Endocrine - ch 19

Alla Inga Spara

• Radiographic abnormalities of the sella turcica, visual field, Incr. intracranial pressure, cranial nerve palsy, Seizure or obstructive hydrocephalus, Pituitary apoplexy Local mass affect
• most common cause of hyperpituitarism adenoma of anterior lobe
• acute hemorrhage into an adenoma causing rapid enlargement of lesion & decr. consciousness (rapidly fatal) Pituitary apoplexy
• GNAS 1, MEN1, CDKNIB, PRKARIA , AIP , TP53 genes involved in the abnormalities of hyperpituitarism
• G protein mutation (acquired) in hyperpituitarism interferes with GTPase activity GNAS 1
• Gene for cell cycle checkpoint regulator p27 or KIP1 (“MEN-1 like” syndromes) mutated in hyperpitutarism CDKN1
• Smaller ones are confided to sella turcica. Larger ones may compress optic chiasm & cause hemorrhage & necrosis. Cellular monomorphism & absence of reticulin network helps to distinguish them from normal parenchyma. No rich or extensive network of vessels. Pituitary adenomas morphology
• Prolactinomas most common type of pituitary adenoma
• Manifestation is more common in young, premenopausal women (of reproductive age) – than in men & postmenopausal women (may become really big before they come to clinical attention) Manifestation of prolactinomas (type of adenoma)
• masses in suprasellar compartment disturbing normal inhibitory function of hypothalamus on prolactin secretion causing hyperprolactin stalk effect
• Pregnancy, high-dose estrogen therapy, renal failure, hypothyroidism, hypothalamic lesions, dopamine-inhibting drugs, stalk effect Other causes for increased prolactin ((less than 200 μg/L)
• GH - producing (Somatotroph cells) adenomas Second most common type of adenoma
• staining of cytoplasm How to know which type of adenoma causing the hyperpituitarism
• Which types of hormones in the hyperpituitarism are often manifested together (simce they come from the same cell)? GH and Prolactin – both come from Mammocorticotrophs
• stimulates the hepatic secretion of insulin-like growth factor I (somatomedin C), which causes many of the clinical manifestations of hyperpituitarism Persistent hypersecretion of GH
• Most causes of hyperpitutarism occur sporacially but ca 5 % are familial
• Nonfunctioning & hormone negative tumors are likely to come to attention when they are macroadenomas Can cause hypopituitarism as the destroy the adjacent pituitary parenchyma
• GH-producing ademonas occurring before the epiphyses close (e.g. in prepubertal children) will cause Gigantism which is the generalized incr. in body size w/ disproportionately long arms and legs.
• If elevated levels of Growth hormones persist & occurs after the epiphyses close it will result in Acromegaly and proganthism
• broadening of the lower face and separation of the teeth prognathism
• abnormal glucose tolerance, diabetes, generalized muscle weakness, hypertension, arthritis, osteoporosis, congestive HF, hyperprolactinemia Other disturbances assoc. w/ Growth Hormone excess
• Most ACTH producing adenomas are microadenomas at the time of diagnosis
• ACTH producing adenomas stain positively with PAS staining because of the accumulation of glycosylated ACTH protein.
• Clinical manifestation of ACTH producing (corticotroph) adenomas include hyperpigmentations, hypercortisolism (as cushing syndrome) and depression psychosis
• Large, clinically aggressive corticotroph cell adenomas may develop – after surgical removal of the adrenal glands for treatment of Cushing syndrome. This is known as Nelson syndrome and resutls from . loss of the inhibitory effect of adrenal corticosteroids on a preexisting corticotroph microadenoma.
• Clinical manifestation of gonadotroph (LH-producing & FSH producing) adenomas are virilization, impaired vision, headaches, diplopia, pituitary apoplexy and immunoreactivity for the common gonadotropin α-subunit & the specific β-FSH and β-LH subunits.
• Accounting for about 1% of all pituitary adenomas are thyrotroph (TSH-producing) adenomas who manifests as sweating, heat intolerance, hypermobility, tachycardia, diarrhea, malabsorption, tremor. nervousness, CHF, myopathy!!!, lid lag & staring gaze.
