Endocrine Flashcards
1
Q
What is the embryologic origin of the thyroid gland?
What is the most common location of ectopic thyroid tissue? What is a complication of removing such tissue?
A
The floor of the primitive pharynx (it descends into the neck from there)
The tongue is the most common location; removal may result in hypothyroidism if it is the only thyroid tissue present
2
Q
A girl presents with an anterior midline neck mass that moves with swallowing. Differential diagnosis?
How could they be differentiated?
A
Thyroglossal duct cyst vs branchial cleft cyst
Thyroglossal duct cysts are anterior and move with swallowing; branchial cleft cysts are in the lateral neck and do not move with swallowing
3
Q
Why would someone have three lobes in his or her thyroid gland?
A
The pyramidal lobe of the thyroid can be a persisting remnant of the thyroglossal duct
4
Q
What is the foramen cecum?
A
The foramen cecum is a normal remnant of the thyroglossal duct
5
Q
Are all cell types in the thyroid derived from the same embryologic tissue?
A
No, thyroid tissue is derived from endoderm, whereas parafollicular cells (ie, C cells) are derived from neural crest
6
Q
A patient has congenital aplasia of her adrenal cortex. From what embryologic tissue did this dysfunction arise?
Which part of the adrenal gland is derived from the same cells as melanocytes?
A
The adrenal cortex is derived from mesoderm
Medulla/Chromaffin cells of the adrenal medulla are also derived from neural crest [recall, medulla makes teh catecholamines used for sympathetic NS pathway - neural]
7
Q
What are the three zones of the adrenal cortex, from outermost to innermost?
What does each zone produce?
A
Zona Glomerulosa, zona Fasciculata, zona Reticularis (GFR corresponds with Salt [Na+], Sugar [glucocorticoids], and Sex [androgens])
- sweeter as you go down: salt –> sugar –> sex*
- MGS: mineralcords, glucocords, sex hormones*
8
Q
Which hormonal system controls levels of aldosterone?
A
The renin-angiotensin axis
9
Q
Cortisol and androgens in the zona reticularis are regulated by which hormones?
A
ACTH, CRH
ACTH is also a trohpic factor for zona fasciculata and zona reticularis [increase cholesterol uptake and enzyme ezpression; without ACTH, adreanl cortex zona’s fasciulata and reticularis will atrophy]
10
Q
A man has hypertension, low potassium, and high sodium. Renin levels are low. Which part of the adrenal gland is causing this pathology?
A
The zona glomerulosa of the adrenal cortex secreting aldosterone; the patient’s presentation is consistent with hyperaldosteronism
11
Q
What is the primary regulator of chromaffin cells in the adrenal medulla?
What are the secretory products?
A
Preganglionic sympathetic fibers
–> catecholamines (epinephrine, norepinephrine)
12
Q
What is the most common tumor of the adrenal medulla in adults?
In children?
A
Adults: pheochromocytoma - episodic hypertension
Children: neuroblastoma, rarely casues hypertension
13
Q
What are the embryologic origins of the anterior and posterior pituitary?
A
Anterior: oral ectoderm (Rathke pouch)
posterior: neuroectoderm
14
Q
What hormones does the posterior pituitary secrete? Where are these hormones made, and how are they transported?
A
Vasopressin (ADH) and oxytocin;
made in hypothalamus (supraoptic and paraventricular nuclei, respectively) and carried via neurophysins to posterior pituitary
ADH=vasopressin=AVP
Posterior Pitutitary=PP=pressors and pregnancy
15
Q
Which pituitary hormones have a common α subunit? What is the significance of the β subunit?
A
alpha- Thyroid-stimulating, luteinizing, follicle-stimulating, human chorionic gonadotropin hormones
beta - it determines hormone specificity
16
Q
In a patient with a nonsecreting anterior pituitary adenoma, production of which hormones could still be affected?
What is one difference among these hormones?
A
FSH, LH, ACTH,TSH, Prolactin, GH (FLAT PiG)
basophils (FLAT) = FSH, LH, ACTH, TSH
Acidophils = Prolactin, GH
17
Q
A man craving salty food is very tan. An MRI reveals adrenal atrophy. What is the precursor to the molecule responsible for the tanning?
A
POMC is the precursor to ACTH and MSH, both of which are likely increased
(He has primary adrenal insufficiency.)
MSH = melanocyte stimulating hormone
hyperpigmentation with increased ACTH, could indiate PRIMARY adrenal insufficiency – anterior pituitary is increasing ACTH in an attempt to increase output of the adrenal glands
18
Q
What do α, β, and δ endocrine cells of the pancreas produce, respectively? Where are these cell types found in the typical islet?
A
α cells (periphery): glucagon
A(alpha)lmost gone (in the periphery)
β cells (central): insulin (found inside);
queen B is in the middle
δ cells (interSpersed): somatostatin
19
Q
A depressed woman overdoses on a sulfonylurea. Blood work is done in the ED. What do you expect her insulin and C-peptide levels to be?
A depressed man who self-injects various drugs has a glucose of 50. What do you expect his insulin and C-peptide levels to be?
A
Both insulin and C-peptide levels will be high (Sulfonylureas promote endogenous insulin release.)
If injecting insulin will be high & C-peptide will be low
20
Q
A nurse is hypoglycemic. Insulin/C-peptide levels are high; a sulfonylurea screen is negative. Why do you perform an abdominal CT scan?
A
Sulfonylurea negative = no exogenous
Both high = endogenous INC in insulin, that is increasing the uptake of her glucose and thus causing her to be hypoglycemic
Order a CT to look for evidence of an insulinoma, which coudl be secreting excess endogenous insulin!
21
Q
How is insulin made and secreted into the blood system?
A
Preproinsulin forms in RER,
Cleavage of the “presignal” –> forms proinsulin (stored in granules), then
Cleavage of proinsulin –> into C-peptide and insulin –>released into blood, via exocytosis
22
Q
Which organs/tissues do not require insulin to take up glucose?
