Endocrine Flashcards
1
Q
What are notable sites of extragonadal production of testosterone and other androgens?
A
Skin, adipose tissue, adrenals
2
Q
What can testosterone be converted into?
A
Androstenedione (reverse rxn! This is a testosterone precursor), estradiol, and DHT
3
Q
What enzyme converts testosterone to DHT?
A
5α-reductase
4
Q
The hypothalamus secretes ______, which acts on gonadotrophs in the anterior pituitary
A
GnRH
5
Q
GnRH stimulates the release of ________ from the gonadotrophs of the anterior pituitary
A
LH and FSH
6
Q
GnRH secretion is _______
A
pulsatile
7
Q
Continuous secretion of GnRH does what?
A
Suppresses the release of LH and FSH
8
Q
LH acts on _______ cells
A
Leydig
9
Q
What are Leydig cells? What do they do?
A
Interstitial cells in the testes
Produces testosterone
10
Q
FSH acts on _______ cells
A
Sertoli
11
Q
What are Sertoli cells? What do they do?
A
Cells in the testes in direct contact with the seminiferous tubules
Functions:
- synthesis of P450 aromatase (converts testosterone to estradiol)
- production of growth factors that support spermatogenesis
- synthesis of inhibins
12
Q
What does aromatase do?
A
Converts testosterone to estradiol
13
Q
20,22-desmolase
A
Enzyme that converts cholesterol into pregnenolone
Rate limiting step
LH stimulates this rxn
14
Q
What type of G protein receptor does GnRH bind to in the anterior pituitary?
A
Gq –> PLC –> IP3 + DAG
15
Q
Theca cells have receptors for what hormone?
A
LH
16
Q
Granulosa cells have receptors for what hormone?
A
LH and FSH
17
Q
Which hormone decreases the release of GH?
A
Somatostatin
18
Q
Mecasermin
A
Recombinant IGF (insulin-like growth factor)
Used to treat pts w/ growth hormone insensitivity
Ex: Laron dwarves
Concern for hypoglycemia, so ingest carbs prior to taking
19
Q
Recombinant GH
A
Replacement tx in children w/ deficiency
20
Q
Octreotide
A
Somatostatin analogue
Uses:
- excess GH 2/2 pituitary adenoma
21
Q
Pegvisomant
A
GH receptor antagonist
1x daily dose, SQ
22
Q
What molecule directly controls the release of prolactin?
A
Dopamine at D2 receptors in the hypothalamus
Dopamine INHIBITS prolactin release
23
Q
Cabergoline
A
Dopamine agonist used to treat hyperprolactinemia (prolactinomas)
Preferred agent; more selective for D2 receptors and more effective
May cause hypotension, dizziness; valvular HD at higher doses
May inhibit GH secretion in some pts, but not as effective as SST analogues.
24
Q
Bromocriptine
A
Dopamine agonist
Used to treat hyperprolactinemia
Also activates D1 receptors
Frequent side effects include N/V, headache, and postural hypotension; less frequently can see psychosis or insomnia
25
Vasopressin
= ADH
Tx parenteral admin, t1/2 = 20 min
Endogenous release occurs w/ rising blood osmolality --> retain water in body via adding water channels (aquaporins) in luminal membrane
26
Desmopressin (DDAVP)
ADH analogue that is more stable; t1/2 = 1.5-2.5 hours
No vasopressor effect
27
Central diabetes insipidus
Can result from head injury, pituitary tumors, cerebral aneurysm, or ischemia = inadequate secretion of ADH from posterior pituitary
Tx: desmopressin, chlorpropamide (1st gen sulfonylurea)
28
Nephrogenic diabetes insipidus
Congenital or drug-induced (lithium) = inadequate ADH action
Tx: fluids, low salt/protein diet, thiazide diuretics (paradoxical mechanism), NSAIDs like indomethicin (inhibit PGs, which lower ADH effects)
29
Syndrome of Inappropriate Secretion of ADH (SIADH)
Incomplete suppression of ADH secretion under hypoosmolar conditions. Thus, people retain water & urine is inappropriately concentrated.
