Endocrine Flashcards
Derivations of the anterior pituitary and posterior pituitary:
Anterior = oral ectoderm (Rathke pouch)
Posterior = neuroectoderm
Where is the most common site of ectopic thyroid?
Lingual thyroid- due to failed migration
Child presents with a midline anterior neck mass that moves when he swallows or sticks out his tongue
thyroglossal duct cyst
Origin of parafollicular cells (C cells) of the thyroid
neural crest (remainder of thyroid tissue is derived from endoderm)
How to distinguish between central diabetes insipidus and nephrogenic diabetes insipidus
water deprivation test
o Central DI- urine osmolality will inc after administration of ADH
o Nephrogenic DI- urine osmolality doesn’t change after administration of ADH
Adrenal gland derivations
Cortex = mesoderm
Medulla = neural crest cells
Adrenal cortex layers and functions
GFR corresponds with Salt (Na), Sugar (glucocorticoids), and Sex (Androgens) – the deeper you go the sweeter it gets
Zona Gomerulosa
Regulated by: renin angiotensin system
Secretes: aldosterone
Zona Fasciculata
Regulated by: ACTH, CRH
Secretes: Cortisol
Zona Reticularis
Regulated by: ACTH, CRH
Secretes: sex hormones (androgens)
Medulla (Chromaffin Cells)
Regulated by: Preganglionic sympathetics (ACh)
Secretes: catecholamines (epinephrine, norepinephrine)
What amino acid are the thyroid hormones derived from?
Tyrosine
Wolff Chaikoff effect
excess iodine temporarily inhibits thyroid peroxidase and causes dec iodine organification → dec T3/T4 production
How does a dietary deficiency of iodine cause goiter?
The gland enlarges in an attempt to access more blood to inc iodine uptake
Functions of T3
Brain maturation
Bone growth
B adrenergic effects (Inc CO, HR, SV, and contractility)
Basal metabolic rate increases (Via inc Na/K ATPase activity)
Inc glycogenolysis, gluconeogenesis, and lipolysis
Graves Disease
Hyperthyroidism – autoantibody that stimulates TSH receptor – Thyroid Stimulating Immunoglobulin (TSI) – and causes increased synthesis and release of thyroid hormone
(Type 2 hypersensitivity)
Goiter, exopthalmos, and pretibial myxedema
Graves Disease
o Goiter: constant TSH stimulation causes thyroid hyperplasia and hypertrophy
o Exopthalmos and pretibial myxedema fibroblasts behind the orbit and overlying the shin express the TSH receptor → inflammation due to infiltration of T cells that release cytokines and inc fibroblast secretion of glycosaminoglycan
Baby presents with developmental delay, a umbilical hernia, and a protruding tongue. What do you suspect?
Congenital hypothyroidism (cretinism)
pot bellied, pale, puffy faced, protruding umbilicus (hernia), protuberant tongue, and poor brain development
What drugs cause hypothyroidism?
Lithium and Amiodarone
Hashimoto Thyroiditis
autoimmune destruction of the thyroid gland – due to T cell sensitization to thyroid antigen and antibodies against thyroglobulin and thyroid peroxidase
What HLA subtype is Hashimoto thyroiditis associated with? What are patients with Hashimoto thyroiditis at inc risk of?
What other disease is associated with this HLA type?
HLA DR5 (Pernicious anemia)
Inc risk of non Hodgkin lymphoma
Patient presents with jaw pain, tender thyroid, and inc ESR after a recent viral infection
Subacute Granulomatous (De Quervain) Thyroiditis
Granulomatous thyroiditis- may be hyperthyroid early on and then progresses to hypothyroid
Patient presents with signs of hypothyroidism and a rock hard thyroid
Riedel Fibrosing Thyroiditis (hypothyroidism)
Chronic inflammation with extensive fibrosis of the thyroid gland
Thyroid histo: branching papillary structures with interspersed calcified bodies
Papillary thyroid cancer
Thyroid histo: tall/crowded follicular cells with scalloped colloid
Graves disease
Thyroid histo: Extensive stromal fibrosis that extends beyond the capsule
Riedel thyroiditis
Thyroid histo: Mixed cellular infiltration with occasional multinucleated giant cells
Subacute granulomatous thyroiditis (de Quervain)
Thyroid histo: Mononuclear parenchymal infiltration with well-developed germinal centers
Hashimoto thyroiditis
Thyroid histo: Empty appearing nuclei with central clearing (Orphan Annie eyes), psammoma bodies and nuclear grooves (coffee beans):
Papillary carcinoma
Thyroid histo: sheets of cells in an amyloid stroma
medullary carcinoma (from parafollicular “C cells” – produces calcitonin
Hypothyroid myopathy
Dec tendon refelxes and myoedema
Patient presents with decreased lateral vision. If you suspect a brain lesion, where would it be?