A
(BRICK L)
Brain, B-cells of pancreas,RBCs,Intestine,Cornea,Kidney,Liver have
insulin-independent glucose uptake
23
Q
What stimulates and how is insulin released into our blood system?
A
Glucose is the main regulator of insulin release
Glucose uptake via GLUT 2 enters β cells to make ATP via glycolysis
ATP closes an ATP-sensitive K+ channel –> DEPOLARIZATION of the cell –> opens voltage-gated calcium channels –> allows Ca2+influx –> increased calcium stimulates the exocytosis of insulin granules
24
Q
Match the tissue/organ with the glucose transport:
Glut 1-
Glut 2-
Glut 3-
Glut 4-
Glut 5-
which are insulin dependent/which are independent?
A
Glut 1- RBC, brain, cornea, placenta (insulin INDEPENDENT)
Glut 2- bidirectional, b-islet cells, liver, s. intestines, kidney (insulin INDEPENDENT)
Glut 3- brain, placenta (insulin INDEPENDENT - 3 kinda looks like a B)
Glut 4- adipose tissue, striated muscle, insulin DEPENDENT
Glut 5- Fructose, spermatocytes, GI tract (insulin INDEPENDENT)
25
What is the effect of insulin on electrolyte (Na+, K+) and amino acid transport?
It **increases Na+** **retention** by the kidneys and
shifts both **K+ and amino acids INTO cells** (cellular uptake)
26
A pregnant woman with type 1 diabetes mellitus injects insulin before a meal. How does this insulin affect her fetus?
Insulin does not cross the placenta, but it indirectly lowers the fetus's blood glucose levels by lowering the mother's blood glucose level
27
How does insulin affect these processes: lipolysis, glucagon synthesis and release, triglyceride synthesis, muscle protein synthesis?
Decreases lipolysis
increases glucagon synthesis
decreases glucagon release
increases triglyceride synthesis
increases muscle protein synthesis
28
What effect would a drug that keeps K+ channels open have on insulin release in β islet cells?
It would decrease insulin release (as the β cells could not depolarize)
29
A student studies for 24 consecutive hours without eating. What fuel does his brain use during starvation? Why can't RBCs do the same?
The brain uses ketone bodies during starvation; RBCs cannot do this because they lack mitochondria for aerobic metabolism
30
A patient eats fruit after exercise. He says that muscles take up energy quite well during this time. Via what mechanism does this occur?
GLUT-4 receptor expression on striated muscle and adipose tissue increases after exercise, so glucose is taken into cells more efficiently
31
A cognitively impaired newborn has a congenital decrease in GLUT-3 transporter activity. What tissue type will be most affected by this?
The brain; GLUT-3 is an insulin-independent transporter of glucose there (The placenta also uses this transporter.)
32
Do spermatocytes use GLUT-5 for insulin-independent glucose transport?
No, spermatocytes do use GLUT-5, but for fructose transport rather than glucose transport
*others that use GLUT 5 = GI tract*
33
In patient A, you give 50 g of oral glucose. In patient B, you inject it instead. Patient A's blood sugar is much lower after 2 hours. Why?
The insulin response to oral glucose is superior due to **incretins** (eg, **GLP-1)** that **only act with _oral_ glucose**
34
glucago:
where is it made?
main functions (2)
Regulation?
Made in the ALPHA cells (*almost glucaGONE - periphery of pancreas)*
Fxn = CATABOLIC
Glycogenolysis --\> gluconeogenesis
lipolysis
ketone production
Secreted in response to HYPOglycemia
inhibited by insulin, hyperglycemia and somatoSTOPin
35
You are 20 hours without food. Hypoglycemia induces which cells to produce glucagon? Which hormones inhibit glucagon production?
A patient eats a large meal. The blood sugar rises and insulin is secreted. What will blood measurements of glucagon activity show?
The α cells of the pancreas release glucagon; *_insulin and somatostatin both inhibit glucagon production_*
Glucagon activity will be low, as it is inhibited by both hyperglycemia and insulin
36
A patient is taking octreotide (somatostatin analog) for acromegaly. What effect will this drug have on glucagon?
It will inhibit glucagon secretion
37
CRH
Fxn:
Increase ACT, MSH, B-endorphin
CRH decreases with exogenous steroid use
38
Dopamine
Fxn
DECREASES prolactin, TSH
dopamine antagonist (ie - antipsychotics) can cause galactorrhea due to hyperprolactinemia/lack of negative control of prolactin release
39
GHRH
FXN?
A 10-year-old boy, short for his age, is found to have GH deficiency. High/low levels of which hormone(s) may cause this?
INCrease growth hormone
**GH analong (tesamorelin) used to treat HIV-associated lipodystrophy**
Low growth hormone–releasing hormone (GHRH) or
high somatostatin levels decrease the level of GH
40
GnRH
FXN?
A woman has trouble getting pregnant. She is given pulse doses of GnRH. What does this do?
INC FSH, LH
Suppressed by hyperprolactinemia (ie-breast feeding women)
**_Tonic_ GnRH _suppress_ HPG axis**
PULSATILE GnRH leads to puberty, fertility [It elevates FSH and LH, thus increasing her fertility]
41
Prolactin
fxn?
A woman with visual defects is found to have a prolactinoma. Why did she stop menstruating?
Lactation let down
decreases GnRH
Pituitary prolactinoma --\> amenorrrhea, osteoporosis, hypogonadism, galactorrhea
Prolactin BLOCKS GnRH --\> LH and FSH are thus also reduced; no LH surg, no menstruation
42
Somatostatin
fxn?
A man is found to have a somatostatin-secreting tumor. How does this affect pituitary hormone secretion?
DEC GH, TSH
Analogs used to treat acromegaly
also decrease glucagon release
Excess somatostatin inhibits GH and TSH secretion
43
TRH
FXN?
increase TSH, prolactin
44
A woman with paranoid schizophrenia thinks she is pregnant because of galactorrhea and a lack of menses. Why did she get these symptoms?
