Disorders of the endocrine system 38 Disorders of endocrine system mainly are caused by: A-Deficiency or an excess of a single hormone or several hormones: - deficiency :can be congenital or acquired. -Excess: can be endogenous production or exogenous: overmedication. B-Resistance to the action of hormones, Hormone resistance characterized by receptor mediated, postreceptor. 1
Part 1: Thyroid disorders Problem with thyroid hormone secretion can arise either -in the thyroid gland -along the control pathway of thyroid hormones Clinical condition is often referred to thyrotoxicosis and affected individuals present with characteristic features.> 2
Thyroid disorders are classified broadly to 2 classes: ( clinical features reffered to myxoedema) Q/Hyperthyrodism prevalence : 3
Hyperthyroidism : More prevalent in women than in men. Causes of hyperthyrodism : A-The most common causes are : 1-graves disease 2 toxic multi nodular Goitre B-Less commonly: 1- thyroxine therapy 2-ectopic thyroid tissue might produce excess TH C-Rarely, hyperthyroidim might be caused by TSH secreting tumours 4
TMNG age of onset is typically over 50 years, with females being affected more than males. Cardiovascular features tend to predominate Grave predominantly affects females, with a peak incidence in the 3 rd and fourth decades of life. 5
Management of hyperthyroidism treatment o falls into 3 broad categories: 1-anti-thyroid drugs, 2-radioactive iodine,3 or subtotal thyroidectomy. -Some of the symptoms such as tachycardia and tremor can be controlled with β-blocking drugs for the first few weeks of therapy. -Radioactive iodine ( 131 I) * can be used to treat hyperthyroidism and works by initially interfering with organification of iodine and then induces radiation damage to the thyroid. *The major side effect 80% of subjects will develop hypothyroidism *No malignancy by radioiodine -Subtotal thyroidectomy is highly effective In elderly patients with a multi-nodular goitre, radioiodine is the treatment of choice, although anti-thyroid drugs can be used until radioiodine treatment becomes effective. Surgery may be required in patients who present with symptoms of hyperthyroidism and an enlarged thyroid gland compressing structures in the neck. 6
Hypothyroidism high morbidity, subtle non specific signs are often associated with other conditions. More common in women, specially elder women Causes of hypothyroidism 1 o : the thyroid gland is affected, the most common cause is Autoimmune condition called hashimoto s thyroiditis (antibodies cause destruction of the patients own thyroid gland Loss of functioning thyroid tissue following thyroidectomy or radioiodine treatment and may lead to hypothyroidism. These patients will have an increased TSH concentration with a low free T4 concentration Drugs Li and I can also result in hypothyroidism 2 o : anterior or hypothalamus 7
-Congenital hypothyroidism is a defect in the development of the thyroid gland Resulting in either the absence or undeveloped gland. If treated early, prognosis is usually good -Untreated children develop CRETINISM, In which the children will have growth failure, developmental delay, deafness Q) What are the effects of amiodarone on thyroid? 8
Normally TSH stimulate thyroid to secrete thyroid hormones Elevated TSH cause enlargement of the thyroid and form a huge mass called Goiter. This is because TSH also has a trophic (growth stimulating) effect on the thyroid gland. Goiter might be caused by two mechanisms: 1-Primary hypothyroidism :(caused by lack of iodine in diet). No iodine =No thyriod hormones= T 3 and T 4 in blood removes negative feedback on the anterior pituitary= TSH=Goiter (figure2 ) 2-Grave s disease: (caused by Hypersecretion of T 3 and T 4 ) Autoantibodies exert TSH-like effect on thyroid And production of these antibodies is not inhibited by ve feedback= overstimulating thyroid hormone production= Goiter *Note TSH is inhibited ( TSH)because of high concentrations of T 3 and T 4 9
Figure2 : Endemic goiter is caused by insufficient iodine in the diet. A lack of iodine causes hypothyroidism, and the resulting elevation in TSH secretion stimulates the excessive growth of the thyroid 10
Figure 3: How iodine deficiency causes a goiter? Lack of adequate iodine in the diet interferes with the negative feedback control of TSH secretion, resulting in the formation of goiter 11
Management of hypothyroidism -Involves replacement of thyroid hormones, usually T4, T3 may sometimes be used. Therapy monitored by regular measurement of TSH and free T4. -careful with elderly Patients ( especially those with pre-existing ischaemic heart disease), -being started on a low dose and titrating the dose slowly. 12
Diagnosis and practical investigation of thyroid disorders Diagnosis of hyperthyroidism * pituitary adenoma: A TSH secreting adenoma is a rare cause of hyperthyroidism. TSH is usually within the reference range, or inappropriately normal, or only slightly raised above it, with an increased free T4 and T3. In such cases imaging will often identify a pituitary lesion. -TSH low in most cases *The exception to this is a TSH secreting pituitary tumour (rare) *T3-toxicosis: In some cases free T3 alone may be increased, with a normal T4 low or undetectable levels of TSH 13
*Graves disease: finding of hyperthyroidism on biochemical testing, the presence of goitre, and extra-thyroidal signs such as eye signs. In other cases the (TSH receptor antibody) and diffuse increased iodine uptake on thyroid scanning confirms the diagnosis. *Toxic multi-nodular goitre : suppression of TSH concentration causing increased Free T4 and T3 although they may not be grossly abnormal, with values at or just above the reference range. 14
Diagnosis of hypothyroidism -Routine tests are TSH and T4, T3 is misleading in hypothyroidism -Hashimotos: TSH high, low T4 and may be thyroid Ab And thyroid peroxidase abs. patients might have other autoimmune disease Such as diabetes, addisons disease, perncious anemia -2 O hypothyroidism Will have low TSH and Low T4, the distinguishing feature is that TSH is inappropriately low 15
Thyroid test in pregnancy In a normal pregnancy TBG increases due to the action of oestrogen. Free thyroid hormone increase due to the weak thyroid stimulating effect of high concentrations of human chorionic gonadotrophin (hcg) in early pregnancy. TSH is increased compared to the non-pregnant state, but remains within the non-pregnant reference range. -a state of severe vomiting during the1st trimester is frequently associated with very high concentrations of free T4 and free T3 making it difficult to differentiate from true thyrotoxicosis. It is thought that very high concentrations of hcg are also responsible for this condition. 16