Endocrine Pathology

Front 1

What HLAs is Type I DM associated with?

Back 1

HLA-DR3 and HLA-DR4

Front 2

Metabolic ketoacidosis

Back 2

• Hyperglycemia (>300mg/dL), anion gap metabolic acidosis, and hyperkalemia
• Presents with Kussmaul respirations, dehydration, nausea, vomiting, mental status changes, and fruity smelling breath (due to acetone)

Front 3

How do insulin levels differ in the disease course of Type II DM?

Back 3

Insulin levels are increased early in disease, but later, insult in deficiency develops due to beta cell exhaustion; histology reveals amyloid deposition in the islets

Front 4

Diagnosis of Type II DM

Back 4

• Random glc > 200 mg/mL
• Fasting glc > 126 mg/dL
• Glc tolerance test with serum vlc level > 200 mg/dL two hours after glc loading

Front 5

Long-term consequences of diabetes

Back 5

• Nonenzymatic glycosylation (NEG) of vascular basement membranes leads to atherosclerosis (CVD, peripheral vascular disease, kidney damage)
• Osmotic damage (peripheral neuropathy, impotence, blindness, and cataracts)

Front 6

How does diabetes result in kidney damage?

Back 6

• Neg of small vessels leads to hyaline arteriolosclerosis
• Involvement of renal arterioles leads to glomerulosclerosis, resulting in small, scarred kidneys with a granular surface
• Preferential involvemne tof effereent arterioles leads to glomerular hyper filtration injury with microalbuminuria that eventually progresses to nephrotic syndrome; characterized by Kimmelstiel-Wilson nodules in glomeruli

Front 7

How does kidney damage result in blindness?

Back 7

• Glc freely enters into Schwann cells (which myelinate peripheral nerves), pericytes of retinal blood vessels, and the lens
• Aldose reductase converts glc to sorbitol, resulting in osmotic damage

Front 8

Pancreatic endocrine neoplasms

Back 8

• Tumors of islet cells; account for <5% of pancreatic neoplasms
• Often a component of MEN 1 along with parathyroid hyperplasia and pituitary adenomas
• Can be insulinomas, gastrinomas, somatostatinomas, VIPomas

Front 9

Insulinomas

Back 9

Present as episodic hypoglycemia with mental status changes that are relieved by administration of glc; diagnosed by decreased serum glc levels, increased insulin, and increased C-peptide

Front 10

Gastrinomas

Back 10

Present as treatment-resistant peptic ulcers (Zollinger-Ellison syndrome); ulcers may be multiple and can extend into the jejunum

Front 11

Somatostatinomas

Back 11

Present as achlorhydria (due to inhibition of gastrin) and cholelithiasis with steatorrhea (due to inhibition of cholecystokinin)

Front 12

VIPomas

Back 12

secrete excessive vasoactive intestinal peptide leading to watery diarrhea, hypokalemia, and achlorhydria

Front 13

How does hyperaldosteronism present?

Back 13

As HTN, hypokalemia, and metabolic alkalosis; edema is often absent due to aldosterone escape

Front 14

Primary Hyperaldosteronism

Back 14

• High aldosterone and low renin (increased renal perfusion pressure down regulates renin)
• First-line treatment is mineralocorticoid receptor antagonist (e.g. spironolactone or eplerenone); adenomas are usually surgically resected

Front 15

Causes of primary hyperaldosteronism

Back 15

Bilateral adrenal hyperplasia is most common; adrenal adenoma (Conn syndrome), and andrenal carcinoma are less common causes

Front 16

Secondary hyperaldosteronism

Back 16

• Seen with activation of RAAS system
• High aldosterone and high renin

Front 17

Familial hyperaldosteronism

Back 17

Can rarely be due to glucocorticoid-remediable aldosteronism (GRA)

• aberrant expression (AD) of aldosterone synthase in the fasciculata
• presents in children as TNA, hypokalemia, high aldosterone, and low renin
• responds to dexamethasone, confirmed with genetic testing

Front 18

Liddle syndrome

Back 18

• Mimics hyperaldosteronism
• Decreased degradation of sodium channels (AD) in collecting tubules
• Classically presents as HTN, hypokalemia, and metabolic alkalosis in a young patient
• Low aldosterone and low renin
• Treatment is potassium-sparing diuretics (e.g. amiloride or triamterene), which block tubular sodium channels; spironolactone is not effective

Front 19

Clinical features of Cushing's syndrome (hypercortisolism)

Back 19

• Muscle weakness with thin extremities
• Moon facies, buffalo hump, truncal oesity
• Abdominal striae (due to impaired collagen synthethis)
• HTN with hypokalemia and metabolic acidosis
• Osteoporosis
• Immune suppression

Front 20

Diagnosing Cushing's syndrome

Back 20

24 hr urine cortisol level (increased), late night salivary cortisol level (increased), and low-dose dexamethasone suppression test

Front 21

When is used to suppress ACTH production?