She is likely on antipsychotic medications (**dopamine receptor antagonists**), which *_block dopamine activity and thus **elevate prolactin levels --\> galactorrhea + no menstruation since prolactin blocks GnRH and thus LH and FSH too.**_*
45
A patient with AIDS receiving HAART has a slender face/arms/legs, but a big gut. What intrinsic hormone analog can be used to treat him?
He has HIV-associated lipodystrophy from HAART, which is treated with **tesamorelin, a GHRH analog**
46
A 20-y/o woman has had no menses for 3 months but has a white discharge from her nipples. What two hormone levels do you want to check?
β-hCG (for pregnancy) and prolactin (for possible prolactinoma)
47
A man with temporal arteritis runs out of prednisone. Which hormone had primarily been suppressed by long-term steroid use?
**CRH is decreased** with long-term steroid use
48
A man with schizophrenia complains he "can't get it up for the ladies" anymore. What medication caused this, and how?
Some antipsychotic medications are **dopamine anatgonist** --\> blocking dopamine activity --\> **increase prolactin**
Prolactin --\> **DEC GnRH** --\> decreasing GnRH, inhibits spermatogeneis syntheis and release and causing erectile dysfunction and decrease libido.
49
A woman with Graves disease undergoes thyroid irradiation and now complains of amenorrhea. What is the treatment?
Thyroid irradiation --\> decrease levels of T3 and T4 / hypothyrodism--\> increasing TRH --\> TRH induces prolactin secretion
Prolactin --\> inhibits GnRH and thus inhibits ovulation due to decrease FSH and LH levels
Treatment for this is thyroid replacement therapy; as T3 and T4 inhibit TRH release and thus less stimulation for the release of prolactin
50
What reproductive complication is possible with high prolactin levels in men? From where is it released?
Decreased spermatogenesis by inhibition of GnRH synthesis and release; the anterior pituitary
51
A woman presents with vision changes and galactorrhea. How do you treat her?
A man reports impaired peripheral vision and decreased libido. What single cause could account for both of these changes?
A prolactinoma (causing visual changes by impinging optic chiasm) is treated with dopamine agonists (eg, bromocriptine) to lower prolactin
A prolactinoma compressing the optic chiasm, leading to bitemporal hemianopsia, and secretion of excess prolactin, decreasing libido
52
What inhibits prolactin release and what stimulates it?
Dopamine agonists; dopamine antagonists, estrogens, and TRH
53
By what mechanism could a patient with SLE and ESRD experience elevated prolactin levels?
Renal failure can **reduce prolactin elimination**, leading to elevated prolactin levels
54
In addition to medications, what are two physical methods by which dopamine levels can be reduced?
Nipple stimulation and chest wall injury (via ANS)
55
A mother sees and hears her baby crying. Shortly afterwards she has a desire to nurse the baby. What is driving her to do this?
The sight and cry of her baby stimulate the higher cortical centers, which inhibit hypothalamic dopamine, thus increasing prolactin levels
56
A very tall teenage boy is found to have GH excess. How does GH mediate growth? What other disease is he at risk for?
A very tall man has coarse facial features and visual defects. What tumor does he have? What hormone normally inhibits his condition?
GH increases IGF-1 and somatomedin C secretion, which increases linear growth and muscle mass -- giantism?!
Diabetes (GH **increases insulin resistance**)
A pituitary adenoma causing acromegaly; somatostatin inhibits GH
57
A mom wants her child to grow taller. What lifestyle changes can optimize GH release in her child?
Deep sleep, exercise
58
A diabetic injects too much insulin and becomes hypoglycemic. What is the role of GH in response to his low blood sugar?
Its **secretion increases**, as it helps to i**ncrease insulin resistance**
## Footnote
**(--\> more glucose in the bloodstream, less inside)**
59
Why do patients have an increased appetite when they are sleep deprived?
Sleep loss increases ghrelin and decreases leptin, stimulating hunger (Ghrelin makes you hunghre, leptin keeps you thin.)
Ghrelin - produced in the stomach; orexigenic effect (not anorexic but orexigenic)
Lectin - produced in adipose tissue
60
How does marijuana act to increase appetite?
Endocannabinoids **stimulate receptors in the _hypothalamus_ and _nucleus accumbens_**, increasing desire for _high-fat foods_
## Footnote
*the munchies*
61
What is the function of ghrelin? What key hormone is released in response to ghrelin activity?
what increases Ghrelin?
Ghrelin stimulates hunger (orexigenic effect—ghrelin makes you hunghre) and **GH release via a GH secretagogue receptor**
**Increases** with **_lack of sleep**_ and _**Prader-Willi syndrome_**
62
Arising at 4 AM each day for a surgery clerkship, you find yourself snacking more often than usual. Is there a biochemical reason for this?
Yes, sleep deprivation both increases ghrelin production and decreases leptin production; the net effect is increased appetite
63
An intoxicated man is found down in the park. In the ED, he has massive urine output and hypernatremia. What might be the cause?
A lack of ADH production due to pituitary trauma, causing central diabetes insipidus
64
What receptors are involved in ADH's function?
What is the site of action of ADH in the kidney? What channel is involved?
Where is antidiuretic hormone synthesized, stored, and secreted?
What two systems are responsible for regulating antidiuretic hormone?
V1-receptors regulate blood pressure;
V2-receptors regulate serum osmolarity (ADH's primary function.)
Principal cells of the renal collecting duct; aquaporin channels
It is synthesized in the hypothalamus (supraoptic nuclei) and both stored in and secreted by the posterior pituitary
Osmoreceptors in the hypothalamus and receptors detecting hypovolemia
65
What is the serum ADH level in nephrogenic diabetes insipidus? Central diabetes insipidus?
