thyrotoxicosis refers to the clinical features of thyroid hormone excess. This is not the same as Hyperthyroidism which is the state of having a hyperfunctioning thyroid (increased function in order to maintain normal output). Aetiology Graves disease, multinodular goitre and a solitary thyroid nodule account for 90% of causes. Other causes include excess pituitary secretion of TSH. Subacute thyroiditis and rare tumours such as ovarian teratomas containing thyroid tissue cause thyrotoxicosis without hyperthyroidism. Clinical Features of Thyrotoxicosis Include Goitre=diffuse (+/- bruit), nodular, G.I.T., weight loss with a normal or increased appetite, hyper defecation, diarrhoea, vomiting. Cardiorespiratory, Palpitations, sinus tachycardia, atrial fibrillation, increased pulse pressure, dyspnoea on exertion, exacerbation of asthma, ankle oedema in the absence of cardiac failure. Neuromuscular, nervousness, irritability, emotional lability, psychosis, tremor, hyper- reflexia, muscle weakness, proximal myopathy. 6
  • 7. Dermatological, pruritis, increased sweating, palmar erythema, spider naevi, alopecia. Reproductive, amenorrhoea/oligomenorrhea, infertility, loss of libido, impotence. Ocular, lid retraction, lid lag, excessive lacrimation, exophthalmos, corneal ulceration, ophthalmoplegia, diplopia, papilledema, loss of visual acuity. Other, heat intolerance, fatigue, apathy, thirst, lymphadenopathy. Usually the disorder develops insidiously and there is a large variation in the presenting symptoms and signs. Often in the elderly the features are increased angina, CCF or the recent onset of atrial fibrillation and nothing else. GRAVES DISEASE = TOXIC DIFFUSE GOITRE Commonest form of thyrotoxicosis. Commonly affects 30-50 year old age group. It is characterised by the presence of diffuse thyroid enlargement, and/or ophthalmopathy and and/or rarely pretibial myxoedema. Aetiology and Pathology The exact cause is unknown however in at least 50% of sufferers there are circulating thyroid autoantibodies which stimulate the TSH receptors on the thyroid follicular cells producing increased thyroid hormone production and often goitre. Although the reason for the development of these antibodies is yet to be definitively determined there is an association with certain HLAs, indicating a genetic factor, and there is qualitative evidence that major stresses such as the death of a near relative may trigger the antibodies. As there are TSH receptors on some gut micro-organisms such as E. coli, it is postulated that antibodies produced to these organisms might cross react with TSH receptors on the host’s thyroid follicular cells. As the severity of Graves disease varies over time it is suggested that the levels of antibodies also fluctuate. The eye changes are not mediated by the TSH antibodies but by antibodies against particular antigens in extraocular tissue. They are attributed to proliferation of fibroblasts which secrete hydrophilic glycosaminoglycans. Thus there is an increased interstitial fluid content and chronic inflammatory cell infiltrate causing considerable swelling of the extraocular muscles and an increase in the retrobulbar pressure. The eye is displaced forward and in severe cases there can be optic nerve compression. Clinical Features Features of hyperthyroidism including a variety from the list above. Goitre, 2-3 times enlarged and the increased blood flow may produce a bruit. Eye changes are present in 50% of patients at diagnosis but may precede the hyperthyroidism by many years or can occur after it has been successfully treated. Rarely pretibial skin changes such as a marked thickening of the skin are due to accumulation of glycosaminoglycans. Investigations Elevated T3 and T4, low or undetectable TSH and the presence of thyroid autoantibodies. Management 7
  • 8. Antithyroid drugs which reduce the synthesis of the hormone by inhibiting iodination. Beta blockers (propanol = Inderal) are used to reduce sweating, tremor and tachycardia Sub-total thyroidectomy, there is a risk of hypothyroidism and the recurrence of thyrotoxicosis in the long term and a risk of damaging the laryngeal nerves and removing all the parathyroids. This procedure is used especially for large goitres, in those who are pregnant and the very young. Radioactive iodine destroys functioning thyroid cells or inhibits their ability to replicate. This is the treatment of choice except in pregnancy and the young. The eye changes usually resolve albeit very gradually. The dermopathy rarely requires treatment. Complications Thyrotoxic crisis is an acute exacerbation of all the symptoms of thyrotoxicosis and can be life threatening. It may be precipitated by stress, acute infection, uncontrolled diabetes, trauma, AMI or a severe drug reaction. It is believed to occur in response to an outpouring of catecholamines which combine with the high levels of T3 and T4 to cause the acute situation. There is marked hypermetabolism with a high fever, marked tachycardia and sometimes heart failure and even coma. Treatment is i.v. propanolol, specific treatment of the associated problems, ie. heart failure and drugs to reduce the formation of thyroid hormones. TOXIC MULTINODULAR GOITRE Results from one of the nodules in a multinodular goitre becoming capable of producing excess thyroid hormone thus causing thyrotoxicosis after a long period of euthyroidism in the presence of a goitre. Is another form of hyperthyroidism more common in women, it is particularly found in the over 60 age group. Clinical features are often cardiovascular eg. atrial fibrillation or cardiac failure although weight loss, tremors and sweating may also be present without any CVS features. Investigations reveal a high T3 and less elevated T4 with suppressed TSH levels. Treatment is usually with radioactive iodide although if the enlarged gland is pressing on the trachea a subtotal thyroidectomy is preferable. TOXIC ADENOMA The presence of a follicular adenoma (which is almost never malignant) which autonomously secretes excess thyroid hormone and inhibits TSH secretion with a resultant atrophy of the rest of the gland. Clinical features may include weight loss, weakness, shortness of breath, palpitations, tachycardia and heat intolerance. Physical findings are of a thyroid nodule on one side and very little thyroid tissue on the other side. Investigations reveal an elevated T3 but the T4 may not be high, TSH is suppressed. Treatment is hemi-thyroidectomy or radioactive thyroid. SUBACUTE THYROIDITIS 8
