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171 Cards in this Set

  • Front
  • Back

What is the initial thyroid precursor? Source?

Thyroid Diverticulum - arises from floor of primitive pharynx
What happens to the Thyroid Diverticulum? What is it connected to?
- Descends into neck from origin in floor of primitive pharynx
- Connected to tongue by thyroglossal duct
- Descends into neck from origin in floor of primitive pharynx
- Connected to tongue by thyroglossal duct
How is the Thyroid initially connected to the Tongue? What happens to this connection?
- Thyroid diverticulum is connected to the tongue by the Thyroglossal Duct
- Normally disappears, but may persist as pyramidal lobe of thyroid
- Foramen cecum is a normal remnant of the thyroglossal duct
- Thyroid diverticulum is connected to the tongue by the Thyroglossal Duct
- Normally disappears, but may persist as pyramidal lobe of thyroid
- Foramen cecum is a normal remnant of the thyroglossal duct
What is the normal remnant of the thyroglossal duct (connects tongue to thyroid diverticulum)?
Foramen Cecum
Foramen Cecum
What is the most common ectopic thyroid tissue site?
Tongue
What diagnosis should you consider in a patient presenting with an anterior midline neck mass that moves with swallowing or protrusion of the tongue?
Thyroglossal Duct Cyst
Thyroglossal Duct Cyst
What diagnosis should you consider if your patient presents with a mass in their lateral neck?
Branchial Cleft Cyst - persistent cervical sinus
What are the adrenal cortex and medulla derived from?
- Adrenal cortex: mesoderm
- Adrenal medulla: neural crest
What are the layers of the adrenal cortex from external to internal?
- Zona Glomerulosa
- Zona Fasiculata
- Zona Reticularis
What is the primary regulatory control of the Zona Glomerulosa? Secretory product?
- Controlled by Renin-Angiotensin
- Secretes Aldosterone
What is the primary regulatory control of the Zona Fasiculata? Secretory product?
- Controlled by ACTH and CRH
- Secretes cortisol and sex hormones
What is the primary regulatory control of the Zona Reticularis? Secretory product?
- Controlled by ACTH and CRH
- Secretes sex hormones (eg, androgens)
What kind of cells are in the Adrenal Medulla?
Chromaffin cells
What is the primary regulatory control of the Adrenal Medulla? Secretory product?
- Controlled by preganglionic sympathetic fibers
- Secretes catecholamines (epinephrine and norepinephrine)
What is the most common tumor of the adrenal medulla in adults? What does it characteristically cause?
Pheochromocytoma
- Episodic hypertension
What is the most common tumor of the adrenal medulla in children? What does it characteristically cause?
Neuroblastoma
- RARELY causes hypertension
How is the adrenal gland drained on the left side?
Left adrenal gland → Left adrenal vein → Left renal vein → IVC
How is the adrenal gland drained on the right side?
Right adrenal gland → Right adrenal vein → IVC
What tissue are the anterior and posterior pituitary made from?
- Anterior Pituitary: oral ectoderm (Rathke pouch)
- Posterior Pituitary: neuroectoderm
What is the other name for the posterior pituitary? What does it secrete?
Neurohypophysis
- Vasopressin / ADH
- Oxytocin
What is the source of ADH and Oxytocin?
They are both made in the hypothalamus and shipped to the posterior pituitary via the neurophysins (carrier proteins)
What is the other name for the anterior pituitary? What does it secrete?
Adenohypophysis

