Endocrine abnormalities Hyperthyroidism and Hypothyroidism

endocrine abnormalities of thyroid

1. Hypothyroidism and hyperthyroidism Dr Shikha Pandey Resident CMC-TH, Bharatpur

2. Anatomy GROSS Consists of two bulky lateral lobes connected by a thin isthmus Located below and anterior to larynx. (C5 and T1) Weight= ~25gm.

3. MICROSCOPY Consists of numerous follicles divided by thin fibrous septae . 20 to 40 follicles make up thyroid lobules. Follicles are lined by follicular epithelial cells which are cuboidal to columnar and are filled with thyroglobulin or colloid. Follicles also contain parafollicular C cells.

4. Homeostasis in the hypothalamus-pituitary-thyroid axis and mechanism of action of thyroid hormones

5. Hyperthyroidism Thyrotoxicosis is a hypermetabolic state caused by elevated circulating levels of free T3 and T4. The three most common causes of thyrotoxicosis associated with hyperfunction of the gland and include the following: Diffuse hyperplasia of the thyroid associated with Graves disease (accounts for 85% of cases) Hyperfunctional multinodular goiter Hyperfunctional adenoma of the thyroid

6. Clinical features: Includes changes referable to the hypermetabolic state induced by excess thyroid hormone and to overactivity of the sympathetic nervous system. Excess thyroid hormone  increase in basal metabolic rate resulting in: Soft, warm and flushed skin because of increased blood flow and peripheral vasodilatation Increased sweating because of higher level of calorigenesis Weight loss due to heightened catabolic metabolism despite increased appetite

7. Cardiac Manifestations: Elevated cardiac contractility and output in response to increased peripheral oxygen requirement Tachycardia Palpitations Cardiomegaly Arrythmias such as atrial fibrillation Congestive heart failure Myocardial changes : Focal lymphocytic and eosinophilic infiltrate Mild fibrosis Myofibril fatty change Increase in size and number of mitochondria

8. Overactivity of sympathetic nervous system produces: Tremor Hyperactivity Emotional lability Anxiety Inability to concentrate Insomnia Proximal muscle weakness and decreased muscle mass (thyroid myopathy) In GI  hyperdefecation due to hypermotility and reduced transit times

9. Ocular changes : Wide staring gaze Lid lag True thyroid ophthalmopathy associated with proptosis occurs only in Graves disease Skeletal system : Osteoporosis Increased risk of fractures Atrophy of skeletal muscles with fatty infiltration and focal interstitial lymphocytic infiltrates

10. Mild hepatomegaly due to hepatic steatosis Generalised lymphoid hyperplasia Thyroid storm : Abrupt onset of severe hyperthyroidism It is a medical emergency Occurs most commonly in patient with Graves disease Results from acute elevation in catecholamines levels as might be encountered during infection, surgery, cessation of anti-thyroid medication or any form of stress Patient are often febrile and present with tachycardia

11. Investigation TFTS: Primary: <TSH, >T3 & T4 Secondary: Normal or > TSH, Radioiodide scan ELISA for anti –TSH receptor/TSI, antimicrosomal ab LFTS – elevated CBC- mild normocytic anemia, mild neutropenia , < Platelets Biopsy- FNA cytology USG CT/MRI – head/ chest

12. Graves Disease Characterized by a triad of clinical findings:    1. Hyperthyroidism due to diffuse, hyperfunctional enlargement of the thyroid    2.Infiltrative ophthalmopathy with resultant exophthalmos    3.Localized, infiltrative dermopathy , sometimes called pretibial myxedema , which is present in a minority of patients Peak incidence: 20 and 40 years of age Women are affected as much as 10 times more frequently than men. Patients are at increased risk for other autoimmune diseases, such as systemic lupus erythematosus , pernicious anemia, type 1 diabetes, and Addison disease.

13. Pathogenesis: An autoimmune disorder characterized by the production of autoantibodies against multiple thyroid proteins , most importantly the TSH receptor . Other: Thyroid peroxisomes and Thyroglobulin . The most common antibody subtype, known as thyroid-stimulating immunoglobulin (TSI) , is observed in approximately 90% of patients. Genetic susceptibility is associated with polymorphisms in immune-function genes like CTLA4 , PTPN22 , and IL2RA .

14. Clinical Features: Diffuse enlargement of the thyroid is present in all cases. Infiltrative ophthalmopathy is characteristic of Graves disease.

15. Protrusion of the eyeball ( exopthalmos ) is caused by an increase in the volume of the retro-orbital connective tissues and extraocular muscles, which occurs for several reasons: Marked infiltration of connective tissue by mononuclear cells, predominantly T cells Inflammation, edema, and swelling of extraocular muscles Accumulation of extracellular matrix components, specifically hydrophilic glycosaminoglycans such as hyaluronic acid and chondroitin sulfate Increased numbers of adipocytes (fatty infiltration).

