Endocrine Pathology

  1. Pituitary Gland
    What regulates pituitary trophic hormones?
    • Regulates most other endocrine glands/organs
    • in the sella turcia.
    • Connected to the hypothalamus via stalk.
    • The hypothalamus regulates pituitary trophic hormones
  2. What are the the cell types and hormones the Anterior Lobe of the Pituitary gland secrete?
    • Somatotroph 50% Growth Hormone
    • Mammotroph 10-20% Prolactin
    • Corticotroph 10-20% Corticotropin (ACTH)
    • Gonadotroph 10% Gonadotropins (LH, FSH)
    • Thyrotroph 5% thyrotropin (TSH)
  3. What are some hormones that the posterior lobe of the pituitary gland secrete? What is it composed of?
    • Composed of unmyelinated nerve fibers:
    • Oxytocin
    • Antidiuretic hormone (ADH, aka vasopressin)
  4. Anterior lobe of Pituitary pathology
    Hyperfunction (hyperpituitarism)
    what is it's main cause/what is it almost always associated with?
    How are the symptoms produced? two ways...
    • Almost always associated with adenoma
    • Symptoms produced via
    • 1. Hormone production (over production)
    • 2. Mass effect: Gets so big it compresses surrounding structures. Hypertrophy.
  5. What happens during hyperfunction (hyperpituitarism) with Adenomas affecting
    Growth hormone
    • Prolactin 30%: amenorrhea, infertility, galactorrhea, loss of labido
    • Growth Hormone: 17%: Gigantism (prepubertal), acromegaly (adults)
    • Corticotropin 14%: Cushing's syndrome (hypercortisolism)
    • Mixed, Gonadotropin, Thyrotropin = rare
    • Nonfunctional 25%: mass effect
  6. Anterior Lobe of the Pituitary Gland
    Hypofunction (hypopituitarism)
    What is it?
    • Deficiency of one or multiple hormones
    • Causes:
    • Nonfunctional pituitary adenoma (mass effect)
    • Ischemic necrosis: Need over 75% destruction to cause problems
    • Ablation/destruction by surgery, radiation or adjacent tumor.
  7. Manifestations of hypofunction (hypopituitarism)
    Growth Hormone
    • GH: Pituitary dwarfim
    • Gonadotropin: major sex hormone regulator, deficiency causes Amenorrhea and infertility in women. Decreased libido, impotence and lack of pubic/axillary hair in men.
    • Prolactin: No post partum lactation
    • TSH: Hypothyroidism
    • ACTH: Hypoadrenalism
  8. Posterior Lobe of the Pituitary Gland Pathology
    Oxytocin: ?
    • Oxytocin: involved in brith, no significant clinical abnormalitites
    • ADH: Functions in kidneys to promote resorption of free water. If there is a decrease in ADH too much water loss through urine can cause diabetes insipidus.
  9. Thyroid Gland
    How does it develop?
    Normal histology?
    • Develops from an invaginationof endoderm which arises at the base of the tongue, migrates caudally to its location anterior to the thyroid cartilage.
    • Histology: Follicles filled with colloid. Glassy, icy, smooth, pink looking.
  10. Hyperthyroidism
    most common causes: (4)
    • Graves disease (number 1 cause)
    • Ingestion of excessive exogenous thyroid hormone (TH) - this happens when someone has hypothyroidism and take too much TH = overcompensate.
    • Hyperfunctional multinodular goiter
    • Hyperfunctional thyroid adenoma
  11. Hyperthyroidism:
    Clinical manifestations? (2 main ones)
    • Diagnosis: elevated TH and decreased TSH (primary hyperthyroidism)
    • Clinical manifestations: Hypermetabolic state and overactivity of the sympathetic nervous system.
  12. How does the thyroid gland regulate the body?
    Manifestations of Hyperthyroidism (8)
    • Thyroid gland is like the thermostat of the body, regulator of energy, mood and other organ functions.
    • Hyperthyroid people = hypermetabolic state, increase sympathetic nerve activity.
