Endocrine - Pathology Part 2 Flashcards
What is the risk of the nodules in a toxic multinodular goiter becoming malignant?
None; the nodules in a toxic multinodular goiter are not malignant
What mutation is responsible for the activity of the follicles in a toxic multinodular goiter?
A mutation in the thyroid-stimulating hormone receptor makes these cells function independently of thyroid-stimulating hormone
What is the Jod-Basedow phenomenon?
Thyrotoxicosis when a patient with endemic goiter moves to an iodine-replete area
Which thyroid cancer is the most common?
Papillary carcinoma
Which thyroid cancer has the best prognosis?
Papillary carcinoma
What are the histological findings of papillary carcinoma of the thyroid?
Psammoma bodies, “ground-glass” nuclei (Orphan Annie), nuclear grooves
Place the following thyroid cancers in order from best to worst prognosis: follicular, undifferentiated/anaplastic, and papillary.
Papillary, follicular, and undifferentiated/anaplastic
Medullary carcinoma of the thyroid originates from which cells?
Parafollicular C cells
Medullary carcinoma of the thyroid produces what substance?
Calcitonin
What are the histological findings of medullary carcinoma of the thyroid?
Sheets of cells in amyloid stroma
Medullary carcinoma of the thyroid is associated with what two genetic syndromes?
Multiple endocrine neoplasia types 2A and 2B
Undifferentiated/anaplastic carcinoma of the thyroid is most commonly found in what population?
Older patients
What type of cancer is associated with Hashimotos thyroiditis?
Lymphoma of the thyroid
What risk factor is associated with papillary carcinoma of the thyroid?
Childhood irradiation
What mnemonic illustrates the causes of hypercalcemia?
Calcium ingestion, Hyperparathyroidism, Hyperthyroidism, Iatrogenic (thiazides), Multiple myeloma, Pagets disease, Addisons disease, Neoplasms, Zollinger-Ellison syndrome, Excess vitamin D, Excess vitamin A, Sarcoidosis (remember: CHIMPANZEES)
What is the most common cause of primary hyperparathyroidism?
A parathyroid adenoma
What are the relative levels of parathyroid hormone, calcium, phosphate, and alkaline phosphatase in primary hyperparathyroidism?
Increased parathyroid hormone, calcium, and alkaline phosphatase and decreased phosphate
What is the classic triad of symptoms in primary hyperparathyroidism?
When present, symptoms include weakness, constipation, and renal stones (remember: stones, bones, and groans)
What is the mechanism by which a patient develops secondary hyperparathyroidism?
Decreased calcium absorption from the gut and increased levels of phosphate lead to secondary hyperplasia of the parathyroid gland
What is the most common cause of secondary hyperparathyroidism?
Chronic renal disease
What are the relative levels of parathyroid hormone, calcium, phosphate, and alkaline phosphatase in secondary hyperparathyroidism?
Increased parathyroid hormone, phosphate, and alkaline phosphatase, and decreased serum calcium
How does chronic renal disease contribute to secondary hyperparathyroidism?
Renal failure leads to decreased activation of vitamin D which, in turn, leads to decreased absorption of calcium from the gut
What is the bone pathology associated with osteitis fibrosa cystica?
Cystic bone spaces filled with brown fibrous tissue causing pain; due to elevated levels of parathyroid hormone
What bone pathology might you see in a dialysis patient?
Renal osteodystrophy, caused by secondarily elevated parathyroid hormone levels
What neuromuscular finding is common among patients with hypoparathyroidism?
Tetany, secondary to hypocalcemia
Following thyroid surgery, a patient presents with muscle spasms; what electrolyte abnormality is likely present?
Hypoparathyroidism and resultant hypocalcemia
List three causes of hypoparathyroidism.
Accidental surgical excision (thyroid surgery), autoimmune destruction and DiGeorges syndrome
Upon tapping the facial nerve, a patient has twitching in the ipisilateral facial muscles; what is the sign?
