Week 1 Flashcards
(196 cards)
1
Q
What are the three categories of hormones?
A
- protein/peptide
- amino acid derivatives
- Lipid based
2
Q
Describe the following hormonal rhythms
1. ultradian
2. circadian
3. circalunar
4. circannual
A
- oscillation of less than 24 hours
- follow roughly 24 hour cycle
- corresponds to lunar cyclce (approx 29.5 days)
- yearly
3
Q
Receptors for water soluble hormones are found where?
What about receptors for lipid solube hormones?
A
- cell surface
- intracellularly
4
Q
Hormone levels are most commonly measured by what analysis technique?
A
ELISA - using specific antibodies
5
Q
Peptide hormone
1. water soluble?
2. uses carrier protein in plasma?
3. Stored in vesicle prior to secretion?
A
- yes
- No (but IGFs and GH have binding proteins in circulation)
- Yes
6
Q
Steroid hormone
1. water soluble?
2. uses carrier protein in plasma?
3. Stored in vesicle prior to secretion?
A
- No
- Yes
- NO
7
Q
Catecholamine hormone
1. water soluble?
2. uses carrier protein in plasma?
3. Stored in vesicle prior to secretion?
A
- Yes
- No
- Yes
8
Q
Thyroid hormone
1. water soluble?
2. uses carrier protein in plasma?
3. Stored in vesicle prior to secretion?
A
- No
- Yes
- No (bound to thyroglobulin)
9
Q
Peptide hormone
1. Receptor location at target cell?
2. MOA (2nd messengers, altered gene expression, or gene transcription)
3. Speed and duration of action
A
- Plasma membrane
- 2nd messengers
- Usually fast onset but short acting responses
10
Q
Steroid hormone
1. Receptor location at target cell?
2. MOA (2nd messengers, altered gene expression, or gene transcription)
3. Speed and duration of action
A
- Intracellular
- Altered gene expression
- Usually slow onset but long lasting responses
11
Q
Catecholamine hormone
1. Receptor location at target cell?
2. MOA (2nd messengers, altered gene expression, or gene transcription)
3. Speed and duration of action
A
- Plasma membrane
- 2nd messengers
- Fast onset but short acting responses
12
Q
Thyroid hormone
1. Receptor location at target cell?
2. MOA (2nd messengers, altered gene expression, or gene transcription)
3. Speed and duration of action
A
- Nucleus
- Gene transcription
- Usually slow onset but long lasting responses
13
Q
- How are protein hormone synthesized?
- How are they secreted
A
- hormone coding genes need to be transcribed first into mRNA
- Synthesis of peptide hormone is done in rough ER lumen and hormones remain in rough ER
- In the golgi apparatus, if needed, some hormones are cleaved into biologically active hormones
- all protein hormones are stored in secretory granules that bud off of golgi apparatus
- Stimulation of endocrine cells will cause fusion of granules and release of hormones
14
Q
What two groups of hormones are derived from tyrosine?
A
- catecholamines
- thyroid hormones (iodine is attached to the tyrosine residues of a protein called thyroglobulin)
15
Q
- What are the two catecholamine hormones?
- What are they released by?
A
- epinephrine and norepinephrine
- Adrenal medulla is the main source of circulating epinephrine. Then epinephrine can be converted to dopamine and then NE. NE is released by most catecholamine producing cells of the body.
16
Q
- Where are steroid hormones produced? (4)
A
- adrenals, ovaries, testes, and placenta
17
Q
Where are hormone binding proteins synthesized?
A
Liver
18
Q
Hormone actions can be controlled by what 4 things?
A
- rate of secretion
- plasma binding
- rate of elimination
- peripheral conversion
19
Q
Ion channel receptors
1. MOA
2. They regulate levels of what?
3. Lead to activation of what?
A
- Hormone binds to these receptors and they open ion channels - lead to increase of intracellular Calcium
- Calcium levels
- Activation of enzymes such as PKC and calcium calmodulin kinase
20
Q
What is the structure of a receptor tyrosine kinase (3 main parts)
A
- amino-terminal extracellular domain
- Single transmembrane domain
- carboxy termianl intracellular domain that has intrinsic enzymatic activity
21
Q
How are cytokine receptors different than receptor tyrosine kinase?
A
- For cytokine receptor - a separate soluble enzyme (like JAK, a tyrosine kinase) associates with the intracellular domain of the cytokine receptor
Remember that in receptor tyrosine kinase the intracellular part is the enzyme
22
Q
The G-protein coupled receptors have 3 subunits (alpha, beta, gamma) - which binds GTP or GDP and functions as primary signal transducer
A
alpha subunit
23
Q
What receptor exists as dimers or dimerize after binding of ligand?
A
Receptor Tyrosine kinase and also cytokine receptor
24
Q
Once a steroid hormone binds intracellular receptor what occurs to cause a change?
A
- hormone-receptor complex binds DNA and activates transcription directly
25
1. Pituitary gland (hypophysis) sits in what bone?
2. What is the name of the anterior and posterior lobe?
1. sella turcica of the sphenoid bone
2. Adenohypophysis is anterior and neurohypophysis is posterior lobe
26
1. What is the parts tuberalis
2. What is the pars distalis
*Both part of anteiror lobe of pituitary gland*
1. tubular sheath that extends the pars distalis and winds around pituitary stalk
2. portion in which majority of hormone production occurs
27
Development
1. Anterior lobe is made from what?
2. Posterior lobe is made from what?
1. evagination of ectoderm of oropharynx (Rathke's pouch)
2. neuroectoderm from the diencephalon
28
1. Blood enters pituitary gland via what structures?
2. Blood exits via what?
1. superior and inferior hypophyseal arteries
2. hypophyseal veins -> flows into cavernous sinus -> carries pituitary secretions into body
29
1. What is the function of portal system near pituitary gland?
1. Arteries flow into fenestrated capillaries -> Blood flows into portal veins -> infundibulum -> 2nd fenestrated capillary bed
2. The purpose is to allow for hypothalamic secretions to go into the pituitary gland
30
1. What is the pars intermedia
1. This is the boundary between anterior and posterior lobes of pituitary (arrowhead)
31
1. Paraventricular nucleus - where is it and what does it produce?
2. What about the supraoptic nucleus?
1. It is in the hypothalamus and produces oxytocin
2. also in hypothalamus and produces ADH
32
What is the hypothalamohypophyseal tract?
