Lecture 1: Endocrinology Review Flashcards
1
Q
Which endocrine hormones utilize the PLC mechanism? (GOAT HAG mnemonic)
A
GnRH + Oxytocin + ADH + TRH + Histamine + Angiotensin II + GHRH
GOAT HAG
2
Q
Which enzyme is responsible for the degradation of intracellular cAMP to inactive 5’ AMP in the adenylyl cyclase/cAMP pathway?
A
Phosphodiesterase
3
Q
What are the 2 classes of homrones which are amines?
A
- Catecholamines (epinephrine, NE, and dopamine)
- Thyroid hormones
4
Q
When a steroid hormone binds its receptor what occurs to the hormone-receptor complex?
A
Dimerizes and binds via zinc fingers to specific DNA sequences, called steroid-responsive elements (SREs)
5
Q
Once the steroid hormone-receptor complex dimerizes and binds to the SREs of the target gene, what has this complex now become and what does it regulate?
A
A transcription factor that regulates the rate of gene transcription
6
Q
What is the epithelial and neural portion of the pituitary gland?
A
- Anterior pituitary (adenohypophysis) = epithelial portion
- Posterior pituitary (neurohypophysis) = neural portion
7
Q
Generally cancers of the pituitary expand where and compress what?
A
Up into the brain and compress the optic nerves
8
Q
The posterior pituitary is a collection of axons whose cell bodies are located in the hypothalamus; what are these 2 cell bodies and which neuropeptides is each cell body associated with?
A
- Supraoptic nucleus (SON) –> mainly ADH
- Paraventricular nucleus (PVN) –> mainly oxytocin
9
Q
Which 6 hormones are secreted by the anterior pituitary?
A
- FSH
- LH
- ACTH
- TSH
- Prolactin
- GH
*FLAT PiG*
10
Q
How is the anterior pituitary connected to the hypothalamus?
A
Hypothalamic-hypophysial portal vessels
11
Q
Which portion of the pituitary gland has both neural and endocrine connections with the hypothalamus; which has exclusively neural?
A
- Anterior pituitary = BOTH endocrine and neural
- Posterior pituitary = only neural
12
Q
Contrast primary endocrine disorder, secondary endocrine disorder, and tertiary endocrine disorder.
A
- 1° disorder = due to defect in the peripheral endocrine gland
- 2° disorder = due to defect in the pituitary gland
- 3° disorder = due to defect in the hypothalamus
13
Q
Gonadotrophs release what hormone(s)?
A
FSH and LH
14
Q
Somatotrophs release what hormone?
A
GH
15
Q
What is the most important somatomedin mediating the indirect effects of GH?
A
IGF-1
16
Q
What is the effect of GH on insulin, blood glucose levels, and adipose tissues?
A
- Causes insulin resistance –> ↑ blood insulin
- Effects are diabetogenic –> ↑ in blood glucose levels
- ↑ lipolysis in adipose tissue
17
Q
What are 2 metabolic effects of GH which are mediated by somatomedins (IGF-1)?
A
- ↑ protein synthesis and organ growth (↑uptake of AA’s)
- ↑ linear growth (↑ metabolism in cartilage-forming cells and chondrocytes proliferation)
18
Q
What are 2 of the most potent stimuli for GH secretion?
A
Hypoglycemia and starvation
19
Q
Conditions with excess secretion of GH are treated with what?
A
Somatostatin analogs –> ocreotide
20
Q
What are 4 ways that GH deficiency can result?
A
- ↓ secretion of GHRH (hypothalamic dysf.)
- ↓ GH secretion (pituitary dysf.)
- Failure to generate somatomedins in the liver
- GH or somatomedin resistance (deficiency of receptors)
21
Q
GH excess causes what if before puberty or what if after puberty?
A
- Before puberty = gigantism
- After puberty = acromegaly
22
Q
Where does prolactin released from the anterior pituitary act and what is its function?
A
Acts on the hypothalamus to ↓ GnRH secretion —-> ↓ FSH and LH
23
Q
What is the inhibitory and stimulatory pathway from the hypothalamus regulating prolactin release from the anterior pituitary?
A
- Inhibitory = Dopamine (aka PIF)
- Stimulatory = TRH
24
Q
How does prolactin inhibit its own secretion?