Causes: malignancy, pulmonary diseases, trauma, infections
One of the most common causes of hyponatremia; occurs in 15-22% of hospitalized pts
Tx: restrict free water intake, V2 receptor antagonists, demeclocyline
30
What drugs induce SIADH?
SSRIs, haloperidol, TCADs
31
Demeclocyline
Inhibits ADH effect on distal tubule
Treats hyponatremia in SIADH
32
Tolvaptan or Conivaptan
V2 receptor antagonists
Tx for hyponatremia in SIADH
Warning against rapid correction of hyponatremia: cerebellar pontine myelinolysis!!!
33
What is an example of an adrenal glucocorticoid?
Cortisol
34
What is an example of an adrenal mineralocorticoid?
Aldosterone
35
What controls the release of ACTH? Where is it released from?
CRF (from hypothalamus) controls release of ACTH
ACTH is released from the anterior pituitary
36
If there's an -OH group at 11 in corticosteroids, it's _____.
active
Ex: cortisol, prednisolone
Liver does this
37
If there's a ketone group at 11, it's ______.
inactive
Ex: prednisone, cortisone
Kidney does this
38
When using corticosteroids to treat Addison's Disease (physiologic use), what drug(s) should be used and why?
Cortisol (aka hydrocortisone)
It's necessary to use an agent with both glucocorticoid and mineralocorticoid properties (cortisol is 1:1) to mimic the physiologic effects of the adrenals.
Unless the disease is mild, fludrocortisone (high mineralocorticoid activity) is usually required for sufficient salt-retaining effect.
39
When using corticosteroids to treat inflammation (pharmacologic use), what drug(s) should be used and why?
Prednisone, triamcinolone, dexamethasone
All have significantly higher glucocorticoid properties, which = anti-inflammatory properties
40
Which hormones are produced by the adrenal cortex?
1. Cortisol
2. Aldosterone
3. Sex hormones (small amounts)
41
Which hormones are produced by the adrenal medulla?
Epinephrine and norepinephrine
42
Which one is active, prednisone or prednisolone?
Prednisolone is the active form
Prednisone gets converted by liver into active form
43
Ketoconazole
Inhibits downstream conversion of cholesterol into other hormones. Blocks 17α-hydroxylase and 17,20-lyase.
Used to treat Cushing's Syndrome (hypercortisolism)
May inhibit androgen synthesis, leading to gynecomastia & impotence
44
Mifepristone
Glucocorticoid receptor antagonist
Used in Cushing's Syndrome
Not a first-line drug - approved to control hyperglycemia secondary to hypercortisolism
Contraindicated for use during pregnancy - women of child-bearing age should use contraception
"My wife has pristine cushions"
45
Congenital adrenal hyperplasia
Due to congenital enzyme defects, the production of cortisol is severely diminished
Cortisol normally has negative feedback effect on ACTH levels; thus, here, ACTH levels are extremely high
Increased ACTH leads to overstimulation of adrenal gland and adrenal hyperplasia
46
How is congenital adrenal hyperplasia treated in children vs. adults?
Children - hydrocortisone
Adults - prednisone or dexamethasone
The goal of therapy is to replace deficient steroids while minimizing adrenal sex hormone (overproduction) and glucocorticoid excess (via overtreatment).
47
Pheochromocytoma
Excess epinephrine/norepinephrine production due to a tumor in the adrenal medulla
48
What does the pharmacological preparation for pheochromocytoma surgery consist of?
Prep w/ α-blockers for several days to control blood pressure
THEN, beta-blockade to control tachycardia and arrhythmias
Can supplement with CCBs (nefidipine) if blood pressure control is inadequate or side effects are not tolerated
49
Phenoxybenzamine
Irreversible α1-α2 receptor antagonist
Initial step of pheochromocytoma surgery prep
50
Metyrosine
Competitive inhibitor of catecholamine synthesis
Can be added to antihypertensive regimen to reduce catecholamine synthesis for inoperable or metastatic pheochromocytoma tumors
51
Propylthiouracil (PTU)
Antithyroid agent - prevents the oxidation of iodide and thus blocks production of thyroid hormone
(Also inhibits the peripheral diodination of circulating T4 into T3, thus ameliorating sx of thyroid hormone excess)
52
Pendred Syndrome
Characterized by hypothyroidism and sensorineural deafness
Mutation in the SLC26A4 gene, whose product, pendrin, is an anion transporter expressed on the apical surface of thyrocytes and in the inner ear
53
What are some hormones that are tyrosine derivatives?