1. This tract is unmyelinated axons in infundibulum. These axons terminate in pars nervosa (part of posterior pituitary)
2. Axon terminals store oxytocin and ADH
33
1. What is the function of TRH?
2. Where is it released from?
1. Stimulates release of TSH or thyrotropin
2. Hypothalamus
34
1. What is the function of GnRH?
2. Where is it released from?
1. Stimualtes release of FSH and LH
2. Hypothalamus
35
1. What is the function of Somatostatin?
2. Where is it released from?
1. Inhibits release of somatotropin (Growth Hormone) and TSH
2. Hypothalamus
36
1. What is the function of GHRH?
2. Where is it released from?
1. Stimulates release of growth hormone
2. Released from hypothalamus
37
1. What is the function of Dopamine?
2. Where is it released from?
1. Inhibits release of prolactin
2. Hypothalamus
38
1. What is the function of CRH?
2. Where is it released from?
1. Stimulates release of corticotropin (ACTH)
2. Hypothalamus
39
Cells of Adenohypophysis
1. Identify the cells: arrow, arrowhead, triangle
1. Arrows: Basophils (stain blue)
2. Arrowheads: Acidophils (stain red)
3. Triangle: Chromophobes (clear - after secretion)
40
1. What type of cells can basophils be in adenohypophysis?
2. What about acidophils?
3. What about chromophobes?
1. Corticotrophs, gonadotrophs, thyrotrophs
2. Somatotrophs, lactotrophs
3. These are precursor cells - empty cells after secretion
41
1. What are Pituicytes in posterior pituitary?
2. What are herring bodies in post. pituitary?
1. majority of visible nuclei in image -> these are supportive glial cells
2. eosinophilic patches (red patches) - swellings of neuron axon terminals
42
OXYTOCIN
1. Function
2. Stored in..?
1. Increases contraction of myoepithelial cells in mammary glands. Also, increases uterine smooth muscle contraction during pregnancy.
2. Posterior pituitary
43
ADH/Vasopressin
1. Function
2. Stored in..?
1. Increases water absorption in kidney, decreases sweating, increases blood pressure by artery contraction
2. Posterior lobe
44
Somatotrophs are found in anterior pituitary
1. What simulates these endocrine cells?
2. What do they release?
1. GHRH from hypothalamus
2. Growth Hormone
45
Lactotrophs are found in anterior pituitary
1. What simulates these endocrine cells? (2)
2. What do they release?
1. Low levels of dopamine (since dopamine is typically inhibitory) + elevated TRH
2. Prolactin (PRL)
46
Corticotrophs are found in anterior pituitary
1. What simulates these endocrine cells?
2. What do they release? (4)
1. CRH frome hypothalamus
2. Produces POMC that is cleaved to make multiple hormones like the following ....
2. ACTH (adrenocorticotropic hormone) -> lead to release of glucocorticoids from adrenal glands
3. MSH (melanocyte stimulating hormone) -> lead to skin pigmentation
4. Lipotropin (LTH) - increase fat mobilization and metabolism
47
Gonadotrophs are found in anterior pituitary
1. What simulates these endocrine cells?
2. What do they release?
1. GnRH from hypothalamus
2. FSH and LH
48
Thyrotrophs are found in anterior pituitary
1. What do they release?
1. Thryotropin (TSH) -> cause increase thyroid gland growth and increase release of thyroid hormone
49
Explain these structures found in pineal gland
1. Pinealocytes
2. Glial cells
3. Brain sand (corpora arenacea)
*1 and 2 are in the image*
1. (arrow) - responsible for secreting melatonin
2. (arrowhead) - supportive cells
3. calcified concretions that often increase with age - just a histological identifier for pineal gland
50
1. What can melatonin inhibit secretion of?
1. Melatonin can inhibit hypothalamic secretion of GnRH
51
What is the median eminence?
1. The location where hypothalamus releases hormones and the primary portal plexus picks them up before going into portal system.
2. This is how signals arrive at anterior pituitary! Remember hormones get to posterior pituitary via axons.
52
What affect does a lot of ACTH have on gums? and why?
1. hyperpigmentation
2. Because when ACTH is made so is MSH which causes hyperpigmentation
53
What is the stimulus that causes the production of ADH/Vasopressin?
1. Osmoreceptors in hypothalamus dectect osmolality of blood and protect water and salt balance
2. Baroreceptors also detect volume and pressure of vascular system
54
1. What does primary endocrine disease mean?
2. What about secondary?
3. What about tertiary?
1. Lesion in peripheral endocrine gland
2. Lesion in anterior pituitary gland
3. Lesion in hypothalamus
55
What is the pattern in which growth hormone is secreted?
1. pulsatile diurnal manner - greatest secretion during deep, slow wave sleep (between stage 3 and 4) - lowest secretion during the day
56
1. What stimulus can cause secretion of Growth Hormone? (7)
1. Arginine
2. Fasting
3. Exercise
4. Stress
5. Hormones Ghrelin, Estrogen, and Testosterone
6. Low serum glucose
7. Low Fatty acids
57
What is Growth Hormone secretion inhibited by? (6)
1. Increased serum glucose
2. Increaed Fatty Acids
3. Obesity
4. Aging
5. Somatostatin
6. IGF-1 (negative feedback)
58
Secretion of GH is constant throughout childhood but surges at puberty from stimluation by what two hormones?
1. estrogen and testosterone
59
1. What type of receptors are GH receptors?
2. Where are these receptors found
1. Cytokine receptor - JAK/STAT signaling pathway
2. Liver, adipose tissue, muscle, and growth plate in bone
60
Gigantism vs Acromegaly
1. What causes them
2. What is the difference
1. GH excess causes both of these - generally due to a pituitary adenoma
2. Gigantism is seen in children and lead to very tall children. Acromegaly is in adults and leads to enlarged jaw, course facial features, enlargement of nose, enlarged hands and feet, etc
61
What changes are seen in someone with acromegaly in terms of
1. physical appearance
2. Insulin interaction
3. organ size
4. Joints
5. CV
How do you dx this?