Think FLAT PiGs eat MuSH:
- FSH
- LH
- ACTH
- TSH
- Prolactin
- GH
- MSH (Melanotropin)
What kind of cells are there in the anterior pituitary? Functions?
- Acidophils: secretes Prolactin and GH
- Basophils: FSH, LH, ACTH, and TSH
What are the subunits of the hormones released from the anterior pituitary? Functions?
- α subunit: hormone subunit common to TSH, LH, FSH, and hCG
- β subunit: determines hormone specificity
Which hormones have the same α subunit?
- TSH
- LH
- FSH
- hCG
What part of TSH, LH, FSH, and hCG is the same? Which part determines its hormonal specificity?
- α subunit is the same
- β subunit gives specificity
What are the types of pancreatic cells with endocrine function?
Islets of Langerhans:
- α cells
- β cells
- δ cells
What is the source of Islets of Langerhans in the pancreas?
Arise from pancreatic buds
What is the function of the α, β, and δ cells in the Islets of Langerhans in the pancreas? Relative locations in Islet?
- α cells: glucagon (peripheral)
- β cells: insulin (central) = Insulin is Inside
- δ cells: somatostatin (interspersed)
- α cells: glucagon (peripheral)
- β cells: insulin (central) = Insulin is Inside
- δ cells: somatostatin (interspersed)
How is insulin synthesized? Where?
Takes place in β cells in Islets of Langerhans:
- Preproinsulin is synthesized in RER
- Cleavage of "presignal" generates Proinsulin
- Proinsulin is stored in secretory granules
- Cleavage of Proinsulin → exocytosis of Insulin and C-peptide
Takes place in β cells in Islets of Langerhans:
- Preproinsulin is synthesized in RER
- Cleavage of "presignal" generates Proinsulin
- Proinsulin is stored in secretory granules
- Cleavage of Proinsulin → exocytosis of Insulin and C-peptide
If you see both elevated Insulin and C-peptide vs only elevated Insulin, how does this help your differential?
- Elevated Insulin and C-peptide: Insulinoma
- Elevated Insulin without C-peptide: Exogenous Insulin administration
- Elevated Insulin and C-peptide: Insulinoma
- Elevated Insulin without C-peptide: Exogenous Insulin administration
How does insulin mediate its effects?
1. Binds insulin receptors (tyrosine kinase activity)
2. Induces glucose uptake (carrier-mediated transport) in insulin dependent tissues
- Also induces gene transcription
1. Binds insulin receptors (tyrosine kinase activity)
2. Induces glucose uptake (carrier-mediated transport) in insulin dependent tissues
- Also induces gene transcription
What happens when insulin binds to its receptor?
- Tyrosine phosphorylation
- Phosphoinositide-3 kinase pathway
- Induces glycogen, lipid, and protein synthesis
- Vesicles containing GLUT-4 are placed in membrane to allow entry of glucose into cell

INsulin moves glucose INto cells
- Tyrosine phosphorylation
- Phosphoinositide-3 kinase pathway
- Induces glycogen, lipid, and protein synthesis
- Vesicles containing GLUT-4 are placed in membrane to allow entry of glucose into cell

INsulin moves glucose INto cells
What are the anabolic effects of insulin?
- ↑ Glucose transport in skeletal muscle and adipose tissue
- ↑ Glycogen synthesis and storage
- ↑ Triglyceride synthesis
- ↑ Na+ retention (kidneys)
- ↑ Protein synthesis (muscles, proteins)
- ↑ Cellular uptake of K+ and amino acids
- ↓ Glucagon release
What are the insulin-dependent glucose transporters? Locations?
GLUT-4: adipose tissue and skeletal muscle
What are the insulin-independent glucose transporters? Locations?
- GLUT-1: RBCs, brain, cornea
- GLUT-5 (fructose): spermatocytes, GI tract
- GLUT-2 (bidirectional): β islet cells, liver, kidney, small intestine
What type of glucose transporters are in the adipose tissue? Characteristics?
GLUT-4: insulin-dependent glucose transporter
What type of glucose transporters are in the skeletal muscle? Characteristics?
GLUT-4: insulin-dependent glucose transporter
What type of glucose transporters are in RBCs? Characteristics?
GLUT-1: insulin-independent glucose transporter
What type of glucose transporters are in the brain? Characteristics?
GLUT-1: insulin-independent glucose transporter
What type of glucose transporters are in the cornea? Characteristics?
GLUT-1: insulin-independent glucose transporter
What type of sugar transporters are in the spermatocytes? Characteristics?
GLUT-5 (fructose): insulin-independent transporter
What type of sugar transporters are in the GI tract? Characteristics?
- GLUT-5 (fructose): insulin-independent transporter
- GLUT-2 (bidirectional): insulin-indepdent transporter - small intestine
What type of sugar transporters are in the β islet cells? Characteristics?
GLUT-2 (bidirectional): insulin-indepdent transporter
What type of sugar transporters are in the liver? Characteristics?
GLUT-2 (bidirectional): insulin-indepdent transporter
What type of sugar transporters are in the kidneys? Characteristics?
GLUT-2 (bidirectional): insulin-indepdent transporter
What kind of fuel does the brain use?
- Glucose for metabolism normally
- Ketone bodies during starvation
What kind of fuel do RBCs use?
Always utilize glucose because they lack mitochondria fro aerobic metabolism
How do you remember the sites of insulin-indepdent glucose uptake?
BRICK L:
- Brain
- RBCs
- Intestine
- Cornea
- Kidneys
- Liver
What regulates insulin release?
- Glucose
- GH
- β2-agonists
How does glucose enter pancreatic β cells? What are the effects?
3. Glucose enters β cells via GLUT-2 (bidirectional) channels
4. ↑ ATP generated from glucose metabolism
5. Closes K+ channels
6. Depolarizes β cell membrane
7. Opens voltage-gated Ca2+ channels, resulting in Ca2+ influx
8. Stimulates ins...
3. Glucose enters β cells via GLUT-2 (bidirectional) channels
4. ↑ ATP generated from glucose metabolism
5. Closes K+ channels
6. Depolarizes β cell membrane
7. Opens voltage-gated Ca2+ channels, resulting in Ca2+ influx
8. Stimulates insulin exocytosis
What is the source of glucagon? Function?
- Made by α cells of pancreas