• Makeup for 25 % of all pituitary tumors are the nonfunctioning pituitary adenomas which may compromise the residual anterior pituitary sufficiently to produce hypopituitarism
• Are pituitary tumors common in general? no, they only make up 10-15 % of all
• Most common type of adenoma of pituitary? nonfunctional adenomas
• Most common type of functional adenomas? Prolactinoma
• Second most common type of functional pituitary adenoma? GH producing (somatotroph) adenomas
• May occur with loss or absence of 75% or more of the anterior pituitray parenchyma Hypopituitarism
• congenital (rare), acquired (intrinsic) & less frequently disorders that interfere with the delivery of pituitary hormone–releasing factors fr. the hypothalamus – e.g hypothalamic tumors cause of hypopitutarism
• Nonfunctioning pituitary adenomas, Ischemic necrosis, ablation of the pituitary because of surgery/injury /irradiation, inflammation, sarcoidosis, TB, trauma, metastatic neoplasm acquired causes of hypopituitarism
• How much of pituitray parenchyma must be lost for hypopituitarism to occur? 75 % or more
• Postpartum necrosis of anterior pituitary, is the most common form of clinically significant ischemic necrosis sheehan syndrome
• In children: growth failure (pituitary dwarfism) is seen Clinical manifestation of GH deficiency by hypopituitarism
• in women: amenorrhea, infertility, decr. libido, impotence, loss of pubic & axillary hair Clinical manifestation of GnRH deficiency by hypopituitarism
• symptoms of hypothyroidism and hypoadrenalism Clinical manifestation of TSH & ACTH deficiency (hypopituitarism)
• failure of postpartum lactation is seen Clinical manifestation of Prolactin deficiency
• ADH deficiency (cause it acts on the collecting tubules of the kidney to promote the resorption of free water) Cause of diabetes insipidus
• polyuria (caused by an inability of the kidney to properly resorb water from the urine) Clinical manifestation of ADH deficiency
• renal tubular unresponsiveness to circulating ADH, leads to polyuria cause of nephrogenic diabetes insipidus
• several extracranial and intracranial disorders e.g. secr. of ectopic ADH by malignant neoplasms (particularly small cell carcinomas of the lung), non-neoplastic diseases of the lung, & local injury to the hypothalamus or neurohypophysis Causes of Syndrome of inappropriate ADH (SIADH)
• hyponatremia, cerebral edema, and resultant neurologic dysfunction. total body water is incr – blood volume remains normal, and peripheral edema does not develop. Clinical manifestation of Syndrome of inappropriate ADH (SIADH)
• Primary hyperparathyroidism, Secondary hyperparathyroidism, Tertiary hyperparathyroidism types of hyperparathyroidism
• Most common cause of hyperpituitarism? Primary hyperparathyroidism
• Most common cause of primary hyperpituitarism? adenoma (85-95%)
• Second most common cause of primary hyperparathyrpidism? Primary hyperplasia (diffuse or nodular) – 5-10 %
• Least common cause of primary hyperpituitarism? Parathyroid carcinoma (1 %)
• Are the most of the primary hyperparathyroidism familial or sporadic? sporadic (95%)
• Men 1 & Men2A and Familial hypocalciuric hypercalcemia Familial causes of primary hyperparathyroidism
• caused by inactivating mutations in calcium-sensing receptor gene on parathyroid cells, leading to constitutive PTH secretion Familial hypocalciuric hypercalcemia
• Cyclin D1 gene inversion, MEN1 genes involved in the pathogenesis of primary hyperparathyroidism
• By an inversion on chromosome 11 or by an overexpression of the gene Cyclin D1 gene inversion primary hyperparathyroidism occurs
• solitary (in 75-80 of cases), may lie close to thyroid gland or ectopic (e.g mediastinum), Invested by a delicate capsule, Invariably confided to a single gland – remiaining gland look normal or slightly shrunken (b.c.o feedback inhibition by elevated calcium). There are mostly chief cells but some oxyphil cells can be seen. Endocrine atypia seen, mitotic figures are rare, adipose tissue is not clear. Morphology of adenomas causing hyperparathyroidism
• Multiglandular hyperplasia of the chief cells, "water clear cells hyperplasia", adipose tissue is not clearly visible Morphology of Parathyroid hyperplasia causing primary hyperparathyroidism
