Endocrinology and

Metabolic Diseases

Qian Xing, MD, PhD

Division of Endocrinology and Metabolic Diseases,

The First Affiliated Hospital of Dalian Medical University
The Endocrine System
Composition
Traditional endocrine glands
pituitary, thyroid, parathyroids,
adrenals, pancreatic islets, gonadal

Endocrine tissues
brain, heart, gastrointestinal tract, kidney
What is endocrine?
The term endocrine was coined by
Starling to contrast the actions of
hormones secreted internally
(endocrine) with those secreted
externally (exocrine )or into a lumen,
such as the gastrointestinal tract.
Endocrine and Exocrine

Endocrine

Exocrine
The capacity of specialized tissues is
made by three systems
 the endocrine system
– releases hormones into the circulation for action
away from their sites of origin
 the nervous system
– transmits electrochemical signals as two way
traffic between the brain and peripheral tissues
or between tissues in reflex circuits
 the immune system
– protects the organism against external and
internal threats
History of Endocrinology

Organic Endocrinology

Histological Endocrinology

Moleculer Endocrinology
Hormone

 The term hormone, derived from a

Greek phrase meaning “to set in
motion”
 Aptly describes the dynamic actions
of hormones as they elicit cellular
responses and regulate physiologic
processes through feedback
mechanisms.
What are hormones?
 Hormones are chemical
messengers produced by a variety
of specialized secretory cells.
 Hormonal function involves four
broad domains:
– reproduction;
– growth and development;
– maintenance of homeostasis.
Hormones
ACTH = adrenocorticotrophic hormone
ADH = antidiuretic hormone, arginine vasopressin
CRH = corticotrophin-releasing hormone
FSH = follicle-stimulating hormone
GH = growth hormone
GHRH = growth hormone-releasing hormone
GnRH = gonadotrophin-releasing hormone
IGF-1 = insulin-like growth factor-1
IGF-BP3 = IGF-binding protein
LH = luteinising hormone
T3 = triiodothyronine
T4 = thyroxine
TRH = thyrotrophin releasing hormone
TSH = thyroid-stimulating hormone
Functions of hormones
 Reproduction
– Sex determination during fetal development;
– Sexual maturation during puberty;
– Conception, pregnancy, lactation, and childrearing;
– Cessation of reproductive capability at menopause.
 Growth and development
 Maintenance of homeostasis
– Thyroid hormone — Basal metabolism
– Cortisol — Permissive action for many hormones
– PTH — Calcium and phosphorus
– Vasopressin — Osmolality
– Mineralocorticoids — Vascular volume and serum
electrolyte (Na ,K) concentrations
– Insulin — Glucose
Chemical structures of hormones
insulin , parathyroid hormones,
Polypeptide all of the pituitary hormones
(GH, TSH, ACTH, LH, FSH, PRL)

thyroid hormones, catecholamines and etc

Amine

all derived from cholesterol ,

Steroid adrenal steroids (cortisol and aldosterone),
gonadal steroids (testosterone, progesterone),
vitamin D.
Fashions of hormonal action

Hormone

Endocrine Paracrine Autocrine Neurocrine Intracrine

 Hormone action through receptors

Membrane Receptors

Nuclear Receptors
G-protein-coupled 7-membrane spanning receptor
Regulation of Endocrine System

 Regulation of nervous system

and endocrine system
 Feedback regulation of
endocrine system
 Regulation of immune system
and endocrine system
Control and feedback

 Negative feedback regulation

TRH ↑ → TSH ↑ → T3, T4 ↑

_ _

 Positive feedback regulation

classically seen in the regulation of the normal
menstrual cycle.
 Hypothalamus-anterior pituitary

Neurosecretory
neurons
Hypothalamus

Systemic artery inflow

Hypothalamic-
hypophyseal portal
system

Anterior pituitary
Posterior pituitary
Systemic venous outflow
Hypothalamus-pituitary-target glands

Hypothalamus Pituitary Target glands

ADH/AVP ADH/AVP Kidney
GHRH GH Muscle, Bone, Liver
CRH ACTH Cor
TRH TSH TH
GnRH FSH E 2 、 P (F)
LH T (M)
DA PRL Breast
HPT axis
Negative feedback regulation
(HPT axis)
（－）
Hypothalamas
Negative feedback
TRH inhibition
（+） （－）
Pituitary

TSH

（+）
Thyroid

T4→T3
Peripheral
effects
Negative feedback regulation
Hypothalamus （－）

TRH
CRH
GnRH （+ （－）
Pituitary ）

TSH
ACTH
LH
Thyroid FSH （+
Adrenal ）
Gonads
T4→T3 Cor T E2 P
Negative feedback regulation of RAAS

