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Introduction
to
endocrinology
Department of endocrinology and metabolism
Homeostasis
 Cells (pancreas) liver, muscle, adipose tissue, et al
Insulin
Blood glucose
meal
Time(min)
insulin receptor
The endocrine system
Endocrine glands
APUD cells
cells not belong to endocrine glands
Hormone
Regulate specific function
Receptor (target organs )
The endocrine system
Endocrine glands
APUD cells
cells not belong to endocrine glands
Hormone
Regulate specific function
Receptor (target organs )
peptide
Synthesis and Degradation
Hormone synthesis and degradation employs the
same machinery used to produce, modify or
degrade these compounds.
Hormone release
In many cases, hormones are released by
the endocrine gland in a less active or
inactive form,as prohormone.
Hormone transport

Hormones circulate both free and bound to
plasma proteins.
eg. FT4 Vs TT4
TT4 = FT4 + FT4 combine to TG
free hormone




Is the fraction available for binding to
receptors and therefore represents the
active hormone.
Dictates the magnitude of feedback
inhibition that controls hormone release.
Is the fraction that is cleared from the
circulation .
Correlates best with clinical states of
hormone excess and deficiency.
HORMONE
-combined to plasma protein

The binding of hormones to plasma proteins
is through noncovalent interactions and
tends to increase the half life of the
hormone in the circulation.
The endocrine system
Endocrine glands
APUD cells
cells not belong to endocrine glands
Hormone
Regulate specific function
Receptor (target organs )
Mechanism of hormone action
RECEPTOR

The actions of hormone are mediated by binding
of the hormone to receptor molecules.


Hormones are allosteric effectors that alter the
conformation of the receptors to which they bind.
The receptors are cellular proteins that have
bifunctional properties of both recognition and
signal activation.
RECEPTOR
1. Nuclear receptors
2. Cell surface receptors
Nuclear receptors


Superfamily - Steroid hormone,
Vitamin D, thyroid hormone, retinoids
Nuclear receptors are ligand-regulated
transcription factors that control gene
expression by binding to target genes
usually in the region near their promoters.
Nuclear receptors

Nuclear receptor superfamily have
generally similar structures and functions,
but there are subclasses that differ in the
details of their actions - especially in their
interaction with other proteins - and
function in the unliganded state.
RECEPTOR
2. Cell surface receptors
a)Seven-transmembrane domain
b)Single-transmembrane domain
Growth
factor receptor
Cytokine receptor
Guanyl cyclase-linked receptors
Catecholamine
ACTH
Glucagon
TSH
LH
PTH
Coupled to the “G proteins.”
Effectors: adenylyl cyclase and phospholipase C
Regulate the production of second messenger, cAMP
•Insulin: homodimers – tyrosine kinase domain
•TGF: heterodimer - serine-threonine kinase
Growth hormone
Cytokine
interferons
•ANP: monomer - guanylyl cyclase – cGMP
Regulation of the endocrine system
synthesis
secretion
transport
degradation
Hormone
Quantity
Activity
Receptor (target organs )
Neuro-system
Endocrine system
Immune system
pulsatile
ultradian(< 24h)
circadian (24h)
infradian (> 24h)
spontaneous CNS input
rhythms
Immunal input
Other input
hypothalamus
releasing hormone
pituitary
tropic hormone
Peripheral glands
hormone
thyroid
adrenal cortex
ovaries
Hormone-transport protein
receptor
Target cell
Cascade
effect
Target cell
Blood flow of kidney-input
renin
angiotensin
Aldosterone
ACTH
+
Urine K excretion
Serum K 
+
Disorders of the endocrine
system




Excess of hormone
Deficiency of hormone
Resistance to hormone
Administration of exogenous
hormone or medication
Approach to the patient with
endocrine disease
•Function diagnosis
•Pathology diagnosis
•Etiology adiagnosis

History & physical examination

Laboratory studies

Screening for endocrine diseases
History & physical examination







Amenorrhea or
oligomenorrhea
Anemia
Anorexia
Conspitation
Depression
hair change
Hypothermia








Lipido change
Polynuria
Skin changes
Weakness and fatigue
Weight gain
Weight loss
Nervousness
Diarrhea
Laboratory studies

Laboratory evaluations are critical both
for making and confirming endocrine
diagnose.
Laboratory studies