    • heat intolerance
    • weight loss despite increased appetite
    • irritability
    • muscle weakness
    • diarrhea
    • tachycardia
    • congestive heart failure
  13. What is a thyroid Storm
    • Abrupt onset of hyperthyroidism
    • patients can die of cardiac arrhythmia due to sudden onset of aggressive hyperthyroidism or it goes undiagnosed for a while.
  14. Grave's Disease:
    Gender predominance?
    What is it?
    Manifestations? (3)
    • Female predominance, common, 5F:1M
    • Autoimmune disease where thyroid is overactive producing excessive amounts of thyroid hormones. Has a significant genetic component
    • Manifestations:
    • 1. Hyperthyroidism
    • 2. Exophthalamos (40%) buldging of the eye out of the socket, bug eyes
    • 3. Skin lesions: pretibial myxedema pink thickening/scaly skin over tibia.
  15. Graves Disease:
    Autoimmune significant genetic component?
    enlargement of what?
    Hyperplasia or what?
    Increase/decrease of serum components?
    • Autoimmune disease where autoantibodies attack TSH receptor so it's constantly stimulated secreting TH
    • Pathology:
    • diffuse enlargement of the thyroid on gross examination
    • Hyperplasia of follicles with lymphoid infiltrates
    • Increase in serum-free TH, decreased serum TSH
  16. Hypothyroidism:
    Common causes (3)
    • Ablation by surgery or radiation therapy (removal of thyroid/damage by radiation)
    • Hashimoto thyroiditis: autoimmune disease, inflammation of the thyroid.
    • Iodine deficiency: Was more of a problem before iodine was common in the diet.
  17. Hypothyroidism: Clinical Manifestations
    Serum TSH?
    • Cretinism: Children with hypothyroidism, rare, iodine in diet prevents this (it's caused by iodine deficiency). Impaired development of skeleton and CNS (mental problems) coarse facial features.
    • Myxedema: Adults, generalized apathy, mental sluggishness, listless, cold-intolerance, obese, coarse facial features, enlargement of tongue, deepening of voice, constipation, late cardiac effects.
    • Serum TSH: Increased TSH due to loss of feedback inhibition (thyroid can't detect it). Not increased in cases caused by primary hypothalamic or pituitary disease.
  18. Hashimoto Thyroiditis:
    Gender predominance?
    Common cause of what disease?
    What is it/how is it caused?
    Patients at risk for other autoimmune disease?
    • Female predominance, older women, significant genetic component 10-20F:1M
    • Common cause of hypothyroidism
    • Autoimmune; progressive destruction of gland: initially euthyroid (normally) progress to hypothyroid.
    • Patients usually at risk for other autoimmune disease and B-cell Non-Hodgkin lymphomas
    • No established risk of development of thyroid neoplasm.
  19. Goiters: what is it?
    most common manifestation of what?
    Impaired synthesis of what? What is their cause?
    Clinical features are due to what effect?
    • Goiters are enlargements of the thyroid. They reflect impaired synthesis of thyroid hormone.
    • Most often due to iodine dietary deficiency, some idiopathic
    • most common manifestation of thyroid disease.
    • Most common clinical features are due to mass effect: cosmetic problem, airway obstruction, dysphagia, compression of vessels.
  20. Hyperfunctional, "toxic" goiter
    what is it, how is it caused?
    • In a minority of patients with goiters, a "toxic" nodule may develop in a long-standing non-toxic goiter.
    • Hyperthyroidism causes goiters
  21. Thyroid Neoplasms:
    benign or malignant?
    genetic/environmental factors?
    • Thyroid nodules are common
    • Most nodules are non-neoplastic disease
    • 1% are carcinomas
    • Noducles in males and young patients are more likely to be neoplastic
    • Genetic and environmental factors: exposure to radiation in first 2 decades of life.
  22. What are 5 types of thyroid neoplasms?
    • Follicular adenoma
    • Papillary thyroid carcinoma
    • Follicular carcinoma
    • Anaplastic thyroid carcinoma
    • Medullary thyroid carcinoma
  23. Thyroid Neoplasms: Papillary Thyroid Carcinoma
    cause of thyroid cancer?
    radiation exposure?
    genetic mutation of what genes?