Chvosteks sign, indicating hypocalcemia
After occluding the brachial artery with a blood pressure cuff, your patient has spasms in the wrist; what is the name of the sign?
Trousseaus sign, indicating hypocalcemia
What is the name of the condition in which the kidneys are unresponsive to parathyroid hormone?
Pseudohypoparathyroidism, a genetic condition
In what manner is pseudohypoparathyroidism inherited?
Autosomal dominant
A patient with hypocalcemia is of short stature and has shortened fourth/fifth digits. What genetic condition should be considered?
Pseudohypoparathyroidism, also known as Albright hereditary osteodystrophy
Would parathyroid hormone be increased or decreased in pseudohypoparathyroidism?
Increased; since the end-organ targets are resistant to the hormone, serum calcium levels will remain low, causing increased secretion of parathyroid hormone.
What is the most common type of pituitary adenoma?
Prolactinoma
A patient complains of amenorrhea, galactorrhea, and low libido. She has been trying to get pregnant for 3 years. What tumor should be considered?
Prolactinoma
What is the medical treatment for a prolactinoma?
Bromocriptine or cabergoline (dopamine agonists)
A 40-year-old patient presents with a headache and cannot see on the temporal sides of his visual fields; what should you look for?
Brain imaging may reveal a pituitary adenoma, which can impinge on the optic chiasm and cause bitemporal hemianopsia
Acromegaly is the result of an excess of what hormone?
Growth hormone
Excess growth hormone in children causes what disease?
Gigantism (increased linear bone growth)
A 50-year-old patient has a large tongue with deep furrows, a deep voice, large hands and feet, and coarse facial features; what is the likely diagnosis?
Acromegaly
What is the treatment of acromegaly?
Pituitary adenoma resection followed by octreotide administration
A patient has an elevated growth hormone level; what are three situations in which this increase in growth hormone production is normal?
Stress, exercise, and hypoglycemia
How is acromegaly diagnosed with lab tests?
Increased insulin-like growth factor-1 or failure to suppress serum growth hormone following oral glucose tolerance test
What causes Sheehans syndrome?
Postpartum infarction of the anterior pituitary gland following severe bleeding during delivery
Why are pregnant women more susceptible to pituitary infarction?
An increased number of lactotrophs without an increase in the blood supply to the anterior pituitary
A postpartum patient has fatigue, anorexia, difficulty lactating, and thin sparse pubic and axillary hair; what is the likely diagnosis?
Postpartum hypopituitarism, or Sheehans syndrome
A patients comes to the emergency room with intense thirst, polyuria, and very dilute urine; what endocrine disorder should be on your differential?
Diabetes insipidus
What is the primary defect in central diabetes insipidus?
Lack of antidiuretic hormone production
What is the primary defect in nephrogenic diabetes?
Lack of renal response to antidiuretic hormone
What are some causes of central diabetes insipidus?
Pituitary tumor, trauma, surgery, histocytosis X
What are some causes of nephrogenic diabetes insipidus?
Hereditary or secondary to hypercalcemia, lithium, demeclocycline
What test is used to diagnose diabetes insipidus?
Water deprivation test (urine osmolality does not increase even with low fluid intake)
How does the urine-specific gravity help diagnose patients with diabetes insipidus?
It is low, often below 1.006 g/mL
How does the serum osmolality help diagnose patients with diabetes insipidus?
It is high, often above 290 mOsm/L
What lifestyle change can be used to manage both central and nephrogenic diabetes insipidus?
Adequate fluid intake
What treatment is specifically used for central diabetes insipidus?
Intranasal desmopressin, an antidiuretic hormone analog
Name three drugs used in the treatment of nephrogenic diabetes insipidus.
Hydrochlorothiazide, indomethacin, and amiloride
How can one distinguish between central and nephrogenic DI?
