DIT review - Endocrinology 1

Question 1

Which hormones use the cAMP pathway (Gs and Gi)

Answer 1

• Most hormones of anterior pituitary
• FSH, LH, ACTH, TSH, hCG, MSH, GHRH, CRH, PTH, calcitonin, glucagon, V2 vasopressin receptor

Question 2

Which hormones use IP3 pathway (Gq)

Answer 2

• Hormones of posterior pituitary minus V2
• GnRH, TRH, oxytocin, V1 vasopressin receptor, H1 histamine receptor, angiotensin II, gastrin

Question 3

Which hormones use cGMP pathway

Answer 3

• Vasodilators
• Nitric oxide (NO), Atrial natriuretic peptide (ANP)

Question 4

Which hormones use steroid receptors

Answer 4

Estrogens, progesterone, testosterone, glucocorticoids, aldosterone, thyroid hormone (T3/T4), vitamin D

Question 5

Which hormones use tyrosine kinase receptors

Answer 5

• Insulin, insulin-like growth factor (IGF-1), platelet derived growth factor (PDGF), fibroblast growth factor (FGF)

Question 6

Which hormones use nonreceptor tyrosine kinase (e.g. JAK/STAT)

Answer 6

• Prolactin, cytokines (IL-2, IL-6, IFN), GH, G-CSF, Erythropoietin, Thrombopoeitin

Question 7

Causes of hyperprolactinemia

Answer 7

• Pregnancy/nipple stimulation
• Stress
• Prolactinoma
• Dopamine antagonists

Question 8

Presentation of hyperprolactinemia

Answer 8

• Due to prolactin’s inhibitory effects on GnRh
• Premenopausal women:
  
  • Hypogonadism, infertility, oligo/amenorrhea, galactorrhea (rare)
• Postmenopausal women:
  
  • Asymptomatic
• Males:
  
  • Hypogonadism, decreased libido, impotence, infertility, gynecomastia, galactorrhea (rare)

Question 9

Effects of growth hormone on insuline

Answer 9

• Increases insulin resistance (diabetogenic)

Question 10

How do you diagnose acromegaly?

Answer 10

Increased serum IGF-1

Growth hormone is secreted in a pulsatile fashion and levels fluctuate throughout the day by IGF-1 levels are generally consistent

Confirmatory test - failure to suppress serum GH following oral glucose tolerance test

Question 11

What disorder is characterized by failure to breast-feed, absent menstruation, and cold intolerance after giving birth

Answer 11

Sheehan Syndrome - ischemic infarct of pituitary following postpartum bleeding

Question 12

Draw out the steroid synthesis pathway, including enzymes

Answer 12

Question 13

Describe the main features of each of the congenital adrenal hyperplasia enzyme deficiencies (21 a-hydroxylase, 17 a-hydroxylase, 11 b-hydroxylase)

Answer 13

• HINTS:
  
  • If there is a 1 in the first digit of deficient enzyme (11 or 17) – will be HTN
  • If there is a 1 in the second digit of deficient enzyme (11 or 21) – will be masculinization
  • K+ does the opposite of whatever Na+ does
• 21 a-hydroxylase
  
  • Hypotension
  • Hyperkalemia
  • Masculinization
• 11 b-hydroxylase
  
  • Hypertension
  • Hypokalemia
  • Masculinization
• 17 a-hydroxylase
  
  • Hypertension
  • Hypokalemia
  • Ambigious genitalia in XY
  • Lack of secondary sexual development in XX

Question 14

What are the actions/effects of cortisol

Answer 14

• Increased BP
  
  • Upregulates a1 receptors in arterioles, thus increasing sensitivity to NE and Epi
• Increases insulin resistance (diabetogenic)
• Increases gluconeogenesis, lipolysis, proteolysis
• Decreases fibroblast activity (skin thinning and striae)
• Decreases inflammatory and immune response
  
  • Will initially see neutrophilia due to decreased WBC adhesion
• Decreases bone formation

Question 15

Causes of Cushing syndrome

Answer 15

• Exogenous corticosteroids (most common cause)
• ACTH-secreting pituitary adenoma (Cushing disease)
• Paraneoplastic ACTH secretion (e.g. small cell lung cancer)

Question 16

Describe how a Dexamethasone suppression test helps to differentiate between different causes of Cushing syndrome

Answer 16

• First give low-dose dexamethasone (synthetic glucocorticoid)
• Measure ACTH:
  
  • If low, suspect adrenal tumor or exogenous glucocorticoids
  • If high, suspect Cushing disease (ACTH-pituitary adenoma) or ectopic ACTH secreting tumor
    
    • Give high dose Dexamethasone:
      
      • Cortisol levels will decrease if Cushing Disease
      • Cortisol levels will remain elevated if ectopic tumor

Question 17

What is the effect of glucocorticoids on bones?