1. enlarged jaw with course facial features, enlargement of nose, enlarged hands and feet
2. Risk of insulin resistance leading to diabetes (GH is anti-insulin)
3. Organ enlargement
4. Joint pain
5. CV disease
1. dx by measuring GH levels after a glucose tolerance test and observing no reduction in GH after high glucose levels are present. (Remember high serum glucose decreases GH levels)
62
Laron's Syndrome
1. What causes this
2. What symptoms are seen
3. Treatment
1. GH receptors are mutation - so IGF-1 is not produced
2. Severe growth retardation, short stature
3. Recombinant IGF-1
63
1. What type of receptor is IGF-1 receptor?
1. Tyrosine Kinase Receptor
64
1. When amino acids and glucose are in ample supply **in the tissues**, what happens to GH levels in muscle?
2. What about when glucose but NOT amino acids are available
1. GH levels increase leading to amino acid uptake and protein synthesis in muscle + IGF-1 production by liver
2. GH secretion is inhibited - promoting caloric storage but not muscle growth
65
When doing pituitary function testing what does cosyntropin stimulation test test for and how?
1. Undersecretion in adrenal axis - Cosyntropin is an ACTH so when given it should increase cortisol production. If it doesn't then there is undersecretion.
66
When doing pituitary function testing what does stimulation via insulin, glucagon, arginine test for?
1. To assess undersecretion of GH - when given insulin, glucagon, and arginine it stimulates increase in GH hormone production/release
67
When doing pituitary function testing what does water deprivation test for?
1. ADH undersecretion - when water is deprived ADH is produced to keep water balance but if undersecreted then this will not occur normally.
68
When doing pituitary function testing what does dexamethasone suppression test test for?
1. To assess hypersecretion of adrenal axis- Dexamethesone acts like a cortisol which lowers ACTH released by pituitary gland. If this does not occur then there is hypersecretion of ACTH
69
When doing pituitary function testing what does oral glucose tolerance test test for?
1. Tests for hypersecretion of GH - when given oral glucose then GH should go down but if it doesn't then there is hypersecretion of GH
70
Craniopharyngioma
1. What is it?
2. What hormone abnormalities can occur
1. A benign tumor that derives from rathke's pouch
2. Due to compression can lead to hypopituitarism, headache, visual defects, behavioral changes
71
Empty Sella Syndrome
1. what is it
2. what hormone changes are seen
3. What is the typical patient
1. When a small anatomical defect above the pituitary gland allows CSF to partially or completely fill the sella turcica and it presses on pituitary gland.
2. Hypopituitarism
3. Usually in women who are obese or have HTN
72
Pituitary Apoplexy
1. What is it
2. What hormone changes occur?
1. Condition where a pituitary tumor spontaneously hemorrhages into the pituitary gland.
2. Hypopituitarism
73
Sheehan syndrome
1. What is it
2. Hormone changes that occur?
1. Excessive blood loss during or after delivery of baby may affect function of pituitary gland - leading to form of maternal hypopituitarism
2. In pregnancy pituitary gland is enlarged by blood supply to it doesn't increase so this leaves pituitary gland at risk for infarction if there is excessive blood loss with delivery of baby.
74
Kallmann Syndrome
1. What is it
2. What symptoms are common
3. What imaging findings are common?
1. the body does not make enough of GnRH - hypopituitarism
2. Seen with delayed or absent puberty and impaired sense of smell
3. MRI brain shows olfactory bulb hypoplasia
75
What are pituitary tumors called if
1. they are <10 mm
2. >10 mm
3. 40 mm
1. microadenomas
2. macroadenomas
3. giant adenomas
76
Pituitary Adenomas
1. What is it?
2. what hormone changes occur?
3. most common type?
1. Tumors of the anerior pituitary
2. Can cause hypo or hypersecretion of hormones - depends on tumor
3. Prolactinoma - increased prolactin release
77
For someone with acromegaly what are the treatment options?
1. surgery
2. medical therapy (dopamine agonist, somatostatin receptor ligand, GH receptor antagonist) - octreotide, pegvisomant, carbergoline
3. radiation therapy
78
How is acromegaly diagnosis confirmed?
1. via IGF-1 levels
2. via GH levels
1. serum IGF-1 concentration - unlike GH, serum IGF-1 concn do not vary hour to hour according to stimuli. Thus if serum IGF-1 is elevated this is most likely acromegaly.
2. If normal serum IGF-1 then patient doesn't have acromegaly
3. If serum IGF-1 concn is equivocal (uncertain) then serum GH should be measured after oral glucose admin. If GH is not suppressed then you can confirm acromegaly.
79
What is initial treatment for pituitary microadenomas?
1. Medical therapy without surgical intervention
2. This is often enough to tx and alleviate sx - may even shrink tumor
3. If it doesn't work then sx or radiation can be done
80
Craniopharyngioma vs pituitary adenoma
Pituitary adenomas are tumors that come from your pituitary gland, and craniopharyngiomas are located near that gland
81
Cushing syndrome
1. What is it?
2. Common signs and sx?
1. this is excess cortisol in body due to various reasons.
2. Moon face, stripes on belly, weight gain and fatty tissue deposits like buffalo hump, thinning fragile skin that bruises easily, HTN, hyperglycemia, etc
82
Cushing syndrome or Cushing disease- How to diagnose this (3 main ones and 2 other ones)
1. late night salivary cortiosl (2 measurements)
2. 24 hours urinary free cortisol excretion
3. Overnight dexamethasone suppresion
4. ACTH level - to understand if cushing disease, cushing syndrome
5. Localize possible adenoma via MRI
83
Cushing DISEASE treatment
1. surgery
2. medical therapy (target pituitary, Block glucocorticoid receptor, target adrenal gland to inhibit adrenal steroidogenesis)
3. radiation
84
Syndrome of Inappropriate ADH secretion (SIADH)
1. What is it?
2. pathogenesis? (multipe)
1. too much ADH production -> leads to hyponatremia
2. Certain cancers (tumors producing their own ADH such as SCLC), CNS issues, meds, sx under anesthesia, lung disease, hormone deficiency (adrenalcortical deficiency is a stimulus for ADH secretion, hypothyroidism can cause decreased CO which makes baroreceptors think BP is low and increase ADH production -> both lead to SIADH sx)
85
1. What is multiple endocrine neoplasia? (MEN)
2. inheritence pattern?