Levels are elevated in nephrogenic diabetes insipidus and depressed in central diabetes insipidus
No matter how much ADH there is, in nephrogenic DI, V2 is not working, therefore ADH will not have its effect in the kidney
66
A patient has SIADH as a result of lung cancer. What changes would you expect in his serum and urine osmolarity?
Decrease in serum osmolarity, increase in urine osmolarity (urine more concentrated because free water is reabsorbed back into blood)
67
Parents are adamant that their 6-year-old son be given pharmacotherapy for his bed-wetting. Is there a role for a hormone analog here?
Yes, desmopressin acetate (an ADH analog) is a first-line pharmacotherapy for nocturnal enuresis
68
A boy has 17α-hydroxylase deficiency. What levels of aldosterone, cortisol, and K+ do you expect? blood pressures affected?
Do XY subjects have male or female internal anatomy?
High aldosterone, low cortisol, and low K+
blood pressures are elevated
**XY** subjects have ambiguous external genitalia and undescended testes (low sex hormone, estrogen DHT) = pseudo-hermaphroditism
**XX** subjects lack secondary sex development (low estrogen); but have both internal and external femal anatomy
69
Why do patients with a deficiency in 11β-hydroxylase have hypertension despite having hypoaldosteronism?
They have an increase in 11-deoxycorticosterone (11B-hydroxylate would normally conver 11-deoxycorticosterone to corticosterone), which has **mineralocorticoid properties** and therefore causes **hypertension**
70
What does aromatase convert androstenedione into? The product is then converted into what other hormone in peripheral tissue?
Aromatase converts androstenedione into estrone; in peripheral tissue, estrone is converted into estradiol
71
A woman taking long-term high-dose ketoconazole for a fungal infection exhibits hypotension and a reduction in breast size. Why?
Ketoconazole **inhibits cholesterol desmolase**, reducing the conversion of cholesterol to pregnenolone (a precursor for all adrenal hormones)
**cholesterol desmolase (CYP11 A1)** - primary enzyme that **converts cholesterol into pregneolone** ---\> starts the enzymatic reactions
72
A licorice "addict" presents with hypertension. Excess cortisol activity in the kidneys is to blame. What enzyme is responsible for this?
Glycyrrhetic acid (in licorice), inhibiting cortisol conversion into cortisone (This is syndrome of apparent mineralocorticoid excess.)
73
An XX infant has the most common form of congenital adrenal hyperplasia. She is hypotensive with elevated K+. Name the genital phenotype
**XX** infants with 21-hydroxylase deficiency have ambiguous genitalia (**_pseudohermaphroditism_**) because high androgens cause **virilization**
74
Why do patients with a deficiency in 11β-hydroxylase have hypertension despite having hypoaldosteronism?
They have an increase in 11-deoxycorticosterone, which has mineralocorticoid properties and therefore causes hypertension
Angiotension II blocks Aldosterone synthase which overts corticosterone to aldosterone but 11BHSD2 enzyme converts 11-deoxycorticosterone to corticosterone, so we have no aldosterone being produced.
75
What does aromatase convert androstenedione into? The product is then converted into what other hormone in peripheral tissue?
Aromatase converts androstenedione into estrone; in peripheral tissue, estrone is converted into estradiol
76
A woman taking long-term high-dose ketoconazole for a fungal infection exhibits hypotension and a reduction in breast size. Why?
**Ketoconazole inhibits cholesterol desmolase/CYP11-A1**, reducing the conversion of cholesterol to pregnenolone (a precursor for all adrenal hormones)
77
While on service, you see a newborn with ambiguous genitalia. What lab findings would support a diagnosis of 17α-hydroxylase deficiency?
[mineracorticoids, cortisol, sex hormones, K+, other??]
Increased mineralocorticoids, decreased cortisol, decreased sex hormones, decreased K+, decreased androstenedione
78
21-Hydroxylase deficiency can present either in infancy or childhood. How do these two presentations typically differ?
**Infants** typically present with **salt wasting**, whereas **children** typically present with **precocious puberty**;
XX subjects experience virilization
INC rening activity, increase 17-hydroxy-progesterone
79
Researchers design a chemical to block the 21-hydroxylase enzyme. What lab findings show that this drug is having the proper effect?
Decreased mineralocorticoids, decreased cortisol, increased sex hormones, increased K+, increased renin, increased 17-hydroxyprogesterone
80
After cholesterol becomes pregnenolone, it can be acted on by one of two enzymes. What are they? What are their respective products?
3B-hydroxysteroid dehydrogenase
17-hydroxypregnenolone
17α-hydroxylase can convert it into 17-hydroxypregnenolone (go to the fasiculata path), or
3β-hydroxysteroid dehydrogenase can convert it into progesterone
81
Progesterone can be acted on by one of two enzymes in the adrenal cortex. What are they? What are their respective products?
17α-hydroxylase can convert it into 17-hydroxyprogesterone, or 21-hydroxylase can convert it into 11-deoxycorticosterone
82
Is blood pressure elevated or decreased in subjects with deficiencies of 17α-hydroxylase, 21-hydroxylase, and 11β-hydroxylase, respectively?
17α-hydroxylase - INCREASED
21-hydroxylase - DECREASED
11β-hydroxylase - INCREASED
*Although aldosterone synthesis is decreased, 11-deoxycorticosterone can still elevate the blood pressure due to mineralocorticoid activity*
83
To lower estrogen levels, a new drug acts by inhibiting 17-hydroxyprogesterone. Unfortunately, bilateral adrenal enlargement is seen. Why?
Inhibiting 17-hydroxyprogesterone will block cortisol synthesis, which will secondarily increase ACTH levels and cause adrenal enlargement
84
What two reactions catalyze the transformation of pregnenolone into DHEA?
Pregnenolone to 17-hydroxypregnenolone via 17α-hydroxylase, 17-hydroxypregnenolone to DHEA via 17,20-lyase
85
What two reactions catalyze the transformation of progesterone into androstenedione?