The patient appears to have bitemporal hemianopia, which is characteristic of a pituitary adenoma
Patient will likely have inc prolactin levels, as prolactinomas are most common
Which MEN is associated with Pheochromocytomas, Medullary thyroid carcinoma, and parathryoid hyperplasia?
MEN2A
(Mutation in RET gene)
2 P’s: parathyroid and pheochromocytoma
Which MEN is associated with pheochromocytomas, medullary thyroid carcinoma, mucosal neuromas, and marfanoid habitus?
MEN2B
(Mutation in RET gene)
1 P: pheochromocytoma
Which MEN is associated with pituitary tumors, pancreatic endocrine tumors, and parathyroid adenomas?
MEN1
(Mutation in MEN1 tumor suppressor gene)
3 P’s: parathyroid, pancreas, and pituitary
Zollinger Ellison syndrome is associated with which MEN?
MEN1
as are insulinomas and VIPomas
Pheochromocytoma is associated with which other disorders?
MEN2A/MEN2B, Von Hippel Lindau, and Neurofibromatosis type 1
What cells do pheochromocytomas arise from? What do they secrete?
Arise from chromaffin cells of the adrenal medulla – secrete catecholamines (epinephrine, norepinephrine, and dopamine)
Cortisol functions
Catabolic BIG FIB Blood pressure inc Insulin resistance Gluconeogenesis, lipolysis, and proteolysis inc Fibroblast activity dec Inflammatory/immunosuppression Bone formation decrease
What is the most common cause of Cushings syndrome?
Exogenous corticosteroid use
causes dec ACTH and bilateral adrenal atrophy
Patient presents with HTN, weight gain, moon facies, abdominal striae, truncal obesity, osteoporosis, hyperglycmeia
Cushing Syndrome
- HTN: cortisol increases BP
- Striae: fibroblast inhbition
- Osteoporosis: dec in bone formation
Cushing Disease vs Cushing Syndrome
Disease – pituitary hypersecretion of ACTH usually from a pituitary adenoma
high ACTH –> high cortisol
Syndrome (many causes): low ACTH –> high cortisol
Cushing Disease
Pituitary hypersecretion of ACTH usually from a pituitary adenoma
Excess ACTH leads to adrenal cortical hyperplasia and excess cortisol secretion
How can you distinguish between Cushing syndrome caused by pituitary secretion of ACTH vs ectopic ACTH secretion
Both will have inc ACTH
Use dexamethasone suppression test
Pituitary secretion: ACTH will dec
Ectopic: ACTH will not dec
17a hydroxylase deficiency
Inc mineralocorticoid (aldosterone) production, dec cortisol, and dec sex hormones
Inc BP and dec serum K+
Ambiguous genitalia, undescended testes, lack of secondary sex characterisitcs
21 hydroxylase deficiency
Inc sex hormones, dec aldosterone and cortisol
Dec BP, inc serum K+
Salt wasting in infants
Precocious puberty in children
11B hydroxylase deficiency
Dec aldosterone, inc 11-deoxycortisone (causes inc BP), dec cortisol, inc sex hormones
Inc BP, dec serum K, dec renin, virilization
Dec renin
Inc Aldosterone
Primary hyperaldosteronism: the adrenal is making a lot of aldosterone and renin system shuts off
Inc renin
Inc aldosterone
Secondary hyperaldosteronism: abnormal activation of the renin-angiotensin system
ex. juxtaglomerular cell tumor
Waterhouse-Friedrichsen syndrome
Acute adrenal insufficiency due to bilateral adrenal hemorrhage associated with septicemia (N meningitidis)
Addison disease
Chronic destruction of the adrenal cortex due to autoimmune destruction or TB infection
How does diabetes lead to ketoacidosis?
Usually only in T1DM
Dec insulin in the blood causes lipolysis to proceed unregulated. Inc FFA are converted to acetyl-CoA and are used for ketogenesis –> ketone body formation!!
C-peptide
Secreted from secretory granules with endogenous insulin
Do not see C peptide with exogenous peptide administration
Insulin: catabolism or anabolism?
Anabolism!!