• The affected cells in parathyroid hyperplasia contain abundant clear cytoplasm as a consequence of accumulation of glycogen. Seen in hyperparathyroidism. "water clear cell hyperplasia"
• Circumscribed lesions that are difficult to distinguish from adenomas or – clearly invasive neoplasms. gray-white, irregular masses that sometimes exceed 10 g in weight. Arrayed in nodular or trabecular patterns with a dense, fibrous capsule enclosing the mass. Morphology of Parathyroid carcinomas causing hyperparathyroidism
• unreliable on cytologic details – invasion of surrounding tissues and metastasis are the only definitive criteria diagnosis of Parathyroid carcinoma
• In what other organs would hyperparathyroidism manifest in? skeleton and kidney
• incr. osteoclastic activity, erosion of bone matrix, mobilization of calcium salts (especially in the metaphyses of long tubular bones), formation of new bone trabeculae, osteitis fibrosa cystica, Brown tumors of hyperparathyroidism Morphologic changes of hyperparathyroidism in skeleton
• cortex grossly thinned, marrow contains increased fibrous tissue accompanied by foci of hemorrhage & cysts osteitis fibrosa cystica (in primary hyperparathyroidism)
• Aggregates of osteoclasts, reactive giant cells & hemorrhagic debris → that form masses that may be mistaken for neoplasms (occasionally found) Brown tumors of hyperparathyroidism (seen in primary hyperparathyroidism)
• Nephrolithiasis, Nephrocalcinosis Morphologic changes in kidney during hyperparathyroidism
• Primary hyperparathyroidism is mostly seen in adult females
• How is the prognosis of hyperparathyroidism associated iwth malignancy and bone metastasis? poor
• adenoma, carcinoma, hyperplasia, hyerfunctioning parathyroid, nonparathyroid diseases causes of hypercalcemia
• drugs causing low levels of PTH and Ca2+ thiazide diuretics
• Granulomatous disease causing decrease in PTH and Ca2+ sarcoidosis
• usually clinically silent – manifest later with “painful bones, renal stones, abdominal groans, and psychic moans. Less commonly constipation, nausea, peptic ulcers, pancreatitis (GI), depression, lethargy, & seizures (CNS), weakness & hypotonia (NM), Polyuria & secondary polydipsia (renal) clinical manifestation of hyperparathyroidism
• secondary phenomena in patients with chronic renal insufficiency cause of both secondary and tertiary hyperparathyroidism
• Any condition associated w/ a chronic depression in the serum Ca2+ level (low serum Ca2+ leads to compensatory overactivity of the parathyroids) --> e.g. renal failure (most common), chronic renal insufficiency, loss of renal substance cause of secondary hyperparathyroidism
• reduces the activity of α1-hydroxylase enzyme necessary for the synthesis of the active form of vitamin D ⇒ which in turn reduces intestinal absorption of calcium loss of renal substance in secondary hyperparathyroidism
• metastatic calcification of blood vessels (2ndary to hyperphosphatemia) ⇒ results in ischemia of skin & other organs Calciphylaxis
• In a minority of patients, parathyroid activity may become autonomous and excessive, with resultant hypercalcemia TERTIARY HYPERPARATHYROIDISM
• surgery (most common), congenital, Autoimmune causes of hypoparathyroidism
• most common cause, after removal of parathyroids during thyroidectomy or other surgical neck dissections surgical causes of hypoparathyrodism
• thymic aplasia (Di George syndrome), cardiac defects, secondary to deletions on chromosome 22q11.2 Congenital absence of parathyroid gland
• A hereditary polyglandular deficiency syndrome, Chronic fungal infections, mutation in AIRE gene. Some patients make autoantibodies against their own IL-17. Autoimmune causes of hypoparathyroidism
• Glucocorticoids produced primarily in the zona fasciculata, with a small amount fr. the zona reticularis
• Mineralocorticoids (e.g. aldosterone) produced by the zona glomerulosa
• Sex steroids (estrogens and androgens) produced by largely in the zona reticularis
• How does hypercortisolism maniefest? Cushing syndrome
• Cause of cushing syndrome? any condition that produces an incr. in glucocorticoid levels (exogenous or endogenous)
• Most common cause of hypercortisolism ? unilateral adrenocortical neoplasm (benign or malignant)
• another name for exogenous glucocorticosteroid administration? iatrogenic