Renin ACE H2O Na+ UK+↑

A AI AII ALD↑ BK+ ↓

To determine primary or secondary aldosteronism

according to measuring plasma renin activity (PRA),
angiotensin Ⅱ and aldosterone.
Hypothalamus-posterior pituitary
Paraventricular
nucleus
Neurosecretory
neurons

Supraoptic
nucleus Hypothalamus

Hypothalamic-
pituitary stalk

Posterior pituitary
Anterior pituitary

Artery inflow

Venous outflow
Feedback regulation of
hypothalamus-posterior pituitary-kidney
Hypothalamas

AVP
+ Pituitary diabetes insipidus
Posterior
pituitary
Nephrogenic diabetes insipidus
AVP
+
Kidney

AQP

Plasma
osmolality
Positive feedback regulation

Menstrual cycle

– Negative
– Positive
 Other regulatory factors
 Strss
– produce rapid increases in ACTH and cortisol,
GH, prolactin, epinephrine (adrenaline) and
norepinephrine (noradrenaline) within seconds
or minutes.
 Sleep
– Secretion of GH and prolactin is increased
during sleep, especially the rapid eye movement
(REM) phase.
 Feeding and fasting
– secretion of insulin is increased and GH
decreased after ingestion of food
Plasma growth hormone

20
GH (pmol/min)

10

0
06:00 10:00 14:00 18:00 22:00 02:00 06:00
Time

Plasma growth hormone concentrations

in a normal adult over 24h
Insulin secretion
800
Insulin (pmol/min)

600

400

200

Breakfast Lunch Diner

0
06:00 10:00 14:00 18:00 22:00 02:00 06:00
Time
Insulin concentrations change
with the meals
Biological rhythms
 The circadian rhythm means changes over
the 24 hours of the day-night cycle and is
best shown for the pituitary-adrenal axis.
It is seen in reverse with the pineal
hormone, melatonin, which shows high
levels during dark.
 The menstrual cycle is repeated on
average every 28 days, reflecting the time
required to follicular maturation and
ovulation.
Disorders of the Endocrine System
Hormones Excess Syndrome
Neoplastic, Autoimmune, Iatrogenic,
Infectious/inflammatory,
Activating receptor mutations
Hormones Deficiency Syndrome
Autoimmune, Iatrogenic, Infectious,
Hormone mutations, Enzyme defects
Developmental defects,
Nutritional/vitamin deficiency
Hormones Resistance Syndrome
Receptor mutation
Singnaling pathway mutation
Postreceptor
Common presenting symptoms of endocrine disorder(s)
Symptom Mosy likely endocrine disorder(s)
Weight gain Hypothyroidism, Cushing’s syndrome
Weight loss Hyperthyroidism, adrenal insufficiency, DM
Amenorrhoea/ Menopause, polycystic ovarian syndrome, hyperprolactinaemia,
oligomenorrhoea Hyperthyroidism, premature ovarian failure, Cushing’s syndrome
Polyuria and polydipsia DM, diabetes insipidus, hyperparathyroidism, Conn’s syndrome
Heat intolerance Hyperthyroidism, menopause
Palpitations Hyperthyroidism, phaeochromocytoma
Thyroid nodule Solitary thyroid nodule, dominant nodule in multinodular goiter
Generalized thyroid Simple goiter (nodular or diffuse), Graves’disease,
enlargement Hashimoto’s thyroiditis
Pain over thyroid Haemorrhage into nodule, de Quervain’s thyroiditis,
Rarely Hashimoto’s thyroiditis
Prominence of eyes Graves’ disease
Hirsutism Idiopathic, PCOS, congenital adrenal hyperplasia,
Cushing’s syndrome
Galactorrhoea Hyperprolactinaemia
Impotence Hyperprolactinaemia, hypogonadism, DM
Visual dysfunction Pituitary tumour
Headache Acromigaly, pituitary tumour, phaeochromocytoma
Muscle weakness Hyperthyroidism, Cushing’s syndrome, hyperparathyroidiam,
(usually proximal) hypokalaemia (Conn’s syndrome), hypogonadism
Paraesthesiae and tetany Hypoparathyroidism
Recurrent ureteric colic Hyperparathyroidism
Coarsening of features Acromegaly, hypothyroidism
Asymptomatic endocrine disease
 This may be detected as a result of
screening or indiscriminate biochemical
testing, the most common being:
 Subclinical hypothyroidism (raised serum
TSH, normal T4).
 Hyperglycaemia.
 Mild primary hyperparathyroidism with
serum calcium concentrations between 2.70
and 2.90 mmol/L.
Investigations
Principles of endocrine investigation
 Timing of measurement
– Release of many hormones is rhythmical (e.g. pulsatile, circadian
or monthly), so random measurement may be invalid and
sequential or dynamic tests may be required.
 Choice of dynamic biochemical tests
– Abnormalities are often characterized by loss of normal
regulation of hormone secretion.
– If hormone deficiency is suspected, choose a stimulation test.
– If hormone excess is suspected, choose a suppression test.
– The more tests there are to choose from, the less likely it is that
any single test is infallible, so do not interpret one result in
isolation.
 Imaging
– Secretory cells also take up substrates, which can be labeled.
– Most endocrine glands have a high prevalence of
‘incidentalomad’, so do not scan unless the biochemistry
confirms endocrine dysfunction or the primary problem is a
tumour.
 Biopsy
– Many endocrine tumours are difficult to classify histologically
(e.g. adrenal carcinoma and adenoma).
Clinical Assessment of
Endocrine Status
 History and physical examination
 Laboratory testing
• Level of hormone
• Result of function testing
• Pathological finding
 Radionuclide imaging
 Radiologic procudures
Functional diagnosis
 Clinical manifestations