    Indolent lesions
    • most common of thyroid cancers, peak 3-5th decade F>>M
    • Some cases related to radiation exposure
    • RET proto-oncogene mutation
    • Pathology:
    • Microscopically characterized by papillary projections
    • nuclear clearing - orphan annie nuclei
    • nuclear grooves
    • Indolent lesions, 10 year survival rates >95%
  24. Thyroid Neoplasms: Follicular Thyroid Carcinoma
    % of thyroid cancers
    dietary affect?
    • 10-20% of thyroid cancers
    • Older age than papillary
    • Occurs in areas with dietary iodine deficiency
    • May resemble a follicular adenoma
    • must see invasion through the capsule or into the blood vessels.
  25. Thyroid Neoplasm: Medullary Thyroid Carcinoma
    Derived from what cells?
    Sporadic or familial?
    Mutation in what genes?
    serum affects?
    • Uncommon 5% of thyroid cancer
    • Derive from the parafollicular (C) cells: which produce calcitonin (acts in opposition to parathyroid hormone)
    • May be sporadic or familial: Component of MEN syndromes.
    • All have mutation in the RET proto-oncogene
    • Increased serum calcitonin
  26. Parathyroid Glands:
    how many glands?
    What are the two types of cells and what do they secrete?
    • 4 glands located at each pole of the thyroid
    • Chief cells: secrete PTH
    • Oxyphil cells: unknown function.
  27. Hyperparathyroidism:
    What does PTH do?
    Patients with hyperparathyroidism develop what?
    • PTH activates osteoclasts: breakdown bone and increase serum calcium concentrations.
    • Patients with hyperparathyroidism develop skeletal changes. Ground glass appearance, brown tumor.
  28. Primary Hyperparathyroidism:
    clinical features:
    • Caused by adenoma or hyperplasia causing hypercalcemia: very common
    • Clinical features/symptoms:
    • more common in women, often clnically silent
    • Bones, stones, groans, moans!
    • weakness and fatigue
    • Metastatic calcifications: deposition of calcium throughout body, including blood vessels.
  29. Secondary Hyperparathyroidism:
    most common cause: describe mechanism
    Symptoms dominated by what?
    • Renal failure
    • Symptoms dominated by renal disease: decreased phosphate excretion causes hyperphophatemia depresses serum calcium levels stimulates parathyroid glands.
    • Normally kidneys would increase vit D synthesis to increase Ca absorption in gut, but they're not working so reduced intestinal absorption of calcium.
    • symptoms as in primary, renal osteodystrophy.
  30. Hypoparathyroidism:
    Clinical manifestations (4)
    • uncommon
    • Causes: surgical removal, congenital absence (DiGeorge's syndrome), autoimmune.
    • Clinical manifestations: hypocalcemia, increased neuromuscular excitability, cardiac arrhythmias, increased intracranial pressure and seizures.
  31. Endocrine Pancreas
    What are Islets of Langerhans
    Cell types? (4)
    Exocrine pancreas makes what enzymes?
    • Islets of Langerhans: clusters of endocrine cells interspersed among the acinar groups (that make up the exocrine pancreas.
    • Cell types:
    • Beta: 70% insulin
    • Alpha: 20% glucagon
    • Delta: 10% somatostatin
    • PP 1-2% pancraetic polypeptide
  32. Diabetes Mellius:
    What is it?
    what is it's main pathology/effect?
    Leading cause of what disease?
    • Group of metabolic disorders resulting in hyperglycemia due to defects in insulin secretion, insulation action or both.
    • Vasculopathy: with long-term complications involving the kidneys, eyes, nerves and blood vessels.
    • 21 million americans affected
    • leading cause of ESRD (endstage renal disease, blindness and amputation.
  33. Classification of Diabetes
    Type 1:
    Type 2:
    • Type 1: aka juvenile, insulin dependent, 10% of cases, severe insulin deficiency.
    • Type 2: aka adult onset, non-insulin dependent. Peripheral resistance to insulin action and inadequate response to insulin secretion by Beta cells.
  34. Presenting symptoms of DM Type 1
    what is the main/worse symptom.
    • usually presents by age 35
    • polyuria
    • polydyspia
    • polyphagia with weight loss
    • Ketoacidosis: fat is primary energy source, excess ketones produced because of fat metabolism, decreases blood pH can lead to diabetic coma.
