Shared Flashcard Set

Details

Endocrine Pathology
Path shelf review
44
Pathology
Graduate
03/27/2012

Additional Pathology Flashcards

 


 

Cards

Term
Endocrine System
Definition
  • Group of glands that maintain body homeostasis
  • Functions by release of hormones that travel via blood to distant organs
  • Feeback mechanisms control hormone release
Term
Pituitary Adenoma
Definition
  • Benign tumor of anterior pituitary cells
  • may be funtional (hormone producing) or nonfunctional (silent)
  • nonfunctional tumors often present with mass effect
  • bitemporal hemianopsia occurs due to compression of the optic chiasm
  • hypopituitarism occurs due to compression of normal pituitary tissue
  • headache
Term
Prolactinoma
Definition
  • Presents as galactorrhea and amenorrha (females)
  • deceased libido and headache (males); most comon type of pituitary adenoma
  • treatment =dopamine agonists (ex bromocriptine or cabergoline) to suppress prolactin production (shrinks tumor) or surgery for larger lesions
Term
Growth Hormone Cell Adenoma
Definition
  • Gigantism in children- increased linear bone growth (epiphyses are not fused)
  • acromegaly in Adults-enlarged bones of hands, fee, and jaw, growth of visceral organs leading to dysfunction (ex cardiac failure), enlarged tongue
  • secondary diabetes mellitus is often present (GH induces liver gluconeogenesis)
  • diagnosed by elevated GH and insulin growth factor-1 (IGF-1) levels along with lack of GH suppression by oral glucose
  • Treatment is octreotide (somatostatin analog that suppresses GH release), GH receptor antagonists, or surgery
Term
ACTH Cell adenomas
Definition
  • secrete ACTH-->cushing syndrome
Term
Hypopituitarism
Definition
  • Insufficient production of hormones by the anterior pituitary gland; symptoms areise when >75% of the pituitary parenchyma is lost
Term
Pituitary Adenoma
Definition
  • Adults
  • hypopituitarism
  • due to mass effect or pituitary apoplexy (bleeding into an adenoma)
Term
Sheehan Syndrome
Definition
  • pregnancy-related infarction of the pituitary gland
  • gland doubles in size during pregnancy, but blood supply does not increase significantly; blood loss during parturition precipitates infarction
  • presents as poor lactation, loss of pubic hair, and fatigue
Term
Craniopharyngioma
Definition
  • hypopituitarism
  • due to mass effect or pituitary apoplexy (bleeding into an adenoma)
  • Kids
Term
Empty Sella syndrome
Definition
  • congenital defect of the sella
  • herniation of the arachnoid and CSF into the sella compresses and destroys the pituitary gland
  • pituitary gland is absent aka empty sella on imaging
Term
Posterior Pituitary Gland
Definition
  • ADH and oxytocin are made in the hypothalamus and then transported via axons to the posterior pituitary for relase
  • ADH acts on the distal tubules and collecting ducts of the kidney to promote free water retention
  • oxytocin mediates uterine contraction during labor and release of breast milk "aka let down" in lactating mothers

[image]

 

[image]