Administration of desmopressin. In central diabetes insipidus symptoms will improve with exogenous antidiuretic hormone; in nephrogenic diabetes insipidus the kidneys are resistant to antidiuretic hormone and addition of antidiuretic hormone will have no effect
A patient with pneumonia is found to be hyponatremic with high urine osmolarity and low serum osmolarity; what is the likely diagnosis?
Syndrome of inappropriate antidiuretic hormone secretion
In patients with syndrome of inappropriate antidiuretic hormone secretion, there is excessive retention of what substance in the kidneys?
Water
What serum electrolyte abnormality is characteristic of syndrome of inappropriate antidiuretic hormone secretion?
Hyponatraemia
What neurologic condition is associated with severe hyponatremia?
Seizures; hyponatremia must be corrected slowly to avoid central pontine myelinolysis
How do you treat a patient with syndrome of inappropriate antidiuretic hormone secretion?
Water restriction or demeclocycline are the treatments for syndrome of inappropriate antidiuretic hormone secretion
Give an example of an ectopic source of antidiuretic hormone.
Small cell lung cancer (paraneoplastic syndrome)
Name four causes of syndrome of inappropriate antidiuretic hormone secretion.
Ectopic antidiuretic hormone (small cell lung cancer), central nervous system disorders/head trauma, pulmonary diseases, drugs (eg, cyclophosphamide)
List four acute manifestations that can be seen in both type 1 and 2 diabetes mellitus.
Polydipsia, polyuria, polyphagia, and weight loss
________ ________ is an acute manifestation of type 1 diabetes; it is not generally seen in type 2 diabetes.
Diabetic ketoacidosis
_____ _____ is an acute manifestation of type 2 diabetes; it is not generally seen in type 1 diabetes.
Hyperosmolar coma
What three direct effects on cellular metabolism can a diabetic insulin deficiency create?
Decreased glucose uptake, increased protein catabolism, and increased lipolysis
What are the effects of decreased cellular glucose uptake?
Hyperglycemia, glycosuria, osmotic diuresis, and electrolyte depletion
List two direct effects of increased protein catabolism in diabetes.
Increased plasma amino acids and nitrogen loss in urine
In diabetes, what process directly causes ketogenesis and increased plasma free fatty acids?
Increased lipolysis
In diabetic patients, what is the underlying mechanism of dehydration?
Hyperglycemia overwhelms the ability of the renal tubules to reabsorb glucose leading to increased glucose in the urine; this, in turn, leads to osmotic diuresis and dehydration
Why are patients with uncontrolled diabetes often acidemic?
Ketone bodies are acids, and osmotic diuresis causes lactic acidosis by decreased intravascular volume and decreased perfusion of the vital organs
Failure to treat a diabetic patient who is severely volume depleted and has a low serum pH may result in what?
Coma and death
The chronic manifestations of diabetes can be broken down into what two categories on the basis of pathogenesis?
Nonenzymatic glycosylation and osmotic damage
In patients with diabetes, the chronic manifestations of nonenzymatic glycosylation can be broken down into what two categories?
Small-vessel disease and large-vessel disease
You are looking at histological samples from a patient with longstanding diabetes mellitus; what do you expect to see in the small vessels?
A diffuse thickening of basement membrane
List three pathologic processes caused by small-vessel disease in patients with diabetes.
Retinopathy, glaucoma, and nephropathy
What might you see on fundoscopic exam of a patient with longstanding diabetes mellitus?
Hemorrhages, exudates, microaneurysms, and vessel proliferation
List four forms of renal disease that can occur as a result of diabetic nephropathy.
Nodular sclerosis, progressive proteinuria, chronic renal failure, and arteriosclerosis leading to hypertension
Name three specific vascular diseases that can result from large vessel atherosclerosis as a result of diabetes.
Coronary artery disease, peripheral vascular occlusive disease and gangrene, and cerebrovascular disease
In patients with chronic diabetes, osmotic damage can cause what two disease states?
