Ant and post pituitary gland

Tuesday, August 18, 2015

3:29 PM
 
Hormones by hypothalamus Hormones made by ant. pituitary

1. Thyrotropin releasing hormone (TRH) 1. Thyrotropin (aka thyroid stimulating hormone)

2. Gonadotropin releasing hormone (GNRH) 2. Gonadotropin (FSH and LH)

3. Corticotropin releasing hormone (ACRH) 3. Adrenocorticotropin (ACTH)

4. Growth hormone releasing hormone 4. Growth hormone

5. Somatostatin 5. Prolactin (lactotropin) - most common pituitary adenoma

6. Prolactin inhibiting hormone (dopamine)  

   

  Hormones in post. Pituitary (made in

hypothalamus)

  1. ADH (aka vasopressin)

  2. Oxytocin - uterine contraction during

pregnancy
Anterior pituitary
1. What type of tumor is pituitary adenoma?
 Benign tumor of anterior pituitary cells.
 Can be functional (hormone producing) or non-functional (silent)
 
2. What are clinical presentation of non-functional tumor of pituitary?
 Bitemporal heminopsia (due to mass effect)
 Hypopituitarism (due to mass effect)
 Headache
 
3. What are most common functional tumor of ant. Pituitary?
 Prolactionma (most common pituitary adenoma) - 50% of adenomas
 Growth hormone (somatostatin) cell adenoma - 10-15% of adenomas
 ACTH cell adenoma - 10% of adenoma
 TSH cell, LH producing, and FSH producing adenomas are rare
 
4. What are clinical presentation of prolactinoma? How do you treat?
 In females - galactorrhea and amenorrhea (prolactin inhibits GNRH synthesis and release)
 In males - decreased libido and headache. Males don't get galactorrhea because they don't
have sufficient breast tissue.
 Treat - give prolactin inhibiting hormone (aka dopamine), dopamine agonists (bromocriptine or
cabergoline) or surgery
 
5. What is functional unit of breast?
 Terminal duct-lobular unit. Lobular unit has glands that make milk. Males only have terminal
duct but not lobular unit so can't make milk. Females develop lobular unit after puberty.
 Fig - rough sketch of terminal duct (TD) and lobular unit (LU)
 
6. What is clinical presentation of Growth hormone adenoma?
 In kids - gigantism
 In adults - acromegaly
o Enlarged bones of hand, feet, jaws, large tongue.
o Growth of visceral organs (cardiac failure is most common cause of death in these
patients)
 Secondary diabetes mellitus present (because GH inhibits glucose intake by cells; GH induces
gluconeogenesis by liver)
 
7. How do you diagnose growth hormone adenoma? How do you treat?
 Elevated GH and IGF-1 (insulin like growth factor) - IGF is made by liver in response to GH
 Lack of GH suppression in response to oral glucose (why)
 Treatment-
o Octreotide (somatostatin analog)
o GH receptor antagonist
o Surgery
 
Hypopituitary
8. When do we see hypopituitarism?
 When >75% of pituitary parenchyma is lost
 
9. What are some causes of hypopituitarism?
 Pituitary adenoma (common cause in adults ) - mass effect or apoplexy (bleeding in adenoma)
reduces hormone production
 Carniopharyngioma (common cause in kids) - same reason as above
 Sheehan syndrome (HY) - during pregnancy, there's high need of hormones so pituitary
doubles in size but its blood supply doesn't. Blood loss during parturition can trigger pituitary
infraction.
o Presents as poor lactation, loss of pubic hair (HY) and fatigue.
 Empty sella syndrome - herniation of arachnoid or pia into pituitary can damage pituitary.
o Can occur congenitally too
 
Posterior pituitary
10. What are clinical presentation and causes of central diabetic insipidus? What is diagnosis and
treatment?
  Presentation (based on loss of free water)
o Polyuria and polydipsia
o Hypernatremia and high serum osmolality
o Low urine osmolality and specific gravity
 Causes - damage (tumor, trauma, infection or inflammation) to hypothalamus or pituitary
 Diagnosis - urine osmolality doesn't increase in response to water deprivation
 Treatment - Desmopressin (ADH analog)
 
11. What are clinical presentation and causes of nephrogenic diabetic insipidus?
 Presentation - same as central DI but no response to desmopressin
 Causes - mutation or drugs (demeclocycline - old antibiotic, not used often now; and lithium)
 
