Pathology of the thyroid 1 Dr: Salah Ahmed

- diseases of the thyroid include: 1- conditions associated with excessive release of thyroid hormones (hyperthyroidism 2- conditions associated with thyroid hormone deficiency (hypothyroidism) 3- mass lesions - thyroid diseases: 1- thyroiditis 2- Graves disease (PBL) 3- Goiter (case discussion) 4- tumors - first we talk about the clinical consequences of disturbed thyroid function (hyper- and hypothyroidism) then we focus on the disorders that generate these problems

Normal thyroid tissue

Hyperthyroidism - Thyrotoxicosis: hypermetabolic state caused by elevated circulating levels of free T3 and T4 - referred to hyperthyroidism because it is caused most commonly by hyperfunction of the thyroid gland - Causes: 1- those associated with hyperthyroidism a) primary i- diffuse toxic hyperplasia (Graves disease) ii- hyperfunctioning ("toxic") multinodular goiter iii- hyperfunctioning ("toxic") adenoma b) secondary i- TSH-secreting pituitary adenoma (rare) 2- those not associated with hyperthyroidism i- subacute granulomatous thyroiditis (painful) ii- subacute lymphocytic thyroiditis (painless) iii- struma ovarii (ovarian teratoma with thyroid) iv- exogenous thyroxine intake

- Clinical manifestations: - include changes referred to the hypermetabolic state and overactivity of the sympathetic nervous system: 1- Constitutional symptoms: - skin: soft, warm (vasodilatation, increased flow -heat intolerance and excessive sweating are common (hypermetabolism - weight loss despite increased appetite( increased muscle protein catabolism) 2- Gastrointestinal:- hypermotility, malabsorption, and diarrhea (stimulation of gut) 3- Cardiac: palpitations and tachycardia are common (B adrenorgenic receptors, catecholamine) elderly patients may develop congestive heart failure (aggravation of preexisting heart disease) 4- Neuromuscular:- overactivity of sympathetic produces tremor, hyperactivity, anxiety, irritability and nervousness. Nearly 50% develop muscle weakness (thyroid myopathy). 5- Ocular manifestations: a wide, staring gaze and lid lag (sympathetic overstimulation of the levator palpebrae superioris ), associated with proptosis (exophthalmos) in Graves due to: 1- marked infiltration of the retro-orbital space by mononuclear cells ( T cells) 2- inflammatory edema

3- accumulation hydrophilic glycosaminoglycans such as hyaluronic acid and chondroitin sulfate 4-fatty infiltration 6- Thyroid storm: - used to designate the abrupt onset of severe hyperthyroidism - occurs commonly in Graves disease - results from acute elevation in catecholamine levels: 1- infection 2- surgery 3- stress 4- cessation of treatment - patients often febrile and present with tachycardia - it is a medical emergency - most patients die of cardiac arrhythmias 7- Apathetic hyperthyroidism: thyrotoxicosis occurring in the elderly, in whom old age and various co-diseases may blunt the typical features of thyroid hormone excess seen in younger patients.

Ocular manifestation: wide, staring gaze and lid lag

- Diagnosis: is based on clinical features and laboratory data 1- measurement of serum TSH concentration (decreased, in rare cases of secondary hyperthyroidism, TSH levels are either normal or raised) 2- free thyroid hormone assay: increased levels of free T 4, occasionally T 3 (T 3 toxicosis) 3- measurement of radioactive iodine uptake by the thyroid gland: useful in determining the etiology. For example i- diffuse increased uptake (Graves disease) ii- increased uptake in a solitary nodule (toxic adenoma) iii- decreased uptake (thyroiditis).

Hypothyroidism - is caused by any structural or functional derangement that interferes with the production of thyroid hormone. - either primary (thyroid abnormality) or secondary ( hypothalamic or pituitary disease) - causes: 1- Primary 1- surgery, radioiodine therapy, or external radiation 2- Hashimoto thyroiditis 3- iodine deficiency 4- inborn error of metabolism (enzyme deficiency) 5- drugs (lithium, iodides, p- aminosalicylic acid) 6- rare developmental abnormalities of the thyroid (thyroid dysgenesis) 2- Secondary 1- Pituitary or hypothalamic failure (uncommon)

- Clinical manifestations: - two forms: 1- cretinism 2- myxedema 1- Cretinism: - hypothyroidism developing in infancy or early childhood - common in areas of endemic dietary iodine deficiency (Himalayas, China, Africa, and other mountainous areas) - now becomes less frequent because of the widespread supplementation of foods with iodine - rarely cretinism may also result from inborn errors in metabolism (e.g., enzyme deficiencies) - Clinical features: impaired development of the skeletal system and central nervous system with severe mental retardation, short stature, coarse facial features, a protruding tongue, and umbilical hernia 2- Myxedema: - hypothyroidism developing in older children and adults (Gull disease)

- Manifestations: 1- generalized fatigue, apathy 2- patients are cold intolerant, and often obese 3- mucopolysaccharide -rich edema accumulates in skin, subcutaneous tissue, and number of visceral sites, with broadening and coarsening of facial features, enlargement of the tongue, and deepening of the voice iv- Bowel motility is decreased, resulting in constipation v- shortness of breath and decreased exercise capacity (reduced cardiac output) vi- pericardial effusions are common; in later stages the heart is enlarged, and heart failure may supervene. - Laboratory diagnosis: - Measurement of the serum TSH is the most sensitive screening test (increased in primary, not increased in secondary hypothyroidism) - Serum T4 is decreased

Cretinism

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