• Endogenous causes of hypercortisolism? Primary hypothalamic-pituitary diseases, Primary adrenocortical neoplasm, Non-pituitary neoplasm
• (Cushing disease) = Associated w/ hypersecretion of ACTH. Account for 70 % of spontaneous endogenous cushing syndromes. Seen in: mostly women, occurs in young adult (20-30s) Primary hypothalamic-pituitary diseases
• includes adenoma, carcinoma & rarely primary pituitary hyperplasia (accounting for 15-20% of endogenous causes of hypercortisolism) Primary adrenocortical neoplasm
• Which cancer of the lung may secrete ACTH and cause hypercortisolism? Small cell carcinoma of the lung
• Which cancer of the endocrine pancreas may secrete ACTH and cause hypercortisolism? PanNETs
• Which cancer of the thyroid may secrete ACTH and cause hypercortisolism? Medullary carcinoma
• Which organ is the most affected by cushing syndrome? pituitary gland
• Most common alteration of cushing syndrome in adrenal gland (b.c.o high glucocorticoid levels). The normal “granular, basophilic cytoplasm” of the ACTH-producing cells in the anterior pituitary is replaced by “homogeneous, lightly basophilic material “ ⇒ b.c.o of accumulation of intermediate keratin filaments in the cytoplasm crooke hyaline change
• Bilateral. Seen patients where hypercortisolism results from exogenous glucocorticoids. Suppression of endogenous ACTH results causes this attenuation of zona reticularis & Zona fasciculata (dependant on ACTH). Zona glomerulosa (outer layer) is normal cause of ACTH independence Adrenal cortical atrophy
• seen In cases of endogenous hypercortisolism with ACTH dependent Cushing syndrome. The adrenal cortex is diffusely thickened and variably nodular (not pronounced) in cases of ACTH-independent nodular hyperplasia. yellow color comes fr. lipid-rich cells which appear vacuolated Diffuse hyperplasia in hypercortisolism
• seen In primary cortical hyperplasia. Some are composed of darkly pigmented nodules (lipofuscin) “wear & tear” pigment. Macronodular or Micronodular hyperplasia
• Hypertension & weigh gain (early). central obesity, moon facies, accumulation of fat in the neck & back ⇒ “buffalo hump”. Proximal muscle weakness. Hyperglycemia, glucosuria, and polydipsia. hin, fragile, easily bruised, cutaneous striae found on stomach. Osteoporosis. Patient more susceptible to infections. hirsutism & mental disturbances. Clinical manifestation of cushing syndrome/hypercortisolism
• Causes of Hyperaldosteronism include primary and secondary causes
• Primary cause of Hyperaldosteronism includes a primary autonomous overproduction of aldosterone resulting in suppression of renin-angiotensin system & decr. plasma renin activity
• Primary cause of Hyperaldosteronism is? Bilateral idiopathic hyperaldosteronism (most common) & Adrenocortical neoplasm & Familial hyperaldosteronism
• most common cause of hyperaldosteronism, characterized by bilateral nodular hyperplasia of adrenal glands, pathogenesis is unclear Bilateral idiopathic hyperaldosteronism
• an aldosterone-producing adenoma (most commonly,) which is solitary, in 35 % of cases conn syndrome
• may result from a genetic defect leading to overactivity of the aldosterone synthase gene, CYP11B2. Familial hyperaldosteronism
• Gene involved in Familial hyperaldosteronism? CYP11B2
• Occurs in response to activation of renin-angiotensin system. characterized by incr. in plasma renin levels. Ecountered in association with decr. renal perfusion, arterial hypovolemia and edema, pregnancy. secondary hyperaldosteronism
• eosinophilic, laminated cytoplasmic inclusions, found after treatment with the antihypertensive agent spironolactone (OBS drug of choice for 1ary hyperaldosteronism an antihypertensive drug used instead of surgery) Spironolactone bodies
• Hypertension seen in 5-10 % patients. It is most common cause of secondary hypertension. The long term effect of this hypertension could lead to cardiovascular comprise (e.g. left ventricular hypertrophy & reduced diastolic volumes) AND increase in the prevalence of adverse events such as stroke & MI. Hypokalemia can also be seen. Clinical manifestation of hyperaldosteronism
• Why does hypokalemia in hyperaldosteronism occur? renal potassium wasting caused by an increased excretion in the urine. Can lead to neuromuscular manifestations (e.g weakness, paresthesias, visual disturbances & occasionally frank tetany.