Promotes the storage of protein, glucose, and lipids
Prevents glycogenolysis by activation of protein phosphatase
Prevents gluconeogenesis by increasing F26BP
What type of fuel do RBCs utilize and why?
ONLY glucose. They lack mitochrondria so they can’t metabolize FFA or ketones
What enzyme does insulin activate, which promotes the storage of glucose as glycogen?
Protein phosphatase
Autonomic nervous system effects on insulin
Sympathetics (epinephrine) prevents insulin release: because during fight or flight, the body wants to mobilize glucose
Parasympathetics (ACh) causes insulin release: during rest or digest, the body wants to store glucose as glycogen for future use
What is the major regulator of insulin release?
Glucose - enters pancreatic B cells via GLUT2 and promotes insulin secretion
Insulin receptor
Tyrosine kinase (MAP Kinase)
Which transporters are insulin dependent and where are they located?
GLUT4, on adipose and skeletal muscle tissue
Steps of insulin release
- glucose enters pancreatic B cells via GLUT2
- Glucose undergoes glycolysis to produce ATP
- ATP binds to K+ channels and shuts them
- K+ cannot leave the cell, causing cell depolarization
- Voltage gated Ca2+ channels open and Ca2+ enters the cells
- Inc Ca2+ in the cell stimulates the exocytosis of insulin granules
Glucagon action: catabolism or anabolism?
Catabolism
Promotes glycogenolysis, gluconeogenesis, lipolysis, ketogenesis
Histology of T1DM vs T2DM
Type 1: leukocytic infiltrate (autoimmune destruction)
Type 2: amyloid polypeptide deposition
14 year old boy presents with delayed puberty and complaints of anosmia
Kallmann syndrome
Defective migration of GnRH cells and formation of the olfactory bulb – leads to dec GnRH synthesis (synthesis)
Dec GnRH, LH, FSH, and testosterone
What cancer can cause SIADH
Small cell lung cancer
Findings on SIADH
Euvolemic hyponatremia: no edema or JVD, due to compensatory suppression of the renin-angiotensin system (water is absorbed, inc extracellular volume, dec renin ang system, salt wasting)
Urine osmolality>Serum osmolality
Roles of prolactin
Stimulates milk production and decreases GnRH secretion
Effects of dopamine on prolactin
Dopamine inhibits secretion of prolactin – dopamine antagonists cause prolactin levels to rise –> galactorrhea
What do you use to treat prolactinomas?
Dopamine agonists (Bromocriptine)
Corticosteroid effects on WBCs
Neutrophilia – induces demargination of neutrophils previously attached to the vessel wall
Neutrophil recruitment to fight infection in tissues is dcreased
What is the primary site of PTH action?
The kidney -
- inc calcium reabsorption in the DCT
- dec phosphate reabsorption in the PCT
- inc activation of vitamin D
PTH effects on bone
Stimulates Osteoblasts to secrete RANKL – which increases the number and function of osteoclasts
Bone resorption and inc Ca release
PTHrP
Actions?
When do you see it?
PTH related peptide – Functions like PTH
Commonly increased in malignancies (squamous cell carcinoma of the lung, renal cell carcinoma)
What lung cancer secretes PTHrP?
Squamous cell carcinoma of the lung
Vitamin D functions
Inc Ca and phosphate absorption in the intestines
What activates Vitamin D? Where does this occur?
Vitamin D is activated in the kidney by 1a hydroxylase to 1,25 OH2 D3
24,25 OH2 D3 is the inactive form
Activated by inc PTH or by dec phosphate
What pathology can increase vitamin D and lead to hypercalcemia?
Granulomatous disease
Macrophages cause inc activation of vitamin D
Signs of hypocalcemia vs hypercalcemia
Hypocalcemia:
- neuromuscular excitability
- muscle cramps, perioral paresthesias, hypotension, chvostek sign, trousseau sign
(common cause = parathyroid damage in thyroid surgery)
Hypercalcemia:
- constipation, polyuria/polydipsia, muscle weakness
(thiazides, bones mets, multivitamin overdose)
Hypercalcemia is seen in which MEN syndrome(s)?
MEN1
MEN2A
Due to parathyroid pathology
POMC gives rise to what?
ACTH
Beta endorphins (opioids)
MSH
Patient presents complaining of recent weight gain, inc bruising, and hyperpigmentation of the skin. He has epigastric abdominal pain that is relieved by over the counter antacids. He has elevated BP and a CXR shows an irregular mass in the right lung field. What is the mass and what is likely responsible for his symptoms?