1. group of rare autosomal dominant genetic disorders (germline mutations) → leads to multiple endocrine gland tumors
2. Autosomal dominant
86
MEN1
1. Where are the tumors found?
2. Which tumor is usually first finding?
3. Which tumor is not seen in other MEN syndromes?
4. What is the gene mutation with this?
1. Parathyroid adenoma (on parathyroid glands), Pituitary adenoma (on pituitary gland), Pancreatic tumors (neuroendocrine type tumor)
2. Parathyroid adenoma
3. Pituitary adenoma
4. MEN1 gene mutation - unable to code for menin protein
87
MEN2A
1. Where are the tumors/abnormalities found? (3)
2. What is the gene mutation with this?
1. Medullary thyroid carcinoma, pheochromocytoma (on adrenal gland) + Parathyroid hyperplasia (not really a tumor)
2. RET gene mutation
88
MEN2B (or MEN3)
1. Where are the tumors/abnormalities found? (4)
2. What is the gene mutation with this?
1. medullary thyroid carcinoma, pheochromocytomas (on adrenla gland), mucosal neuromas, marfanoid body habitus
2. RET gene
89
Which adrenal gland is larger?
The one on the left- crescent shaped
90
1. What are adrenal glands surrounded by?
2. Where are the adrenal glands in relation to peritoneum?
1. perinephric fat and renal fascia
2. retroperitoneal
91
1. What innervates the adrenal glands?
1. Innervation from celiac plexus and abdominopelvic splanchnic nerves
92
1. What are the 3 primary sources of blood supply to adrenal glands
2. What is the venous drainage of adrenal glands?
1. superior, middle, inferior suprarenal artery
2. Suprarenal vein
93
1. What is the function of the adrenal gland medulla?
2. What are chromaffin cells?
1. secretes epinephrine, norepinephrine (fight or flight response)
-Blue bracket
2. large pale staining cells that secrete epinephrine and norepinephrine
94
What are the three main parts of the cortex of the adrenal gland that make steroid hormones?
1. Zona glomerulosa (black)
2. Zona fasciculata (blue)
3. Zona reticularis (dotted)
95
What steroid hormone does the zona glomerulosa make?
1. mineralcorticoids (aldosterone)
96
What steroid hormone does the zona fasciculata make?
1. glucocorticoids (cortisol and corticosterone)
97
What steroid hormone does the zona reticularis make?
1. Secretes adrenal androgens (DHEA, androstenedione) - promotes growth of axillary and pubic hair
98
How is mineralcorticoids (aldosterone) made in zona glomerulosa? (start with cholesterol)
1. Cholesterol goes into mitochondria and is converted to pregnenolone.
2. Pregnenolone moves out of mitochondria and into cytosol
3. pregnenolone converts into progesterone
4. progesterone becomes 11-deoxycorticosterone via **21 A hydroxylase**
5. 11-deoxycorticosterone becomes corticosterone via **11 B hydroxylase**
4. **aldosterone synthase** converts corticosterone into final aldosterone product (ALL IN ZONA GLOMERULOSA)
| theres no 17A hydroxylase in glomerulosa cells, why one path is followed
99
How is glucocorticoids made in zona fasciculata?
1. pregnenolone and progesterone come from zona glomerulosa and into zona fasciculata
2. **17 alpha hydroxylase** converts them into 17 (OH) pregnenolone into 17 (OH) progesterone
3. 17 (OH) pregnenolone converts into 17 (OH) progesterone
4. **21 A hydroxylase** converts 17 (OH) progesterone into 11-deoxycortisol
5. **11 B hydroxylase** converts 11-deoxycortisol into cortisol
6. cortisol converts into cortisone
100
How are androgens made in zona reticularis?
1. 17 (OH) pregnenolone and 17 (OH) progesterone come from zona fasciculata into zona reticularis
2. 17 (OH) pregnenolone becomes DHEA via **17,20 lyase**
3. Both DHEA and 17 (OH) progesterone can become androstenedione and estrone.
4. Androstenedione becomes testosterone and estrone becomes estradiol-17B
5. Testosterone can become Estradial - 17B via **aromatase**
101
1. What is the delta 4 pathway
2. What is the delta 5 pathway
1. Delta 4 pathway causes pregnenolone to progesterone (uses 3 beta hydroxysteroid dehdyrogenase)
2. Delta 5 pathway terminates with DHEA (uses 17 alpha hydroxylase)
102
1. which delta pathway is necessary for aldosterone production (zona glomerulosa)
2. which delta pathway is necessary for cortisone production (zona fasciculata)
3. which delta pathway is necessary for androgen production (zona reticularis)
1. Delta 4
2. Delta 4
3. Delta 5
103
What zone(s) in adrenal cortex atrophy when exogenous corticoids are given?
1. Zona fasciculata and zona reticularis
104
How does cortisol affect...
1. serum glucose
2. immune system
3. Lipids
4. Skin
5. Bone
1. INCREASE SERUM GLUCOSE, more gluconeogenesis in liver, less glucose taken up peripherally
2. suppress immune system and inactivate NF-kB (protects body from uncontrolled inflammatory and immune responses)
3. Increases lipolysis to have more FA -> in effort to create more glucose in serum
4. Decreased collagen, thin skin, easy bruising, striae
5. Osteoporosis
105
1. Cortisol can activate the mineralcorticoid receptor but why is this not an issue usually?
2. How does licorice come into play?
1. cortisol is converted into inactive cortisone via 11B-HSD2 - this prevents the activity on mineralcorticoid receptor
2. Licorice can inhibit 11B-HSD2 and cause HTN and Hypokalemia bc of "apparent mineralcorticoid excess"
106
What stimulates release of aldosterone?
1. The release is controlled by the RAAS system - specifically angiotensin II stimulates release of aldosterone
106
1. What system regulates release of aldosterone?
2. How are glomerulosa cells stimulated to release aldosterone?
1. The release is controlled by the RAAS system - specifically angiotensin II stimulates release of aldosterone
-----
1. Ang II stimulates glomerulosa cells
2. Stimulates Increase Ca2+ via IP3 and stimulates opening of voltage gated Ca channels
3. Sustained increase in Ca increases shuttling of cholesterol into mitochondria and rest of the pathway occurs to make aldosterone
107
1. Where does aldosterone work on the nephron?
2. What changes does it cause?
1. works on the principal cells of the distal nephron (collecting duct)
2. Increased expression of Na/K ATPases on basolateral side of principal cells (for Na uptake)
3. Increased ENaCs on apical side of principal cells (for Na uptake)
4. ROMK channels on apical side of principal cells (to allow for K+ excretion after increased Na/K ATPases)
## Footnote
also stimulates H/K ATPase in intercalated cells (excrete H and uptake K) - bc hyperkalemia promotes ADH secretion
108
How does adrenal insuffiency (lack of cortisol) lead to hyponatremia?