Functions in catabolism:
- Glycogenolysis and gluconeogenesis → make more glucose
- Lipolysis and ketone production → make alternative sources of energy
What stimulates and inhibits glucagon secretion?
- Secreted in response to hypoglycemia
- Inhibited by insulin, hyperglycemia, and somatostatin
What is the function of CRH?
↑ ACTH, MSH, and β-endorphin
What causes ↓ CRH?
Chronic exogenous steroid use
What is the function of Dopamine on the pituitary?
↓ Prolactin
What is the effect of Dopamine Antagonists (eg, anti-psychotics) on the pituitary?
Can cause galactorrhea (↑ prolactin)
What is the function of GnRH?
- ↑ FSH and LH
- Tonic GnRH suppresses the HPA axis
- Pulsatile GnRH leads to puberty and fertility
What regulates GnRH?
Regulated by Prolactin
What is the effect of tonic GnRH release?
Suppresses HPA axis
What is the effect of pulsatile GnRH release?
Leads to puberty and fertility
What is the function of Prolactin?
↓ GnRH
What are the consequences of a pituitary prolactinoma?
Amenorrhea (↓ GnRH) and Osteoporosis
What is the function of Somatostatin on the pituitary?
↓ GH and TSH
How can you treat acromegaly?
Somatostatin analogs (↓ GH)
What is the function of TRH?
↑ TSH and Prolactin
What are the effects of Prolactin?
- Stimulates milk production in breasts
- Inhibits ovulation in females and spermatogenesis in males by inhibiting GnRH synthesis and release
- Excessive prolactin associated with ↓ libido
- Stimulates milk production in breasts
- Inhibits ovulation in females and spermatogenesis in males by inhibiting GnRH synthesis and release
- Excessive prolactin associated with ↓ libido
How is Prolactin regulated?
- Tonically inhibited by Dopamine from hypothalamus
- Prolactin inhibits its own secretion by ↑ Dopamine synthesis and secretion
- TRH ↑ Prolactin secretion
- Tonically inhibited by Dopamine from hypothalamus
- Prolactin inhibits its own secretion by ↑ Dopamine synthesis and secretion
- TRH ↑ Prolactin secretion
What drugs can be used to treat excess prolactin (such as prolactinoma)?
Dopamine Agonists - eg, Bromocriptine
- Dopamine inhibits Prolactin secretion
Dopamine Agonists - eg, Bromocriptine
- Dopamine inhibits Prolactin secretion
What drugs may stimulate prolactin secretion?
- Dopamine antagonists (eg, anti-psychotics)
- Estrogens (OCPs, pregnancy)
What are the effects of Growth Hormone (Somatotropin)?
- Stimulates linear growth and muscle mass through IGF-1 / somatomedin secretion
- ↑ Insulin resistance (diabetogenic)
What is the effect of GH on insulin?
GH increases insulin resistance (diabetogenic)
What regulates Growth Hormone release?
- Released in pulses in response to GHRH (GH releasing hormone)
- Increases during sleep and exercise
- Inhibited by glucose and somatostatin
What can excess secretion of GH be due to? What can it cause?
- Could be due to pituitary adenoma