Term
Central Diabetes Insipidus
Definition
  • ADH deficiency
  • b/c hypothalamic or posterior pituitary pathology (ex Tumor, trauma, infection, or inflammation)
  • clinical features are based on loss of free water
  • polyuria and polydipsia w/ risk of life-threatening dehydration
  • hypernatremia and high serum osmolality
  • low urine osmolality and specific gravity
  • water deprivation test FAILS to increase urine osmolality (useful for diagnosis)
  • treatment is desmopressin (ADH analog)
Term
Neurogenic Diabetes Insipidus
Definition
  • Impaired renal response to ADH
  • due to inherited mutations or drugs (ex lithium and demeclocycline)
  • clinical features are similar to central diabetes insipidus, but there is no response to desmopressin
Term
SIADH
Definition
  • Excessive ADH secretion
  • most often due to ectopic prod (ex small cell carcinoma of the lung)
  • other causes include CNS trauma, pulmonary infection, and drugs (ex cyclophosphamide)
  • Clinical features are based on retention of free water
  • hyponatremia and low serum osmolality
  • mental status changes and seizures-hyponatremia leads to neuronal swelling and cerebral edema
  • treatment is free water restriction or demeclocyline
Term
Thyroglossal Duct Cyst
Definition
  • Cystic dilation of throglossal duct remnant
  • thyroid develops at the base of tongue and then travels along the thyroglossal duct to the anterior neck
  • thyroglossal duct normally involutes; a persistent duct, however, may undergo cystic dilation
  • presents as an anterior neck mass
Term
Lingual Thyroid
Definition
  • Persistence of thyroid tissue at the base of tongue
  • presents as a base of tongue mass
Term
Hyperthyroidism
Definition
  • increased level of circulating thyroid hormone
  • increases BMR (due to increased synthesis of Na-K ATPase)
  • increases SNS activity b/c of increased expression of B2-adrenergic receptors
  • weight loss w/ increased appetite
  • heat ntolerance and sweating
  • tachycardia w/ increased CO
  • arrhythmia ex atrial fibrillation, especially in the elderly
  • tremor,anxiety, insomnia, and heightened emotions
  • staring gaze with lid lag
  • diarrhea w/ malabsorption
  • oligomenorrhea
  • bone resorption w/ hypercalcemia (risk for osteoporosis)
  • decreased muscle mass w/ weakness
  • hypocholesterolemia
  • hyperglycemia b/c gluconeogenesis and glycogenolysis
Term
Graves Disease
Definition
  • Autoantibody (IgG) that stimulates TSH receptor (Type II hypersensitivity)
  • leads to increased synthesis and release of thyroid hormoe
  • most common cause of hyperthyroidism
  • classically occurs in women of childbearing age (20-40 years)
  • clinical features include
  • hyperthyroidism
  • diffuse goiter-constant TSH stimulation leads to thyroid hyperplasia and hypertrophy
  • Exopthalamus and pretibial myxedema b/c fibroblasts behind the orbit and overlying the shin express the TSH receptor.  TSH activation results in glycosaminoglycan (chondroitin sulfate and hyaluronic acid) buildup, inflammation, fibrosis, and edema leading to exopthalamus and pretibial myxedema.
  • Irregular follicles with scalloped colloid and chronic inflammation are seen on histology
  • lab findings include
  • increased total and free T4, decreased TSH (free T4 downregulates TRH receptors in the anterior pituitary to decrease TSH release)
  • hypercholesterolemia
  • increased serum glucose
  • treatment involves Beta blockers, thioamide, and radioiodine ablation
  • thyroid storm is a potentially fatal complication
  • due to elevated catecholamines and massive hormone excess, usually in response to stress (ex surgery or childbirth)
  • presents as arrhythmia, hyperthermia, and vomiting with hypovolemic shock
  • treatment is propylthiouracil (PTU), beta blockers, and steroids
  • PTU inhibits peroxidase-mediated oxidation, organification, and coupling steps of thyroid hormone synthesis, as well as peripheral conversion of T4 -->T3
Term
Multinodular Goiter
Definition
  • Enlarged thyroid gland with multiple nodules
  • due to relative iodine deficiency
  • usually nontoxic (euthyroid)
  • rarely, regions becom TSH- independent leading to T4 release and hyperthyroidism (toxic goiter)
Term
Cretinism
Definition
  • Hypothyroidism in neonates and infants