12. What are clinical presentation and causes of syndrome of inappropriate ADH (SIADH)?
 Presentation -
o Hyponatremia and low serum osmolality
o Mental status change and seizure. - due to nerve swelling
 Causes - ectopic production (ex - small cell carcinoma of lung)
o CNS trauma
o Pulmonary infection
o Drugs (cyclophosphamide)
 Treatment - free water restriction, demeclocycline
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
☺

ufo
 
 
Thyroid
Tuesday, August 18, 2015
4:41 PM
1. Differentiate T3 and T4
T4 (thyroxine) T3 (triiodothyronine)

Both are made from tyrosine 10 times more potent than T4

  Most of it made from T4

Thyroid secretes T4>>T3  

T1/2 = 7 days T1/2 = 7 days

  T4--> T3 conversion reduced in severe illness

 
2. How are thyroid hormones transported in blood?
 Tyrosine binding protein (carries 70%)
 Albumin (carries 20%)
 Transthyretin (pre-albumin) (carries 10%)
 Free T4 is 0.04% and free T3 is 0.03%
 
 How are T3 and T4 made in thyroid gland? What is the key enzyme?
 Key enzyme is thyroid peroxidase
 Thyroglobulin are long chain of tyrosine that's stored as colloid in thyroid gland. T3/T4 are
made from it.
 Steps
o Iodine is oxidized to oxidized iodine by thyroid peroxidase (oxidation step)
o Oxidized iodine reacts with tyrosine to make monoiodotyrosine
o Oxidized iodine reacts with monoiodotyrosine to make diiodotyrosine
o The last two steps are called organification
o Monoiodotyrosine + diiodotyrosine = triiodothyronine
o Diiodotyrosine + diiodotyrosine = thyroxine
o The last two steps are called coupling
 
 What are functions of thyroid hormones?
o Increase or decrease gene transcription by binding to nuclear receptor
 o Imp in development (Cretinism is mental retardation and dwarfism caused due to
impairment of brain and skeletal development due to hypothyroidism)
o Increase BMR, O2 consumption and free radical formation
o Exacerbate diabetes mellitus (increase glycogenolysis and increase hepatic
gluconeogeneis) (hyperthyroid = DM)
o Increase LDL receptors (hyperthyroidism = low serum LDL)
o Increase ionotropy (contractility), chronotropy (HR),
o Increase sensitivity to catecholamine for B1 receptors(hyperthyroidism = hyperactive
SANS)
o Pulm - maintains hypoxic and hypocapnic drive (hypothyroid = hypoventilation and
respiratory arrest)
o GI - increase gastric motility (hypothyroid= constipation, hyperthyroid = diarrhea)
o Skeletal - increase bone reasborption and decrease bone formation (hyperthyroid =
osteopenia)
o Neuromuscular - (hyperthyroid = increased reflex, anxiety, hyperactivity; hypothyroid =
decreased reflexes, fatigue and sluggish)
 
 What causes thyroglossal duct cyst? (HY)
 Thyglossal duct is a path for descent of thyroid from tongue to its location in neck. The cyst
dies out normally; if it persists, it may cause cystic dilation and seen as anterior neck mass.
 
 What causes lingual thyroid?
 If thyroid tissue persists at base of tongue, it's present as a mass.
 
Hyperthyroidism (thyrotoxicosis)
 What are presentation of hyperthyroidism?
o Increased basal metabolic rate (due to increased synthesis of Na/K pump) (HY) -
i. wt loss despite increase hunger
ii. Tremor, anxiety, insomnia, and heightened emotions
iii. Heat intolerence and sweating
o Increased SANS (due to increased expression and activity of B1 s)
i. Cardiac - tachycardia, arrhythmia (esp in elderley)
o Hyperglycemia (increased gluconeogenesis and glycogenolysis) (HY)
o Hypocholesteremia and low serum LDL (increased LDL receptors) (HY)
o Diarrhea and malabsorption (increased GI motility)
o Osteopenia and hyercalcemia (increased bone reabsorption)
o Decreased muscle mass and weakness
o Oligomenorrhea
 
 What is epidemiology of Grave's disease? What is it?
 Most common cause of hyperthyroidism
 Classically occurs in women of childbearing age (this group has high incidence of autoimmune
disease)
 Grave's is autoantibody IgG generation that stimulates TSH receptor leading to
hyperthyroidism (type II hypersensitivity)
 
 What are clinical presentation of grave's disease?
 Diffuse goiter - TSH hormone is a trophic hormone that leads to hyperplasia and hypertrophy
 Tibial myxedema and exopthalmus
 
 What causes exopthalmos and pretibial myxedema (characterstic finding) in grave's?
 o Fibroblast behind eye and in tibia has TSH receptors. Excitation leads to
glycosaminoglycan (chondroitin sulfate and hyaluronic acid) buildup, inflammation,
fibrosis, and edema.
o Myxedema feels like dough. And myx refers that edema is not caused by water.
 What is histology of Grave's?
 Histology shows irregular follicle and scalloped colloid and chronic inflammation
 

Fig - Thyroid in grave's. Notice irregular follicles. Also, the white space between colloid
and thyroid tissue is called scalloped and is classic occurrence in Grave's.
 
