Tuesday, March 27 (shayna)

Endocrine Pathology

March 27, 2007

New assignment: Define cortisol and name 5 effects cortisol has on the body. Due next week. Point form is fine. • • • •

Hormonal system responsible for homeostasis Very complex system Cancer in endocrine organ can act as SOL which can cause it to under-secrete d/t pressure on the gland Or growth can over-secrete hormone

Review of Endocrine System: • Metabolism • Reproduction • Circadian Rhythms • Regulation of BP • Electrolyte balance • Blood sugar levels Hormones: float around in blood and bind to receptor on cells. Cell responds according to signal from receptor. Feedback: mainly negative feedback. Oxytocin is only hormone with positive feedback mechanism. Diseases: Overproduction of TH: increases activity of thyroid. Pituitary Gland • Sits at base of brain in the sella turcica (bony fossa) • Anterior and posterior different communications with hypothalamus • Anterior- venous connection. Receives messages hormonally from hypothalamus. Receives blood from hypothalamus. Gland structure • Posterior- neural connection. Has an external blood supply other than the hypothalamus. Neuronal structure • Anterior: FSH, LH, ACTH, TSH, GH, Prolactin, MSH (melanocyte stimulating hormone) • Posterior: vasopressin (ADH), oxytocin • Lots of different cell type in anterior pituitary • Hormones secreted by hypothalamus: Somatostatin (inhibits GH release), Dopamine (inhibits prolactin). All other hormones released by hypothalamus are excitatory. • Abhorrent = out of whack • Adenoma = glandular tissue, nonmalignant, solitary, well defined, harmful b/c space

occupying. Can be functional- hypersecrete a hormone. Anterior Pituitary Adenoma • m/c pathology of pituitary • pituitary adenoma can impinge on optic chiasm- affects peripheral vision • can secrete different hormones, depends which cells type is forming adenoma • Nonfunctional adenoma→ (doesn’t secrete hormones) normally larger when discovered b/c no symptoms to give us an idea that there is an adenoma there. • Nonfunctional adenoma can put pressure on gland and cause undersecretion • Often found at autopsy • GH: affects all cells • Gigantism: before adolescents, typically d/t tumour, proportional growth b/c epiphyseal plates haven’t closed yet. • Acromegaly: after adolescents, plates in long bones have fused. Increase in size of head, thickening of structures: face, vertebrae, heart, other soft tissue • Both conditions: often have undersecretion of other hormones: like low FSH/LH. Lack of development of sexual characteristics • DM common with these conditions b/c growth hormone inhibits insulin • Pituitary Dwarfism: decreased proportional growth. D/t decreased GH • if this is d/t Panhypopituitarism all other hormones will be low • • • •

Prolactin: stimulates milk production and breast tissue. Excess: galactorrhea often w/amenorrhea (amenorrhea comes first) Deficiency: difficulty producing milk in response to childbirth If a disease originates in thyroid gland (primary thyroid problem) . If there is a problem in the thyroid and problem is in pituitary (secondary thyroid problem) and if problem in hypothalamus (tertiary problem in thyroid)

Panhypopituitarism Causes: 1. Nonsecretory adenoma- takes up space and puts pressure on glands so can’t secrete properly. 2. Ischemic necrosis- Death of gland so can’t produce hormones. Common in Sheehan’s 3.Iatrogenic-Medically induced, perhaps d/t radiation 4.Hypothalamus not functioning properly 5.Congential •

This would be secondary hypothyroidism b/c problem at level of anterior pituitary

Posterior Pituitary •

ADH- Acts on collecting tubules of Kidney. Monitors osmolarity of blood. Retains sodium and water. Decrease urination. Increases BP

•

Deficient in ADH: Excessive loss of water. Large quantities of dilute urine. Diabetes Insipidus. Kidney problems can cause similar symptoms (i.e nephrogenic- Kidnery tubules can’t respond to ADH)

•

Syndrome of inappropriate ADH secretion: Lung cancers can cause this

•

ADH in excess: scanty dark urine, edema, retaining way too much water, hyponatremia, increased osmotic pressure, water moves in cells. Most dangerous in brain- neurological symptoms. Can cause herniation in brain.

Thyroid Gland •

T3 (triidothyronine) & T4 (thyroxine) secreted from follicular cells

•

T4 is secreted in greater quantity

•

T3 active form

•

T4 converted to T3 in periphery

•

T3 carried with receptor into nucleus of cells

•

T3 & T4 increase metabolism, increase heart rate, increase sympathetic nervous system

•

Hyperthyroidism: Hot, sweaty, increased heart rate, diarrhea, anxiety, eyelids wide open.

•

Thyroid hormone very connected to adrenal gland.

•

Calcitonin: lays calcium in bones, decreases concentration of calcium in blood.

Goiter: •

Enlargement of thyroid

•

Normally d/t iodine deficiency

•

Thyroid telling brain to increase TSH to stimulate thyroid gland

•

Hypertrophy/ hyperplasia of gland

•

Endemic- can affect entire populations. Mountainous areas, away from water. Himalayas. Solution: iodine in salt.

•

Sporadic goiter: problems with absorption, changes in life cycles ex. teen years need more. Congenital enzymatic defects, can’t incorporate iodine for production of thyroxine.

•

Brasica family (broccoli, cauliflower) can interfere w/thyroid hormone formation

•

Toxic Goiter: excessive secretion of thyroid hormone

•

Nontoxic Goiter: don’t have enough secretion of thyroid hormone. This is what most goiters are. Activating TSH receptor like in Graves.