  • characterized by mental retardation, short stature with skeletal abnormalities, coarse facial features, enlarged tongue, and umbilical hernia
  • thyroid hormone is required for normal brain and skeletal development
  • causes include maternal hypothyroidism during early pregnancy, thyroid agenesis, dyshormonogenetic goiter, and iodine deficiency
  • dyshormonogenetic goiter is due to a congenital defect in thyroid hormone production; most commonly involves thyroid peroxidase
Term
Myxedema
Definition
  • hypothyroidism in older children or adults
  • clinical features are based on decreased BMR and decreased SNS activity
  • myxedema-accumulation of glycosaminoglycans in the skin and soft tissue results in a deepening of voice and large tongue
  • weight gain despite normal appetite
  • slowing of mental activity
  • muscle weakness
  • cold intolerance with decreased sweating
  • bradycardia w/ decreased CO, leading to SOB and fatigue
  • oligomenorrhea
  • hypercholesterolemia
  • constipation
  • most common causes are iodine deficiency and Hashiomoto thyroiditis, other causes include drugs (ex Lithium) and surgical removal or radioablation of the thyroid
Term
Hashimoto Thyroiditis
Definition
  • Autoimmune destruction of the thyroid gland; associated with HLA-DR5
  • most common cause of hypothyroidism in regions where iodine levels are adequate
  • initially may present as hyperthyroidism (due to follicle damage)
  • progresses to hypothyroidism: decreased T4 and increased TSH
  • antithyroglobulin and antimicrosomal antibodies are often present (sign of thyroid damage)
  • chronic inflammation with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles)
  • Increased risk for B-cell (marginal zone) lymphoma; presents as an enlarging thyroid gland late in disease course
Term
Subacute Granulomatous (De Quervain) thyroiditis
Definition
  • Granulomatous thyroiditis that follows a viral infection
  • presents as a tender thyroid with transient hyperthyroidism
  • self-limited; does not progress to hypothyroidism
Term
Reidel Fibrosing Thyroiditis
Definition
  • chronic inflammation with extensive fibrosis of the thyroid gland
  • presents as hypothyroidism with a hard as wood, nontender thyroid gland
  • fibrosis may extend to involve local structures (ex airway)
  • clinically mimics anaplastic carcinoma, but patients are younger (40s) and malignant cells are absent
Term
Thyroid Neoplasia
Definition
  • usually presents as a distinct, solitary nodule
  • thyroid nodules are more likely to be benign than malignant
  • I131 radioactive uptake studies are useful to further characterize nodules
  • increased uptake (hot nodule) is seen in Graves disease or nodular goiter
  • decreased uptake (cold nodule) is seen in adenoma and carcinoma; often warrants biopsy
  • Biopsy is performed by fine needle aspiration (FNA)
Term
Follicular adenoma
Definition
  • Benign proliferation of follicles surrounded by a fibrous capsule
  • usually nonfunctional; less commonly, may secrete thyroid hormone
Term
Medullary Carcinoma
Definition
  • malignant proliferation of parafollicular C cells; comprises 5% of thyroid carcinomas
  • C cells are neuroendocrine cells that secrete calcitonin
  • calcitonin lowers serum calcium by increasing renal calcium excretion but is inactive at normal physiologic levels
  • high levels of calcitonin produced by tumor may lead to hypocalcemia
  • calcitonin often deposits within the tumor as amyloid
  • biopsy reveals sheets of malignant cells in an amyloid stroma
  • familial cases are often due to multiple endocrine neoplasia (MEN) 2 A and 2B, which are associated with mutations in the RET oncogene.
  • MEN 2 results in medullary carcinoma, pheochromocytoma, and parathyroid adenomas (2A) or ganglioneuromas of the oral mucosa (2B)
  • detection of RET mutation warrants prophylactic thyoidectomy
Term
Anaplastic Carcinoma
Definition
  • Undifferentiated Malignant tumor of the thyroid; usually seen in elderly
  • often invades local structures, leading to dysphagia or respiratory compormise
  • poor prognosis
Term
Parathyroid Glands
Definition
  • Chief cells regulate serum free (ionized) calcium via parathyroid hormone secretion
  • an increased serum ionized calcium levels provide negative feedback to decrease PTH secretion