 What is treatment of Grave's?
 B-blockers
 Antithyroid durgs (methimazole, propylthiouracil, thyoamide) - concentrate in thyroid and
block thyroid peroxidase; also prevent T4 --> T3 conversion in peripheral tissue
 I-131 - thyroid takes it and gets destroyed (permanent hypothyroidism major complication)
 Total thyredctomy
 
12.5. What are lab findings in Grave's?
 Increased total and free T4
 Decreased serum TSH
 Hypocholesteremia (HY)
 Hyperglycemia (HY)
 
 Differentiate thyroid storm vs myxedema coma
Thyroid storm (hyperthyroid emergency) Myxedema coma (hypothyr
emergency)

Presentation - fever (>400C), sweating, tachycardia/afib, delirium, nausea, Presentation- mental status
vomiting change from confusion to c

Cause - increased catecholamines action and massive T3/T4 excess. Most Hypoglycemia, hypothermi
common trigger - acute stress such as surgery, childbirth, MI. hypothermia, hypoventilism

Treatment High incidents of death

 B-blockers, propylthiouracil, and steroids
 give Iodine salt (wolff-chaikoff block - increased iodine in blood leads to
decreased iodine uptake by thyroid and decreased production of thyroid
 hormones)

  Treatment- high dose of

levothyroxine

  Cause- infection, stroke, in

patients with hypothyroidis

   

   
 
 What causes multinodular goiter? Is it toxic?
 Multiple nodules and enlarged thyroid
 Caused due to relative iodine deficiency
 Usually nontoxic (rarely, some regions can be toxic, i.e., produce T3/T4)
 

Fig - multinodular goiter

 
Hypothyroidism
 What is cretinism? What are it's findings?
 It's developmental delay caused due to hypothyroidism.
 Classic findings
o Mental retardation and dwarfism due to poor brain and skeletal development
o Enlarged tongue (due to myxedema)
o Umbilical hernia
 
 What are causes of cretinism?
 Maternal hypothyroidism during early pregnancy
 Thyroid agenesis (pt don't develop thyroid)
 Dyshormonogenic goiter (pt can't make thyroid hormones - ex - pt with mutation in thyroid
peroxidase gene)
 Iodine deficiency
 
 What's classic findings in myxedema (hypothyroidism in old kids and adults)?
o Myxedema - classically in tongue (large tongue) and larynx (gives deep voice) (HY) - due
to increased TSH
o Decreased BMR and decreased SANS
i. Wt. gain despite normal activity
ii. Cold intolerane and decreased sweating
iii. Bradycardia
o Hypoventilation and respiratory arrest - thyroid maintains respiratory drive
 o Slow mental activity
o Muscle weakness
o Hypoglycemia, hypercholesteremia
o Oligomenorrhea (seen in both hyper and hypothyroidism)
o Constipation
 
 What are causes of hypothyroidism?
 Hashimoto's (most common cause)
 Iodine deficiency
 Drugs (lithium)
 
Thyroiditis
 What is presentation of hashimoto's thyroiditis? What chemical is is associated with? What are
lab results?
 It's an autoimmune attack to thyroid peroxidase and thyroglobulins
 Associated with HLA-DR5 (HY)
 Initially see increase T3/T4 (and low TSH) due to gland destruction. Later on, we see
decreased T3/T4 (and high TSH) due to gland destruction.
 Suspect other autoimmune disease - type 1 DM, pernicious anaemia, rheumatic disease.
 Lab results - anti TPO, anti-thyroglobulin, anti-microsomal antibodies, high TSH, low T3/T4
 
 What is histologic appearance of Hashimoto's thyroditis? (HY)
 Chronic inflammation (see lymphocytes) with germinal cells.
 Presence of Hurthle cells (eosinophilic metaplasia of cells that line follicles).
 

Fig - Hashimoto's thyroiditis. CI is chronic inflammation. GC is germinal center. Little

circles on left are herthel cells.
 
 What disease do pt. with Hashimoto's have increased risk of? How? What's presentation?
 B cell lymphoma.
 How - Germinal center makes post germinal center B cells. It makes marginal zone which
results in marginal zone lymphoma.
 Presentation is pt with long standing hypothyroidism that presents with enlarged thyroid.
 