Small cell carcinoma of the lung that is secreting ACTH
excess ACTH leads to adrenal cortical hyperplasia and excess glucocorticoid secretion
o Will see hyperpigmentation of the skin because ACTH directly stimulates melanotropin receptors due to significant sequence homology with a-MSH
Laryngeal nerves
o Superior laryngeal nerve (branch of CNX) – innervates the cricothyroid muscle – 4th branchial arch
o Recurrent laryngeal nerve (branch of CNX) – innervates the rest of the laryngeal muscles – 6th branchial arch (can be damaged during thyroid surgery)
Why is there pigmentation in primary adrenal insufficiency?
Increased levels of ACTH (in an attempt to stimulate the adrenal gland) stimulates melanocytes
**ACTH and MSH are both derived from POMC
Patient presents with progressive lethargy. She has had a loss of appetite, constipation, muscle weakness, and inc thirst and urination. She admits to taking large doses of vitamin and mineral substances to help boost her health. What do you suspect?
Hypercalcemia
Likely due to inc vitamin D intake from multivitamins
A patient with a past medical history of pheochromocytoma presents with a thyroid mass and is diagnosed with thyroid cancer. What type of cancer is most likely in this patient and why?
Medullary carcinoma
With a past hx of pheochromocytoma, the patient likely has MEN2A/2B.
What are neurophysins?
carrier proteins for oxytocin and vasopressin (ADH) – act as chaperone molecules and shuttle these hormones from the hypothalamus to the nerve terminals in the posterior pituitary
Familial Hypocalciuric Hypercalcemia
defective Ca2+ sensing receptor (G coupled proteins) causing higher than normal calcium levels to suppress PTH
o Inc PTH → inc Calcium renal reuptake → mild hypercalcemia with normal to inc PTH levels
Pathophysiology of cataracts and peripheral neuropathy in diabetes:
during hyperglycemia, excess plasma glucose is converted to sorbitol by aldose reductase. Sorbitol accumulates in some cells (eye lens and schwann cells) and attracts water into these tissues leading to osmotic cellular injury.
Patient presents with several month history of diabetes and a month history of a rash that are coalescing erythematous lesions with crusting and scaling at the borders and central areas of bronze colored necrosis. Biopsy shows superficial necrolysis.
Glucagonoma
tumor of pancreatic a cells → overproduction of glucagon o Presents with the D’s o Dermatitis (necrolytic migratory erythema) o Diabetes (hyperglycemia) o DVT o Declining weight o Depression o Tx: octreotide, surgery
How does increased ethanol intake cause hypoglycemia?
Ethanol metabolism uses up NAD+ to form NADH, which causes an increase in the NAD+/NADH ratio.
Lack of NAD+ causes inhibition of gluconeogenesis (lactate cannot be converted to pyruvate and the reaction is instead driven from pyruvate to lactate due to excess NADH).
Postpartum female presents with cold intolerance and failure to lactate. What should you be concerned about?
Sheehan syndrome: ischemic infarct of pituitary following postpartum bleeding
o During pregnancy, the pituitary enlarges due to estrogen-induced hyperplasia of the lactotrophs → more susceptible to ischemia
Hormone changes in chronic glucocorticoid use in response to stress?
Tertiary adrenal insufficiency
Dec CRH
Dec ACTH
Dec cortisol
What should you be concerned about in a patient with Grave’s disease who comes in with fever and sore throat?
Agranulocytosis
This is a rare complication of thionamides (propylthiouracil and methimazole)
Estrogen effects in TBG
o Inc estrogen → Inc TBG → inc total T4 and T3 (normal levels of free T3 and T4)
o They remain Euthyroid!
If patient is exposed to radioactive iodide, what is the best medical management?
Potassium iodide
Child presents with abdominal distention and myoclonus. Parents report that they have noticed spontaneous bursts of non-rhythmic conjugate eye movements in various directions. What is the likely diagnosis?
Neuroblastoma - tumor of the adrenal medulla seen in children
Originates from neural crest cells
Child presents with abdominal distention, hypertension, and opsoclonus-myoclonus syndrome (dancing eyes and dancing feet)
Associated with N-myc oncogene
Peripheral artery disease:
Pathophys
Risk factors
Treatment
Atherosclerotic plaques causing luminal narrowing
Common in diabetes, hyperlipidemia, HTN, smoking, age >70
Intermittent claudication: symptoms occur with exercise and resolve with rest
Cilostazol: reduces platelet activation by inhibiting platelet phosphodiesterase and is a direct arterial vasodilator