Progesterone to 17-hydroxyprogesterone via 17α-hydroxylase, 17-hydroxyprogesterone to androstenedione via 17,20-lyase
86
A woman with estrogen receptor-positive breast cancer is prescribed aromatase inhibitors. How do they help treat her cancer?
Biopsy of a man's prostate cancer shows that it grows in response to DHT. How might finasteride help to treat him?
They (anastrozole/exemestane) **block the conversion of androstenedione to estrone and testosterone to estradiol**, lowering estrogen levels
Finasteride inhibits 5α-reductase, which converts testosterone into DHT; this reduces the levels of DHT in the peripheral tissues
87
What two reactions catalyze the transformation of progesterone into corticosterone?
Progesterone to 11-deoxycorticosterone via 21-hydroxylase, 11-deoxycorticosterone to corticosterone via 11β-hydroxylase
88
What two reactions catalyze the transformation of 17-hydroxyprogesterone into cortisol?
17-hydroxyprogesterone to 11-deoxycortisol via 21-hydroxylase, 11-deoxycortisol to cortisol via 11β-hydroxylase
89
What enzyme converts corticosterone into aldosterone? What molecule stimulates this enzyme? Where in the adrenal cortex does this occur?
Aldosterone synthase; angiotensin II; the zona glomerulosa (site of mineralocorticoid production)
90
What two reactions catalyze the transformation of DHEA into testosterone?
DHEA to androstenedione via 3β-hydroxysteroid dehydrogenase, androstenedione to testosterone via 21-hydroxylase
91
Which enzyme catalyzes the conversion of testosterone to dihydrotestosterone?
5α-reductase
92
Which congenital adrenal enzyme deficiencies are characterized by bilaterally enlarged adrenal glands?
All of them, because decreased cortisol production increases ACTH levels, leading to adrenal enlargement
93
What stimulates aldosterone synthase to convert corticosterone into aldosterone?
Angiotensin II
94
How is cortisol found in the bloodstream?
What are the main effects of cortisol?
It is bound to corticosteroid-binding globulin
_Raises:_ BP, Insulin resistance,Gluconeogenesis; D_ecreases:_ Fibroblast activity (--\>striae), Inflammatory/Immune responses, Bone formation
(**BIG FIB**- *BIG* *as in it raises, lowers FIB*)
95
How do steroids help people with cat allergies? With inflammation?
They decrease leukotriene and prostaglandin production, reduce eosinophil counts, and block mast cell histamine output
inhibition of WBC--\> neutrophilia
REduces eosinophils
96
A man needs steroids for a multiple sclerosis flare. He is otherwise healthy. Inpatient labs show hyperglycemia. Do you diagnose diabetes?
No, you prescribed steroids, which increase insulin resistance (diabetogenic); this will subside once the steroids are discontinued
97
A patient needs high-dose steroids for a long period. Why do you provide a calcium/vitamin D supplement as well?
How does this affect the natural mechanism for cortisol regulation?
Steroids **suppress osteoblast activity,** resulting in decreased bone formation and *_increased risk for osteoporosis_*
Excess cortisol decreases CRH, ACTH, and endogenous cortisol secretion
98
A patient presents w/a 4th case of pneumonia in a year. He reports chronic stress. ROS: only positive for weight gain. What could this be?
Chronic stress can lead to an increased cortisol level, thereby blunting the immune response and increasing the risk for infection
Chronically high cortisol increases risk for TB reactivation and candidiasis (by blocking IL-2 production)
99
A patient is taking high-dose prednisone for her lupus. On a regular lab checkup, you notice hypokalemia and hypernatremia. Why?
**At high concentrations**, cortisol can bind to and act as an agonist on aldosterone receptors, thus mimicking hyperaldosteronism
[normally, there is 11BD2 that _inactivates cortisol_ in the kidney, so that it won't have an effect on B]
100
Before a patient begins receiving an oral corticosteroid, a PPD should be performed. Why?Exogenous corticosteroids are immunosuppressive; TB or candidiasis reactivation can occur due to decreased IL-2 production
Exogenous corticosteroids are immunosuppressive;
TB or candidiasis reactivation can occur **_due to decreased IL-2 production_**
101
A surgery resident who is always angry is noted to have elevated cortisol levels. What cortisol regulation derangement is likely to blame?
Chronic stress (as seen in a surgical residency) can induce prolonged secretion of CRH, thus increasing ACTH levels and cortisol production
102
A patient with lupus receives steroids. Days later, she has a severe leukocytosis but reports feeling better. Do you treat for an infection?
No, steroids inhibit WBC adhesion and thus **cause a neutrophilia;** it is *_unlikely that she has an infection requiring treatment_*
103
In what three forms is Ca2+ found in plasma? Which is the most common? The least common?
Ionized, bound to albumin, and bound to anions; ionized is the most common form, and Ca2+ bound to anions is the least common
104
What are the clinical manifestations of a respiratory alkalosis, specifically in regard to Ca2+?
Ionized, bound to albumin, and bound to anions; ionized is the most common form, and Ca2+ bound to anions is the least common
105
What are the clinical manifestations of a respiratory alkalosis, specifically in regard to Ca2+?
Increased pH allows more albumin to bind Ca2+, causing clinical hypocalcemia (cramps, pain, paresthesias, carpopedal spasms - trousseau's sign, chvostek cheek sign)
106
What are the two sources of the precursors for activated vitamin D?
D2 = ergocalciferol [**TWO**lips = plants]
D3 = cholecalcifero [SUN = **3** words]
Plants, fungi, and yeasts for D2; fish, plants, and skin sun exposure for D3
107
A boy living in Minnesota has **bowed legs**. You suspect that a vitamin deficiency is to blame. How do you treat him?
This is likely rickets; treat with vitamin D supplementation
108
Patients on dialysis often develop osteomalacia. Why?
These patients with _no kidney function_ cannot convert inactive vitamin D into the active form: 1,25-(OH)2
109
PTH increases Ca2+ and decreases serum PO43–.