• Adrenocortical neoplasms and Congenital adrenal hyperplasia Adrenal causes of androgen excess
• Which gene is defective in 21-hydroxylase deficiency (enzyme involved in adrenal steroid biosynthesis)? CYP21A2
• thickened, nodular, brow on cut surface, Proliferating cells present Morphology of adrenal cortex in adrenogenital syndrome
• dysplasia is seen, incomplete migration of the chromaffin cells to the center of the gland – with pronounced intermingling of nests of chromaffin and cortical cells in the periphery, loss of sodium in urine Morpholgy of adrenal medulla in salt-wasting 21-hydroxylase" androgenital syndrome?
• masculinization, ranging from clitoral hypertrophy and pseudohermaphroditism in infants to oligomenorrhea, hirsutism, and acne in postpubertal girls, Clinical manifestation in females with 21-hydroxylase deficiency?
• enlarged external genitalia, oligospermia in older Clinical manifestation in males with 21-hydroxylase deficiency?
• ambiguous genitalia, can be a life-threatening condition, with vomiting, dehydration, and salt wasting Clinical manifestation in neonate with 21-hydroxylase deficiency?
• An enzyme defective in congenital adrenal hyperplasia where accumulated intermediary steroids have mineralocorticoid activity (e.g. aldosterone), with resultant sodium retention and hypertension. 11β-hydroxylase deficiency
• Hypofunction of adrenal cortex may be caused by? (1) 1ary = a disease (2) 2ndary = decreases stimulation resulting from deficiency of ACTH
• Primary acute adrenocortical insufficiency, Primary chronic adrenocortical insufficiency, Secondary adrenocortical insufficiency 3 group tat the patterns of insufficiency can be divided into
• Person w/ chronic developing an acute crisis after any stress that burdens the physiologic reserves (e.g. withdrawal of long-term cortisol use), Massive adrenal hemorrhage, in patients maintained on anticoagulant therapy, in postoperative patients who develop disseminated intravascular coagulation, during pregnancy, Waterhouse-Friderichsen syndrome causes of Primary acute adrenocortical insufficiency (adrenal crisis)
• primary acute adrenocortical insufficiency in patient suffering from severe sepsis by e.g. Neisseria meningitidis, Pseudomonas spp., pneumococci, & Haemophilus influenzae Waterhouse-Friderichsen syndrome
• autoimmune adrenalitis, tuberculosis, AIDS, or metastatic cancer causes of chronic adrenocortical insufficiency
• What is the most common cause of chronic adrenocortical insufficiency? autoimmune adrenalitis
• Autoimmune polyendocrine syndrome 1 & 2 occurs in addison disease (chronic adrenocortical insufficiency) and id characterized by autoantibodies formed against key steroidogenic enzymes.
• gene defective in Autoimmune polyendocrine syndrome 1 (addison)? AIRE on chromosome 21
• chronic mucocutaneous candidiasis, abnormalities of skin, dental enamel, and nails (ectodermal dystrophy) is seen in APS 1 but not on the other.
• Manifests in early adulthood & manifest as a combination of adrenal insufficiency & autoimmune thyroiditis or diabetes type 1 OBS! No mucocutaneous candidiasis, ectodermal dysplasia & autoimmune hypoparathyroidism Autoimmune polyendocrine syndrome 2
• Extensive mononuclear cell infiltrate, autoantibodies, loss of all but subcapsular rim of cortical cells, Irregularly shrunken glands, Cortex contains only scattered residual cortical cells in a collapsed network of connective tissue, variable infiltrates of lymphoid infiltrates – that may extend to the medulla Morphology of Autoimmune polyendocrine syndrome
• Most common infections in addison disease? Tuberculosis
• A common site of metastasis in patients with disseminated carcinomas e.g from lung and breast (also GI, melanomas, hematopietic) all causing addison disesase? adrenal cortex
• clinical manifestations of primary or secondary adrenocortical insufficiency do not appear until at least 90% of the adrenal cortex has been compromised
• progressive weakness & easy fatigability (nonspecific) Initial manifestation of primary acute & chronic adrenocortical insufficiency
• Any disorder of the hypothalamus and pituitary – e.g metastatic cancer, infection, infarction, or irradiation, that reduces the output of ACTH cause of secondary adrenocortical insufficiey?