 What is SUBACUTE GRANULOMATOUS (DE QUERVAIN) THYROIDITIS? What's its presentation?
What's its prognosis?
  It's granulomatous thyroiditis that follows viral infection (subacute means it occurs after acute
process).
 Presentation - Hypothyroidism is transient, and pt has tender thyroid (if a young female has
tender thyroid, think subacute granulomatous thyroiditis).
 Prognosis - It's self-limited and don't progress to hypothyroidism.
 
 What is Reidel Fibrosing thyroiditis? What is presentation?
 Chronic inflammation of thyroid with extensive fibrosis
 Presentation -
o hard as wood thyroid that's non tender
o Fibrosis may extend to local structures - ex - airway
o Clinically mimics anaplastic carcinoma but pt are younger and usually female(in
anaplastic, pt are older)
 
Thyroid cancer
 What are basics of thyroid cancer?
 Most nodules are distinct and solitary
 Most nodules are likely to be benign than malignant
 
 What causes positive and negative in radioiodine uptake study?
 Positive is when thyroid takes radioiodine injected in blood - Graves, nodular goiter
 Negative - adenoma and carcinoma (do biopsy by FNA)
 
 Describe follicular adenoma (adenomas are benign; adenocarcinoma are cancerous).
 Follicle proliferate in a benign way and are surrounded by a fibrous capsule
 Called follicular because tumor also makes thyroid follicle.
 Tumor mostly non-functional (don't secrete hormone)
 

Fig - follicular adenoma. Red line is the capsule that divides adenoma (bottom half) from
normal thyroid (top half)
 
 What are 4 types of thyroid carcinomas (malignant stuff)?
o Papillary carcinoma
o Follicular carcinoma
o Medullary carcinoma
o Anaplastic carcinoma
 
 What is epidemiology, risk factor, prognosis and histologic feature of papillary carcinoma?
 Most common thyroid carcinoma (80% of thyroid carcinoma)
 Major risk - exposure to ionizing radiation in childhood
 Prognosis - excellent even though often spreads to cervical nodes
 Histology -
- Papillae of cells seen (so called papillary carcinoma
- Diagnosis is made by nuclear features -
 Coffee bean nucleus (presence of nuclear groove)
 Orphan eye annie nucleus (nucleus has white stuff resembling white of eye)
 Psammomma bodies (concentric calcification of papillaes).
 

Fig - Papillary carcinoma. red circles indicate orphan eye annie nucleus. Turquoise circle
shows coffee bean nucleus.
 

Fig - Psammoma bodies in papillary carcinoma shown in black circle.

 
 What is histologic feature of follicular carcinoma? Can you diagnose by FNA?
 Similar to follicular adenoma (has fibrous capsule) but cells invade through capsule (hallmark)
 FNA can't distinguish between follicular adenoma and follicular carcinoma because capsular
invasion can't be assessed by FNA.
  Even though most carcinomas spread via lymph nodes, follicular carcinoma spreads
hematogenously (by blood).
 

Fig - follicular carcinoma. Red line shows the capsule and the break in it.
 
 What are 4 carcinomas that spread by blood instead of lymph? (HY)
 Renal cell carcinoma
 Follicular carcinoma of thyroid
 Hepatocellular carcinoma
 Corneal carcinoma
 
 Describe medullary thyroid carcinoma (MTC). How is it diagnosis?
 Malignant proliferation of parafollicular C cells that produce calcitonin
 Diagnosis -
o Malignant cells in amyloid stroma - indicates MTC. (Calcitonin deposits in tumor as
amyloid (cause localized amyloidosis), and +ve calcitonin immunostain)
o Pt has high level of calcitonin which can lead to hypocalcemia
 Fig - MTC biopsy. All the pink stuff seen is calcitonin amyloid.
 
 Describe familial cases of MTC (HY). What's significance of RET oncogene (HY)?
 Often associated with MEN 2A or 2B phenotype. (MEN = muliple endocrine neoplasia)
 MEN 2A - often see MTC, pheochromocytoma and parathyroid adenomas
 Men 2B - often see MTC, pheochromocytoma and ganglioneuroma of oral mucosa
 Familial cases of MTC is classically associated with mutation in RET oncogene
 If a person has RET oncogene, do a prophylactic thyroidectomy
 
 Describe anaplastic carcinoma. How do you diagnose?
 Has the worst prognosis of all thyroid carcinomas
 It is undifferentiated and classically seen in old people
 Tumor has +ve keratin stain
 Often invades local structures leading to dysphagia or respiratory compromise.
 Clinically similar to Reidel fibrosing thyroidiyis but cancer is often seen in old people and
thyroidiyis in young females.
 

