Introduction to endocrinology

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Introduction to endocrinology

• Department of endocrinology and metabolism

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Homeostasis
? Cells (pancreas) Insulin Blood glucose
liver, muscle, adipose tissue, et al
insulin receptor
meal
Time(min)
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The endocrine system
Endocrine glands APUD cells cells not belong to
endocrine glands
Hormone
Regulate specific function
Receptor (target organs )
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The endocrine system
Endocrine glands APUD cells cells not belong to
endocrine glands
Hormone
Regulate specific function
Receptor (target organs )
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peptide
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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.
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Hormone transport

• Hormones circulate both free and bound to plasma
  proteins.
• eg. FT4 Vs TT4
• TT4 FT4 FT4 combine to TG

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• 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.

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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.

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The endocrine system
Endocrine glands APUD cells cells not belong to
endocrine glands
Hormone
Regulate specific function
Receptor (target organs )
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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.

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RECEPTOR
1. Nuclear receptors 2. Cell surface receptors
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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.

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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.

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RECEPTOR
2. Cell surface receptors
a)Seven-transmembrane domain
b)Single-transmembrane domain

• Growth factor receptor
• Cytokine receptor
• Guanyl cyclase-linked receptors

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Catecholamine ACTH Glucagon TSH LH PTH
Coupled to the G proteins.
Effectors adenylyl cyclase and phospholipase C
Regulate the production of second messenger, cAMP
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• Insulin homodimers tyrosine kinase domain
• TGF heterodimer - serine-threonine kinase

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Growth hormone Cytokine interferons
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• ANP monomer - guanylyl cyclase cGMP

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Regulation of the endocrine system
synthesis secretion transport degradation
Hormone
Quantity Activity
Receptor (target organs )
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Neuro-system
Endocrine system
Immune system
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spontaneous rhythms
CNS input
Immunal input Other input
pulsatile ultradian(lt 24h) circadian (24h)
infradian (gt 24h)
hypothalamus
releasing hormone
pituitary
tropic hormone
thyroid adrenal cortex ovaries
Peripheral glands
hormone
Hormone-transport protein
receptor
Cascade
Target cell
Target cell
effect
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Blood flow of kidney-input
renin
angiotensin
Aldosterone
ACTH
Urine K excretion?
Serum K?
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Disorders of the endocrine system

• Excess of hormone
• Deficiency of hormone
• Resistance to hormone
• Administration of exogenous hormone or medication

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Approach to the patient with endocrine disease

• History physical examination
• Laboratory studies
• Screening for endocrine diseases

• Function diagnosis
• Pathology diagnosis
• Etiology adiagnosis

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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

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Laboratory studies

• Laboratory evaluations are critical both for
  making and confirming endocrine diagnose.

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Laboratory studies

• Measure the level of hormone

• total vs. free
• Plasma vs. urine

• The effect of hormone
• The sequelae of the process

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spontaneous rhythms
CNS input
Immunal input Other input
pulsatile ultradian(lt 24h) circadian (24h)
infradian (gt 24h)
hypothalamus
releasing hormone
pituitary
tropic hormone
thyroid adrenal cortex ovaries
Peripheral glands
hormone
Hormone-transport protein
receptor
Cascade
Target cell
Target cell
effect
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Laboratory studies

• Basal level
• Stimulation test
• Inhibitory test

• Imaging studies
• Biopsy procedures

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spontaneous rhythms
CNS input
Immunal input Other input
pulsatile ultradian(lt 24h) circadian (24h)
infradian (gt 24h)
hypothalamus
releasing hormone
pituitary
tropic hormone
thyroid adrenal cortex ovaries
Peripheral glands
hormone
Hormone-transport protein
receptor
Cascade
Target cell
Target cell
effect
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spontaneous rhythms
CNS input
Immunal input Other input
hypothalamus
Diurnal rhythms disappear
CRH
?
pituitary
ACTH
?
Glucocorticoid-secreting adrenal adenomas
Low dose Dex test large dose Dex test
glucocorticoid
?
receptor
Cascade
Target cell
Target cell
effect
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Diagnosis
1.Urine K excretion?
Blood flow of kidney-input
Serum K?
S K lt3.5mM, urine K excretiongt30mM/24h
renin
S K lt3.0mM, urine K excretiongt25mM/24h
angiotensin
Serum K
2.Aldosterone ?
Serum, urine excretion
Aldosterone
ACTH
Urine K excretion?
basal
3.renin ?
stimulated
Serum K?
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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)

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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.

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Screening is important for some endocrine
diseases

• Hypertension
• Hypothyroidism
• Diabetes

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Approach to the patient with endocrine disease

• History physical examination
• Laboratory studies
• Screening for endocrine diseases

• Function diagnosis
• Pathology diagnosis
• Etiology adiagnosis

• immunologic examination
• genetic examination
• Chemical examination

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HRT etiology
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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

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Surgery Radiation drug
HRT etiology
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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, its necessary to control squeal
  of hormone excess by alternative means.

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The endocrine system
Endocrine glands APUD cells cells not belong to
endocrine glands
Hormone
Regulate specific function
Receptor (target organs )
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Disorders of the endocrine system

• Excess of hormone
• Deficiency of hormone
• Resistance to hormone
• Administration of exogenous hormone or medication

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Approach to the patient with endocrine disease

• History physical examination
• Laboratory studies
• Screening for endocrine diseases

• Function diagnosis
• Pathology diagnosis
• Etiology adiagnosis

• immunologic examination
• genetic examination
• Chemical examination

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Surgery Radiation drug
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??
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Precipitating factors Infection,
diet,surgery,trauma,pregnancy
DKA
ID
IR
Insulin-antagonistic hormone
Utilization is reduced
hyperglycemia
Mobilization of energy from lipid and protein
Osmotic diuresis
Ketone production?
polyuria
Ketone accumulation
Pletion of intravascular volume
acidosis
Disturbance of electrocytes