• Why is the hyperpigmentation of primary Addison disease lacking in secondary adrenocortical insufficiency? melanotropic hormone levels are low
• Size is reduced – to small, flattened structures, yellow color – b.c.o of small amount of residual lipid, no hyperpigmentation, A uniform, thin rim of atrophic yellow cortex surrounds a central, intact medulla Morphology of secondary adrenocortical insufficiency
• Virilizing neoplasm in adrenal cortex is more likely to be a carcinoma
• Called "adrenal incidentalomas" sometimes becuase they are usually encountered incidentally. They look yello-borwn (because of lipids within neoplastic cells). They have endocrine atypia. Adrenocortical adenomas
• Adrenocortical carcinoma are associated with Li-Fraumeni syndrome and Beckwith-Wiedemann syndrome which is a TP53 mutation and an overgrowth disorder
• What does the rule of 10 (adrenal medulla) take into account? Extraadrenal, bilateral, maligant, familial
• Paragangliomas location organ of Zuckerkandl & the carotid body
• 10% of pheochromocytomas are malignat – but higher malignancy is associated with in extraadrenal sites
• Genes involved in the familail cases of pheochromocytomas of the adrenal medulla? RET, NF1, VHL, SDHB, SDHC, SDHD
• Palpitation, pain, pallour, pressure, perspiration 5 p's in clinical manifestation on pheochromocytoma
• the most common extracranial solid tumor of childhood Neuroblastoma
• the most common location of neuronblastoma abdomen (retroperitoneal sympathetic ganglia)
• Occur at a younger age, arise in multiple organs, often preceded by an asymptomatic stage of endocrine hyperplasia involving the cell of origin of the tumor, more aggressive & recur features of MEN that are not shared with the sporadic counterparts
• Parathyroid gland (hyperplasia & adenoma). Pancreas (microadenomas, gastrinoma (ZE syndrome), Insulinoma). Pituitary (prolactin-secreating macroadenoma) 3 P's of MEN 1 syndrome
• Gene mutation in MEN 2 syndromes? RET proto-oncogene on chromosome 10q11.2
• Tumors usually occur in the first 2 decades of life in associated with MEN2A syndrome thyroid
• marfanoid habitus – with longer axial bones. Extraendocrine involvement of GI, lips, tongue with ganglion formation MEN type 2B
• a hypermetabolic state due to elevated circulating levels of free T3 and T4 cause by hyperpituitarism or by extrathyroidal source (e.g. stroma ovarii) Thyrotoxicosis
• stimulation of gut ⇒ hypermobility, malabsorption, diarrhea GI manifestations of thyrotoxicosis
• Palpitations, tachycardia, CHF in elderly with preexisting heart disease Cardiac manifestation of thyrotoxicosis
• nervousness, tremor, irritability, proximal muscle weakness (thyroid myopathy, in 50%) Neuromuscular manifestation of thyrotoxicosis
• wide staring gaze, lid lag due to sympathetic overstimulation of levator palpebrae superioris, True thyroid ophthalmopathy = assoc. w/ proptosis, seen in Grave’s disease Ocular manifestations of thyrotoxicosis
• medical emergency, abrupt onset of severe hyperthyroidism, occurs mostly in patients with underlying Graves disease – resulting fr. acute incr. in catecholamines (e.g. during stress) Thyroid storm
• occurs in elderly – symptoms are bilder than in younger, diagnosis is made by unexplained weight loss or worsening cardiovascular disease Apathetic hyperthyroidism
• Most common cause of hypothyroidism (worldwide)? Dietary deficiency of iodine
• Most common cause of hypothyroidism (in most developed countries)? autoimmune causes
• Clinical manifestation of hypothyroidism in infancy & children. Was formerly common in areas of the world dietary iodine def. is endemic (incl. mountain areas e.g. Himalaya, andes) Endemic cretinism
• enzyme defects that interfere with thyroid hormone syntheis causes the hypothyroidism in infancy & childhood Sporadic cretinism
• How does the maternal thyroid hormones (T3 & T4) affect the child? important for fetal brain development cause it croses the placenta
• What happens If thyroid deficiency occur before the development of fetal thyroid? severe mental retardation "stupid soldier"
• What happens If the thyroid deficiency occur after the development of fetal thyroid? the child gets normal brain development