Neuropathy and cataracts
Does diabetic neuropathy affect the motor, sensory, or autonomic nervous systems?
Diabetic neuropathy can affect motor, sensory, and autonomic nerves
What accumulates in the lens to cause cataracts in patients with diabetes mellitus?
Sorbitol, due to high circulating glucose levels
What three glucose-related tests are diagnostically useful for diabetes?
Fasting serum glucose, glucose tolerance, and glycosylated hemoglobin (HbA1c)
Which blood test is used to monitor long-term diabetic control?
Glycosylated hemoglobin (HbA1c)
What is the underlying etiology of type 1 diabetes mellitus?
The viral or immune destruction of -cells
What is the underlying etiology of type 2 diabetes mellitus?
Increased resistance to insulin
Insulin is always necessary for the treatment of which type of diabetes mellitus?
Type 1 diabetes mellitus; it is sometimes necessary to treat type 2 diabetes mellitus
What age group is most commonly affected by type 1 diabetes mellitus?
Individuals who are less than 30 years old
What age group is most commonly affected by type 2 diabetes mellitus?
Individuals who are greater than 40 years old
Which form of diabetes mellitus has an association with obesity?
Type 2 diabetes is associated with obesity
Whereas diabetes mellitus always has a polygenic inheritance, familial history is a strong predictor in type _____ and weak in type _____ diabetes.
Type 2; type 1
Which human leukocyte antigen types are associated with diabetes mellitus?
Human leukocyte antigens DR3 and DR4 are associated with type 1 diabetes mellitus; there is no association between human leukocyte antigen and type 2 diabetes mellitus
Glucose intolerance is severe in patients with type _____ diabetes mellitus but is mild to moderate in patients with type _____ diabetes mellitus
Type 1; type 2
Ketoacidosis is common in patients with what form of diabetes mellitus?
Type 1; ketoacidosis is rare in type 2 diabetes mellitus
What happens to the number of beta cells in the islets of patients with type 1 diabetes mellitus?
They are decreased
What happens to the number of β-cells in the islets of patients with type 2 diabetes mellitus?
Their numbers are variable; amyloidosis is seen
What happens to the serum insulin level in patients with type 1 diabetes mellitus?
The serum insulin level is decreased
What happens to the serum insulin level in patients with type 2 diabetes mellitus?
The serum insulin level is elevated initially and is variable during disease progression, often low late in the course
The classic symptoms of polyuria, polydipsia, thirst, and weight loss are common with what form of diabetes mellitus?
Type 1
What is the pathogenesis of diabetic ketoacidosis?
Diabetic ketoacidosis is usually caused by an increase in insulin requirements as a result of an increase in stress (eg, infection)
A diabetic patient has high circulating levels of ketone bodies and is determined to be in diabetic ketoacidosis; how were the ketone bodies formed?
Increased fat breakdown and free fatty acids increase the ketogenesis pathway, converting free fatty acids into ketone bodies
A diabetic patient presents with Kussmauls respirations, nausea and vomiting, abdominal pain, and delirium; what is the diagnosis and volume status?
This patient is likely in diabetic ketoacidosis and is dehydrated
Describe Kussmauls respirations.
Deep respirations and air-hunger characteristic of diabetic ketoacidosis
The fruity breath sometimes encountered in patients with diabetic ketoacidosis is the result of what?
Exhaled acetone
You suspect diabetic ketoacidosis in an emergency room patient; what would the glucose, pH, and bicarbonate levels be?
Increased glucose, low pH (increased H+levels), and decreased bicarbonate
What acid-base disturbance is found in patients with diabetic ketoacidosis?
Anion gap metabolic acidosis
The chemistry panel on a patient with diabetic ketoacidosis shows a high potassium level. Why?
Although the extracellular potassium is elevated, the intracellular and total potassium levels are depleted because of the body’s excess of hydrogen ions
What causes intracellular potassium depletion in diabetic ketoacidosis?