16. Graves Disease Eye Signs

17. Graves Disease Other Manifestations  Pretibial myxedema  Thyroid acropachy  Onycholysis  Thyroid enlargement with a bruit frequently audible over the thyroid

18. Morphology: Gross: Thyroid gland is usually symmetrically enlarged due to diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells. Increases in weight to over 80 g On cut section: Parenchyma has a soft, meaty (beefy deep red)appearance resembling muscle

19. Microscopic: Follicle epithelial cells in untreated cases are tall and more crowded than usual. Crowding often results in the formation of small papillae that project into the follicle lumen and encroach on the colloid, sometimes filling the follicles. Such papillae lack fibrovascular cores. Colloid within the follicle lumen is pale, with scalloped margins. Lymphoid infiltrates, consisting predominantly of T cells, along with scattered B cells and mature plasma cells, are present throughout the interstitium . Germinal centers are common.

20. Graves disease

21. Changes in extrathyroidal tissue include: Lymphoid hyperplasia, especially enlargement of the thymus in younger patients. Heart may be hypertrophied, and ischemic changes may be present. Dermopathy , if present, is characterized by thickening of the dermis due to deposition of glycosaminoglycans and lymphocyte infiltration.

22. Laboratory findings: Elevated free T4 and T3 levels Depressed TSH levels Radioiodine scans show a diffusely increased uptake of iodine in the thyroid gland.

23. Hypothyroidism Fairly common disorder Defn : A condition caused by a structural or functional derangement that interferes with the production of thyroid hormone. Divided into primary and secondary categories, depending on whether the hypothyroidism arises from an intrinsic abnormality in the thyroid itself, or occurs as a result of pituitary and hypothalamic disease Primary hypothyroidism can be congenital, acquired, or autoimmune. Acquired hypothyroidism can be caused by surgical or radiation-induced ablation of thyroid parenchyma, Drugs, hypopituitarism

24. Primary hypothyroidism can be congenital, autoimmune or iatrogenic. Congenital Autoimmune Iatrogenic Most often result of endemic iodine deficiency in diet Most common cause in iodine sufficient areas of the world Either surgical or radiation- induced ablation Dyshormonogenetic goitre due to inborn errors of thyroid metabolism Hashimoto’s thyroiditis Resection of large portion of gland for treatment of hyperthyroidism or primary neoplasm Thyroid agenesis In isolation or in conjunction with autoimmune polyendocrine syndrome type 1 and 2 External radiation therapy to neck Thyroid hypoplasia Radioiodine for treatment of hyperthyroidism Drugs(e.g. thionamides like Methimazole , PTU and lithium, α - aminosalicylic acid )

25. Secondary or central hypothyroidism is caused by: Deficiency of TSH Deficiency of TRH- less common Any causes of hypopituitarism Hypothalamic damage

26. Investigations: TFTs Primary: High TSH & low T4 Central (2˚ & 3˚): Low T4, TSH inappropriately normal for the low T4, coexisting hormone def. Lipid profiles – Fasting cholesterol and triglycerides may be raised Muscle enzymes (CPK) – elevated CBC- anaemia ( normocytic normochromic ) CXR- Effusions CT head- sellar / suprasellar region.

27. HASHIMOTO THYROIDITIS Defn : An autoimmune disease that results in destruction of thyroid gland and gradual and progressive thyroid failure. Most common cause of hypothyroidism. Goiter and intense lymphocytic infiltration of the thyroid ( struma lymphomatosa ) . 45 and 65 years of age, common in women than in men. (10:1 to 20:1)

28. Pathogenesis: Antithyroglobulin Antithyroid peroxidase antibodies

29. Clinical Features: Painless enlargement of the thyroid, associated with hypothyroidism, in a middle-aged woman. Symmetric and diffuse enlargement Increased risk for developing other autoimmune diseases, endocrine: type 1 diabetes, autoimmune adrenalitis non- endocrine: systemic lupus erythematosus, myasthenia gravis and Sjögren syndrome.

30. Morphology: Gross: Thyroid is usually diffusely enlarged. Capsule is intact, and the gland is well demarcated from adjacent structures. Cut surface is pale, yellow-tan, firm, and somewhat nodular.

31. Microscopic: Extensive infiltration of the parenchyma by a mononuclear inflammatory infiltrate containing small lymphocytes, plasma cells, and well-developed germinal centers. Thyroid follicles are atrophic and are lined in many areas by epithelial cells with abundant eosinophilic , granular cytoplasm, termed Hürthle cells . Interstitial connective tissue is increased and may be abundant.

32. Hashimoto thyroiditis . The thyroid parenchyma contains a dense lymphocytic infiltrate with germinal centers. Residual thyroid follicles lined by deeply eosinophilic Hürthle cells are also seen.

33. Thank you