• Another name for gull disease? myxedema
• hypothyroidism in older children & adults characterized by generalized apathy, mental sluggishness (early stages of disease may mimic depression), listlessness, cold intolerance, obese, mucopolysaccharide-rich edematous fluid accum. in skin, subcutaneous tissue, visceral sites Gull disease
• Myxedema & creitinism Clinical manifestation of hypothyroidism
• Mucopolysaccharide-rich edematous fluid accumulation in skin, subcutaneous tissue, visceral sites ⇒ result: broadening & coarsening of facial features, enlargement of tongue, deepening of voice. Found in Hypothyroidim (myxedema)
• chronic lymphocytic , subacute granulomatous, subacute lymphocytic types of thyroiditis
• Other name for hashimoto disease? Chronic lymphocytic thyroditis
• Other name for de Quervain disease? subacute granulomatous thyroiditis
• CD8+ cytotoxic T cell-mediated cell death, Cytokine mediated cell death by T cells, Antithyroid antibodies causes of hashimoto disease
• Name of antibodies formed in hashimoto disease? antithyroglobulin & antithyroid peroxidase
• Gene involved in hashimoto disease? CTLA4
• Hürthle/oxyphil cells found in which of the 3 thyroiditis? chronic lymphocytic thyroiditis
• small, atrophic & extensively fibrotic thyroid. OBS! fibrosis does NOT extend beyond the capsule of the gland fibrosing variant of chronic lymphpocytic thyroiditis?
• Age and sex of the people mostly affected by hashimoto disease? females, 45-65
• Age and sex of the people mostly affected by De Quarvain disease? females, 30-40 years old
• Age and sex of the people mostly affected by subacute lymphocytic thyroiditis? female, middle aged
• Other name for silent or painless thyroiditis? subacute lymphocytic thyroiditis
• Other name for Grave's disease? Basedow’s disease
• violent and long continued palpitations in females” associated with enlargement of the thyroid gland GRAVES DISEASE
• Graves diease Most common cause of endogenous hyperthyroidism.
• Thyrotoxicosis, Ophthalmopathy, Dermopathy triad of manifestations of grave's disease
• Age and sex of the poeple mostly affected by Grave's disese? women , 20-40
• Thyroid-stimulating immunoglobulin, Thyroid growth-stimulating immunoglobulins, TSH-binding inhibitor immunoglobulins Autoantibodies formed in Grave's disease
• nfiltration of retroorbital space by mononuclear cells, Inflammatory edema & swelling of extraocular muscles, accumulation of ECM components, increased numbers of adipocytes cause of the opthalmopathy formed in Grave's disease?
• Scalloped appearance by hyperplasia & hypertrophy, papillae formation, colloid found, edema, lymphocytic infiltration, 3 types of autoantibodies, myxedema morphology of Grave's disease
• The endemic kind is the most common type of diffuse & multinodular goiter.
• Age and sex of people mostly affected by diffuse & multinodular goiter? females, in puberty/ young adulthood (they are mostly in need of T4)
• Ingestion of substances that interfere w/ thyroid hormone (e.g cabbage), Hereditary enzymatic defect (e.g. dysmorphogenetic goiter) causes of sporadic types of diffues & multinodular goiter
• Hypertrophy & hyperplasia of thyroid follicular cells in diffuse, symmetric enlargement of the gland, “scalloped margins”, Diffuse goiter (in goiter of thyroid gland)
• If dietary iodine intake incr. (or the demand decr.) – the stimulated follicular epithelium involutes to form an enlarged, XXXX-rich gland, cut surface look brown & glassy Colloid goiter (in thyroid gland)
• with time in almost all long-standing diffuse goiter, recurrent episodes of hyperplasia & involution combine ⇒ produce a more irregular enlargement of the thyroid, no well formed capsule, does not compress thyroid parenchyma" Multinodular goiter
• thyrotoxicosis 2ndary to development if autonomous nodules producing thyroid hormone independently of TSH Plummer syndrome
• Solitary nodules are more maligant, Nodules in younger patients are more malignat, Nodules in males are more malignant, previous Radiation treatment incr. malignancy risk, Nodules taking up radioactive iodine are more BENIGN Clinical criterias for neoplasms of thyroid gland
• Genes involved i thyroid adenoma? TSHR & GNAS, RAS, PIK3CA, PAX8/PPARG