1. Cortisol inhibits ADH secretion
2. Without cortisol, CRH is able to induce ADH secretion (usually inhibited by cortisol) -> there will be excess ADH and more water reuptake leading to hyponatremia
## Footnote
Note that primarily CRH induces ACTH and then cortisol release but effect on ADH is an added function
109
1. How are different parts of androgen steroid hormones made in zona reticularis vs periphery
2. What is the function of sulfotransferase for androgen production?
1. In zona reticularis - DHEA is made
2. In periphery - potent androgens are produced from DHEA sulfate and androstenedione
3. Sulfotransferase makes DHEA into DHEAS and dramatically extends half life of DHEA
110
What does 17,20 lyase need to function?
cytochrome b5
111
How does lack of corticol synthesis affect DHEA production?
1. If no cortisol then ACTH is most likely increased in an effort to make more cortisol
2. most often cortisol cannot be made due to a enzyme that is lacking -> this pushes the pathway toward more production of DHEA
112
1. How is androgen production regulated?
2. How is cortisol production regulated?
3. How is aldosterone production regulated?
1. there is no negative feedback or axis so it relies solely on cortisol doing negative feedback on ACTH.
2. This is an axis (review) - has negative feedback
3. This is via the RAAS system
113
1. What enzyme deficiency most commonly leads to congenital adrenal hyperplasia, salt **WASTING**, and excess adrenal androgens?
2. Explain
1. 21 alpha hydroxylase - gets pushed toward DHEA production
## Footnote
salt wasting is innapropriate Na excretion due to low aldosterone
114
1. What enzyme deficiency most commonly leads to congenital adrenal hyperplasia, salt **RETENTION**, and excess adrenal androgens?
2. Explain
1. 11B hydroxylase deficiency - pushes pathway towards production of DHEA and 11-DOC (which is a mineralcorticoid! so can do some activity that aldosterone does)
115
1. Synthesis of epinephrine in the adrenal medulla is regulated by what hormone?
2. Why
1. cortisol - Cortisol facilitates expression of PNMT which is necessary for epinephrine production
116
What is the stimulus for epinephrine and norepinephrine release?
1. adrenal medulla is innervated by sympathetic preganglionic neurons that release ACh
2. Occur on fight or flight response situations
| Released directly into blood
117
How does direction of blood supply help with production of epinephrine in adrenal medulla?
1. Blood flows from cortex to medulla and so it picks up cortisol from the cortex and takes it to the medulla where it can facilitate Epi production
2. It helps that in fight or flight situations both cortisol and epinephrine are expected to be released.
118
What type of imaging is done first to assess HPA axis?
1. MRI - best choice because it is noninvasive
119
What are the 4 main causes of CUSHING SYNDROME
1. Exogenous corticosteroids
2. Pituitary adenoma (Cushing DISEASE) - secreting ACTH
3. Adrenal gland tumors - secreting cortisol
4. ACTH producing non-pituitary tumors (like SCC in lungs)
*all leads to increased cortisol levels*
120
1. What is Cushing DISEASE?
2. How do you test for cushing disease pathology?
1. pituitary adenoma that secretes ACTH - Leads to increased cortisol levels (cushing syndrome)
2. dexamethasone testing - dexamethasone is given and this acts like a cortisol analog which should ideally reduce ACTH but this may not happen in cushing disease
121
How does dexamethasone suppresion test results indicate various reasons for cushing syndrome?
1. low dose test
2. high dose test
1. **Low Dose:** tells you if pt has cushing syndrome - if at pt of measurement cortisol is low then person is "normal" bc dexamethasone did its job of reducing cortisol
2. **Low Dose:** if at pt of measurement cortisol is high or normal then patient has cushing syndrome - inhibiting ACTH did not work to suppress cortisol
3. **High Dose:** tells you what is causing pts cushing syndrome - if at pt of measurement cortisol is low - then Cushing Disease (pituitary adenoma)
4. **High Dose:** if at pt of measurement cortisol is high/normal - then measure ACTH levels
- *ACTH low* -> indicates Adrenal Cushing - bc ACTH was inhibited correctly but cortisol is still being made (most likely abnormality at adrenal glands)
- *ACTH high *-> Ectopic ACTH - most likley at lung - even with inhibition ACTH is still coming from somewhere else that is not pituitary gland
| Dexamethasone reduces ACTH release in healthy patients
122
Primary Hyperaldosteronism
1. What is it?
2. What causes it?
3. What pathology/abnormalities does it cause?
1. Increased aldosterone production within adrenal gland cortex
2. Can be due to zona glomerulosa hyperplasia, cortical adenoma, cortical carcinoma, etc
3. Leads to hypertension
123
Secondary Hyperaldosteronism
1. What is it?
2. What causes it?
3. What pathology/abnormalities does it cause?
1. When there is a problem elsewhere in the body that causes the adrenal glands to release too much aldosterone. Primary - the issue was in the adrenal gland
2. Renin driven due to reduced renal perfusion or ineffective circulating volume + pregnancy
124
Congenital Adrenal Hyperplasia
1. Due to what deficiency?
2. Inheritance pattern?
1. deficiency in 21 hydroxylase - pushes production of steroids in cortex towards androgens (DHEA)
2. Autosomal recessive
125
Congenital Adrenal Hyperplasia
1. what are the affects on boys vs girls
1. Girls get ambiguous genitalia, virulization
2. Boys - precocious (early than normal) puberty
126
What are some causes of acute hypocortisolism?
1. abrupt withdrawal of exogenous steroids
2. Adrenal crisis -
3. Massive adrenal destruction due to thinks like DIC, neonatal hypoxia, waterhouse-friderichsen syndrome
127
What are some causes of chronic hypocortisolism?