Fig - highly malignant cells in anaplastic carcinoma that don't resemble anything seen in
thyroid usually
 
 
Parathyroid
Thursday, August 27, 2015
12:10 AM
1. What is vitamin D? How do we get it?
 Two most imp vitamin D are vit D3 (cholecalciferol) and vit D2 (ergocalciferol)
 Cholecalciferol (D3) is made from 7-dehydrocholesterol by UV in skin
 Ergocalciferol (D2) is taken from food.
 Both of those are activated by liver in unregulated way, and kidney in regulated way
 
2. How does kidney activate vitamin D?
 Vit D itself is a prohormone. Kidney uses alpha 1 hydroxylase to make 1,25 OH D (active
vitamin D).
 
  What are functions of PTH hormone?
 Chief cells make PTH that increase free serum calcium
 PTH acts on 3 main tissue
o Stimulate kidney to increase vit D activation
o Increase Ca absorption from kidney and phosphate excretion (phosphate excretion key
because it increases free Ca in blood)
o Increase Ca and PO4 absorption from gut - this action is via Vit D
o Increase osteoclast activity (PTH activates osteoblast which secretes M-CSF (macrophage
colony stimulating factor) which increase osteoclast differentiation and activation) (HY)
 
 What regulates blood PTH hormone?
 PTH release is highly sensitive to serum ca.
 Vitamin D also reduces PTH release
 Increase Ca ---> Gq and Gi activation. Gq increase calcium release in parathyroid cells --->
Decreases PTH synthesis. Gi decreases cAMP which reduces PTH synthesis
 Low Ca ---> Gs activation. Gs increases cAMP which increases PTH synthesis
 
 What are functions of Vit D?
 Main function is to maintain bone mineralization
 Increase Ca and PO4 reabsorption in kidney
 Increase Ca and PO4 absorption in gut
 Decrease PTH secretion
 
 What are function of calcitonin and phosphatonin?
 Tone down serum Ca and PO4
 Phosphatonins are important because intestinal absorption of phosphate is unregulated
 
Primary hyperparathyroidism
 Explain primary hyperparathyroidism.
 Excess PTH; most common cause is PT adenoma (80%)
 Other causes - PTH hyperplasia, PTH carcinoma
 
 Describe presentation of PT adenoma (i.e., symptoms of hypercalcemia).
 Benign; mostly asymptomatic
 If symptomatic
o Nephrolithiasis - kidney stone (classic is calcium oxalate)
o Nephrocalcinosis - example of metastatic calcification - Ca deposits in tubules
o CNS disturbance - depression, seizure
o Constipation, peptic ulcer, acute pancreatitis (HY) - think Ca as an enzyme activator that
activates pancreatic enzymes.
o Osteitis fibrosa cystica - massive reabsorption of bone leading to fibrosis and cyst
formation
 Treatment - surgery
 
 What are lab findings in primary hyperparathyroidism?
 Increase serum PTH
 High serum Ca
 Low serum phosphate (PTH increase phosphate excretion)
 High urine cAMP (HY)
o PTH works in kidney via Gs to increase cAMP. Some cAMP gets to urine.
 High serum alkaline phosphatase (HY)
 o Alkaline phosphatase generates alkaline environment in bone so that new bone can be
laid down. Alk Phos is a sign of osteoblast activity. Remember that PTH first activates
osteoblast which in turn activates osteoclast. Osteoblast activation leads to high alk
phos.
 
Secondary hyperparathyroidism
 What are some causes for 20 hyperparathyroidism?
 Most common is chronic renal failure (HY)
o Decreased phosphate excretion --> reduced free calcium in blood as most of it is bound
to phosphate ---> increased PTH production and increased bone reabsorption
 
 What are lab findings in 20 hyperparathyroidism?
 Increased PTH
 Decreased serum Ca (remember that the whole process is driven by high PO4. It binds to free
serum Ca and reduces it)
 Increased serum PO4
 Increased alkaline phosphatase (increased PTH leads to increase alk phos)
 
Hypoparathyroidism
 What are causes of hypoparythoroidism?
 Autoimmune
 DiGeorge syndrome (failure of develop 3rd and 4th pharyngeal pouch. Parathyroids develop
from 3rd and 4th pharyngeal pouch).
 