A
By increasing the synthesis and secretion of dopamine from the hypothalamus (negative feedback)
25
What are the 2 most important stimuli for prolactin secretion?
- **Breast feeding**
- **Pregnancy**
26
Secretion of ADH is most sensitive to changes in what?
Plasma osmolarity
27
What are 6 triggers for the secretion of ADH from the posterior pituitary?
- ↑ plasma osmolarity = **most important stimulus**
- ↓ BP
- ↓ blood volume
- ↑ Angiotensin II
- Sympathetic stimulation
- Dehydration
28
In volume expansion (aka hypervolemia) what occurs with ADH secretion even in the presence of increased plasma osmolarity?
ADH secretion is **inhibited**
29
What is the major action of ADH and via what receptor?
- **↑ water permeability** of principal cells in the late distal tubule and collecting duct
- Via the **V2** receptor on **principal cells**
30
What is the effect of ADH on vascular smooth muscle and via which receptor?
**Contraction** of vascular smooth m. (aka **vasoconstriction**) via the **V1 receptor**
31
Central diabetes insipidus is caused by what; what are ADH levels like?
- Caused by: **damage to posterior pituitary** or **destruction** of **hypothalamus**
- **LACK** of **ADH** so will see **↓ plasma ADH**
32
What will be seen in terms of urine production and serum osmolarity in patient with central DI?
- **Large** volumes of **dilute** urine
- Bodily fluids are concentrated i.e., **↑ serum osmolarity** and ↑ serum [Na+]
33
What is occuring in nephrogenic DI; what are plasma levels of ADH like?
Kidneys are **unable** to **respond** to **ADH** (**↑ plasma ADH**)
34
What are 2 major causes of nephrogenic DI?
- Drugs like **lithium**
- Chronic disorders i.e., **polycystic kidney disease**, **sickle cell anemia**
35
What is the Tx of Central DI vs. Nephrogenic DI?
- **Central** DI is treated with **desmopressin** (ADH analogue)
- **Nephrogenic** DI is treated with **thiazide diuretics** (desmopressin does **NOT** work)
36
What is the serum and urine osmolarity like in SIADH?
- **Serum** osmolarity is **decreased** due to excess water reabsorption by collecting ducts ---\> **HYPO**osmolarity fails to inhibit ADH release
- **Urine** is **inappropriately concentrated** (i.e., too concentrated for the serum osmolarity)
37
What are the 3 layers of the adrenal cortex and what are the main hormones produced by each layer?
- Zona **G**lomerulosa --\> mineralocorticoids (**aldosterone**)
- Zona **F**asciculata --\> glucocorticoids (**cortisol**)
- Zona **R**eticularis --\> androgens (**DHEA**)
38
Which hormones are produced by the adrenal medulla?
Catecholamines (**epinephrine** and **NE**)
39
What is the precursor for all adrenal cortex hormones?
Cholesterol
40
Which pathway(s) of hormone synthesis in the adrenal cortex does the enzyme 17α-hydroxylase play a role in?
- **Cortisol** synthesis
- **Androgen** synthesis
41
Which pathway(s) of hormone synthesis in the adrenal cortex does the enzyme 21β-hydroxylase play a role in?
- **Aldosterone** synthesis
- **Cortisol** synthesis
42
Which pathway(s) of hormone synthesis in the adrenal cortex does the enzyme 11β-hydroxylase play a role in?
- **Aldosterone** synthesis
- **Cortisol** synthesis
43
For each indicate if the levels will be ↑ or ↓ in 17α-hydroxylase deficiency: mineralocorticoids, cortisol, sex hormones, BP, and [K+]
- ↑ mineralocorticoids
- ↓ cortisol
- ↓ sex hormones
- ↑ BP
- ↓ [K+]
44
Which enzyme deficiency is associated with ↓ androstenedione levels?
17α-hydroxylase
45
For each indicate if the levels will be ↑ or ↓ in 21β-hydroxylase deficiency: mineralocorticoids, cortisol, sex hormones, BP, and [K+]
- ↓ mineralocorticoids
- ↓ cortisol
- ↑ sex hormones
- ↓ BP
- ↑ [K+]
46
Which enzyme deficiency of the adrenal cortex is associated with ↑ renin and ↑ 17-hydroxy-progesterone?