Epinephrine, norepinephrine, and dopamine
Also thyroid hormone (but it defies the rule of transporter, etc.)
54
Prolactin acts via what pathway in the cell?
Cytokine receptors --> JAK/STAT pathway
55
How is prolactin regulated?
Inhibitory control by dopamine (also called Prolactin Inhibitory Hormone, or PIH), released from the hypothalamus
56
What type of meds will cause an increase in prolactin?
Dopamine D2 antagonists - commonly found in antipsychotic meds
57
Growth hormone acts via what pathway in the cell?
Cytokine receptors --> JAK/STAT pathway
58
What are the effects of GH?
- increased lipolysis (via hormone-sensitive lipase) --> increased FFA
- increased gluconeogenesis, glycogenolysis = antagonizes effects of insulin
- increased uptake of aa into muscle tissue
Thus, diabetogenic
59
What happens with an excess of prolactin?
Decrease in GnRH
= amenhorrhea, decreased sex drive
60
What is the blood test to check GH levels?
IGF-1
61
Galactorrhea
Excessive or inappropriate production of milk
62
Cushing's Syndrome - definition? Sx?
Excess cortisol - either meds or a tumor
Sx:
- moon facies
- central obesity
- osteoporosis
- HTN
- peripheral wasting of fat/muscle
- diabetes
- hypertriglyceridemia
- amenhorrhea/infertility
- excess hair growth
- impotence
- edema
- impaired immunity
- neurocognitive changes/depression
- acne
- violaceous abdominal striae >1 cm
- easy bruising, spontaneous ecchymoses
63
Cushing's Disease
Excess cortisol due to a pituitary adenoma
64
What is the suppression test for Cushing's Syndrome? Explain the 2 versions.
Low dose (1 mg) or high dose (8 mg) dexamethasone suppression test
If neither test suppresses high cortisol levels + low ACTH levels: hyper cortisol production is primary, from the adrenals
If cortisol is not suppressed by 1 mg test, but suppressed by 8 mg test (and high ACTH): Cushing's Disease. Lots of ACTH being produced, but pituitary retains some feedback inhibition, and thus a high enough dose will downregulate ACTH (& cortisol) production
If cortisol is not suppressed by either test + ACTH is VERY high (hundreds): ectopic ACTH production from a tumor outside of pituitary
65
What is the gold standard test for central adrenal insufficiency?
Insulin-induced hypoglycemia
Assesses entire HPA axis
66
What is the cosyntropin test?
Test for central adrenal insufficiency
Give them cosyntropin, which is an ACTH analogue, at supraphysiologic dose; see if adrenals respond
67
Apoplexy
Sudden infarct or hemorrhage of the pituitary gland
Causes headache, vision changes, ophthalmoplegia, and altered mental status
68
Hyperpigmentation is a sign of?
ACTH excess and/or adrenal insufficiency
Reason: melanocyte-stimulating hormone (MSH) is a byproduct of the creation of ACTH from the larger molecule POMC
69
What are the mechanistic actions of ADH?
V1 receptors --> vascular vasoconstriction, platelet aggregation
V2 receptors --> antidiuretic effects in the kidneys via moving aquaporins to the cell membrane = water reabsorption
70
What is the type of pituitary tumor that frequently looks like other tumors and has a "sheet-like" appearance?
Gonadotroph adenoma
= most common type of clinically non-functional adenoma; most common type to come to surgery
71
What is the one type of pituitary tumor that does not have surgery as a first-line treatment?
