Endocrine Day 1 template

Thyroid development
What are the steps? Thyroid diverticulum arises from the floor of the primitive pharynx
and descends into the neck. Connected to the tongue by the
thyroglossal duct, which normally disappears. May persist as cyst
or the pyramidal lobe of the thyroid. Foramen cecum is a normal
remnant of the thyroglossal duct
What is a thyroglossal Persistence of the thyroglossal duct. Presents as an anterior
duct cyst and how does midline neck mass that moves with swallowing or protrusion of the
it present? tongue.
Thyroid follicular cells Endoderm.
derived from?

Adrenal cortex Adrenal cortex derived from = mesoderm

and medulla Medulla derived from = neural crest
Regulated by Hormone class Main
hormone
produced

CORTEX Zona Angiotensin 2 Mineralocorticoids Aldosterone

Glomerulosa (salt)
Zona Fasciculata ACTH, CRH Glucocorticoids Cortisol
Zona Reticularis ACTH, CRH Androgens DHEA
MEDULLA Chromaffin Cells PRE-ganglionic Catecholamines Epi, NE
Sympathetic
fibers

Pituitary gland Anterior pituitary Posterior pituitary

Also called what? adenohypophysis neurohypophysis
Secretes what Secretes FSH, LH, ACTH, TSH, vasopressin and oxytocin
prolactin, GH, and β-
endorphin.
Stores and secretes vasopressin (antidiuretic hormone,
what? or ADH) and oxytocin
Derived from what? neuroectoderm
Hypothalamic-pituitary hormones
Hormones ADH CRH Dopamine GHRH GnRH
Function increases ↑ ACTH, ↓ prolactin, ↑ GH ↑ FSH, LH
water MSH, β- TSH
permeability endorphin
of distal
convoluted
tubule and
collecting
duct cells in
kidney to
increase
water
reabsoprtion

Regulates b1ood
pressure (V1-
receptors) and
 serum osmolality
(V2-receptors).
Primary
function is serum
osmolality regulation
(ADH
  serum osmolality,
  urine osmolality)
via
regulation of
aquaporin channel
insertion in
principal cells of
renal collecting duct.

2nd messenger V1 receptor:

Gq

V2 receptor:
Location of anterior Hypothalam Hypothalamus Hypothalamu Hypothalamus
production pituitary us s
Site of action collecting
duct
Stimulated by increased
serum
osmolarity
or profound
decrease in
BP
Inhibited by dehydration GnRH
ADH level is
Clinical ↓ in chronic Also called Analog Suppressed by
decreased  in
relevance central diabetes exogenous prolactin- (tesamorelin)hyperprolactinemi
insipidus (DI), steroid use inhibiting used to treata
normal or
increased  in
factor HIV-associate
nephrogenic DI. d Tonic GnRH analog
Nephrogenic DI can
Dopamine lipodystrophy (eg, leuprolide)
be caused by
mutation in antagonists suppresses
V2-receptor. (eg, hypothalamic–
Desmopressin (ADH
analog) is a
antipsychotics) pituitary–gonadal
treatment for can axis.
central DI and
cause
nocturnal enuresis.
galactorrhea Pulsatile GnRH
due to leads to puberty,
hyperprolactin fertility
emia
Hormones TRH MSH Oxytocin Prolactin Somatostati
n
Function ↓ TSH, ↑ ↑ uterine Stimulates milk ↓GH, TSH
prolactin melanogene contractions production in breast;
sis by inhibits ovulation in
melanocytes females and
spermatogenesis in
males by inhibiting
GnRH synthesis and
release
2nd messenger non receptor tyrosine
kinase
Location of Hypothalam anterior pituitary
production us
Site of action mammary gland
Stimulated by - TRH
- Estrogens(eg,
OCPs,pregnan
cy)
Inhibited by Dopamine - Dopamine
- Prolactin
- Dopamine
agonists
(eg,bromocrip
tine)
Clinical ↑ TRH (eg, Causes Modulates 1) inhibits Also called
relevance in 1°/2° hyperpigme fear, anxiety, ovulation in growth
hypothyroidi ntation in social females and hormone
sm) may Cushing bonding, spermatogen inhibiting
increase disease, mood, esis in males hormone
prolactin as MSH and and by inhibiting (GHIH)
secretion → ACTH share depression GnRH Analogs used
galactorrhea the same synthesis and to treat
precursor release acromegaly
molecule, 2) Excessive
proopiomel amounts of
anocortin prolactin
associated
with
decreased
libido
3) Increased in
 primary
hypothyroidis
m due to
increased TRH

Hormones Glucagon Insulin

Function - Promotes glycogenolysis, Induces glucose uptake
gluconeogenesis,
lipolysis, ketogenesis.