Increased hydrogen ions and decreased insulin cause a shift of potassium out of the cells
Name an infectious complication of diabetic ketoacidosis that can prove fatal if not treated
Mucormycosis, or Rhizopus, infection
Give an example of a common neurologic complication of diabetic ketoacidosis.
Cerebral oedema
Give two examples of common cardiovascular complications of diabetic ketoacidosis.
Arrhythmias and heart failure
List the three core components of the treatment of diabetic ketoacidosis.
Fluids, insulin, and potassium
When would it make sense to give glucose to patients with diabetic ketoacidosis?
When they are becoming hypoglycemic from continuing insulin treatment (so that they can continue to be given insulin)
What are the two types of ketone bodies made during diabetic ketoacidosis?
β-hydroxybutyrate, acetoacetate
What causes carcinoid syndrome?
Neuroendocrine tumors that secrete high levels of serotonin
A patient with a known carcinoid tumor in the small intestine presents with wheezing and flushing; do you expect liver metastases on imaging? Why or why not?
Carcinoid syndrome occurs only with metastasis; this patient likely has liver metastases because serotonin secreted by tumors that have not metastasized undergo first-pass metabolism in the liver
A patient has diarrhea, flushing, and asthmatic wheezing, and you suspect carcinoid syndrome; what might the cardiac exam reveal?
Tricuspid regurgitation due to right-sided valvular disease
What is the most common tumor of the appendix?
Carcinoid tumor
What urinary finding might assist in the diagnosis of carcinoid syndrome?
An elevated urine 5-hydroxyindoleacetic acid
Carcinoid syndrome can be treated with what drug?
Octreotide, a somatostatin analogue
Zollinger-Ellison syndrome is the result of a tumor that secretes what substance?
Gastrin
Gastrinomas causing Zollinger-Ellison syndrome are usually found in which two sites?
The pancreas and the duodenum
A patient has failed several proton pump inhibitors and is noted to have many ulcers on endoscopy, including several in the jejunum; what malignancy should you consider?
Zollinger-Ellison syndrome caused by a gastrin-secreting tumor
Zollinger-Ellison syndrome may be associated with what genetic syndrome?
Multiple endocrine neoplasia type I
What three tumors are associated with multiple endocrine neoplasia 1, or Wermers syndrome?
Multiple endocrine neoplasia 1 = 3 Ps: Pancreas, Pituitary, and Parathyroid
Name four pancreatic endocrine tumors seen in multiple endocrine neoplasia 1.
Zollinger-Ellison syndrome (gastrinomas), insulinomas, vasoactive intestinal peptide tumors, and rarely glucagonomas
Which of the multiple endocrine neoplasia syndromes commonly presents as nephrolithiasis and ulcer disease?
Multiple endocrine neoplasia 1, or Wermers syndrome; elevated parathyroid hormone can cause renal stones, and ulcers may be associated with a gastrinoma
What three tumors are associated with multiple endocrine neoplasia 2A, or Sipples syndrome?
Medullary thyroid carcinoma, Pheochromocytoma, Parathyroid tumors (remember: multiple endocrine neoplasia 2A = 2 Ps)
An elevation in which serum marker may indicate medullary thyroid cancer?
Calcitonin
What three tumors are associated with multiple endocrine neoplasia 2B?
Medullary thyroid carcinoma, Pheochromocytoma, oral or intestinal ganglioneuromas (remember: multiple endocrine neoplasia 2B = 1 P)
Which multiple endocrine neoplasia syndrome is associated with a marfanoid body habitus?
Multiple endocrine neoplasia 2B
What is the likelihood that a child of a parent who has any of the multiple endocrine neoplasia syndromes will also have the disease?
50%; all multiple endocrine neoplasia syndromes have autosomal-dominant inheritance
What gene mutation is seen in multiple endocrine neoplasia 2A and multiple endocrine neoplasia 2B?
A mutation in the ret gene