• Oprhan annie eye nucleui thyroid papillary carcinoma
• Most common type of thyroid carcinomas? papillary carcinoma (85%)
• Genes involved in thyroid papillary carcinoma? BRAF, RET/PTC, NTRK1
• Genes involved in thyroid follicular carcinoma? RAS, PIK3CA, PAX8/PPARG, PTEN
• Genes involved in thyroid anaplastic carcinoma? TP53, RAS, PIK3CA
• Where is "orphan annieeyed" nucleus and psamomma bodies found thyroid papillary carcinoma
• Where are Hürthle cells found (cells adapted to the inflammation by increasing the production of mithochondria)? Hashimoto, thyroid adenoma & follicular adenoma
• characterized by an absolute deficiency of insulin secretion by beta cell destruction Diabetes type 1
• caused by a combination of peripheral resistance to insulin action & an inadequate compensatory response of insulin secretion beta cells ⇒ i.o.w relative insulin def.) Diabetes type 2
• (1) excess free fatty acids – inhibit insulin action (2) inflammation – results in peripheral insulin resistance & beta cell dysfunction (3) adipokines – mediate inflammation and insulin resistance (4) Peroxisome proliferator-activated receptor-γ – role in adiposcyte differentiation Pathways leading to insulin resistance
• (1) Formation of advanced glycation end products – form ROS, cytokines, GF, procoagulants, ECM, vascular smooth muscles (2) Activation of protein kinase C – can lead to neovascularization seen in diabetic retinopathy & profibrogenic molecule deposition in ECM & BM (3) Disturbances in polyol pathways 3 Metabolic pathways are involved in pathogenesis of diabetes
• Genes involved in diabetes type 1? HLA-DR3 (4), CTLA4, PTPN22
• Incr. in number & size of islets (except in newborns of diabetic mothers), amyloid deposits, lymphocytic inflammation diabetes morphology in pancreas
• macroangiopathy – atherosclerosis of large & medium sized vessels, MI (most common cause of death), gnagrene of lower extremities, hyaline arteriolosclerosis (associated with hypertension) Diabetes morphology in arteries
• microangipathy – thickening of BM by deposits of hyaline & collagen T4, increased permabolity "leaky" vessels to plasma proteins leading to edema diabetes morphology in small vessels
• (second most common cause of death) (1) glomerular sclerosis – microangiopathy, diffuse mesangila sclerosis, nodular glomerulosclerosis (kimmelsiel–wilson lesions) (2) renal vessel changes – atherosclerosis & arterioosclerosis (3) pyelonephritis – necrotizing papillitis diabetes morphology in kidney (neophropathy)
• glaucoma, visual impairment, blindness, catarct, retinopathy (non-proliferative (= microangiopathy, "leaky", microaneurysms ) & proliferative (= neovascularization, fibrosis, blindness, vitreous hemorrhage leading to retinal detachement) diabetes morphology in eyes
• microangipathy & "leaky", affects both PNS & CNS, damages axons, sexual incompetence, motor 6 sensory function on lower extremities affected, bladder & bowel dysfunction, mononeuropathy (wrist drop & foot drop) diabetes morphology in neurons (neuropathy)
• Genes involved in PanNETs? MEN1, PTEN & TSC2, ATRXX & DAXX
• What percentage of the most common of PanNETs are malignat? insulinomas: 10
• “attacks of hypoglycemia” – CNS manifestation of stupor, confusion, loss of consciousness clinical manifestation of insulinoma (PanNETs)
• is a disease in which tumors cause the stomach to produce too much acid, resulting in peptic ulcers. Symptoms include abdominal pain and diarrhea. The syndrome is caused by a gastrinoma, a neuroendocrine tumor that secretes a hormone called gastrin. Zollinger–Ellison syndrome
• "salt and pepper cytoplasm" thyroid medullary carcinoma
• "nuclear grooves" papillary carcinoma
• perinuclear halo or perinuclear cytoplasmic vacuolization koilocytic change of condylomata acuminata
• Nuclear pseudoinclusions papillary thyroid carcinoma
• Ground glass nuclei are an important finding in the diagnosis of papillary carcinoma of thyroid
• ground glass appearance is the same as orphan annie eyes nuclei in thyroid gland
• Which of following diagnoses of a thyroid gland tumors CANNOT be made basing on fine needle aspiration (FNA) cytology specimen? Follicular carcinoma

Alla Inga Spara