- Causes acromegaly (adults) or gigantism (children)
What is the source of Anti-Diuretic Hormone (ADH)?
- Synthesized in hypothalamus (supraoptic nuclei)
- Released by posterior pituitary
What is the function of Anti-Diuretic Hormone (ADH)?
- Regulates serum osmolarity (V2 receptors) and blood pressure (V1 receptors)
- ↓ serum osmolarity and ↑ urine osmolarity via regulation of aquaporin channel transcription in principal cells of renal collecting duct
What diseases affect the levels / response to ADH?
- 1° Polydipsia: ADH is suppressed
- Central Diabetes Insipidus (DI): ADH ↓
- Nephrogenic Diabetes Insipidus (DI): ADH ↑ (kidney is resistant to its effects)
What can cause nephrogenic diabetes insipidus?
Resistance to ADH can be mediated by a mutation in the V2 receptor (regulates serum osmolarity)
How do you treat central diabetes insipidus?
Desmopressin (ADH analog) - central DI is caused by insufficient production of ADH
What are the types of receptors that ADH acts on? Effects?
- V2 receptor: regulates serum osmolarity
- V1 receptor: regulates blood pressure
How is ADH regulated?
- Osmoreceptors in hypothalamus (1°)
- Hypovolemia (2°)
What is the first step in production of adrenal steroids?
Conversion of Cholesterol → Pregnenolone via Cholesterol Desmolase
Conversion of Cholesterol → Pregnenolone via Cholesterol Desmolase
How do you produce Aldosterone?
1. Cholesterol → Pregnenolone (Cholesterol Desmolase)
2. Pregnenolone → Progesterone (3β-hydroxysteroid dehydrogenase)
3. Progesterone → 11-deoxycorticosterone (21-hydroxylase)
4. 11-deoxycorticosterone → Corticosterone (11β-hydroxylase)
5. Corticosterone → Aldosterone (Aldosterone Synthase)
What are the molecules on the way from Cholesterol to Aldosterone?
1. Cholesterol
2. Pregnenolone
3. Progesterone
4. 11-deoxycorticosterone
5. Corticosterone
6. Aldosterone
1. Cholesterol
2. Pregnenolone
3. Progesterone
4. 11-deoxycorticosterone
5. Corticosterone
6. Aldosterone
What are the enzymes on the way from Cholesterol to Aldosterone?
1. Cholesterol Desmolase
2. 3β-hydroxysteroid dehydrogenase
3. 21-hydroxylase
4. 11β-hydroxylase
5. Aldosterone Synthase
1. Cholesterol Desmolase
2. 3β-hydroxysteroid dehydrogenase
3. 21-hydroxylase
4. 11β-hydroxylase
5. Aldosterone Synthase
How do you produce Cortisol?
1. Cholesterol → Pregnenolone (Cholesterol Desmolase)
2. Pregnenolone → 17-hydroxypregnenolone (17α-hydroxylase)
3. 17-hydroxypregnenolone → 17-hydroxyprogesterone (3β-hydroxysteroid dehydrogenase)
4. 17-hydroxyprogesterone → 11-deoxy...
1. Cholesterol → Pregnenolone (Cholesterol Desmolase)
2. Pregnenolone → 17-hydroxypregnenolone (17α-hydroxylase)
3. 17-hydroxypregnenolone → 17-hydroxyprogesterone (3β-hydroxysteroid dehydrogenase)
4. 17-hydroxyprogesterone → 11-deoxycortisol (21-hydroxylase)
5. 11-deoxycortisol → Cortisol (11β-hydroxylase)