- Elevates blood sugar

levels to maintain
homeostasis when blood
stream glucose levels fall
too low(ie,fasting state)
2nd messenger cAMP tyrosine kinase activity
Location of alpha cells of pancreas β cells pancreas
production
Synthesis alpha cells of pancreas synthesized in RER of pancreatic β
 cells
Site of action liver Skeletal muscle, liver
Stimulated by hypoglycemia GLP1, GIP after meals
Inhibited by insulin, hyperglycemia, epinephrine
somatostatin
Clinical - Tumor of pancreatic α Diabetes Mellitus
relevance cells >>overproduction of
glucagon
- Presents with
6D's:Dermatitis(necrolyti
c migratory erythema),
Diabetes
(hyperglycemia),DVT,
Declining weight,
Depression, Diarrhea

Insulin dependent glucose uptake Insulin secretion by pancreatic Beta-cells

Thyroid hormones
Thyroid 7B’s
hormone Brain maturation
functions? Bone growth (synergism with GH)
β-adrenergic effects. ↑ β1 receptors in heart → ↑CO, HR, SV, contractility;
β-blockers alleviate adrenergic symptoms in thyrotoxicosis
Basal metabolic rate ↑ (via ↑ Na+/K+-ATPase → ↑O2 consumption, RR,
body temperature)
Blood sugar (↑ glycogenolysis, gluconeogenesis)
Break down lipids (↑ lipolysis)
Stimulates surfactant synthesis in Babies

Hormones Parathyroid Calcitonin

Function -↑ Free Calcium in Blood ↓ Bone Resorption
-↑Calcium & Phosphate
absorption in GIT system
-↑Calcium & Phosphate from
Bone Resorption
-↑ Calcium Resorption From
DCT
-↓Phosphate Resorption in PCT
-↑Vitamin D Production by
activating 1- α hydroxylase in
PCT
2nd messenger cAMP, RANK-L
- PTH ↑ serum Ca2+, ↓ serum
PO4 3- , ↑ urine
PO4 3- , ↑ urine cAMP
- ↑ RANK- L secreted by
osteoblasts and
osteocytes; binds RANK
(receptor) on
osteoclasts and their
precursors to
stimulate osteoclasts and ↑
Ca2+ → bone
resorption
Location of Chief Cells of the Parathyroid Parafollicular Cells of the Thyroid
production (aka “C” cells)
Site of action ● Renal Tubular Cells ● Bones
(Kidneys)
● Bone
● Intestines
Stimulated by ● ↓ Serum Calcium → ↑ ● ↑ Serum Calcium → ↑ PTH
PTH secretion
● ↑Serum Phosphate → ↑
PTH secretion
● ↓ Serum Magnesium →
↑ PTH secretion

Inhibited by ● ↓↓ Serum Magnesium ● ↓ Serum Calcium → ↓ PTH

→ ↓ PTH Secretion Secretion
Clinical ● PTH ↑ serum Ca2+, ● Not an important factor in
relevance ↓ serum PO4 3- , normal Calcium Homeostasis
● urine PO4 3- ,
● ↑ urine cAMP
● ↑ RANK- L secreted by
osteoblasts and
osteocytes; binds RANK
(receptor) on
osteoclasts and their
precursors to
stimulate osteoclasts and
↑ Ca2+ → bone
resorption
NOTE: PTH related peptide
 (PTHrP) functions like PTH and is
noted to commonly increase in
cases of malignancies (eg: RCC,
Squamous Cell Carcinoma of the
Lungs)

Calcium homeostasis
Inc. pH Dec. pH
Describe what happens? ↓ Ionized Calcium → ↑ PTH ↑ Ionized Calcium → ↓ PTH
( In increased pH albumin (In decreased pH albumin
binds more Calcium leading binds less Calcium leading to
to Increase ionized/free decreased ionized/free
calcium = direct relationship) calcium