How are these effects different from 1,25-(OH)2 vitamin D's effects?
1,25-(OH)2 vitamin D **increases Ca2+and phosphate levels** from *_gut absorption and bone resorption_*
110
24,25-(OH)2 D3 is an inactive form of vitamin D. What stimulates production of (active) 1,25-(OH)2vitamin D?
How are inactive forms of vitamin D converted to the active form?High PTH, low Ca2+, and low PO43–increase production of active vitamin D (1,25-(OH)2)
High PTH, low Ca2+, and low PO43–increase production of active vitamin D (1,25-(OH)2)
D3 and D2 are converted to 25-OH in the **liver**, then to 1,25-(OH)2 (active form) in the **kidneys**
111
What is the difference between rickets and osteomalacia?
Rickets: vitamin D deficiency in kids (abnormally formed bone); osteomalacia: vitamin D deficiency in adults (poor bone mineralization)
112
What are the two main functions of active vitamin D?
What form of vitamin D is able to regulate its own production?
Increased gut absorption of dietary Ca2+, and PO43–, enhanced bone mineralization
Active vitamin D (1,25-(OH)2) is able to inhibit its own production
113
Which cells normally produce PTH?
How does PTH affect Ca2+ absorption in the intestines?
Chief cells of the parathyroid glands
It stimulates renal proximal convoluted tubule 1α-hydroxylase, increasing 1,25-(OH)2D3 levels; this promotes intestinal Ca2+ absorption
114
A man has high PTH levels. What serum and urinary findings do you see in a patient with primary hyperparathyroidism?
High serum Ca2+, low serum PO43–, and high urine PO43– and cAMP
[PTH uses cAMP as its signaling pathway]
115
A woman on dialysis is found to have osteoporosis. Her PTH level is normal. What enzyme might she be deficient in?
1α-Hydroxylase (from the renal proximal convoluted tubule) increases 1,25-(OH)2 D3and therefore Ca2+ absorption from the gut
116
What electrolyte changes induce PTH secretion?
Decreased serum Ca2+ and mildly to moderately decreased Mg2+ both increase PTH secretion
**[mildly low Mg2+ will increase PTH; very low Mg2+, will decrease PTH]**
117
An alcoholic, hypertensive man with diarrhea recently started taking gentamicin. How could this affect PTH secretion?
Alcohol abuse, diarrhea, aminoglycosides, & diuretics lower Mg2+; mildly/moderately low Mg2+ boosts PTH, while severely low Mg2+lowers it
118
Almost counterintuitively, PTH can also be given to patients with osteoporosis to help form bone. In what fashion must PTH be given?
Intermittently administered (eg, once-daily injection) PTH can stimulate bone formation
119
In lab rats, adding a RANK-L (receptor activator of NF-κB ligand) inhibitor lowers the serum Ca2+ level. Why might this be?
PTH causes osteoblasts/osteocytes to **make RANK-L**, which **binds osteoclasts/osteoclast precursor RANK**
--\> *_stimulating osteoclasts_*/increasing Ca2+
120
A patient with advanced squamous cell lung cancer has a very low serum phosphate level. Why might this be?
Some cancers secrete PTH-related peptide, which mimics PTH; PTH causes reduced PO43– reabsorption (PTH = PhosphateTrashing Hormone)
121
With which lab findings would a patient who has parathyroid hyperplasia leading to excessive PTH secretion present?
High serum Ca2+, low serum PO43–, and high urine PO43– and cAMP
122
PTH works on two organ systems: bones and kidneys. How does it affect Ca2+/PO43–processing in each?
Bone: Ca2+/PO43– release; kidneys: more 1,25-(OH)2D3 via PCT 1α-hydroxylase and more DCT Ca2+ reabsorption, less PCT PO43–reabsorption
123
A patient with ESRD has severe hypomagnesemia. What would you expect from a lab assay for serum PTH levels?
Decreased PTH; while moderately low Mg2+can increase PTH secretion, a severe hypomagnesemic state can actually decrease PTH secretion
124
What two stimuli can promote the production of active vitamin D? Via what enzyme does this occur, and in which organ?
125
What two stimuli can promote the production of active vitamin D? Via what enzyme does this occur, and in which organ?
Increased PTH and low PO43– both stimulate 1α-hydroxylase to produce active vitamin D (1,25-(OH)2 D3) in the PCT of the kidneys
126
Which stimuli will inhibit PTH synthesis via direct feedback?
Which three stimuli will promote PTH synthesis via direct stimulation?
Increased 1,25-(OH)2 D3, increased Ca2+, or decreased PO43–
Decreased ionized Ca2+, increased PO43–, or decreased 1,25-(OH)2 D3
127
Name two malignancies that commonly increase the secretion of PTHrP.
Squamous cell carcinoma of the lung and renal cell carcinoma
128
1,25(OH)2D 3 works on three organ systems: the bones, intestines, and kidneys. How does it affect Ca2+/PO43– processing in each?
Bone: more Ca2+/PO43– release; intestines and kidneys: more Ca2+ and PO43–absorption
129
How is calcitonin involved in Ca2+homeostasis?
What stimulates the secretion of calcitonin?
It opposes PTH's actions but is not important in normal Ca2+ homeostasis (**calcitonin tones down Ca2+ levels**)
**Increased** serum Ca2+ levels
130
A person with medullary thyroid cancer (cancer of thyroid parafollicular [C] cells) is expected to have an increase in what hormone?
Calcitonin: parafollicular (C) cells secrete calcitonin, lowering bone resorption and thus serum Ca2+ levels
131
What plasma protein binds T3/T4 in blood? Is bound thyroid hormone active? What increases or decreases levels of the binding protein?
Thyroxine binding globulin (TBG)
only free hormone is active;
liver failure/steroids decrease TBG;
estrogen (pregnancy/OCP use) increases TBG
132
Where are T3 and T4 produced? What element is required for their production? What is their main function & by what mxn??