21β-hydroxylase
47
For each indicate if the levels will be ↑ or ↓ in 11β-hydroxylase deficiency: mineralocorticoids, cortisol, sex hormones, BP, and [K+]
- ↓ aldosterone and ↑ 11-deoxycorticosterone (DOC) = ↑ BP
- ↓ cortisol
- ↑ sex hormones
- ↑ BP
- ↓ [K+]
48
Which enzyme deficiency of the adrenal cortex is associated with ↓ renin activity?
11β-hydroxylase
49
What will the presentation in a male vs. female child be with 17α-hydroxylase deficiency?
- **Male** = undescended testes; ambiguous genitalia
- **Female** = lack of 2° sexual development
50
When does 21β-hydroxylase deficiency most commonly present and how?
- In **infancy** w/ **salt wasting** or **childhood** (precocious puberty)
- In **females** = virilization
51
How does 11β-hydroxylase deficiency present in females?
**Virilization** = dev. of male physical characteristics
52
Which endocrine hormones utilize the AC/cAMP pathway (mnemonic from FA)
**F**SH + **L**H + **A**CTH + **T**SH + **C**RH + **h**CG + **A**DH + **M**SH + **P**TH
## Footnote
**FLAT ChAMP**
53
What is the effect of cortisol on the liver, muscle, and adipose tissue?
- **Liver** = gluconeogenesis
- **Muscle** = protein catabolism
- **Adipose tissue** = lipolysis
54
Describe the regulation of cortisol secretion (aka axis)
**CRH** (hypothalamus) stimulates **ACTH** (pituitary) --\> **cortisol** production (adrenal fasciculata)
55
What is the cause of Cushing's Syndrome; what changes are seen in CRH, ACTH and cortisol?
- **Adrenal tumor**
- ↓ CRH
- ↓ ACTH
- ↑ Cortisol
56
What is the cause of Cushing's Disease; what changes are seen in CRH, ACTH and cortisol?
- **Pituitary tumor**
- ↓ CRH
- ↑ ACTH
- ↑ Cortisol
57
What is the cause of Addison's Disease; what changes are seen in CRH, ACTH and cortisol?
- Caused by **autoimmune disease** of the **adrenal gland**
- ↑ CRH
- ↑ ACTH
- **↓ Cortisol**
58
What is the cause of Secondary Adrenal Insufficiency; what changes are seen in CRH, ACTH and cortisol?
- Glucocorticoid drugs suppressing H-P axis
- ↓ CRH
- ↓ ACTH
- ↓ Cortisol
59
Which 2 diseases affecting cortisol secretion will have hyperpigmentation?
- Secondary (**pituitary**) excess
- Primary deficiency
\*Processes where **ACTH** is **elevated**
60
What is responsible for the increased synthesis and secretion of aldosterone by stimulating cholesterol desmolase and aldosterone synthase?
Angiotensin II
61
How does levels of K+ affect aldosterone secretion?
- ↑ [K+] ---\> ↑ aldosterone
- ↓ [K+] ---\> ↓ aldosterone
62
What are the 3 main actions of aldosterone on the late distal tubule an collecting duct of the kidney?
- ↑ Na+ reabsorption
- ↑ K+ secretion
- ↑ H+ secretion
63
What is secreted by the α cells of the endocrine pancreas and where are these cells located?
- Secrete gluc**α**gon
- Located near **periphery** of islet
64
Describe the paracrine mechanism of communication between the alpha, delta, and beta cells of the pancreatic islets.
- **Delta** cells (**somatostatin**) **inhibit** secretion from **both** beta and alpha cells
- **Beta** cells (**insulin**) **inhibit** secretion from **alpha** cells
- **Alpha** cells (**glucagon**) **stimulate** secretion from **beta** cells
65
Describe the downstream effects upon glucose binding its receptor and increasing the intracellular [ATP] for the synthesis of insulin
**↑ ATP** --\> **K+ channels close ---\> cell depolarizes**, which **opens** voltage-sensitivie **Ca2+ channels** ---\> ↑ intracellular Ca2+ leads to **exocytosis** of **insulin**
66
Explain the mechanism which makes sulfonylurea drugs (i.e., tolbutamide and glyburide) useful in the tx of T2DM
Sulfonylurea receptor (SUR) **promotes** the **closing** of ATP-dependent K+ channels --\> depolarization and **↑ release** of **insulin**
67
Why is C peptide useful as a diagnostic tool in the screening of endogenous B cell function?