 What are its presentation - due to low Ca?
 Numbness and tingling (specially perioral)
 Muscle spasm (ex - when you put BP cuff on them or touch their face)
 Low serum Ca and PTH
 
Pseudohypoparathyroidism
 What causes pseudohypoparathyroidism?
 Caused due to end organ resistance of PTH
 Hypocalcemia with increased PTH level (also see this is secondary hyperparathyroidism; but 2 0
hyperparathyroidism has increased serum phosphate levels too)
 Autosomal dominant form (mutation of Gs) associated with short stature and short 4th and
5th digit
 
 
Endocrine pancreas
Thursday, August 27, 2015
1:32 AM
Insulin - major anabolic hormone. Upregulates GLUT4 receptors in muscle and fat. Increased
glucose leads to glycogen synthesis, fat synthesis, protein synthesis
Glucagon - major catabolic hormone. Causes gluconeogenesis from AA, lipolysis and
glycogenolysis.
 
1. Describe the anatomy of endocrine pancreas.
 Composed of cluster of cells called islet of Langerhans
 Single islet has many types of cells; each type producing one type of horome
 Insulin is made by B cells; lie in center of islet
 Glucagon is made by alpha cells.
 
Type 1 DM
2. Explain Type 1 DM
 Autoimmune destruction of B cells by T lymphocytes (type 4 hypersensitivity) - see
inflammation of islets
 Autoantibodies against insulin - can be seen years before disease
 Associated with HLA DR3 and DR4
 
 What's presentation of type 1 DM?
 Classically seen in children
 Presentation (of insulin deficiency)
o High blood glucose
o Weight loss despite polyphagia (high hunger), low muscle mass - due to unopposed
catabolic action of glucagon
o Polyuria, polydipsia, glycosuria
 Treatment - lifelong insulin
 
 Explain mechanism of DKA (feared complication of type 1 DM)
 Excess serum ketoacids; often triggered by stress (ex-infection)
 Epinephrine increases glucagon that exacerbates lipolysis. Free fatty acids generated go to
liver and get converted to ketones.
 
 What is presentation of DKA?
 Hyperglycemia (>300 mg/dl) - due to unopposed glucagon actoin
 Anion gap metabolic acidosis (from ketoacids)
 Hyperkalemia (HY)
o insulin stimulates Na/K pump. Also, acidosis is compensated by exchanging H + from
serum to K in cells. Much of the serum K will be lost in urine. So person has loss of total K
from body; but has hyperkalemia
 Kussmaul respiratin (to compensate for acidosis), dehydration (from diuresis), mental status
change, fruity breath
 
 How do you treat DKA?
 Give fluids - to treat dehydration
 Insulin
 Give potassium - because when you give insulin, K will go inside the cells; also serum K goes
down as acidosis is treated
 
Type 2 DM
 Explain type 2 DM.
 End organ insulin resistance
 Risk factor - obesity; Obesity reduces insulin receptors (HY)
 Higher genetic predesposition compared to type 1 DM
 
 Describe presentation of type 2 DM.
 Initially, see high insulin. Later on B cells get exhausted so see low insulin
 Histology shows amyloid deposition in islets
 Fig - amyloid deposition in Islets in type 2 DM. Amyloid is made of amylin - a protein
produced with insulin.
 
 What is presentation and diagnosis of type 2 DM?
 Polyuria, polydipsia, hyperglycemia, often clinically silent
 Diagnosis
o Random glucose (>200 mg/dl)
o Fasting glucose (>126 mg/dl)
o Glucose tolerance test (>200/dl two hours after glucose load)
 
 How do you treat type 2 DM?
 Weight loss and exercise first line
 Drugs
 Insulin
 
 Describe hyperosmolar non-ketotic coma.
 MOA - High glucose levels (>500 mg/dl) leads to life threatening diuresis
 Don't see ketoacidosis because some insulin is present which prevents lipolysis and fat
breakdown
 Hypotension
 Coma (due to osmolar effect in brain)
 
 What are two major complications of diabetes? Give examples of diseases.(HY)
 Non enzymatic glycosilation (NEG) of vascular basement membrane
o NEG of large and medium vessels lead to artherosclerosis - ex - peripheral vascular
disease leading to amputation
o NEG of small vessel leads to hyaline arteriolosclerosis - ex - diabetic nephropathy
(nephrotic syndrome)
o NEG of hemoglobin leads to HbA1c - long term marker of glycemic control
 Osmotic damage
o Some cells in body can take sugars without insulin
 Schwann cells - aldose reductase reduces glucose to sorbitol in Schwann cells.
Sorbitol leads to osmotic damage. Leads to peripheral neuropathy.
 Pericytes of retinal blood vessel - sorbitol cause osmotic damage and pericytes die.
Leads to anurysm of retinal blood vessel. Rupture leads to blindness.
  Lens - sorbitol build up leads to cataract.
 