Term
Parathyroid Hormone
Definition
  1. increses Osteoclast activity, releasing calium and phosphate
  2. increases Small bowel absorption of calcium and phosphate (indirectly by activating vitamin D)
  3. Increases renal calcium reabsorption (distal tubule) and decreases phosphate reabsorption (proximal tubule)
  4. Increased serum ionized calcium levels provide negative feedback to decrease PTH secretion
Term
Primary hyperparathyroidism
Definition
  • excess PTH due to a disorder of the parathyroid gland itself
  • most common cause is parathyroid adenoma >80% of cases; sporadic parathyroid hyperplasia and parathyroid carcinoma are less common causes
  • Parathyroid adenoma is a benign neoplasm, usually involving one gland.
  • Most often results in asymptomatic hypercalcemia such as
  • nephrolithiasis (calcium oxalate stones)
  • nephrocalcinosis-metastatic claclification of renal tubules potentially leading to renal insufficiency and polyuria
  • CNS disturbances (ex depression and seizures)
  • constipation, peptic ulcer disease, and acute pancreatits
  • osteitis fibrosa cystica- resorption of bone leading to fibrosis and cystic spaces
  • laboratory findings include increased serum PTH, increased serum calcium, decreased serum phosphate, increased urinary cAMP, and increased serum alkaline phosphatase
  • treatment involves surgical removal of the affected gland
Term
Secondary hyperparathyroidism
Definition
  • excess production of PTH due to a disease process extrinsic to the parathyroid gland
  • most common cause is chronic renal failure
  • renal insufficiency leads to decreased phosphate excretion
  • increased serum phosphate binds free calcium
  • decreased free calcium stimulates all four parathyroid glands
  • increased PTH leads to bone resorption (contributing to renal osteodystrophy)
  • Lab findings include increased PTH, decreased serum calcium, increased serum phosphate, and increased alkaline phosphatase
Term
Hypothyroidism
Definition
  • Low PTH
  • causes include autoimmune damage to the parathyroids, surgical excision, and DiGeorge syndrome
  • presents with symptoms related to low serum calcium
  • numbness and tingling (particularly circumoral)
  • muscle spasm (tetany)--may be elicited w/ filling of a blood pressure cuff (Trousseau sign) or tapping on the facial nerve (Chvostek sign)
  • Labs reveal decreased PTH levels and decreased serum calcium
  • Pseudohypoparathyroidism is due to end-organ resistance to PTH
  • Labs reveal hypocalcemia with PTH levels
  • Autosomal dominant form is associated with short stature and short 4th and 5th digits
Term
Endocrine Pancreas
Definition
  • Composed of clusters of cells termed islets of Langerhans
  • A single islet consists of multiple cell types, each producing one type of hormone
  • Insulin is secreted by beta cells, which lie in the center of the islets
  • Major anabolic hormone; upregulates insulin-dependent glucose transporter protein (GLUT4) on skeletal muscle and adipose tissue (glucose uptake by GLUT 4 decreases serum glucose
  • Increased glucose uptake by tissues leads to increased glycogen synthesis, protein synthesis, and lipgenesis
  • Glucagon is secreted by alpha cells; it opposes insulin in order to increase blood glucose levels (ex in states of fasting) via glycogenolysis and lipolysis
Term
Type one Diabetes Mellitus
Definition
  • Insulin deficiency leading to a metabolic disorder characterized by hyperglycemia
  • Due to autoimmune destruction of beta cells by T lymphocytes
  • Characterized by inflammation of islets
  • Associated with HLA-DR3 and HLA-DR4
  • Autoantibodies against insulin are often present (sign of damage) and may be seen years before clinical disease develops
  • Manifests in childhood with clinical features of insulin deficiency
  • High serum glucose-lack of insulin leads to decreased glucose uptake by fat and skeletal muscle
  • weight loss, low muscle mass, and polyphagia--unopposed glucagon leads to gluconeogenesis, glycogenolysis and lipolysis, which further exacerbates hyperglycemia
  • polyuria, polydipsia, and glycosuria--Hyperglycemia exceeds renal ability to resorb glucose; excess filtered glucose leads to osmotic diuresis
  • Treatment involves lifeleong insuling