1. Autoimmune adrenalitis (60-80% of cases)
2. Autoimmune polyendocrine syndromes
3. Granulomatous inflammation due to TB
4. AIDS
5. Metastatic cancer
6. Genetic basis - rare
128
Polyendocrine autoimmune syndrome type 1 vs type 2
1. what are they (generally speaking)
2. which is more common
1. functional impairment of multiple endocrine glands due to loss of immune tolerance. (immune system mistakenly attacks endocrine glands)
2. Type 2
129
What signs and symptoms differentiate polyendocrine autoimmune syndrome 1 vs 2
Type 1
1. 3 cardinal components: **Hypothyroidism, Oral candidiasis, Adrenal insufficiency** (ages 10-15), hypogonadism, malabsorption and GI disorders
2. mutations in AIRE
Type 2
1. 2/3 of the following : **Adrenal insufficiency (the principal manifestation), autoimmune thyroid disease, T1D**
2. other non-endocrine problems like vitiligo, myasthenia gravis,
130
Primary Adrenal Insufficiency
1. what is it?
2. What happens to levels of ACTH and cortisol
3. another name for this?
1. Failure of the adrenal glands - don't make enough hormones.
2. Since this is just an issue of adrenal glands producing hormones, ACTH will be increased in an attempt to increase hormones but adrenal glands simply can't
2. Addison's Disease
131
Secondary Adrenal Insufficiency
1. what is it?
1. Failure of pituitary to release ACTH -> this leads to only cortisol to be low
132
1. What is adrenal crisis
2. what is the symptoms, manifestations
1. adrenal glands are not able to make hormones - specifically cortisol and aldosterone
2. main manifestation is shock - remember cortisol is meant to sustain life and aldosterone maintains BP. Without these hormones then low BP, hypoglycemia, etc - it is life threatening
133
what are some symptoms of cortisol loss?
1. hypoglycemia
2. low BP (postural hypotension)
3. weakness, fatigue
4. nausea, abdominal pain, diarrhea
5. weight loss
134
Waterhouse-Friderichsen Syndrome
1. What is it associated with
2. What is it?
3. Symptoms
1. meningococcal infection in children and adolescents
2. bilateral hemorrhage into the glands causing them not to function properly - usually due to infection
3. Shock and DIC. Risk factors for this to occur are thrombocytopenia, heparin use, sepsis
135
Addison's disease
1. What causes this?
1. Autoimmune adrenalitis - leads to atrophy of cortex, medulla is spared
136
1. What is a pheochromocytoma?
2. What does this tumor derive from
3. Symptoms
4. Histology marker
1. an adrenal medulla neoplasm - tumor secretes catecholamines
2. chromaffin cells in adrenal medulla
3. HTN, headaches, palpitations, sweating, pallor, etc
4. Zellballen pattern in histology
137
1. What are paragangliomas?
2. What does this tumor derive from?
3. What are common locations?
1. Tumor that secretes catecholamines but it does not derive in the medulla of adrenal gland
2. Derives from sympathetic ganglia outside of the adrenal gland.
3. Can occur in any organ containing paraganglionic tissue
138
Neuroblastoma
1. what is it?
2. most often in what type of patient
3. Where can these occur?
1. tumor that grows in immature nerve tissue - causes issues related to tumor mass effects
2. children before age of 3
3. adrenal gland is most common but also abdomen, mediastinum, sympathetic chain, etc
139
1. Mets to what areas can mark paragangliomas as malignant?
2. What about Pheochromocytomas?
1. head/neck, retroperitoneum
2. lymph nodes, lungs, liver, etc
140
1. What is given for cortisol replacement? (3)
2. What is given for mineralcorticoid replacement (2)
1. hydrocortisone, prednisone, dexamethasone
2. Fludrocortisone acetate and extra supplements
141
Glucocorticoids
1. clinical use
2. MOA
3. side effects (many so list a few)
1. Glucocorticoids (GCs) are steroid hormones widely used for the treatment of inflammation, autoimmune diseases, and cancer
2. glucocorticoids are lipophilic nature that rapidly pass plasma membrane and go to the nucleus to lead to gene expression changes.
3. the longer the use, the greater the risk for side effects: fluid retention, HTN, aldosterone like effect, increased likelihood of infection, peptic ulcer disease, myopathy, cataracts, osteoporosis, hyperlipidemia (bc increase of cholesterol), hyperglycemia
142
1. What are the short acting glucocorticoids? (2)
2. anti-inflammatory potency
3. mineralcorticoid/sodium retaining potency?
1. Cortisone and Hydrocortisone
2. least anti-inflammatory potency
3. most mineralcorticoid potency
143
1. What are the intermediate acting glucocorticoids? (3)
2. anti-inflammatory potency
3. mineralcorticoid/sodium retaining potency?
1. prednisone, triamicinolone, methylprednisone
2. mid anti-inflammatory potency
3. prednisone has mid mineralcorticoid potency, the rest have none
144
1. What are the long acting glucocorticoids? (2)
2. anti-inflammatory potency
3. mineralcorticoid/sodium retaining potency?
1. dexamethasone, betamethasone
2. highest anti-inflammatory potency
3. No mineralcorticoid/sodium retaining potency
145
1. What is the purpose of alternate-day therapy for patients on long-term glucocorticoids?
1. uses large dose of intermediate agent in the morning -this will reduce the amount of HPA axis suppression and reduce risk for cushing syndrome
146
1. What is the non-pharmacological therapy for cushing syndrome (3)
1. sx to remove tumor causing issue
2. radiation
3. bilateral adrenelectomy
147
1. Why is adjunctive therapy for cushing syndrome a limited tx option
1. disease usually relapses when medications are discontinued
2. There are increased adverse effects with prolonged use of medications for cushing syndrome
| *patient only lives 4-5 yrs if untreated*
148
Mitotane
1. What is it used for?
2. MOA?
3. Side effects?
1. For cushing syndrome (increased cortisol)
2. Adrenolytic agen (cytotoxic effects on adrenal cortex):: Medical adrenelectomy (complete ablation of cortisol production)
3. GI issues (N/V, anorexia, diarrhea), Neuromuscular issues (fatigue/ muscular weakness, CNS depression)
149
Aminoglutethimide
1. What is it used for?
2. MOA?
3. Side effects?
1. For cushing syndrome (increased cortisol)
2. Targets enzyme that is part of synthesis of corticosteroids - inhibits **cholesterol side chain cleaving enzyme (cholesterol desmolase)**