Back 21

• Used when ACTH-dependent Cushing's is detected
• High-dose dexamethasone suppresses ACTH production by pituitary adenomas; it will not suppress ectopic ACTH production

Front 22

Most common cause of acute adrenal insufficiency

Back 22

Arises secondary to abrupt withdrawal of glucocorticoids (presents as weakness and hypotension)

Front 23

Waterhouse-Friderichsen syndrome

Back 23

• Classic cause of acute adrenal insufficiency
• Characterized by hemorrhagic necrosis of the adrenal glands, classically due to DIC in young children with Neisseria meningitidis infection
• Lack of cortisol exacerbates hypotension, often leading to death

Front 24

Addison disease

Back 24

• Chronic insufficiency due to progressive destruction of adrenal glands (autoimmune, TV, or metastatic carcinoma)
• Hypotension, hyponatremia, hypovolemia, hyperkalemia, metabolic acidosis, weakness, hyperpigmentation (very high ACTH stimulates melanocytes), vomiting, diarrhea

Front 25

What helps distinguish primary from secondary adrenal insufficiency?

Back 25

Hyperpigmentation and hyperkalemia

Front 26

Pheochromocytoma

Back 26

• Tumor of chromatin cells leads to increased serum catecholamines
• Episodic HTN, headache, palpitations, tachycardia, sweating
• Rule of 10s: 10% bilateral, 10% familial, 10% malignant, 10% located outside of adrenal medulla (e.g. bladder wall or organ of Zuckerkandl at IMA root)

Front 27

How is pheochromocytoma diagnosed?

Back 27

By increased serum metanephrines and increased 24 hr urine metanephrines and vanillylmandelic acid

Front 28

How is pheochromocytoma treated?

Back 28

Surgical excision

• Catecholamines may leak into bloodstream upon manipulation of tumor
• Phenobenzamine (irreversible alpha blocker) is adminstered perioperatively to prevent a hypertensive crisis

Front 29

What is pheochromocytoma associated with?

Back 29

MEN 2A and 2B, von Hippel-Lindau disease, and neurofibromatosis type 1

Front 30

Most common iatrogenic cause of Cushing syndrome

Back 30

Exogenous glucocorticoids:

• High cortisol
• Low ACTH
• Bilateral adrenal atrophy

Front 31

Cushing disease

Back 31

• ACTH-secreting pituitary adenoma
• High cortisol
• No suppression by Low-Dose Dexamethasone
• High ACTH; androgen excess may be present
• Suppression by high-dose dexamethasone
• Bilateral adrenal hyperplasia/pituitary adenoma on imaging

Front 32

Findings when cause of Cushing syndrome is ectopic ACTH secretion

Back 32

• High cortisol
• No suppression by Low-Dose Dexamethasone
• Very high ACTH; androgen excess and hyper pigmentation may be present
• No suppression by high-dose dexamethasone
• Bilateral adrenal hyperplasia; ectopic source of ACTH (e.g. small cell carcinoma or carcinoid) on imaging

Front 33

Findings when cause of Cushing syndrome is primary adrenal adenoma, hyperplasia, or carcinoma

Back 33

• High cortisol
• No suppression by Low-Dose Dexamethasone
• Low ACTH
• Adenoma/carcinoma with contralateral atrophy or bilateral nodular hyperplasia on imaging

Front 34

Congenital adrenal hyperplasia

Back 34

• Characterized by enzymatic defects in cortisol production
• High ACTH (due to decreased negative feedback) leads to bilateral adrenal hyperplasia
• Mineralocorticoids and androgens may be increased or decreased depending on the enzyme defect

Front 35

Most common cause of congenital adrenal hyperplasia

Back 35

• 21-hydroxylase deficiency (90%)
• Aldosterone and cortisol are decreased; steroiogenesis shunted towards androgens

Front 36

Classic form of 21-hydroxylase deficiency

Back 36

Presents in neonates as hyponatremia, hyperkalemia, and hypovolemia with life-threatening hypotension (due to salt-wasting); females have clitoral enlargement (genital ambiguity)

Front 37

Nonclassic form of 21-hydroxylase deficiency

Back 37

Presents later in life with androgen excess leading to precocious puberty (males) or hirsutism with menstrual irregularities (females)

Front 38

11-hydroxylase deficiency

Back 38

• Biochemically similar to 21-hydroxylase deficiency, but weak mineralocorticoids are increased
• Leads to HTN (sodium retention) with mild hypokalemia)
• Renin and aldosterone are low

Front 39

17-hydroxylase deficiency

Back 39

• Leads to decreased cortisol and androgens
• Weak mineralocorticoids are increased leading to HTN and mild hypokalemia; renin and aldosterone are low
• Decreased androgens (adrenal and gonads) lead to primary amenorrhea and lack of pubic hair in females or pseudohermaphroditism in males

Front 40

Screening for CAH

Back 40

• Involves serum 17-hydroxyprogesterone levels
• Increased in 11- and 21-hydroxylase deficiency
• Decreased in 17-hydroxylase deficiency

Front 41

Treatment for CAH

Back 41

Glucocorticoids; mineralocorticoids (21-hydroxylase deficiency) or sex steroids (17-hydroxylase deficiency) may also be needed