 What are some pancreatic endocrine tumor?
 MEN 1
o Parathyroid hyperplasia and pituitary adenoma, pancreatic endocrine tumor
 Insulinoma -
o Tumor makes insulin
o Presentation-
 Mental status change due to severe hypoglycemia that is relieved by glucose
 Lab - Low glucose, high insulin, high C peptide (C peptide is made along with
insulin)
 Gastrinoma
o Gastrin induces parietal cells in stomach to make acid
o Presentation
 Treatment resistant peptic ulcers (aka Zollinger Ellison syndrome)
 Ulcers can extend to jejunum
 Somatostatinoma
o Somatostatin reduces acid production and contraction of gall bladder
o Presentation
 Achlorhydria (low acid production in stomach)
 Cholelithiasis and steatorrhea (due to reduced bile release)
 VIPoma
o Vasoactive intensinal peptide greatly stimulates secretion of water and electrolytes in
intestine, reduces gastric acid production.
o Presentation
 Watery diarrhea
 Hypokalemia
 Achlorhydria
 
 What are two proteins that are made together with insulin?
 Amylin - in type 2 DM, we see amyloid buildup due to amylin buildup
 C peptide - can be tested in blood to see if pt is overadminstering insulin
 
 
 
Adrenal
Friday, August 28, 2015
4:45 PM
Crotex - hormones are made from cholesterol (cortex is yellow due to cholesterol)
Medulla- hormones made from tyrosine
 
1. What are three layers of adrenal?
 
Zona glomerulosa Mineralocorticoid (Aldosterone)

Zona fasciculata Glucocorticoid (Cortisol)

Zona reticularis Sex steroids

Pneumonic GFR for the zones.
 
2. Describe metabolism of cortisol.
 Transport
 75% transported by transcortin (aka corticosteroid binding globulin) (made by liver)
 15% bound to albumin
 10% in free form
 Receptor - nuclear receptor. Present in all body cell
 Can bind strongly to mineralocorticoid receptor as mineralocorticoid itself.
 
 How do you get hypokalemia from too much licorice ingestion?
 Cortisol is inactivated to cortisone in kidney tubules by 11-B-hydroxysteroid dehydrogenase
type 2 (reverse reaction by type 1 dehydrogenase). Licorice inactivates the type 2 enzyme,
leading to active cortisol in kidney tubules.
 As cortisol has high mineralocorticoid action, it leads to potassium excretion in kidney tubules
leading to hypokalemia.
 
 What are functions of glucocorticoids (called glucocorticoid because it increases glucose in
blood)?
 Increased glucose output by liver and decrease glucose intake by muscle, adipose (to increase
glucose supply to brain and heart)
 Decreased insulin sensitivity
 Decreased immune activity via
 Decreased arachidonic acid production (due to inhibition of phospholipase A2)
 Low IL-2 production (IL2 important for proliferation of T cells)
 Low histamine production
 Increased alpha one receptor production and sensitivity to catecholamines (lack of cortisol
causes extreme vasodialation, extreme hypotension and death)
 Negative feedback to ACTH
 
 How does adrenal insufficiency cause hypotension?
 ↓glucocorticoid (GC)  too much vasodialation
 ↓mineralocorticoid (MC) hypovolemia (too much Na and water wastage from kidney )
 
 What are clinical features of Cushing’s syndrome (too much GC)?
 Muscle weakness (AA in muscles are used for gluconeogenesis) with thin extremities
 Moon faces, buffalo hump, truncal obesity (high glucose in blood leads to insulin release; insulin
is an anabolic hormone and leads to fat storage)
 Abdominal striae (cortisol impairs collagen synthesis; blood vessels in stomach ruptures leading
to striae formation)
 HTN (increased sensitivity and production of alpha 1 receptor)
 Osteoporosis
 Immune suppression
 
 What are causes of cushings?
Cause Adrenal gland size

Exogenous cortisol (most common) Both atrophied

Primary adrenal adenoma, hyperplasia, carcinoma (aka cushing's disease - 2nd One secreting cortisol big, o
most common) atrophied

ACTH secreting pituitary adenoma Both large

Paraneoplastic ACTH secretion (ex - small cell carcinoma of lung) Both large
  
8. How do you distinguish between cushing's due to ACTH made by pituitary vs pituitary made
somewhere esse (paraneoplastic)?
 Do a dexamethasone suppression test. ACTH produced by pituitary will go down but not the
paraneoplastic one.
 
 What is presentation of hyperadlosteronism?
 Hypernatremia, HTN
 Hypokalemia, metabolic alkalosis
 Aldosterone causes principal cell of kidney to take Na and excrete K.
 