Answer 17

Osteoporosis

Chronic glucocorticoid use should be supplemented with calcium and/or vitamin D

Question 18

What is the most common cause of primary adrenal insufficiency

Answer 18

Aka Addison disease

Most commonly due to autoimmune destruction of adrenal gland

Question 19

Presentation of primary adrenal insufficiency

Answer 19

o Lack of cortisol - Weakness, fatigue, weight loss

o Lack of aldosterone - hypotension, hyponatremia, hyperkalemia

o Increased ACTH - skin hyperpigmentation (due to POMC)

Question 20

Cause of acute primary adrenal insufficiency

Answer 20

Waterhouse-Friederichsen syndrome

Acute primary adrenal insufficiency due to adrenal hemorrhage associated with septicemia (usually Neisseria meningitides), DIC, endotoxic shock

Question 21

What is the presentation of secondary adrenal insufficiency

Answer 21

o Lack of cortisol due to decreased ACTH à weakness, fatigue, weight loss

o Aldosterone synthesis is preserved (controlled by RAAS) à no hypotension or hyperkalemia

o ACTH low à no hyperpigmentation

Question 22

What is the most common cause of tertiary adrenal insufficiency

Answer 22

Usually caused by abrupt withdrawal of exogenous steroids after chronic usage

Question 23

What is Conn syndrome

Answer 23

Primary hyperaldosteronism due to adrenal adenoma

Question 24

What is the classic presentation of hyperaldosteronism

Answer 24

· Hypertension

· Hypokalemia

· Metabolic alkalosis

Question 25

What is the cause of metabolic alkalosis in hyperaldosteronism

Answer 25

o Aldosterone causes increased H+ urinary loss

o Decreased K+ causes cells to push out K+ in exchange for taking up H+

Question 26

What is the basic premise behind secondary hyperaldosteronism

Answer 26

Occurs when kidneys perceive low volume and activate RAAS

o Will see elevated renin

Question 27

Causes of secondary hyperaldosteronism

Answer 27

o Renal artery stenosis

o Congestive heart failure

o Low protein states (decreased osmotic pressure leads to low blood volume) - E.g. Cirrhosis or nephrotic syndrome

Question 28

What is the oncogene associated with neuroblastoma

Answer 28

· Overexpression of N-myc oncogene

Question 29

What are the positive serum markers in neuroblastoma

Answer 29

· Bombesin and NSE (+)

Question 30

What is a neuroblastoma

Answer 30

Tumor of the adrenal medulla (usually in children)

Question 31

What is seen on histology of neuroblastoma

Answer 31

· Homer Wright rosettes (also seen in medulloblastoma)

Question 32

What is the rule of 10’s (or 90’s) associated with pheochromocytoma

Answer 32

o 90% benign

o 90% unilateral

o 90% adrenal medulla (some can be extra-adrenal)

o 90% do not calcify

o 90% adults

Question 33

Treatment of pheochromocytoma

Answer 33

o Surgical resection

o Alpha blockers (phenoxybenzamine)

o Can also add on beta-blockers

§ Do not give beta-blockers first – will lead to unopposed alpha vasoconstriction and hypertensive crisis

Question 34

MEN 1

Answer 34

Mutation of MEN 1

• Pituitary tumors (prolactin or GH)
• Pancreatic endocrine tumors (Zollinger-Ellison syndrome, insulinomas, VIPomas, glucagonomas)
• Parathyroid adenomas

Question 35

MEN 2A

Answer 35

Mutation of RET gene

• Medullary thyroid carcinoma (neoplasm of parafollicular C cells which secrete calcitonin)
• Pheochromocytoma
• Parathyroid hyperplasia

Question 36

MEN 2B

Answer 36

Mutation of RET gene

• Medullary thyroid carcinoma
• Pheochromocytoma
• Mucosal neuromas (oral/intestinal ganglioneuromatosis)