Measure the level of hormone
total vs. free
Plasma vs. urine


The effect of hormone
The sequelae of the process
pulsatile
ultradian(< 24h)
circadian (24h)
infradian (> 24h)
spontaneous CNS input
rhythms
Immunal input
Other input
hypothalamus
releasing hormone
pituitary
tropic hormone
Peripheral glands
hormone
thyroid
adrenal cortex
ovaries
Hormone-transport protein
receptor
Target cell
Cascade
effect
Target cell
Laboratory studies

Basal level

Stimulation test

Inhibitory test
•
Imaging studies
•
Biopsy procedures
pulsatile
ultradian(< 24h)
circadian (24h)
infradian (> 24h)
spontaneous CNS input
rhythms
Immunal input
Other input
hypothalamus
releasing hormone
pituitary
tropic hormone
Peripheral glands
hormone
thyroid
adrenal cortex
ovaries
Hormone-transport protein
receptor
Target cell
Cascade
effect
Target cell
spontaneous CNS input
rhythms
Immunal input
Other input
hypothalamus
Diurnal rhythms
disappear
CRH

pituitary
ACTH
Low dose Dex test
large dose Dex test

Glucocorticoid-secreting
adrenal adenomas
glucocorticoid

receptor
Target cell
Cascade
effect
Target cell
Diagnosis:
+
1.Urine K excretion
+
Serum K 
Blood flow of kidney-input
+
+
+
+
S K <3.5mM, urine K
renin
S K <3.0mM, urine K
angiotensin
Serum K+
excretion>30mM/24h
excretion>25mM/24h
2.Aldosterone 
Serum, urine excretion
Aldosterone
ACTH
+
Urine K excretion
Serum K 
+
3.renin 
basal
stimulated
Clinical interpretation
of lab tests

Any results must be interpreted in light of
clinical knowledge of the patients

Basal levels of hormones or peripheral
effects of hormones must be interpreted in
light of the way the hormone is released and
controlled.

Hormone levels must in many cases be
interpreted conjuctionally (PTH vs. Ca,
Renin vs. aldosterone)
Clinical interpretation
of lab tests

Occasionally, urinary measurements are
superior to plasma tests for assaying the
integrated release of hormone.

Provocative tests are sometime necessary.

Imaging studies may help with the
diagnosis,specially with respect to the
source of hormone hypersecretion.
Screening is important for
some endocrine diseases



Hypertension
Hypothyroidism
Diabetes
Approach to the patient with
endocrine disease
•Function diagnosis
•Pathology diagnosis
•Etiology adiagnosis

History & physical examination

Laboratory studies

Screening for endocrine diseases

immunologic examination

genetic examination

Chemical examination
HRT
etiology
Treatment of endocrine diseases
For hormone Deficiency states:
• Hormones available
 Hypothyroidism- thyroxin
 Adrenal insufficiency-hydrocortisone
 Menopause- estrogen- containing
preparations
• Hormones
unavailable
PTH:
Vit D & Ca
Surgery
HRT
Radiation
drug
etiology
Treatment of endocrine diseases
For hormone Excess states:



Treatment is ordinarily directed at the
cause of the excess,usually a tumor or
autoimmune condition.
Hormone production may also be blocked
by pharmacological means.
In many cases, it’s necessary to control
squeal of hormone excess by alternative
means.
The endocrine system
Endocrine glands
APUD cells
cells not belong to endocrine glands
Hormone
Regulate specific function
Receptor (target organs )
Disorders of the endocrine
system




Excess of hormone
Deficiency of hormone
Resistance to hormone
Administration of exogenous
hormone or medication
Approach to the patient with
endocrine disease
•Function diagnosis
•Pathology diagnosis
•Etiology adiagnosis

History & physical examination

Laboratory studies

Screening for endocrine diseases

immunologic examination

genetic examination

Chemical examination
Surgery
Radiation
drug
Precipitating factors:
Infection, diet,surgery,trauma,pregnancy
Insulin-antagonistic hormone
hyperglycemia
Osmotic diuresis
ID
Utilization is
reduced
DKA
IR
Mobilization of
energy from lipid
and protein
Ketone production
polyuria
Ketone accumulation
Pletion of
intravascular volume
acidosis
Disturbance of electrocytes