Steps 2 and 3 can be switched around, but need both enzymes
What are the molecules on the way from Cholesterol to Cortisol?
1. Cholesterol
2. Pregnenolone
3. 17-hydroxypregnenolone
4. 17-hydroxyprogesterone
5. 11-deoxycortisol
6. Cortisol

OR

3. Progesterone (depending on order of enzymes)
1. Cholesterol
2. Pregnenolone
3. 17-hydroxypregnenolone
4. 17-hydroxyprogesterone
5. 11-deoxycortisol
6. Cortisol

OR

3. Progesterone (depending on order of enzymes)
What are the enzymes on the way from Cholesterol to Aldosterone?
1. Cholesterol desmolase
2. 17α-hydroxylase
3. 3β-hydroxysteroid dehydrogenase
4. 21-hydroxylase
5. 11β-hydroxylase

(Enzymes 2 and 3 can be done in either order)
1. Cholesterol desmolase
2. 17α-hydroxylase
3. 3β-hydroxysteroid dehydrogenase
4. 21-hydroxylase
5. 11β-hydroxylase

(Enzymes 2 and 3 can be done in either order)
How do you produce Estradiol?
1. Cholesterol → Pregnenolone (Cholesterol Desmolase)
2. Pregnenolone → 17-hydroxypregnenolone (17α-hydroxylase)
3. 17-hydroxypregnenolone → Dehydroepiandrosterone (DHEA)
4. DHEA → Androstenedione
5. Androstenedione → Estrone (Aroma...
1. Cholesterol → Pregnenolone (Cholesterol Desmolase)
2. Pregnenolone → 17-hydroxypregnenolone (17α-hydroxylase)
3. 17-hydroxypregnenolone → Dehydroepiandrosterone (DHEA)
4. DHEA → Androstenedione
5. Androstenedione → Estrone (Aromatase)
6. Estrone → Estradiol

OR

5. Androstenedione → Testosterone
6. Testosterone → Estradiol (Aromatase)
What are the actions of Aromatase?
- Androstenedione → Estrone
- Testosterone → Estradiol
- Androstenedione → Estrone
- Testosterone → Estradiol
What are the actions of 5α-Reductase?
Testosterone → Dihydrotestosterone (DHT)
Testosterone → Dihydrotestosterone (DHT)
Which enzyme deficiency would cause:
- Mineralocorticoids: ↑
- Cortisol: ↓
- Sex Hormones: ↓
17α-Hydroxylase (A)

Glucocorticoid and Androgen/Estrogen precursors cannot be produced, which shuttles more Pregnenolone / Progesterone substrate through the Aldosterone pathway
17α-Hydroxylase (A)

Glucocorticoid and Androgen/Estrogen precursors cannot be produced, which shuttles more Pregnenolone / Progesterone substrate through the Aldosterone pathway
Which enzyme deficiency would cause:
- Mineralocorticoids: ↓
- Cortisol: ↓
- Sex Hormones: ↑
21-Hydroxylase (B)

Progesterone and 17-Hydroxyprogesterone cannot continue towards formation of Aldosterone and Cortisol, so they get shuttled to the sex hormone pathway
21-Hydroxylase (B)

Progesterone and 17-Hydroxyprogesterone cannot continue towards formation of Aldosterone and Cortisol, so they get shuttled to the sex hormone pathway
Which enzyme deficiency would cause:
- Mineralocorticoids: ↓ / ↑
- Cortisol: ↓
- Sex Hormones: ↑
11β-Hydroxylase (C)

- ↓ Aldosterone
- ↑ 11-deoxycorticosterone (results in ↑ BP)
- Cortisol can't be made
- Sex hormones increased due to extra substrate
What is similar about 17α-hydroxylase, 21-hydroxylase, and 11β-hydroxylase deficiencies?
All congenital adrenal enzyme deficiencies → enlargement of both adrenal glands due to ↑ ACTH stimulation (due to ↓ cortisol)
All congenital adrenal enzyme deficiencies → enlargement of both adrenal glands due to ↑ ACTH stimulation (due to ↓ cortisol)
What labs are associated with 17α-hydroxylase deficiency?
- ↑ Mineralocorticoids
- ↓ Cortisol
- ↓ Sex hormones (↓ DHT)

- Hypertension
- Hypokalemia
How does a patient with 17α-hydroxylase deficiency present?
↑ Mineralocorticoids, ↓ Cortisol, and ↓ Sex hormones causes:

- XY: pseudo-hermaphroditism (ambiguous genitalia, undescended testes)

- XX: lack secondary sexual development

- Both: hypertension, hypokalemia
What labs are associated with 21-hydroxylase deficiency?
- ↓ Mineralocorticoids
- ↓ Cortisol
- ↑ Sex hormones (↑ 17-hydroxy-progesterone)

- Hypotension
- Hyperkalemia
- ↑ Renin activity
- ↓ Mineralocorticoids
- ↓ Cortisol
- ↑ Sex hormones (↑ 17-hydroxy-progesterone)

- Hypotension
- Hyperkalemia
- ↑ Renin activity
How does a patient with 21-hydroxylase deficiency present?
↓ Mineralocorticoids, ↓ Cortisol, and ↑ Sex Hormones causes:

