HYPERTHYROIDISM AND HYPOTHYROIDISM DCM 2018.pptx

Good work

1. HYPERTHYROIDISM

2. THYROID HORMONE Iodine is the main substrate for the formation of thyroid hormones. After active transport (the thyroid to serum concentration ratio is 25) into the thyroid follicular cells, it is organified , forming the iodotyrosines , mono- and diiodo-tyrosines (MIT and DIT). This is followed by coupling, which leads to the formation of triiodothyronine (T 3 ) and thyroxine (T 4 ). Further, polypeptide chains and carbohydrate moieties combine to form thyroglobulin , the storage form of thyroid hormone. This iodinated thyroglobulin molecule is secreted in the colloid of the follicles and acts as the primary intrathyroid storage form of thyroid hormone. Entry into the circulation is by exocytosis and is followed by proteolysis of thyroglobulin , releasing T 4 and T 3 . Deiodination at the peripheral tissue level brings out the functionality of the thyroid hormone

3. ACTIONS Thyroid hormones increase protein synthesis in all cells. The second important effect is increase in oxygen consumption. Both T 3 and T 4 are active but T 3 is three times more potent

4. IODINE DEFICIENCY DISORDERS These may be characterised by a) Goitre at all ages b) Endemic cretinism with associated mental retardation, deaf- mutism , spastic diplegia and lesser degree of neurological deficit c) Impaired mental function in children and adults d) Increased rates of abortion, stillbirth, and perinatal and infant mortality

5. GOITRE Goitre may be due to iodine deficiency

6. IODINE DEFICIENCY GOITRE The thyroid follicles are hyperplastic . In more advanced stages, nodule formation ensues and vesicles become distended with flattening of epithelium. Nodules may undergo degeneration, and fibrosis of varying degree may ensue. Rarely, this may be followed by calcification.

7. TREATMENT For the management of iodine deficiency, an average daily intake of 150 µg of Iodine has to be ensured. Salt can be easily iodinated. The recommended concentration of iodine of 25 ppm in common salt ensures optimum iodine supply. Lugol’s iodine has 5% iodine and 10% potassium iodide; this contains 126 µg of iodine per ml. A saturated solution of potassium iodide contains 250 µg of iodine in 5 drops

8. HYPERTHYROIDISM Hyperthyroidism or thyrotoxicosis refers to a state where there is an excess of circulating thyroid hormones, T 4 or T 3 Thyrotoxicosis is designated primary when the gland is diffusely enlarged and there are signs of hypermetabolic state; eye signs may or may not be present (Grave’s disease). Thyrotoxicosis is designated as secondary where the patient had previously abnormal gland, i.e. nodular goitre (single or multiple), and now assumes hyperfunctional status (Plummer’s disease).

9. HYPERTHYROIDISM The hyperthyroidism of Grave’s disease results from the presence in the serum of IgG antibodies directed against the TSH receptor of the thyroid follicular cells. These antibodies are unique in that, once bound to the TSH receptor, they stimulate thyroid hormone production via the adenyl cyclase cAMP system in a manner similar to TSH. They are termed thyroid stimulating antibodies ( TSAb ).

10. CAUSES OF HYPERTHYROIDISM Thyroid source 1) Grave’s disease 2) Toxic multinodular goitre 3) Solitary toxic nodule / adenoma 4) Acute thyroiditis viral , autoimmune, post-irradiation

11. CAUSES OF HYPERTHYROIDISM Extrathyroidal source 1) Thyrotoxicosis factitia 2) Exogenous iodine intake 3) Drugs (e.g. amiodarone ) 4) Hyperfunctioning ovarian teratoma ( struma ovaril )

12. CAUSES OF HYPERTHYROIDISM Increase in TSH 1) TSH secreting tumours (e.g. pituitary) 2) HCG producing tumours

13. Clinical features could be broadly stated as follows a) Evidence of hyperkinesis b) Objective evidence of hypermetabolic state (weight loss, catabolic state) c) Presence of goitre , with or without ophthalmopathy

14. FEATURES • Symptoms General Demour of anxiety, tremulousness, generalised  weakness, heat intolerance,  skin tanning, pruritus Signs Restlessness, inability to keep still, objective weight loss, excessive sweating, hair thinning and straightening

15. FEATURES (SYSTEMIC) CVS Symptoms: Palpitation, irregular beats,  shortness of breath Signs: Tachycardia, increased pulse pressure, ectopic beats, atrial fibrillation, sick sinus syndrome, cardiac failure CNS : Hyperactivity, muscle weakness, apathy in older age Signs: Fine tremors, hyperreflexia , proximal muscle weakness, periodic paralysis

16. FEATURES (SYSTEMIC) GIT: Diarrhoea (non-infective) Signs: Rapid bowel transit time, steatorrhoea Reproductive system : Oligomenorrhoea or amenorrhoea, impotence Signs: Gynaecomastia , infertility Thyroid: Enlargement in anterior, neck pressure symptoms Signs: Diffuse or nodular goitre , bruit, thrill