Prolactinomas
72
SF-1 mutation
Gonadotrophs
FSH/LH-secreting pituitary adenoma
Also the mutation in most of the hormone negative adenomas
73
TTF-1 mutation
Expressed in posterior gland and pituicytomas
74
Pit-1 mutation
Somatotroph stem cell lineage
Can be:
- GH secreting
- prolactin secreting
- mixed
Or acidophil stem cell adenoma
75
T-pit mutation
Corticotrophs
ACTH-secreting pituitary adenoma
76
Adamantinomatous craniopharyngioma
Mostly found in children
77
Papillary craniopharyngioma
Mostly found in adults
78
Tesamorelin
GHRH analog
Used in HIV patients with lipodystrophy 2/2 HAART
Reduces excess abdominal fat
79
What is the order in which anterior pituitary hormones are lost (if there is dysfunction)?
1. GH
2. FSH, LH
3. ACTH
4. TSH
5. PRL
80
What two hormones are controlled by TRH from the hypothalamus?
TSH and prolactin
81
What are some confirmation tests for hyperaldosteronism?
Oral salt test (high NaCl diet x3 days) or IV saline infusion (2 L NS x4 hours)
Normally, aldosterone levels should be undetectable (aldo retains Na+, so if you're getting a huge Na+ dose, levels should plummet). If levels are still elevated after these tests = positive
82
NP-59 adrenocortical scintigraphy
NP-59 is a cholesterol analog
Adrenals use it, just as they use cholesterol, as the base for the other hormones
Can be used to visualizes adrenal issues - bilaterally taken up = hyperplasia, unilaterally taken up = adenoma
83
Pheochromocytoma triad (pt sx) + 1 sign?
Headaches, sweating, palpitations
Sign: hypertension
84
What is the rule of 10's for pheochromocytoma?
10% are malignant
10% are familial
10% are ectopic
10% are bilateral
85
What are the tests for pheochromocytoma?
```
Urine metanephrines (=metabolites of catecholamines)
Positive = >1300 ug/24 hr
```
Urine catecholamines
Positive = >2 fold increase
^^More specificity
Plasma metanephrines
Positive = >0.5 nmol/L
^^More sensitivity
86
What is the composition of the colloid in the thyroid gland?
Thyroglobulin (large concentrations thereof)
87
How does estrogen raise the levels of total T4 and T3?
Estrogen causes the production of more TBG and albumin --> raises the total amount of serum binding proteins
Thus, levels of total T4 and T3 are raised, but not free
88
Which of the thyroid hormone assays is not very reliable?
Free T3 is not reliable
If you need to know, order a total T3
89
What is thyrotoxicosis vs. hyperthyroidism?
Thyrotoxicosis: elevated levels of circulating thyroid hormone
Hyperthyroidism: overproduction of circulating T3 and T4
90
What is the name of the teratoma composed of ectopic thyroid tissue in the ovaries that produces TH?
Struma ovarii
91
Methimazole
Antithyroid agent - prevents the production of thyroid hormone
92
What is the clinical course of thyroiditis?
Initially (0-3 months): ↑ T4 (due to being released from dying cells), ↓ TSH (response)
= hyperthyroid picture
Later (3-6 months): ↓ T4 (stores depleted), ↑ TSH (pituitary kicks in, but thyroid is damaged and can't respond)
= hypothyroid picture
20-25% remain hypothyroid
93
Definition of subclinical hypothyroidism
↑ TSH
| Normal free T4
94
C cells
Parafollicular cells
Primary purpose is to secrete calcitonin
In the CT of the thyroid
95
What is the most common type of thyroid cancer?
Papillary carcinoma
96
What are the key diagnostic features of a papillary carcinoma?
Nuclei are empty w/ chromatin on the outside
Nuclei tend to be large w/ grooves in the nuclear envelope
Optically clear nuclei
Papillae with vascular core
On FNA, "coral" appearance
97
Medullary carcinoma of the thyroid
Solid proliferation of cells with granular cytoplasm (C Cells)
Highly vascular stroma
Hyalinized collagen and/or amyloid
98
What are some worrisome signs when you're examining lumps?
```
Hard = more concerning
Fixation = usually means it's invading
```
99
What is the approach to a patient with thyroid nodules?