- Presents in infancy with salt-wasting or in childhood with precocious puberty

- XX: virilization

- Hypotension, hyperkalemia, ↑ Renin activity
What labs are associated with 11β-hydroxylase deficiency?
- ↓ Aldosterone
- ↑ 11-deoxycorticosterone (results in ↑ BP)
- Hypertension
- Low renin

- ↓ Cortisol

- ↑ Sex hormones
- ↓ Aldosterone
- ↑ 11-deoxycorticosterone (results in ↑ BP)
- Hypertension
- Low renin

- ↓ Cortisol

- ↑ Sex hormones
How does a patient with 11β-hydroxylase deficiency present?
↓ Aldosterone, ↑ 11-deoxycorticosterone, ↓ Cortisol, and ↑ Sex hormones causes:

- XX: virilization

- Hypertension
What diagnosis should you consider in an XY patient who presents with pseudo-hermaphroditism (ambiguous genitalia, undescended testes)? Other findings?
17α-hydroxylase deficiency
- Hypertension
- Hypokalemia
- ↓ Sex hormones (↓ DHT)
- ↓ Cortisol
- ↑ Aldosterone
What diagnosis should you consider in an XX patient lacking secondary sexual development? Other findings?
17α-hydroxylase deficiency
- Hypertension
- Hypokalemia
- ↓ Sex hormones (↓ DHT)
- ↓ Cortisol
- ↑ Aldosterone
What diagnosis should you consider in an infant presenting with salt wasting? Other findings?
21-Hydroxylase deficiency
- Hypotension
- Hyperkalemia
- ↓ Mineralocorticoids
- ↓ Cortisol
- ↑ Sex hormones
What diagnosis should you consider in an child with precocious puberty? Other findings?
21-Hydroxylase deficiency
- Hypotension
- Hyperkalemia
- ↓ Mineralocorticoids
- ↓ Cortisol
- ↑ Sex hormones
What diagnosis should you consider in an XX patient with virilization? Other findings?
21-Hydroxylase deficiency
- Hypotension
- Hyperkalemia
- ↓ Mineralocorticoids
- ↓ Cortisol
- ↑ Sex hormones

OR

11β-Hydroxylase deficiency
- Hypertension (d/t ↑ 11-deoxycorticosterone)
- ↓ Aldosterone
- ↓ Cortisol
What is the source of Cortisol? What does it bind in the blood?
- Adrenal Zona Fasciculata
- Binds to corticosteroid-binding globulin
What are the effects of Cortisol?
Cortisol is a BIG FIB:
- ↑ BP
- ↑ Insulin resistance
- ↑ Gluconeogenesis, lipolysis, and proteolysis

- ↓ Fibroblast activity
- ↓ Inflammatory and immune responses
- ↓ Bone formation
How does cortisol affect BP?
↑ BP: upregulates α1-receptors on arterioles → ↑ sensitivity to NE and Epi
How does cortisol affect insulin?
↑ Insulin resistance → diabetogenic
How does cortisol affect stored forms of energy?
- ↑ Gluconeogenesis
- ↑ Lipolysis
- ↑ Proteolysis
How does cortisol affect fibroblasts? Effect?
↓ Fibroblast activity → causes striae
How does cortisol affect inflammation / immune responses?
↓ Inflammatory and Immune responses:
- Inhibits production of leukotrienes and prostaglandins
- Inhibits leukocyte adhesion → neutrophilia
- Blocks histamine release from mast cells
- Reduces eosinophils
- Blocks IL-2 production
How does cortisol affect bones?
↓ Bone formation due to ↓ Osteoblast activity
What infections can be reactivated after administration of exogenous corticosteroids? How?
Reactivation of TB and Candidiasis
- Due to blocked IL-2 production
How is Cortisol regulated?
- CRH (hypothalamus) stimulates ACTH release (pituitary), causing cortisol production in adrenal zona fasciculata
- Excess cortisol ↓ CRH, ACTH, and cortisol secretion
What is the effect of chronic stress on cortisol?
Chronic stress induces prolonged secretion of Cortisol
What is the source of Parathyroid Hormone (PTH)?
Chief cells of parathyroid gland
What are the effects of PTH?
- ↑ Bone resorption of Ca2+ and PO4(3-)
- ↑ Kidney reabsorption of Ca2+ in distal convoluted tubule
- ↓ Reabsorption of PO4(3-) in proximal convoluted tubule
- ↑ 1,25-(OH)2-D3 (Calcitriol) production by stimulating kidney 1α-hydroxylase
How does PTH affect the nephron? Which parts?
- ↑ Kidney reabsorption of Ca2+ in distal convoluted tubule
- ↓ Reabsorption of PO4(3-) in proximal convoluted tubule
How does PTH affect the bones?
↑ Bone resorption of Ca2+ and PO4(3-)