3. Drowsiness, bone marrow suppression, drug induced lupus
| Adrenal enzyme inhibitor
150
Metyrapone
1. What is it used for?
2. MOA?
3. Side effects?
1. For cushing syndrome (increased cortisol)
2. Targets enzyme that is part of synthesis of corticosteroids - inhibits **steroid 11 beta hydroxylase**
3. HTN, headache, lightheaded, rash, hirsutism
| Adrenal enzyme inhibitor
151
Ketaconazole
1. What is it used for?
2. MOA?
3. Side effects?
1. For cushing syndrome (increased cortisol)
2. Targets enzyme that is part of synthesis of corticosteroids - inhibits **steroid 17 alpha hydroxylase, 11 beta hydroxylase, and cholesterol desmolase at higher doses**
3. gynecomastia, decreased libido, impotence
| Adrenal enzyme inhibitor
152
Mifepristone
1. What is it used for?
2. MOA?
3. Side effects?
1. For cushing syndrome (increased cortisol)
2. Progesterone and glucocorticoid receptor antagonist
3. Fatigue, GI , headache, HTN, endometrial thickening, hypokalemia
153
1. Where is insulin released from?
2. what is the role of incretins
3. What can dispose/take up glucose after a meal?
1. beta cells in islets of langerhans of the pancreas
2. incretins are in the gut and they facilitate insulin secretion. 50% of insulin secretion is attributed to this.
3. liver (glycogen storage), fat tissue (uses glucose to synthesize triglycerides), and skeletal muscle (80% is disposed via skeletal muscle)
154
1. What is the dx criteria for someone with diabetic sx
2. What about someone who is asymptomatic but has risk factors
1. sx + glucose >200 mg/dl is enough to dx diabetes in a symptomatic patient (classic triad is polyuria, polydipsia, polyphagia)
2. Check fasting plasma glucose (if 100-125 mg/dl then pre-diabetic but if >= 125 mg/dl then diabetes)
155
1. What is a normal Hemoglobin A1C?
2. Pre-diabetic?
3. Diabetic?
1. <5.7%
2. 5.7-6.4%
3. >= 6.5%
156
1. What test is often used to test for gestational diabetes?
2. Explain it?
1. glucose tolerance test
2. Oral glucose load administered and then plasma glucose measured 1-3 hours later - high enough glucose indicates diabetes.
157
1. When is Hemoglobin A1C used?
2. When is fasting plasma glucose used?
3. When is oral glucose test used?
1. To check longitudinal progress of a patient and at times for dx
2. for diagnosis of asymptomatic patient
3. for gestational diabetes
158
1. What general pathophysiology mechanism leads to Type 1 diabetes?
2. What HLAs are associated with this?
1. Type IV hypersensitivity - T cell mediated destruction of beta cells which release insulin
2. HLA-DR3 and HLA-DR4
159
1. What is ketoacidosis?
2. More common in which type of diabetes? and at what point of the disease?
3. Tx?
1. Increased amounts of ketones - bc body is trying to make energy sources. But too many of these make body acidodic since ketones are acids.
2. Type 1 diabetes. Most often the first symptoms or presentation a patient experiences. Can also occur when patient skips insulin therapy
3. short acting regular insulin and IV fluids
160
1. What is hyperosmolar coma?
2. More common in which type of diabetes?
3. Sx?
1. Markedly elevated - High glucose levels that can be >1000 -> leads to diuresis and severe dehydration. It is life threatening
2. type 2 diabetes - usually in elderly with comorbid conditions
3. CNS dysfunction, polyuria, polydipsia, dehydration
161
1. What are the 4 dominant effects of long term hyperglycemia?
1. AGE-RAGE binding
2. Protein Kinase C function
3. Polyols oxidative stress
4. Hexosamine pathway
162
1. What is AGE-RAGE binding in long term hyperglycemia?
2. What does increased Protein Kinase C function mean?
1. with hyperglycemia there is increased intracellular glucose derivatives that combine with protein amino groups (known as AGE products) ->
2. these AGE products can cross link with extracellular matrix and lead to vascular damage
3. AGE products can bind RAGE receptors on T cells and macrophages and lead to inflammation and tissue damage
-------------------------
1. Protein kinase C function leads to considerable cytokine secretion and then retinal, renal, neuronal, vascular implications
163
1. What is Polyols-oxidative stress in long term hyperglycemia?
2. What about the hexosamine pathway?
1. This promotes depletion of NADPH which leads to oxidant stress, nerve damage, peripheral neuropathy
2. Increase in *growth factor beta* and *plasminogen activator inhibitor* -> can end up in organ damage
164
Atherosclerosis vs Hyaline arteriosclerosis
1. Which one occurs more often in macrovascular or microvascular areas
2. How are they different
3. What can each pathology cause?
1. Atherosclerosis in macrovascular pathology --- hyaline arteriosclerosis in microvascular pathology
2. Atherosclerosis is a plaque formation but hyaline arteriosclerosis is hardening and loss of elasticity in arteries due AGE mediated crosslinking of matrix
3. Atherosclerosis -> can lead to MI, stroke and Hyaline arteriosclerosis-> can lead to nephropathy, retinopathy, some form of neuropathy
## Footnote
Both have narrowing just one is due to internal plaque and other is thickened walls
165
When testing for pheochromocytomas what should be tested for in plasma and why?
1. Check metanephrine and normetanephrine
2. Can’t check plasma catecholamines becuase they have short half life
166
Neuroblastoma
1. Histology marker
2. symptoms
3. What mutations makes neuroblastomas unfavorable
1. Homer-wright pseudorosettes and small round blue cells
2. bilateral periorbital ecchymoses + other depends on tumor mass effects, can get abdominal pain, wheezing or chest pain, etc.
3. N-MYC
167
Insulin Treatment (insulin analogs)
- which are rapid, short, intermediate, long acting insulin analogs-
1. Lispro, aspart, glulisine
2. glargine, detemir, degludec
3. Regular insulin
4. NPH (isophane)
1. Rapid
2. long acting
3. short
4. intermediate
168
Insulin treatment (insulin analogs)
1. Which subtype is used as bolus (include drug names)
2. Which subtype is used as basal (include drug names)
1. rapid acting (lispro, aspart, glulisine)
2. long acting (glargine, degludec, detemir)
169
Insulin analog (lispro, aspart, glulisine)
1. onset and peak
2. duration of action
3. when are they used
1. 15 min - 1 hour
2. rapid acting
2. pre-meal (the bolus treatment)
170
Regular insulin analog
1. onset and peak
2. duration of action
2. when are they used
1. onset 30 min, peak 2-3 hours
2. short acting
3. used in hospitalized patients with diabetic ketoacidosis or hyperkalemia, only type of insulin given IV