What combinations of MIT and diiodotyrosine DIT are needed to make T3and T4, respectively?
T4 and some T3 are formed in thyroid follicles, but most T3 is formed in target tissues; iodine;
Control the **body's metabolic rate**
INC BMR by: stimulating **Na+/K+-ATPase activity,** which increases O2 consumption, RR, and body temperature
MIT + DIT = T3; DIT + DIT = T4
133
What are the four main functions of T3?
4 B's =
Brain maturation,
Bone growth,
β-adrenergic effects in heart (increased CO, HR, SV, contractility),
Basal metabolic rate increased
134
What are the catabolic effects of thyroid hormones?
Increased glycogenolysis, gluconeogenesis, lipolysis
135
Routine neonatal screening shows low thyroid hormone levels. What organ system's development are you concerned about?
The CNS because thyroid hormones are needed for CNS maturation
136
From which large precursor protein is thyroid hormone derived?
thyroglobulin
137
A 50-year-old woman has fatigue, cold intolerance, and weight gain. She has been adding iodized salt to food. Explain the pathophysiology.
**_Wolff-Chaikoff effect:_** *temporary inhibition of thyroid peroxidase* by extra iodine
--\>reducing iodine organification and T3/T4 production
138
What is the major hormone product of the thyroid gland?
Which of the two thyroid hormones is more active (promotes more downstream thyroid function)? Which enzyme generates this active form?
T4 (T3 is a lesser product; the majority of T3 is created peripherally via 5′-deiodinase.)
T3; 5′-deiodinase
139
Both propylthiouracil and methimazole decrease formation of monoiodotyrosine and diiodotyrosine via what mechanism? How do the drugs differ?
PTU and MMI **inhibit thyroid peroxidase**,
but _propylthiouracil also inhibits 5′-deiodinase_ (which converts T4 to T3 in peripheral tissue)
140
A 30-year-old woman complains of weight loss, hair loss, and protruding eyes. What autoimmune process may be at work?
She likely has Graves disease due to thyroid-stimulating immunoglobulins []
which stimulates follicular cells similar to TSH
141
A pregnant woman's lab studies show an increase in total T4 levels. Should she be alarmed?
Not necessarily; total T4 level increases in pregnancy because of increased circulating TBG, **but free T4 should remain normal**
142
Where do T3 and T4 bind to exert their effects? Which of the two has greater affinity?
Where do free T3 and T4 exert negative feedback?
Nuclear receptors; T3
The hypothalamus and anterior pituitary
143
What are the two main functions of thyroid peroxidase?
The oxidation and organification of iodine;
the coupling of MIT and DIT (MIT + DIT = T3, DIT + DIT = T4)
144
A new toxin inhibits various co-transporters that depend on Na+. How might this induce hypothyroidism?
Explain how iodine is transported from the peripheral blood to the thyroid follicular lumen for use in thyroid hormone (T3/T4) production
Iodine (I–) is taken up from the blood by the thyroid via an I–/Na+ co-transporter; inhibiting this co-transporter causes hypothyroidism
I– enters the thyroid via **I–/Na+ co- transporters**; it is then **oxidized (I– to I2**) & exported to the *_follicular lumen via thyroid peroxidase_*
145
Where does the coupling of thyroid hormones take place? What important transporter molecule is required to make this happen?
Thyroid follicular epithelial cells;
TG, carrying organified I2 as MIT and DIT, assists with *endocytosis*
146
What is the "cycle" of TG in the thyroid, and how does this assist with thyroid hormone production?
Lumen TG binds/helps endocytose MIT/DIT into follicular cells;
in cells, **deiodinase/coupling** _remove DIT/MIT from TG_;
TG then reenters lumens
147
Oxidized I2 in the follicular _lumen_ is organified into which two molecules?
What enzyme facilitates this process?
MIT and DIT; thyroid peroxidase
148
In the thyroid follicular epithelial cells, not all MIT and DIT is used to produce thyroid hormones. What happens to these excess molecules?
MIT and DIT are "coupled" into what hormones within the _thyroid follicular_ epithelial cells? What enzyme is responsible for this?
They detach from TG and are converted back into inorganic iodine (I–) and tyrosine via deiodinase
Thyroid hormones (T4 and T3); thyroid peroxidase
149
How do thyroid hormones exerting negative feedback on the anterior pituitary reduce the production of TSH?
They decrease the sensitivity of the anterior pituitary to TRH (produced by the hypothalamus)
150
A toxin causes hyperthyroidism by blocking anterior pituitary T3/T4 negative feedback.
An analog of what hormone may act as an antidote?
**Somatostatin** (inhibits TSH production in the anterior pituitary)
151
What hormones use the IP3 signaling pathway?
GnRH, Oxytocin, ADH (_V1_ receptor), TRH, Histamine (_H1_ receptor), Angiotensin II, Gastrin
**(GOAT HAG)**
152
Which hormones use intracellular receptors in their signaling pathways?
Progesterone, Estrogen, Testosterone,Cortisol, Aldosterone,
T3/T4 Vitamin D
**(PET CAT on TV)**
153
What hormones use cGMP as a signaling molecule?
BNP, ANP, EDRF (NO); with cGMP, think vasodilators
**(BAD GraMPa)**
154
What hormones use a receptor tyrosine kinase/MAP kinase pathway?
Insulin, IGF-1, FGF, PDGF, EGF (think growth factors)
155
What hormones use a nonreceptor/receptor associated tyrosine kinase?
Which tyrosine kinase pathway do they use?
Prolactin, Immunomodulators (eg, cytokines IL-2/IL-6/IFN), GH,
G-CSF, Erythropoietin, Thrombopoietin
**(PIGGLET);**
**JAK/STAT pathway**
*think acidophils and cytokines*
156
Antidiuretic hormone can bind the V1- or V2
The V1-receptor uses the IP3 pathway,
and the V2 receptor uses cAMP
157
You are seeing a patient with malignant hypertension in the ED. Medications acting on which signaling pathway would be most helpful here?