Risk factors

  1. Char. by excessive serum ketones
  2. often arises w/ stress (ex infection); epinephrine stimulates glucagon secretion increasing lipolysis (along with gluconeogenesis and glycogenolysis)
  3. increased lipolysis leads to increased FFAs
  4. Liver converts FFAs to ketone bodies (beta-hydroxybutyric acid and acteoacetic acid)
  5. Results in hyperglycemia >300 mg/dL, anion gap metabolic acidosis, and hyperkalemia
  6. presents with Kussmaul respirations, dehydration, nausea, vomiting, mental status changes, and fruity smelling breath (b/c of acetone)
  7. treatment is fluids (corrects dehydration from polyuria), insulin, and replacement of electrolytes (ex potassium)
Term
Type 2 diabetes Mellitus
Definition
  • End organ insulin resistance leading to a metabolic disorder characterized by hyperglycemia
  • Most common type of diabetes (90%) of cases affects 5-10% of the US population
  • Incidence is rising
  • Arises in middle-aged, obese adults
  • Obesity leads to decreased numbers of insulin receptors
  • strong genetic predisposition exists
  • Insulin levels are increased early in disease, but later, insulin deficiency develops due to beta cell exhaustion; histology reveals amyloid depostion in the islets
  • clinical features include polyuria, polydipsia, and hyperglycemia, but disease is often clinically silent
  • diagnosis is made by measuring glucose lvls (normal is 70-120 mg/dL)
  • random glucose >200
  • Fasting glucose >126
  • Glucose tolerance test with a serum glucose level >200 two hours after glucose loading
  • Treatment involves weight loss (diet and exercise) initially; may require drug therapy to counter insulin resistance (ex sulfonylureases or metformin) or exogenous insulin after exhaustion of beta cells
  • Risk for hyperosmolar non-ketotic coma
  • High glucose >500 leads to life-threatening diuresis w/ hypotension and coma
  • Ketones are absent due to small amounts of circulating insulin
Term
Long-Term Consequences of Diabetes
Definition
  • Nonenzymatic Glycosylation (NEG) of the vascular basement.
  • NEG of large and medium-sized vessels leads to atherosclerosis and its resultant complications
  • cardiovascular disease is the leading cause of death among diabetes
  • peripheral vascular disease in diabetics is the leading cause of nontraumatic amputations
  • NEG of small vessels (arterioles) leads to hyaline arteriosclerosis
  • involvement of renal arterioles leads to glomerulosclerosis, resulting in small, scarred kidneys with a granular surface
  • preferential involvement of efferent arterioles leads to glomerular hyperfiltration injury with microalbuminuria that eventually progresses to nephrotic syndrome; characterized by Kimmelstiel-Wilson nodules in glomeruli
  • NEG of hemoglobin produces glycated hemoglobin (HBA1c), a marker of glycemic control
  • Osmotic damage
  • glucose freely enters inSchwann cells (which myelinate peripheral nerves), pericytes of retinal blood vessels, and the lens
  • Aldose reductase converts glucose to sorbitol, resulting in osmotic damage
  • Leads to peripheral neuropathy, impotence, blindness, and cataracts; diabetes is the leading cause of blindness in the developed world
Term
Pancreatic Endocrine Neoplasms
Definition
  • Tumors of Islet cell; account for <5% of pancreatic neoplasms
  • Often a component of MEN1 along with Parathyroid hyperplasia and pituitary adenomas
  • Insulinomas present as episodic hypoglycemica w/ mental status changes that are relieved by administration of glucose
  • Diagnosed by decreased serum glucose levels (usually less than 50mg/dL), increased insulin, and increased C-peptide
  • Gastrinomas present as treatment-resistant peptic ulcers (zollinger-ellison syndrome); ulcers may be multiple and can extend into the jejunum
  • somastostatinomas present as achlorohydria (due to inhibition of gastrin) and cholelithiasis w/ steatorrhea (due to inhibition of cholecystokinin)
  • VIPomas secrete excessive vasoactive intestinal peptide leading to watery diarrhea, hypokalemia, and achlorhydria