  35. Presenting symptoms of DM type 2
    • Usually presents after age 40
    • Polyuria and polydipsia may occur
    • diagnosis made after routine blood tests
    • enhanced susceptibility to infection: periodontal disease
  36. Laboratory diagnosis of Diabetes Mellitus:
    Normal glucose range
    DM indicated if...
    Blodd glucose concentration is higher than?
    Fasting glucose is greater than?
    Blood glucose is greater than ___ with in 2 hours of ingesting 75g of glucose.
    • Normal glucose is 70-120mg/dL
    • Random blood glucose concentration of 200mg/dL or higher
    • Fasting glucose greater than 126mg/dL on more than one occasion.
    • Blood glucose greater than 200mg/dL within 2 hours of ingesting 75g of glucose.
  37. Etiology of Type 1 Diabetes Mellitus:
    • Absolute lack of insulin secondary to autoimmune destruction of B-cells
    • Genetric susceptibility + autoimmune factors + environmental insult.
    • abrupt onset
    • Patients require insulin from outside sources to survive.
  38. Etiology of Type 2 Diabetes Mellitus:
    • Multiple genes play a role: each has its own risk and modified by the environment.
    • peripheral tissues cannot respond properly to insulin (insulin resistance)
    • B-cell dysfunction: inadequate insulin secretion in the face of insulin resistance and hyperglycemia.
  39. Disposing factors to Type 2 Diabetes Mellitus:
    3 main ones
    • 1. Obesity: 80% are obese, 60% exhibit glucose intolerance, adipose tissue appears to be antagonistic to insulin.
    • 2. Pregnancy
    • 3. Stress.
  40. Manifestations of DM
    what is the big problem/effect of DM?
    what are the affects on the pancreas?
    • Vasculopathy: Big thing is vascular disease, occurs because of sugar problems. Responsible for 80% of DM-related deaths. Atherosclerosis, MI, gangrene of lower extremities, thickend basement membrane, especially around small blood vessels (MICROANGIOPATHY)
    • Pancreas: destruction of islets of langerhans, heavy inflammatory infiltrate, amyloid.
  41. Manifestations of DM on the Kidneys?
    rank of cause of death?
    Diffuse glomerulosclerosis?
    Nodular Glomerulosclerosis?
    • 2nd leading cause of death behind vaculopathy
    • Glomerular lesions
    • Diffuse glomerulosclerosis: 90% of diabetics within 10 years, not specific to diabetics, microangiopathy around glomerular capillaries and depsotion of matrix. Proteinuria, total renal failure.
    • Nodular glomerulosclerosis: 35% specific to diabetics, ball-like deposition of matrix, total renal failure.
  42. Mainfestations of DM to the eye?
    • 4th leading cause of blindness
    • Microangiopathy and microaneurysms
    • Retinal detachment and vision loss.
  43. Islet Cell Tumors:
    What part of the pancreas is affected?
    • uncommon
    • Most are from the exocrine pancreas.
    • May be functional or non-functional
    • Insulinoma occurs.
    • Gastrinoma: 90-95% of patients with really bad peptic ulcers.
  44. What is Zollinger-Ellison Syndrome?
    Pancreatic islet cell tumor, hypersecretion of gastric acid causing severe peptic ulcers. 60% malignant.
  45. Islet Cell Tumors:
    What is Insulinoma?
    • Insulinoma (Insulin secreting Islet Cell tumor)
    • Insulinoma: B-cell tumor, hyperinsulinism, most are adenomas. Hypoglycemia quickly occurs from fasting or exercise. Many are asymptomatic, 5-10% malignant. Nervousness, confusion, stupor. Tx: Surgical excision.
  46. Adrenal Gland:
    Adrenal Cortex: 3 zones, what they secrete
    Adnreal Medulla: what it secretes
    • Adrenal Cortex
    • zona glomerulosa: mineralcorticoids (aldosterone)
    • zona fasciculata: glucocorticoids (cortisol)
    • zona reticularis: sex hormones (estrogen/androgen)
    • Adrenal Medulla: neural origin, chromaffin, source of catecholamines (epinephrine).