•

Goiter should decrease in size when add iodine to diet

•

Multinodular: d/t correction and then deficiency again and again. Thyroid involutes and grows over and over. This cycle of involution and then growth creates a multinodular thyroid, which increases risk for thyroid cancer.

•

Goiter can act as SOL, impinge airway

•

Can mask cancer

Thyrotoxicosis: •

Excess production of T3/T4

•

Can be ectopic: exogenous d/t meds

•

Up regulation of metabolic rate, upregulation of sympathetic nervous system

•

Labs: T3/T4 elevated, TSH down (b/c of negative feedback) If problem at level of thyroid

•

Problem at pituitary: TSH normal or elevated, T3/T4 elevated

•

Toxic adenoma: solitary discrete nonmalignant growth of thyroid gland producing T3/T4

•

Thyroiditis- self study. Compare to grave’s disease.

Graves Disease: •

Antibodies to receptor on thyroid gland (thyroid stimulating immunoglobulins – TSI). Antibodies over-stimulate TSH receptor.

•

Different than goiter b/c this is toxic enlargement. Goiter is nontoxic.

•

Genetic predispostion telling CD4 helper t-cells to turn on B-Cells

•

Antibodies also stimulate receptors behind the eyes and pretibial fibrolasts

•

Fibroblasts turn into adipocytes

•

Adipocytes secrete hydrophilic substances. Attract water---- leads to edema

•

Also lymphoctyic infilitration

•

Exophthalmos- eyes bulging. Risks can push on nerves, can’t close lids which can lead to corneal irritation. Can cause fibrosis of muscles of eye.

•

Non-pitting edema of shins.

Hypothyroidism: •

High TSH, decreased T3/T4 (if primary thyroid problem)

•

Could be d/t iodine deficiency, enzymatic deficiency, thyroid cancer, can be secondary.

•

Problem at pituitary then would have low TSH, low T3/T4 (secondary thyroid problem)

•

Also have myxedema like in Graves

•

Thickening of tissues: tongue, skin etc..

•

Nonpitting edema

•

enlargement of organs- ex. heart enlarges

•

Cretinism- Hypothyroidism in fetus d/t mom’s hypothyroidism. Fetus thyroid tissue not fxning yet. T3/T4 very important for brain development. Mental retardation.

•

Subclinical hypothyroidism: labs normal, but symptoms there: dry skin, hair, cold, constipation, sluggish metabolism etc …

•

Can treat this by managing stress better.

Hashimoto’s Thyroditis •

Lymphocytic infiltration

•

Autoimmune

•

m/c type of hypothyroidism

•

Anti- TSH receptor antibody, other Ab’s produced by B-cell used as marker not part of pathology (antithyroglobulin &antithyroid peroxidase)

•

Flow chart in text: helper T cells activates both plasma cells and cytotoxic t-cells

•

Humoral and cell mediated response (Grave’s only humoral response)

Thyroid Cancer • Always assume cancer with any nodules on the thyroid. Refer always for biopsy! • Solitary- not normally multiple nodules • If nodule in males more likely to be cancer. But cancer is most common in women. • Cold- radioactive iodine not taken up by gland (nonfunctioning) Thyorid Carcinoma • Same distribution among males and females after and before childbearing years • Hormonal influences • Risks: multinodular- cells changing a lot so increased risk of mistakes being made. • Papillary: good prognosis, doesn’t look cancerous, need to do biopsy to diagnose: ground-glass appearance of nucleus • Fill in chart on 4 types of cancer look in text • Anaplastic- locally invasive- veins, arteries, esophagus, trachea Parathyroid gland: • Often parathyroid gland gets removed with thyroid gland • Responds to calcium in blood, not pituitary Primary Hyperparathyroidism • Functioning adenoma- adenoma secrete PTH (m/c casue) • Dx: Increased Calcium, increased PTH. Can lead to osteoporosis • If you have an adenoma in one gland, then the other 3 glands atrophy. • Kidney: KI stones • Calcification of soft tissue • Lethargy, weakness in muscles, constipation, • Increased electrical differential b/w cell and extracellular environment, takes more energy to create an action potential • Calcification of blood vessels- atherosclerosis, high BP • Text book diagram shows different manifestation: polyuria, gallstones… Secondary Hyperparathyroidism

• • • • •

Can be d/t Kidney problems Drop in calcium d/t to renal failure, increases PTH Similar bone changes Won’t have calcification of soft tissue b/c have low serum calcium levels Labs: high PTH, low serum calcium.

Hypoparathyroidism • Low serum calcium • Iatrogenic- removal of parathyroid gland • Congenital- enzyme deficiency • Idiopathic • Familial • Hypertonic muscles, tetany, diarrhea Multiple Endocrine Neoplasia • Cancer development in more than one endocrine organ. • Consistent genetic predisposition • Don’t need to memorize MEN organs affected • Now cancer mutuation in MEN-1 & MEN-2 • Sporadic-happens in one location, when you are older (MEN is not sporadic) • MEN is familial, occurs in many places, recurs. Self Study for this week: Sheehan’s syndrome Empty sella turcica Glioma Cranipharyngioma Subacute thyroiditis Thyroiditis de quevains Self study for next week: Congenital adrenal hyperplasia Waterhouse-Friderichsen syndrome Neuroblastoma Insulinoma Gastrinoma