Term
Adrenal Cortex
Definition
  • Composed of 3 layers that each secrete distinct hormones
  • Glomerulosa produces mineralocorticoids (aldosterone)
  • Fasciculata produces glucocorticoids (ex cortisol)
  • Reticularis prod. Sex steroids (ex Testosterone)
Term
Hypercorisolism (cushing Syndrome)
Definition
  • Excess Cortisol
  • Muscle weakness w/ thin extremeties--Cortisol breaks down muscle for gluconeogenes
  • moon facies, buffalo hump, and truncal obesity--High insulin (due to high glucose) increases storage of fat
  • abdominal striae- due to impaired synthesis of collagen w/ thinning of skin
  • HTN
    osteoporosis
  • Immune suppression
  • diagnosis is made by increased 24 hour urine cortisol levels
  • Causes include:
  • Exogenous corticosteroids-leads to bilateral adrenal atrophy; steroids suppress ACTH secretion (negative feedback)
  • Primary adrenal adenoma, hyperplasia, or carcinoma, leads to atrophy of the uninvolved adrenal gland
  • ACTH- secreting pituitary adnoma leads to bilateral adrenal hyperplasia
  • paraneoplastic ACTH secretion (ex small cell carcinoma of the lung) leads to bilateral adrenal hyperplasia
  • High dose dexamethason (cortisol analog) suppresses ACTH prod. by a pituitary adenoma (cortisol levels decrease), but fails to suppress ectopic ACTH production by a small cell lung carcinoma (cortisol levls remain high)
Term
Congenital Adrenal Hyperplasia
Definition
  • Excess sex steroids with hyperplasia of both adrenal glands
  • Inherited 21 hydroxylase def. is the most common cause
  • 21 hydroxylase is req. for the prod. of aldosterone and corticosteroids
  • in enzyme def, steroidogenesis is pred. shunted toward sex steroid prod. (which does not require 21 hydroxylase)
  • Def. of cortisol leads to increased ACTH secretion (lack of negative feedback), which results in bilateral adrenal hyperplasia
  • Clinical Features:
  • Salt wasting with hyponatremia, hyperkalemia, and hypovolemia due to lack of aldosterone
  • Life-threatening hypotension due to lack of cortisol
  • Clitoral enlargement (females) or precocious puberty (males) due to excess androgens
Term
Adrenal Insufficiency
Definition
  • Lack of adrenal hormones
  • acute insufficiency may arise with Waterhouse-Friederichsen syndrome
  • Char. by hemorrhatic necrosis of the adrenal glands classically due to DIC in young chilren w/ N. meningitidis infection.
  • Lack of cortisol exacerbates hypotension, often leading to death
  • Chronic insufficency (Addison disease) is due to progressive destruction of the adrenal glands
  • Common causes include autoimmune destruction (most common cause in the West), TB (most common cause in the developing world), and metastatic carcinoma (ex arising from lung).
  • Clinical features include hypotension, hyponatremia, hypovalemia, hyperkalemia, weakness, hyperpigmentation (increased ACTH by-products stimulate melanocytic production of pigment), vomiting, and diarrhea
Term
Adrenal medulla
Definition
  • Composed of neural crest-derived chromaffin cells
  • Main physiologic source of catecholamines (epinephrine and norepinephrine)

 

Term
Pheochromocytoma
Definition
  • Tumor of chromaffin cells
  • clinical features are due to increased serum catecholamines
  • episodic HTN, headache, palpitations, tachycardia, and sweating
  • Diagnosed by increased serum metanephrines and increased 24-hour urine metanephrines and vanillylmandelic acid
  • Treatment is surgical excision
  • Catecholamines may leak into the bloodstream upon manipulation of the tumor
  • Phenoxybenzamine (irreversible alpha blocker) is administered perioperatively to prevent a HTN crisis)
  • Often follow the rule of 10s
  • 10% bilateral, 10% familial, 10% malignant, and 10% located outside of the adrenal medulla (ex bladder wall or organ of Zuckerkandl at the inferior mesenteric artery root)
  • Associated with MEN2A and 2B, von Hippel-Lindau disease, and neurofibromatosis type 1
Supporting users have an ad free experience!