- ↑ Production of macrophage colony-stimulating factor and RANK-L (receptor activator of NF-κB ligand)
- RANK-L secreted by osteoblasts and osteocytes binds RANK (receptor) on osteoclasts and their precursors → stimulates osteoclasts and ↑ Ca2+
How does PTH affect the kidney, besides its action on the nephron?
↑ 1,25-(OH)2-D3 (Calcitriol) production by stimulating kidney 1α-hydroxylase
Which enzyme produces 1,25-(OH)2-D3 (calcitriol) in the kidney?
1α-Hydroxylase
What is the net effect of PTH on Ca2+ and PO4(3-) in the serum and urine?
- ↑ Serum Ca2+
- ↓ Urine Ca2+

- ↓ Serum PO4(3-)
- ↑ Urine PO4(3-)

(Phosphate Trashing Hormone = PTH)
What peptide is similar to PTH? Source?
PTH-related peptide (PTHrP)
- Functions like PTH
- Commonly ↑ in malignancies (eg, paraneoplastic syndrome)
How is PTH regulated?
- ↓ Serum Ca2+ → ↑ PTH

- ↓ Serum Mg2+ → ↑ PTH
- ↓↓ Serum Mg2+ → ↓ PTH
What are common causes of ↓ Mg2+?
- Diarrhea
- Aminoglycosides
- Diuretics
- Alcohol abuse
What is the effect of PTH on the intestine?
- Increases intestinal Ca2+ absorption
- Increases intestinal PO4(3-) absorption
What are the forms of calcium in the plasma? What percent is in each form?
- Ionized (~45%)
- Bound to albumin (~40%)
- Bound to anions (~15%)
How does pH affect calcium homeostasis in the plasma?
↑ in pH → ↑ affinity of albumin (negative charge) to bind Ca2+

Clinical manifestations of hypocalcemia:
- Cramps
- Pain
- Paresthesias
- Carpopedal spasm
What are the sources of Vitamin D? Activation?
- D3 from sun exposure in skin
- D2 ingested from plants

- Both converted to 25-OH in liver and to 1,25-(OH)2 (active form) in kidney

- 24,25-(OH)2-D3 is an inactive form
What is the function of Vitamin D (Cholecalciferol)?
- ↑ Absorption of dietary Ca2+ and PO4(3-)
- ↑ Bone resorption → ↑ Ca2+ and PO4(3-)
How is Vitamin D regulated?
- Increased 1,25-(OH)2-D production by: ↑ PTH, ↓ [Ca2+], ↓ [PO4(3-)]

- 1,25-(OH)2 feedback inhibits its own production
What are the implications of a deficiency of Vitamin D?
- Rickets in kids
- Osteomalacia in adults
What can cause a Vitamin D deficiency?
- Malabsorption
- ↓ Sunlight
- Poor diet
- Chronic kidney failure
What is the source of Calcitonin?
Parafollicular cells (C cells) of Thyroid
What is the function of Calcitonin?
↓ Bone resorption of Ca2+ → Tones down Ca2+ levels
What regulates Calcitonin?
↑ Serum Ca2+ causes Calcitonin secretion (to tone down Ca2+ levels in serum)
How do PTH and Calcitonin relate?
- Calcitonin opposes actions of PTH
- Calcitonin is not important in normal Ca2+ homeostasis
Which endocrine hormones signal via "cAMP"?
FLAT ChAMP + CGG:
- FSH
- LH
- ACTH
- TSH

- CRH
- hCG
- ADH (V2 receptor)
- MSH
- PTH

- Calcitonin
- GHRH
- Glucagon
Which endocrine hormones signal via "cGMP"?
Think vasodilators:
- ANP
- NO (EDRF)
Which endocrine hormones signal via "IP3"?
GOAT HAG:
- GnRH
- Oxytocin
- ADH (V1 receptor)
- TRH

- Histamine (H1 receptor)
- Angiotensin II
- Gastrin
Which endocrine hormones signal via "steroid receptors"?
VETTT CAP:
- Vitamin D
- Estrogen
- Testosterone
- T3 and T4