Adrenal steroids and congenital adrenal hyperplasias

Hormones Cortisol
Function “Cortisol is A BIG FIB”
❈ ↑ Appetite
❈ ↑ BP
○ Upregulates 𝝰₁-receptors on arterioles → ↑ sensitivity to
norepinephrine & epinephrine (permissive action)
○ At high concentrations, can bind mineralocorticoid
(aldosterone) receptors
❈ ↑ Insulin resistance
○ Diabetogenic
❈ ↑ Gluconeogenesis, lipolysis, & proteolysis
○ ↓ glucose utilization
❈ ↓ Fibroblast activity
○ Poor wound healing, ↓ collagen synthesis, ↑ striae
❈ ↓ Inflammatory & immune responses
○ Inhibits production of leukotrienes & prostaglandins
○ Inhibits WBC adhesion → neutrophilia
○ Blocks histamine release from mast cells
 ○ Eosinopenia, lymphopenia
○ Blocks IL-2 production
❈ ↓ Bone formation
○ ↓ osteoblast activity
2nd messenger ● N/A - does not have 2nd messenger as it binds to an intracellular
receptor
Location of ● Adrenal cortex - zona fasciculata
production
Site of action ● Intracellular receptor
Stimulated by ● ACTH
● Stress, circadian rhythm
○ Stimulate hypothalamus to release CRH → ACTH → cortisol
Inhibited by ● Endorphins
○ Inhibit anterior pituitary release of ACTH
● Cortisol (self-inhibition)
○ Excess cortisol → ↓ CRH, ACTH, and cortisol secretion
Clinical ● Chronic stress → prolonged cortisol secretion, cortisol resistance,
relevance impaired immunocompetency, dysregulation of HPA axis
● Exogenous corticosteroids can lead to reactivation of TB &
candidiasis via blocking IL-2 production
● Cushing syndrome & disease

Appetite Regulation
Hormones Ghrelin Leptin Endocannabinoids
Function Stimulate hunger Satiety Homeostatic and
hedonic (food
pleasure in absence of
hunger) control of
food intake
2nd PLC/IP3→ PKC JAK/STAT → PI3k/PKB
messenger
Location of Stomach Adipose tissue Various cells
production throughout body
Site of action Lateral hypothalamus Arcuate Nucleus of the Hypothalamus and
Hypothalamus nucleus accumbens
Stimulated Sleep deprivation; Sleep deprivation or
by fasting starvation
Inhibited by Eating Fasting
Clinical Prader-Willi Syndrome (nonfunctional) Mutation “The munchies”
relevance of Leptin gene → Severe
obesity
Signaling pathways for endocrine hormones
cAMP ● FSH FLAT ChAMPs CHuGG
● LH
● ACTH
● TSH
● CRH
● hCG
● ADH (V2 receptor)
● MSH
● PTH
● Calcitonin
● Histamine (H2 receptor)
● Glucagon
● GHRH
cGMP ● BNP BAD GraMPa
● ANP ● vasodilation
● EDRF (NO) ● diuresis
IP3 ● GnRH GOAT HAG
● Oxytocin
● ADH (V1 receptor)
● TRH
● Histamin (H1 receptor)
● Angiotensin II
● Gastrin
Intracellular receptor ● Progesterone PET CAT in TV
● Estrogen
● Testosterone
● Cortisol
● Aldosterone
● T3/T4
● Vitamin D
Receptor tyrosine kinase ● IGF-1 MAP kinase pathway
● FGF Get Found In the MAP
● PDGF
● EGF
● Insulin
Serine/ Threonine kinase ● TGF-beta
receptor
Non Receptor tyrosine kinase ● G-CSF JAK/STAT pathway
● EPO ● acidophils
● Thrombopoietin ● cytokines
● Prolactin GET a JAKed PIG
● Immunomodulators ( Eg.
cytokines, IL-2, IL-6, IFN)
● GH

Signaling pathways of steroid hormones

Steroid hormones are lipophilic and therefore must circulate bound to specific binding
globulins, which increases their solubility.

In men, increase sex hormone-binding globulin (SHBG) lowers free testosterone ->
gynecomastica

In women, decrease SHBG raises free testosterone -> hirsutism

Increase estrogen ( eg: OCPs, pregnancy) -> increase SHBG

Describe the steps