171
Glargine, detemir, degludec insulin analog
1. onset and duration
2. duration of action
2. when are they used
1. 1-1.5 hours and lasts 11-24 hours
2. long acting
3. basal insulin
| *does not contain human insulin molecules*
172
1. What are the 2 most comon side effect of insulin analog tx?
1. hypoglycemia
2. weight gain
173
Sulfonylureas (SUs)
1. type of drug
2. drug names (3)
3. MOA
4. What type of diabetes is this used in?
1. Insulin secretagogues
2. glyburide, glipizide, glimepiride
3. Closure of K+ channels in beta cells making it easier to depolarize and results in easier release of insulin - increases insulin release
4. Type 2 diabetes
174
Meglitinides
1. type of drug
2. drug names (2)
3. MOA
4. What type of diabetes is this used in?
1. secretagogues
2. repaglinide, nateglinide
3. similar mech as sulfonylureas
4. Type 2
175
Thiazolidinediones (TZDs)
1. type of drug
2. drug names (2)
3. What type of diabetes is this used in?
1. secretagogues
2. "glitazones" or TZDs - pioglitazone, rosiglitazone
3. Type 2 diabetes
176
Thiazolidinediones (TZDs)
1. MOA (various potentional mechanisms - 4)
1. bind to PPAR gamma receptors in nucleus of cells -> promotes fatty acid uptake peripherally which leads to increased muscle, fat, and liver sensitivity to insulin
2. GLUT-4 transcription upregulated to increase glucose transport
3. Adiponection is secreted to increase insulin sensitivity
4. Antagonism of TNF alpha insulin resistance
177
GLP-1 agonists
1. type of drug
2. drug names (2)
3. MOA
4. What type of diabetes is this used in?
1. secretagogue
2. exenatide, liraglutide
3. incretin mimetic to potentiate glucose stimulated insulin secretion + suppresses appetite + delays gastric emptying
4. Type 2 diabetes
178
GLP-1 receptor agonists
1. side effects
2. contraindications
1. nausea, vomiting, pancreatitis
2. avoid in CKD stages 4-5
179
Effects on weight from
1. sulfonylureas
2. meglitinides
3. TZDs
4. GLP-1 receptor agonists
5. DPP-IV inhibitors
6. Amylin Analog
7. Metformin
8. SGLT2 inhibitors
1. increased
2. increased
3. increased
4. decreased
5. neutral
6. decreased
7. Neutral
8. decreased
180
DPP-4 Inhibitors
1. type of drug
2. drug names (2)
3. MOA
4. side effects
1. secretagogue
2. sitagliptin, linagliptin
3. DPP normally degrades GIP (incretins) and GLP-1 -> so inhibition of this promotes incretin effects
4. pancreatitis
181
Amylin Analog
1. type of drug
2. drug names (1)
3. MOA
1. secretagogue
2. pramlintide
3. slows gastric emptying, inhibits glucagon production, decreases postprandial glucose
182
Biguanide
1. type of drug
2. drug names (1)
3. MOA
4. side effects
1. secretagogue
2. metformin
3. decreases hepatic glucose output, decreases intestinal glucose absorption
4. B12 deficiency, lactic acidosis
183
SGLT2 inhibitors
1. type of drug
2. drug names (2)
3. MOA
4. side effects
1. secretagogue
2. canagliflozin, dapagliflozin, empagliflozin (-liflozin)
3. SGLT2 is normally responsible in reabsorption of glucose in proximal tubule of the kidney. SGLT2 inhibitors -> reduces glucose reabsorption, thus increasing glycosuria
4. Hyperkalemia, hypotension
184
Alpha-glucosidase inhibitors
1. type of drug
2. drug names (3)
3. MOA
1. secretagogue
2. acarbose, miglitol, voglibose
3. competitive inhibitors of intestinal alpha glucosidases with slows absorption of glucose and makes glucose be absorbed more distally in short intestine
185
What can the following herbal supplements do to tx type 2 diabetes?
1. Ginseng
2. Fenugreek Seed
3. Garlic/Fiber
1. alters lipid and carb metabolism
2. reduces post prandial glucose levels, improves plasma glucose and insulin response
3. reduces BP and increases insulin in healthy volunteers
186
What is the best initial agent for T2DM?
1. metformin - there is no contraindication for its use
187
How does estrogen and testosterone effect growth hormone secretion?
1. Estrogen - stimulates GH secretion indirectly by reducing IGF-1 feedback inhibition
2. Testosterone - stimulates GH secretion centrally by pushing the GH/IGF-1 axis
188
1. how does hypotyroidism affect normal growth?
2. How does elevated cortisol affect normal growth?
1. remember thyroid hormone increases metabolic rate and increases protein syntehsis so without thyroid hormone a person can have slow growth. Serum IGF levels are reduced.
2. Prolonged elevation of cortisol can inhibit growth. Exogenous cortisol reduces GH concentration. Cortisol inhibits osteoblast activity and increases protein catabolism
189
Pituitary Adenoma
1. Microscopic appearance - what do cells and nuclei look like?
1. sheets of uniform cells with round or ovoid nuclei that has "salt and pepper" neuroendocrine type chromatin
190
Rathke's Cyst
1. What is it?
1. fluid filled cyst that compresses the normal pituitary tissue. Forms in the pars intermedia (part that divides anterior from posterior pituitary)
191
Growth Hormone Deficiency
1. What is the treatment?
2. side effects of tx?
1. recombinant human growth hormone (rhGH) or somatotropin (synthetic GH) - daily injections
2. reduced insulin sensitivity, worsening scoliosis, pseudotumor cerebri, etc
191
When would exogenous IGF-1 (mecasermin, increlex) be used?
1. primary IGF-1 deficiency (either due to mutations in GH receptor, post GH receptor signaling pathway issues, or IGF-1 gene mutations)
192
What is the hook effect on prolactin assays
1. With so much analyte, the excess analyte can bind signal antibody on solute instead of when analyte is already attached to capture antibody. This makes results inaccurate and like analyte is lower than it actually is.
193
1. How does Prolactin affect GnRH?
1. Prolactin decreases GnRH
194
1. What is primary therapy for someone with prolactinoma?
2. what about someone wtih stalk effect and prolactinoma?
1. dopamine agonist (bromocriptine and cabergoline)
2. need surgery because by inducing dopamine effects nothing will happen since dopamine needs to get through stalk which is closed off.