- Cortisol
- Aldosterone
- Progesterone
Which endocrine hormones signal via "intrinsic tyrosine kinase"?
MAP kinase pathway, think growth factors
- Insulin
- IGF-1
- FGF
- PDGF
- EGF
Which endocrine hormones signal via "receptor-associated tyrosine kinase"?
JAK/STAT pathway, think acidophiles and cytokines (PIG)
- Prolactin
- Immunomodulators: IL-2, IL-6, IL-8, IFN
- GH
What kind of signaling pathway is important for the MAP kinase pathway?
Intrinsic tyrosine kinase
What kind of signaling pathway is important for the JAK?STAT kinase pathway?
Receptor-associated tyrosine kinase
What is the signaling pathway of steroid hormones?
- Steroid hormone binds to receptor located in nucleus or cytoplasm
- Transformation of receptor to expose DNA-binding domain
- Enters cell and binds to enhancer-like element in DNA
- Affects gene transcription: pre-mRNA → mRNA → protein → response
What happens to steroid hormones in the serum? Why?
Steroid hormones are lipophilic and therefore must circulate bound to specific binding globulins, which ↑ their solubility
What happens to men with increased sex-hormone binding globulin (SHBG)?
Gynecomastia
What happens to women with increased sex-hormone binding globulin (SHBG)?
Hirsutism
What can increase the amount of sex-hormone binding globulin (SHBG)?
- OCPs
- Pregnancy

(Free estrogen levels remain unchanged)
What are the iodine containing hormones that control the body's metabolic rate?
Thyroid Hormones: T3/T4
What is the source of the thyroid hormones (T3/T4)?
- Follicles of thyroid
- Most T3 formed in target tissues
What are the functions of thyroid hormones?
- Bone growth (synergism with GH)
- CNS maturation
- ↑ CO, HR, SV, contractility
- ↑ Basal metabolic rate
- ↑ Glycogenolysis, gluconeogenesis, lipolysis
How do thyroid hormones affect the heart? Effects?
↑ β1 receptors in heart → ↑ CO, HR, SV, contractility
How do thyroid hormones affect the basal metabolic rate? Effects?
↑ BMR by ↑ Na+/K+ ATPase activity → ↑ O2 consumption, RR, and body temperature
What are the effects of thyroid hormones on energy storage?
↑ Glycogenolysis, gluconeogenesis, and lipolysis
What is the mnemonic to remember the T3 functions?
T3 functions - 4 B's:
- Brain maturation (CNS)
- Bone growth
- β-adrenergic effects (↑ β1 receptors)
- Basal metabolic rate ↑
What binds the thyroid hormones in the blood? What hormones are active?
- Thyroxine-binding globulin (TBG) binds most T3/T4 in the blood
- Only the free hormone is active
What can decrease the amount of Thyroxine-Binding Globulin (TBG)?
Hepatic Failure
What can increase the amount of Thyroxine-Binding Globulin (TBG)?
Pregnancy or OCP use (estrogen ↑ TBG)
What is the major thyroid product? What happens to it?
- T4 is the major thyroid product
- Converted to T3 in peripheral tissue by 5'-deiodinase
What enzyme converts T4 to T3 in the peripheral tissues?
5'-deiodinase
Which form of the thyroid hormones can bind receptors with greater affinity?
T3 binds receptors with greater affinity than T4
What enzyme is responsible for oxidation and organification of iodide?
Peroxidase
What enzyme is responsible for coupling of monoiodotyrosine (MIT) and diodotyrosine (DIT)?
Peroxidase
What drug can inhibit both peroxidase and 5'-deiodinase?
Propylthiouracil
What drug can inhibit peroxidase but not 5'-deiodinase?
Methimazole
What regulates Thyroid Hormones (T3/T4)?
- TRH (hypothalamus) stimulates TSH (pituitary), which stimulates follicular cells
- Negative feedback by T3, T4 to anterior pituitary ↓ sensitivity to TRH
- Thyroid stimulating immunoglobulins (TSIs), like TSH, stimulate follicular cells (eg, Graves disease)
What is the name of the effect when excess iodine temporarily inhibits thyroid peroxidase? Effect?
Wolff-Chaikoff effect:
- ↓ Iodine organification → ↓ T3/T4 production