17. FEATURES (SYSTEMIC) Ophthalmic Stare, gritty sensation, increased lacrimal secretion, diplopia , diminished visual acuity Signs: Lid retraction, lid lag, chemosis , infiltrative ophthalmopathy , ocular muscle paresis, exposure keratitis

18. Classification of the eye signs of Grave’s disease Class Definition 0 No signs or symptoms 1 Only signs, no symptoms (signs limited to upper lid retraction, stare, lid lag) 2 Soft tissue involvement (symptoms and signs) 3 Proptosis more than 20 mm (measured by Hertel exophthalmometer ) 4 Extra-ocular muscle involvement 5 Corneal involvement

19. The diagnosis is based on a) Abnormal Free hormone and TSH levels in blood b) TS Ab for the immunological basis for Grave’s disease c) Assessment of end-organ involvement

20. HYPOTHYROIDISM Clinical manifestations due to lack of thyroid hormone are designated as hypothyroidism. The presentation varies depending on (a) the age of the patient, (b) the cause of the disorder, i.e. primary or secondary, and (c) pre-existing health status.

21. CAUSES OF HYPOTHYROIDISM 1.Idiopathic atrophic, seen in middle-aged women with insidious thyroid deficiency state; it is probably the commonest form of primary hypothyroidism. 2. Post-ablative surgical or radioactive 131l therapy; the incidence increases with the time lapse after treatment and figures vary from 5-50% in 10-20 years’ follow up. 3. Autoimmune thyroiditis (Hashimoto’s thyroiditis ), the commonest cause of goitrous hypothyroidism; 35-45 years are the most often affected. This may be in association with manifestations of autoimmune involvement in other systems. 4. Drug-induced, e.g. iodide, lithium carbonate, amiodarone . Such agents affect hormone synthesis or release or its peripheral deiodination . 5. Secondary to pituitary disease due to deficiency of TSH; manifestations include lack of other pituitary hormones, e.g. growth hormone and/or gonadotrophin ; ACTH is probably the last to be affected. 6. Congenital, in childhood. Hypothyroidism may be due to (a) environmental l2 deficiency, (b) hormonal biosynthetic defect or (c) maldevelopment , i.e. cryptothyroidism ( maldescent ).

22. Symptoms Signs • General features Blunting of features, generalised slowing Periorbital puffiness, psychomotor retardation • Skin Dryness, itching Dry, rough, flaky skin; non-pitting oedema; carotenaemia • Hair Hair loss Coarse and brittle; selective areas of alopecia • CVS Shortness of breath Bradycardia Angina pectoris Ischaemic heart disease Congestive cardiac failure Pericardial effusion • CNS Muscle aches and pains Delayed relaxation of Slowing of motor function tendon reflexes Deafness Myotonia and myoedema Somnolence Carpal tunnel syndrome Nerve conduction deafness Slowing of cerebration • GIT Constipation lleus Ascites • Reproductive system Menses irregular , menorrhagia High FSH/LH Infertility Hyperprolactinaemia Galactorrhoea • Haematological Pallor Dimorphic anaemia None-responsive anaemia Megaloblastic anaemia Bleeding tendency Coagulation defects • Miscellaneous Cold intolerance Hypothermia Monotonous, thick, coarse speech Mucous membrane infiltration of laryngeal muscles

23. FEATURES SUMMARISED AS FOLOWS a) Hypokinesis : slowing of physical as well as mental functions. b) i ) Infiltration of body tissues by mucopolysaccharide , hyaluronic acid, and chondroitin sulphate (‘ myxoedema ’ implies mucous swelling). ii) Functional alterations in end-organs. c) Thyroid gland status: goitrous or atrophic.

24. INVESTIGATIONS The diagnosis of hypothyroidism can be confirmed by: a) Level of thyroid hormones in circulation (T 4 , T 3 ) b) Value of TSH and its response to TRH c) Indirect tests: i )   Photomotogram ii)   Serum enzymes ( Creatine phosphokinase , LDH) iii)   ECG d) Thyroid antibody tests

25. TREATMENT Replacement with thyroxine is adequate in a majority of instances of hypothyroidism. There is a peripheral conversion of T 4 to T 3 so as to be available at the tissue level. The usual replacement dose of thyroxine is 1.5-2.5 µg/kg. The normal adult with ideal body weight requires a maintenance dose of 150-200 µg/day. The dose is adjusted to achieve serum TSH and T 3 , T 4 levels in the normal range

26. COMPLICATIONS MYXOEDEMA COMA Cardinal features of myxoedema coma are: a) Hypothermia b) Altered consciousness c) Hypoventilation Extreme cold weather; use of narcotics, phenothiazines or anaesthetic agents; intercurrent infections or situations that can cause hypotension, may be the precipitating events for myxoedema coma.