 Describe features of primary hyperaldosteronism.
 Most commonly due to adrenal adenoma. Less common - hyperplasia and carcinoma
 High aldosterone and low renin
 
 Describe features of secondary hyperaldosteronism
 Causes- fibromuscular dysplasia (classically seen in young woman where renal artery is
stenosed), atherosclerosis of renal artery
o As kidney sees low blood flow, RAAS is activated leading to high aldo
 See high renin and high aldo
 
 Describe cause of congenital adrenal hyperplasia (occurs in both androgen)
 Most commonly seen due to deficiency of 21- hydroxylase (required to make cortisol and aldo)
 Deficiency of cortisol leads to excess production of ACTH leading to hyperplasia of adrenals
(remember ACTH is a trophic hormone)
 Other causes - 11 hydroxylase and 17 hydroxylase deficiency (leads to low cortisol)
 
 What is presentation of congenital adrenal hyperplasia?
 Excess sex steroids (hormone production shunted towards sex hormone production due to
deficient 21-hydroxylase)
 Clitoral enlargement
 Precocious (early) puberty in males
 Life threatening hypotension (cortisol deficiency)
 Hyponatremia, hypovolemia; hyperkalemia, acidosis (aldo deficiency)
 
 How does 11 hydroxylase deficiency present in contrast to 21 hydroxylase deficiency?
 In 11 hydroxylase deficiency, we don't see effects of hypomineralocorticoid; but see effect of
hypocortisol and excess sex hormone
 Reason - Both 21 and 11 hydroxylase are required for cortisol production. 21 hydroxylase can
produce weak mineralocorticoid, and 11 hydroxylase is needed to make strong
mineralocorticoid.
 
Adrenal insufficiency
 What is presentation of Waterhouse-Friderichsen syndrome (acute adrenal insufficiency)?
 Commonly seen in kid with Niserria meningitis infection that causes DIC and then bilateral
necrosis of adrenal glands
 See massive hypotension
 Fig - sac of blood adrenals classically seen in waterhouse friderichsen syndrome
 
 What are causes of chronic adrenal insufficiency?
 Autoimmune (most common cause in developed world)
 TB (most common cause in developing world)
 Metastatic carcinoma to adrenals (lung cancer loves to go to adrenal)
 
 What are presentation of chronic adrenal insufficiency?
 Hypotension (low cortisol)
 Hyponatremia, hypovolemia; hyperkalemia, acidosis (aldo insufficiency)
 Weakness
 Hyperpigmentation (HY) - ACTH is made from POMC. POMC also induces melanin synthesis.
High ACTH means high POMC which leads to high melanin synthesis - classically seen in oral
mucosa and skin. - only see in 10 adrenal insufficiency.
 Vomiting and diarrhea (low cortisol)
 
 Describe pheochromocytoma (tumor of adrenal medulla)
 Medulla is made of neural crest derived chromaffin cells (HY)
 Pheo is tumor of chromaffin cell
 Classic finding - brown tumor (because chromaffin cells are brown)

Fig - pheochromocytoma. Yellow parts seen in left and right are adrenal cortex.
 
 What are presentation of pheochromocytoma?
 Episodic HTN, headache, palpitation
 Orthostatic hypotension may be seen - because alpha receptors are sensitized to high levels of
catecholamines
 Diagnosis -
 increased serum metanephrines
  Increased urine metanephrines and VMA
 Epi and NE are metabolized to metanephrine and normetanephrine respectively. MAO
converts both of them to VMA.
 Treatment - surgery (HY - give phenoxybenzamine (irreversible alpha 1 blocker) before surgery
because mechanical stress of adrenal can leak out epi and NE giving pt HTN and too much
bleeding).
 
 What are rule of 10's involving pheo?
 10% bilateral
 10% familial
 10% malignant
 10% located outside adrenal (HY - a common site is urinary bladder - classic presentation is a
patient who experiences headaches and palpitation while urinating).
 
 What are associations of pheo?
 MEN 2A (MTC, pheo and parathyroid adenoma) and
 2B (MTC, pheo and mucosuloganglio neuroma esp in oral mucosa). MTC can kill pt so people
with MEN go prophylactic thyroidectomy. Ret oncogene linked to MTC.
 VHL disease (autosomal dominant mutation of von hippel lindau tumor suppressor gene -
increased risk of hemangioblastoma of cerebellum, renal cell carcinoma, pheo)
 NF type 1
 
 Why don't you give beta blocker in pheo to control HR?
 B2 is a vasodialator. B1 increases HR. If B blocker is given, we have uncontrolled alpha action
(very severe vasoconstriction).