  47. Hypercotisolism (aka?)
    Causes: 4
    • (cushing syndrome)
    • 1. Excess administration of exogenous glucocorticoids (most common): taking stroids, adrenal cortex atrophy.
    • 2. Primary adrenal hyperplasia or neoplasm (adrenal adenoma).
    • 3. Primary pituitary source (cushing disease): ACTH over-secretion, tumor in pituitary, skin pigmentation.
    • 4. Ectopic ACTH secretion by neoplasm, eg lung.
  48. Hypercortisolism:
    Signs and Symptoms:
    Speed of onset?
    blood pressure? weight? weakness? bone? infection?
    • Usually gradual onset.
    • hypertension, weight gain (moon faces, buffalo hump), muscle weakness, osteoporosis, increased risk of infection, menstrual irregularities, hirsutism, mental disturbances.
  49. Hyperaldosteronism:
    cause: symptoms?
    • caused by sodium retention, potassium excretion: producing hypertension and hypokalemia.
    • Primar: very rare, hyperplasia of adrenal gland, neoplasm, idiopathic, decreased levels of plasma renin.
    • Secondary: Aldosterone release in response to activation of renin-angiotensin system. Increased levels of plasma renin leading to aldosterone release.
  50. Hypoadrenalism:
    decrease in what? because of deficiency of what hormone?
    what % of gland needs to be destroyed for affect?
    • Can be primary or secondary: Secondary-decreased stimulation of adrenals from deficiency of ACTH. Need 90% of gland to be destroyed before you see symptoms.
    • Manifestations: weakness, fatigue, GI disturbances, anorexia, nausea, vomiting, weight loss, diarrhea.
  51. Acute Adrenocortical Insufficiency:
    How is it caused?
    • In patients maintained on exogenous steroids... rapid withdrawal of steroids or failure to increase steroids in response to an acute stress can precipitate an adrenal crisis.
    • Also caused by adrenal hemorrhage or stress in a patient with existing Addison's disease.
    • Symptoms: Vomiting, abdominal pain, hypotension, coma, death.
  52. Primary Chronic Adrenocortical Insufficiency (Addison's Disease).
    What is it?
    Serum hormone level of what?
    • An autoimmune disease usually which causes the progressive destruction of the adrenal cortex.
    • Serum ACTH may be elevated causing skin and mucosal pigmentation.
    • Destruction of cortex prevents response to ACTH.
  53. Causes of Addison's disease
    4 things
    • 1. Autoimmune destruction of steroid-producing cells: most common 60-70% of cases.
    • Also caused by
    • 2. AIDS
    • 3. TB
    • 4. Metastatic disease
  54. Secondary Adrenocortical Insufficiency:
    What is it?
    What is the big difference in symptoms vs Addison's disease?
    • Any disorder of the hypothalamus or pituitary that reduces output of ACTH.
    • Symptoms similar to Addison's disease.
    • BUT NO skin/mucosa pigmentation because of decreased ACTH.
  55. Adrenal Neoplasms:
    What is Pheochromocytoma?
    neoplasm of what cells?
    Main symptom, other symptoms?
    Rule of 10's?
    • Pheochromocytoma: neoplasm of chromaffin cells which make way too much epinepherine therefore causing HYPERTENSION.
    • F>M, 30-60 years old.
    • Symptoms: Hypertension! tachycardia, tremor, headache.
    • Rule of 10's. 10% bilateral, 10% extra-adrenal 10% malignant, 10% familial syndroms. (KNOW THIS)
  56. Multiple Endocrine Neoplasia (MEN) syndrom.
    What is it?
    Gene affected?
    • Types MEN 1, 2A, 2B
    • Tumors of Multiple Endocrine Organs: Medullary thyroid carcinoma, parathyroid, pheochromocytoma, pancreas, pituitary.
    • Caused by: RET proto-oncogene: germ line mutation causes these tumors.
  57. Multiple Endocrine Neoplasia Syndrome:
    MEN 2B
    Where are the neuromas?
    What are the symptoms?
    Whats the persons body look like?
    • Mucosal neuromas (tongue, labial commisure, eyelids)
    • Large blubbery lips.
    • Marfanoid body habitus.
Card Set
Endocrine Pathology
Endocrine Pathology