Is secreted in **equimolar** amounts with insulin and **excreted unchanged in the urine**
68
Which glucose transporter on pancreatic beta cells does glucose use to enter and promote the secretion of insulin?
**GLUT2**
69
What is responsible for down-regulation of the insulin receptor by decreasing the rate of synthesis and increasing the rate of degradation?
**Insulin** down-regulates its own receptor
70
What is the effect of insulin on [K+]?
↑ K+ uptake into cells
71
List 10 factors which stimulate insulin secretion
- ↑ [glucose] + ↑ [AA's] + ↑ [fatty acids] and [ketoacid]
- Glucagon
- Cortisol
- GIP
- Vagal stimulation; ACh
- K+
- Sulfonylurea drugs
- Obesity
72
List 6 factors which inhibit the release of insulin
- ↓ blood glucose
- Fasting
- Exercise (don't want glucose entering cell!)
- Somatostatin
- α-adrenergic agonists
- Diazoxide
73
Insulin receptor signaling causes the translocation of which receptor to the cell membrane for the transport of glucose into the cell?
GLUT4
74
What is the incretin effect and list incretins.
- **Oral** glucose has a **greater** effect on the **secretion of insulin** compared to glucose given via IV
- **Incretins** = GLP-1 and GIP which are secreted in response to GI glucose and fat
75
What are 3 factors that inhibit the secretion of glucagon?
- Insulin
- Somatostatin
- ↑ fatty acid and ketoacid concentration
76
What is the the major factor stimulating the secretion of glucagon?
**Decreased** blood [**glucose**]
77
Which 2 amino acids stimulate the secretion of glucagon?
**Arginine** and **alanine**
78
Which hormone released from the GI tract stimulates the secretion of glucagon?
CCK
79
What are the 4 major actions of glucagon?
- ↑ glycogenolysis
- ↑ gluconeogenesis
- ↑ lipolysis
- ↑ ketoacid formation
80
What effect does ↑ phosphate concentration have on ionized Ca2+ concentration?
↑ phosphate concentration --\> ↓ ionized Ca2+ concentration
81
Which 2 hormones stimulate an increase in bone resorption to ↑ Ca2+ concentration?
**PTH** and **Vit D (1,25-dihydroxy)**
82
The extracellular concentration of what ion is regulated by the same hormone that regulate Ca2+ concentration?
Phosphate (Pi)
83
Which hormone can cross the cell membrane in the parathyroid gland and downregulate PTH gene transcription and upregulate CaSR gene transcription?
1,25-Vitamin D
84
What is responsible for inhibiting the synthesis and secretion of PTH?
↑ **extracellular Ca2+**
85
What can you look for in the urine to assess the action of PTH on the kidney?
Urinary **cAMP** levels will be ↑ with ↑ PTH
86
What levels of [Ca2+], PTH and [Phosphate] **stimulate** 1α-hydroxylase in the renal proximal tubule to ↑ 1,25-(OH)2-cholecalciferol production?
- ↓ [Ca2+}
- ↓ [Phosphate]
- ↑ PTH
87
Which 2 hormones act synergistically to stimulate osteoclast activity and bone resorption?
**PTH** and **1,25-(OH)2-cholecalciferol**
88
How does the short-term vs. long-term action of PTH on bone differ?
- **Short-term** = bone **formation** (via direct action on **osteoblasts**)
- **Long-term** = ↑ bone **resorption** (indirect action on **osteoclasts** mediated by **cytokines** released from **osteoblasts**)
89
What is the effect of vitamin D on the kidney in terms of Pi and Ca2+?
- **Promotes** Pi **reabsorption** by proximal nephrons (stimulates **NPT2a** expression)
- **Minimal actions** on Ca2+
90
Which type of hyperparathyroidism does this represent?
Primary Hyperparathyroidism
91
In terms of secondary hyperparathyroidism, blood levels of what can help you determine if the underlying cause is renal failure vs. vitamine D deficiency?
- **Renal failure** ---\> ↑ **Pi**
- **Vitamin D deficiency** ---\> ↓ **Pi**
92
What are the levels of PTH, Ca2+, Pi, and Vitamin D like in hypoparathyroidism?