**cGMP**
*hormones using this pathway tend to vasodilate (ANP, BNP, and EDRF [NO])*
158
A boy's receptor-associated tyrosine kinase pathway is defective. Do you note decreased Ca2+ levels, a lack of insulin, or impaired growth?
Decreased growth; GH uses this signaling pathway
159
Name the hormones that use the cAMP signaling pathway.
FSH, LH, ACTH, TSH, CRH, hCG, ADH (V2-receptor) MSH, PTH, calcitonin, GHRH, glucagon
## Footnote
**(FLAT ChAMP)**
160
What are the major differences in signaling between insulin and glucagon?
Insulin uses an intrinsic tyrosine kinase pathway, whereas glucagon increases the cAMP concentration in the cell after binding its receptor
161
A patient asks if the prednisone she was prescribed will work within seconds. What is the most appropriate response?
Which elicit a response faster: steroid hormones or peptide hormones?
Steroid hormones have a delayed response; time is required for gene transcription and protein synthesis to be affected
Peptide hormones, as steroid hormones must act at a _transcriptional level_ to evoke cellular changes
162
A steroid hormone acts on a cell. Outline the steps needed for gene expression to be modified.
Steroid hormones are lipophilic, and specific binding globulins increase their solubility
Hormone enters cell and _binds receptor_ (nucleus or cytoplasm), DNA exposed, hormone binds to enhancer, transcription/translation, response
163
As SHBG increases in men, what change would you expect in free testosterone (assuming no compensatory mechanism)?
As **SHBG increases** in men, **free testosterone decreases**, leading to gynecomastia
164
A 31-year-old woman presents with facial hair. Lab values show low SHBG.
What do you expect her free testosterone to be?
A 35-year-old woman is 7 months pregnant. How does pregnancy affect her SHBG level?
Increased (because she has hirsutism); tesosterone increases
Pregnancy (and OCPs) increase SHBG,
though the **free estrogen level remains unchanged**
165
A bodybuilder takes pure testosterone, thinking that it will help him build muscle. Where will this hormone bind to its receptor?
Steroid hormones bind their receptors in ***_either the cytoplasm or nucleus_***
166
Treatmet for
Neprhogenic DI?
Central DI?
Nephorgenic: HCTZ, indomethacin, amiloride, hydration
Central: Intranasal desmopressin acetate (ADH analog), hyrdation
167
What are causes of hypopituitarism? (6)
Nonsecreting pituitary adenoma
Sheehan Syndrome
Empty sella syndrome (atropy or compresison of pitutiary, often idipathic, common in obsese women)
Pituitary apoplexy (sudden hemorrhage of pituitary gland, often due to the presence of pituitary adenoma)
168
What is the change of seen in the plasma (vol and Na+) in a person with SIADH?
Euvolemia hyponatremia with continued urinary Na+ ecretion
Urine osmo \> serum osmo
169
If a person w/ SIADH serum osmolarity is corrected too quickly, what could occur?
Osmotic demyelination syndrome
AKA: central pontine myelinolysis
"low to high your pons will die"
170
Treatment for SIADH?
Fluid restriction, IV hypertonic saline, conivaptan, tolvaptan (ADH anatgonist), demeclocycline (ADH antagonist, part of the tetracycline fam!)
171
How does hyperthyroidism increase BMR and sympathetic activit?
INC BMR via increase activity of Na+/K+ ATPase
INC sympathetic activity via INC in sympathetic NS
172
Jod-Basedow phenomenon VS Wolff-Chaikoff phenomenon?
JB phenomemon - thyrotoxicosis occurs in a patiet with iodine deficiency GOITER when given iodine --\> ramp up TH production
WC phenomenon --\> INC iodine --\> temp DEC in hormone production
173
Hashimotos Thyroiditis:
What pathogenesis it is associated with?
Histological findings?
What are people with hashimoto's thyroiditis increased risk for?
Anti-TPO, Anti-TG, Anti-microsomal
HLA DR 5 (same as pernicious anemia)
Increased risk for: **non-hodgkins lymphoma**
Histo: _**Hurthles Cell**, **lymphoid aggregate with germinal centers**_
moderately enlarged, *_non-tender_* thyroid
174
What are the causes of nephorgenic DI?
Hereditary (ADH receptor mutation) OR
secondary due to: HYPERcalcemia, LITHIUM, **demeclocycline (ADH antagonist- used to treat SIADH)**
175
Tender thyroid??
Think of Subactute granulomatous de Quervain thyroiditis
Occurs post-infection
may have early hyperthyroidism, followed by hypothyroidism but does not progress to full blow hypothyroidism
Histo: granulomatous inflammatoy
TENDER thyroid (vs hashimotos = non-tender thyroid), jaw pain, inc ESR, PAINFUL!
deQuervAIN = pAIN!
176
Hard as wood thyroid?
Riedel thyroiditis
Thyroid is replaced by fibrous tissue and extensive chronic inflammation - fibrosis could extend to local structures.
You have a fixed, hard/rock-like PAINLESS goiter
\*MIMICKS ANAPLASTIC CARCINOMA!! (dz of older ppl vs RT is dz of young female)\*\*
177
What would warrant an FNA biopsy of the thyroid?
Fine Neddle Aspiration, should be done when there is decreased uptake of I(131) radioactive
Could be due to an adenoma or carcinoma
178
What is osteititis fibrosa cystica
cystic BONE spaces filled with brown fibrous tissue
"brown tumor"
consisiting of deposited hemosidern from hemorrhages --\> causing bone pain
*related with hyperparathyroidism*
179
What is Albright hereditary osteodystrophy?
Pseudohypoparathyrodism
unresponsiveness of kidney to PTH / end-organs not responding to PTH
Hypocalcemia, shortened 4th/5th digits, short stature
Autosomal Dominant, due to a mutation at the Gs Receptor