  • 9. Also known as De Quervain’s Thyroiditis, is an acute inflammation of the thyroid caused by a viral infection including mumps, adenoviruses and Coxsackie. Pathology There is moderate thyroid enlargement and a mild inflammatory reaction with some destruction of the thyroid parenchyma and many phagocytic cells. Clinical Features Commonest in women 20-40 years. Symptoms follow those of an URTI and include those indicating an inflamed thyroid and less often thyrotoxicosis. Therefore fever, malaise and neck soreness which may spread to the angle of the jaw and the ears. The pain is exacerbated by swallowing, coughing and neck movement. There may be palpitations, agitation and sweats representing a form of hyperthyroidism. Examination reveals a very tender, probably enlarged, thyroid. Investigations Results vary with the stage of the process. Initially there may be an elevated T3 and FT4I with very low TSH, as the disease progresses the T3 and T4 drop, TSH rises and symptoms of hypothyroidism occur. Treatment Symptomatic although cortisone is sometimes used if the symptoms are debilitating and thyroid hormone may be required. In 90% of patients there is a complete recovery but in 10% permanent hypothyroidism develops. SOLITARY THYROID NODULES May be benign or malignant. Are relatively common being found in 5% of women with a higher incidence on post-mortem. BENIGN Aetiology and Pathology Benign masses such as adenomas, a dominant portion of a multinodular gland, a cyst of the thyroid, focal areas of chronic thyroiditis and agenesis of the left lobe of the thyroid with hypertrophy of the right. Also (rarely) secondary spread from a renal, breast or lung carcinoma. Clinical Features A palpable thyroid lump, maybe painful and rapid in onset if haemorrhage into a cyst. Cervical lymphadenopathy suggests carcinoma. Investigations 9
  • 10. Because of the risk of malignancy needle aspiration of the nodule is the most important test. T3, T4 and TSH should be measured as an undetectable level of TSH is a strong indication of an autonomously functioning thyroid adenoma which is almost always benign. MALIGNANT NEOPLASIA Is uncommon accounting for only 1% of tumours. Aetiology Exposure to ionising radiation either as a treatment for acne or tonsillitis, which it was used for, or, as the result of fallout. The interval between the dose and the disorder is 10- 40 years with a mean of 20 years. There does seem to be a familial tendency for thyroid tumours but no precise factors have been determined. Pathology Papillary Carcinoma is the commonest form and accounts for 90% of the tumours due to radiation. It presents as a solitary nodule, is very slow growing and spreads into the gland and the lymphatics. At a late stage the malignancy can spread into the lungs and trachea. Also there is a possibility that the cells convert to an undifferentiated form which results in a much more aggressive growth and spread. Follicular Carcinoma is distinguished from papillary by the maintenance of follicles. This tumour is slightly more aggressive and spreads in the blood stream to bone, lungs and brain. Medullary Carcinoma is a disease of the C cells, the parafollicular cells, and is capable of producing not only calcitonin but serotonin, histaminase, prostaglandins and other peptides. It spreads into the lymphatic system. Serotonin is a marker of the disease and the cure. There is a strong familial component as >60% of patients have a positive family history with other endocrine tumours eg., parathyroid adenomas and phaeochromocytoma or medullary carcinoma of the thyroid. Clinical Features Suggestive of malignancy include, recent onset or enlarging nodule, history of dysphagia, vocal cord paresis/paralysis, Horner’s syndrome or SVC obstruction, family history of thyroid ca., fixation of nodule to surrounding tissue, cervical node enlargement, being male and less than 40 years old. Investigations Needle aspiration, serum levels of thyroid hormones and scanning to detect metastases. 10
  • 11. Management of Malignant Thyroid Tumours Total thyroidectomy followed by radioactive iodine to ablate any remaining thyroid tissue. Thyroxine is administered at a dose which will suppress TSH because there is evidence indicating that thyroid tumours are TSH dependent. Follow up relies on checking the levels of serum thyroglobulin as any rise suggests a recurrence. Prognosis Usually excellent. If the tumour is less than 2cm in diameter, confined to the thyroid and the patient is less than 50 years old there is no reduction of life expectancy. If there are distant metastases on diagnosis the 10 year survival is 40%. Tutorial questions 1. How and in whom could a pituitary tumour present to you in osteopathic practice? 2. How might someone present to an Osteopath with Cushing’s syndrome and what are the most likely aetiologies? 3. Discuss the possible causes of a palpable lump in the thyroid. 4. What is the relationship between goitres and the activity of the thyroid? 5. Explain the aetiology, pathology and possible clinical features of Hashimoto’s thyroiditis. 6. Discuss the clinical features of Graves disease and describe their underlying pathology. 11

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