- ↓ PTH
- ↓ Ca2+
- ↑ Pi
- ↓ Vitamin D
93
What are the levels of PTH, Ca2+, Pi, and Vitamin D like in albright hereditary osteodystrophy (pseudohypoparathyroidism type 1a)?
- ↑ PTH
- ↓ Ca2+
- ↑ Pi
- ↓ Vitamin D
94
What are the levels of PTH, Ca2+, Pi, and Vitamin D like in humoral hypercalcemia of malignancy?
- ↓ PTH
- ↑ Ca2+
- ↓ Pi
- ↓ Vitamin D
95
How does the congenital disorder pseudovitamin D-deficient rickets type I differ from type II?
- **Type I** = ↓ 1α-hydroxylase
- **Type II** = ↓ vitamin D receptor
96
How does **rickets** differ from **osteomalacia**?
- **Rickets** is due to vitamin D deficiency in **children**; insufficient Ca2+ and phosphate are available to mineralize the growing bone.
- **Osteomalacia** is vitamin D deficiency in **adults**; new bone fails to mineralize, resulting in bendng and softening of weight-bearing bones
97
How does outer ring deiodination vs. inner ring deiodination of T4 in the peripheral conversion to T3 affect its activity?
- **Outer** ring deiodination ---\> **active** T3
- **Inner** ring deiodination ---\> **inactive** T3
98
The "Iodide-trap" for thyroid hormone biosynthesis utilizes which pump on the basolateral membrane of thryoid follicular cells?
Na+-I-cotransport (**symporter**)
99
What 3 steps of thyroid hormone synthesis utilize thyroid peroxidase?
- **Oxidation** of **I- ---\> I2**; moves iodine through **pendrin** channel into the **follicular lumen**
- **Organification** of **I2** w/ **TG** to form **MIT** and **DIT**
- **Coupling reaction** of **MIT** and **DIT** into **T3** and **T4**
100
What are 2 competitive inhibitors of Na+-I- contransport, blocking the uptake of I- into follicular cells?
**Thiocyanate** and **Perchlorate**
101
Why is the administration of **propylthiouracil (PTU)** an effective treatment for hyperthyroidism?
Blocks **all** steps of thyroid hormone synthesis catalzyed by **thyroid peroxidase**
102
Which enzyme found inside follicular epithelial cells is responsible for deiodination of residual MIT and DIT in turn "salvaging" both I- and tyrosine for another cycle of thyroid hormone synthesis?
**Thyroid deiodinase**
103
Deficiency of which enzyme mimics dietary I- deficiency?
**Thyroid deiodinase**
104
What is the Wolff-Chaikoff effect in regards to thyroid hormone synthesis?
**High levels** of **I-** **inhibit** organification and synthesis of thyroid hormones
105
Thyroxine-binding protein (TBG) has a higher affinity for what type of thyroid hormone?
**T4**
106
In hepatic failure there is decreased production of thyroxine-binding protein (TBG) and what effect does this have on levels of free T3 and T4 and the synthesis of thyroid hormones?
- Causes an **↑ in the level of free T3 and T4** because less is bound to TBG
- This **↑ in free thyroid** will **negatively feedback** to thyroid to **inhibit** synthesis of thyroid hormones
107
What is the effect of pregnancy of levels of TBG, free T3,T4 and the synthesis of thyroid hormone?
- **↑ levels TBG** ---\> ↑ bound T3, T4 ---\> **↓ free T3, T4**
- Transient ↓ T3, T4 causes **↑ in the synthesis and secretion** of T3, T4 by the thyroid
- **Overall** = ↑ **total** **T3, T4**, but levels of free, physiologically active, thyroid hormone are **normal** = **clinically euthyroid**
108
Release of TSH from the anteror pituitary is positively and negatively regulated by what?
- **(+) regulated** by **TRH** from the **hypothalamus**
- **(-) regulated** by **free T3**
109
What is the effect of **hyper-** and **hypothyroidism** on bone?
- **Hyperthyroidism** = osteoporosis
- **Hypothyroidism** = stunted growth
110
Explain how thyroid-stimulating immunoglobulins which underlie the pathophysiology of Graves Disease affect the HPT axis and effect levels of TSH and thyroid hormones?
- **TSI's** stimulate the **TSH receptor** without TSH hormone
- Leads to an ↑ in **circulating thyroid hormones** which **inhibit** the secretion of **TSH**