Dysmetabolism
 Laboratory testing Measuring hormones
Time of sampling
Urine over 24h
Stimulation tests
Suppression tests
Diagnostic principles of
endocrine diseases
 Functional diagnosis
Radiologic imaging
 Locational diagnosis Radionuclide examination
Cytological examination
Venous catheter
 Etiological diagnosis
Diagnostic principles of
endocrine diseases
 Functional diagnosis

 Locational diagnosis

Auto antibody

 Etiological diagnosis Chromosome

HLA
 Diagnosis (e.g. Thyroid diseases)
Functional Hypothyroidism T3 ↓
diagnosis T4 ↓

Pathological Thyroidal hypothyroidism TSH↑

Cytology
diagnosis

Etiological Chronic lymphocytic Cytology

Ab
diagnosis thyroiditis
Prevention and treatment for
endocrine diseases
Prevention
 Iodine supply→epidemic goiter
 Reiforce medical care→Sheehan syndrome

Hyperfunction
 Removal of the whole gland or part of the gland
by operation or radiotherapy
 Radiation therapy
 Administration of drugs, hormone antagonism

Hypofunction
 Replacement of hormones
 Replantation of organ

Etilogical treatment
 Gene therapy
 Overlap with Other Diseases (1)
The symptoms of endocrine disorders overlap a great range of
normal characteristics, including:
body contour, facial configurations, weight distributions, skin and
hair coloring, and muscular capacity.
They also overlap with other conditions that are far more
common, including: depression and normal aging.
The added adipose tissue of hyperadrenocorticism is more
difficult to recognize in a person who is already obese.
The nervousness associated with hyperthyroidism is less
apparent in a thin, hyperkinetic man than in a person of moderate
body weight.
The effects of an androgen-producing adrenal tumor are less
likely
to be noticed in a family of swarthy, hirsute individuals.
Overlap with Other Diseases (2)

Finally, most endocrine disorders evolve gradually over months

to years instead of appearing suddenly,.

This combination of varied host background and slow evolution

of disease leads to considerable delay in diagnosis:
both the patient and primary care physician
adapt to the changes as part of the person,
and definitive evaluation, now relatively
easy for most disorders, is not undertaken.

Hypothyroidism and acromegaly are good examples of

this phenomenon.

All series show a remarkable delay in diagnosis

despite sometimes disabling symptoms.
Overlap with Other Diseases (3)

Hormones have more distant effects than local effects.

This, of course, reflects their messenger status.

Unlike an abscess, a myocardial infarction, or an esophageal

cancer, endocrine disorders seldom produce symptoms near
the gland of origin. (Subacute thyroiditis and large pituitary
tumors, of course, are exceptions.)

But because in most endocrinopathies the excess or missing

hormone works on several or many systems, the resulting
syndrome can be enigmatic.
Overlap with Other Diseases (4)
Several endocrine disorders are important not
because of their incidence but because of their
curability: Cushing's disease, acromegaly,
Pheochromocytoma.

Although these disorders enter the differential

diagnosis of common problems such as diabetes,
their occurrence is so rare that the primary care
physician does not easily think of them.
 Questions

 Diagnostic principles of endocrine

diseases.

 Negative feedback regulation of

hypothalamic-pituitary-target glands.
 References

 Cecil Medicine
 Williams Textbook of Endocrinology
 Harrison’s Principles of Internal
Medicine
 Davidson’s Principles and Practice of
Medicine
 Joslin’s Diabetes Mellitus