1. TSH level
2. Diagnostic ultrasound
3. (poss.) FNA
100
What is the most common cellular pathway that is messed up in thyroid cancer?
MAP kinase
Ras --> BRAF --> MEK-ERK
101
PAX8
Function: initiation of thyroid cell differentiation, maintenance of the differentiated state, and essential for thyroid cell proliferation
Mutations can lead to thyroid hypoplasia. AD inheritance
102
TITF2
Migration of thyroid precursor cells and transcriptional control of the TG and TPO gene promoters in thyroid development
Homozygous mutations result in Bamforth-Lazarus syndrome: congenital hypoplasia, cleft palate, spiky hair, and variably bifid epiglottis and choanal atresia
103
Interpret: if T3 uptake and T4 are going in the same direction (both low/both high)
Indicates thyroid disease
Low T3 uptake/low total T4 = hypothyroid
High T3 uptake/high total T4 = hyperthyroid
104
Interpret: if T3 uptake and T4 are in different directions
TBG abnormality
High uptake and low total T4 = TBG deficiency
105
Interpret: an adolescent girl has normal TSH but high total T4
Common, benign. Due to estrogen, likely OCPs
106
Jod-Basedow phenomenon
Hyperthyroidism following administration of iodine, either as a dietary supplement or as contrast medium
107
What does pain/tenderness with a goiter indicate?
Thyroiditis
108
How does thyroid disease affect reproductive function in women?
High free T4 increases sex hormone binding globulin (SHBG) and this results in a lower free estradiol level that leads to lighter menstrual bleeding and amenorrhea
Low free T4 decreases SHBG, increases free estradiol and leads to hypermenorrhea
109
MEN I
"The P's:"
- pituitary tumor
- pancreatic islet tumors
- parathyroid hyperplasia
Germline mutation, so pituitary & pancreatic tumors tend to be multiple.
You can test for menin gene mutations.
110
MEN IIA
- medullary thyroid carcinoma
- pheochromocytoma
- parathyroid hyperplasia
Germline mutation: Ret gene
111
In a hospitalized patient, the most common cause of hypocalcemia is?
Low serum protein level
Thus, find the corrected serum calcium level
112
Serum total calcium correction formula
Add 0.8 mg/dL to total calcium for every 1 g/L albumin is
113
Pseudohypoparathyroidism - lab & clinical features
Labs:
↓ serum calcium
↑ serum phosphate
↑ serum PTH
Clinical:
Short 4th & 5th metacarpals
114
Paracalcitol
Blocks PTH receptors at the parathryoid, but not elsewhere in the body
Treats secondary hyper-PTH via inhibiting release of PTH, but do not cause hypercalcemia
115
Osteoprotegerin (OPG)
Decoy RANK-L receptor
Thus, binds RANK-L on osteoblasts and prevents osteoclasts (with their own RANK receptor) from being activated
116
Effect of estrogen on bones
Major effect: ↓ osteoclast activity and #
Also ↑ osteoblast production of OPG
117
Osteoporosis tx - anti-resorptive drugs
```
Bisphosphonates
Denosumab
Raloxifene
Calcitonin
Estrogen
```
118
Osteopororsis tx - anabolic drugs
Teriparatide
| Romosozumab
119
Bisphosphonates - names? MOA?
Alendronate, risedronate, zoledronate, etc...
Have direct inhibitory effect on osteoclasts (induce apoptosis)
120
Selective estrogen receptor modulator - name? MOA?
Raloxifene
Agonist on receptors in bone - reduces risk of osteoporotic fractures
Will cause hot flashes; increase clotting factor production in liver (due to liver receptors)
121
Teriparatide
Synthetic PTH
Only agent for osteoporosis that stimulates bone formation
122
Denosumab
Ab to RANK-L
Reduces osteoclast activity; improves bone mineral density
123
What is the tx of choice for severe hypocalcemia?
Calcium gluconate
124
```
Number of carbons in:
cortisol
aldosterone
progestin
androgens
estrogen
```
```
cortisol - 21
aldosterone - 21
progestin - 21
androgens - 19
estrogen - 18
```
