Pathophysiology of the endocrine

system.

Violation of hypophysis, thyroid

and adrenal glands.

General adaptation syndrome.

 Pathological processes which are
primarily developed in hypothalamus lead
to disorders of regulation of endocrine
glands .
 The activity of hypothalamic centers can be

disturbed also secondarly due to disorders of

limbic system (hypocampus, olfactory brain) and
upper parts of central nervous system which are
closely connected with hypothalamus.

 The role of mental trauma and other

stress influences аre substantial.
substantial
• So, the function of thyroid gland is determined
not only by TTH, but also by sympathetic n.s.
• The direct activation of sympathetic nerves
increases absorption of iodine by the gland,
synthesis of thyroid hormones and their secretion.
• Denervation of ovaries causes atrophy and
weakened response to gonadotrophic hormones.
Control of hormone release
1. Negative feedback ["stimulatory-inhibitory"]
2. Positive feedback ["stimulatory-stimulatory"]
3. Endocrine gland stimuli: humoral stimuli, neural stimuli, hormonal stimuli
This gland makes me wake up in the
morning and ready to go!

Pineal
Gland
melatonin

"The 3rd Eye"

Tropic effects only:
FSH
LH
TSH
ACTH

Nontropic effects only:

Prolactin
MSH

Nontropic and tropic effects:

GH
 Hormone Major target organs Major physiologic
effects
Promotes growth (indirectly),
Growth hormone Liver, adipose tissue control of protein, lipid and
carbohydrate metabolism

Thyroid stimulating Thyroid gland Stimulates secretion of

hormone thyroid hormones

Adrenocorticotrophi Adrenal gland Stimulates secretion of

Anterior c hormone cortex glucocorticoids
Pituitary
Prolactin Mammary gland Milk production

Luteinizing hormone Ovary and testis Control of reproductive

function

Follicle stimulating Ovary and testis Control of reproductive

hormone function

Antidiuretic Kidney Conservation of

Posterior hormone body water
pituitary Oxytocin Ovary and testis Stimulates milk
ejection and uterine
contractions
 Type of Secretion Staining Pathology
Adenoma

Corticotrophi Secrete Basophilic Cushing’s disease

c adenomas adrenocotrophic
hormone (ACTH) and
Proopiomelanocortin
(POCM)

Somatotrophi Secrete growth Acidophilic Acromegaly

c adenomas hormone (GH) (Gigantism)

Thyrotrophic Secret thyroid Basophilic Occasionally

adenomas stimulating hormone hyperthyroidism
(rare) (TSH) usually does not
cause symptoms

Gonadotroph Secrete luteinizing Basophilic Usually does not

ic adenomas hormone (LH), follicle cause symptoms
stimulating hormone
(FSH)
 Disturbances of functions of hypophysis.
Hypofunction of adenohypophysis
(hypopituitaritism)

There are panhypopituitarity and partial hypopituitarity

 Panhypopituitarity – is the decrease of
formation of  all adenohypophysis hormones
• The following clinical forms of  panhypopituitarity are known:
•    
1) Hypophyseal cachexsia of Simonds;
Simonds

2) After delivery - necrosis of hypophysis – syndrome of Scheehan;

Scheehan

3) Chromophobe hypophysis adenomas, i.e. tumors, which grow from chromophobe cells. the
tumor squeezes and damages glandular cells  of adenohypophysis.
•
Hypophyseal
Simond’s
cachexia
 Causes of Hypopituitarism
Tumors and mass lesions — pituitary adenomas, cysts,
metastatic cancer, and other lesions
Pituitary surgery or radiation
Infiltrative lesions and infections — hemochromatosis,
lymphocytic hypophysitis
Pituitary infarction — infarction of the pituitary gland after
substantial blood loss during childbirth (Sheehan’s
syndrome)
Pituitary apoplexy — sudden hemorrhage into the pituitary
gland
Genetic diseases — rare congenital defects of one or more
pituitary hormones
Empty sella syndrome — an enlarged sella turcica that is
not entirely filled with pituitary tissue
Hypothalamic disorders — tumors and mass lesions
(e.g., craniopharyngiomas and metastatic malignancies),
hypothalamic radiation, infiltrative lesions (e.g., sarcoidosis),
trauma, infections
 Hypophysar
Partial hypopituitarism nanism
is the disorder of
formation of separate
hormones
of adenohypophysis
(not all). The following
variants of partial
hypopituitarism are
described:
1) Hypophysar nanism
(dwarfishness)
dwarfishness - deficiency of STH;
STH
2) Secondary hypogonadism -
deficiency of FSH and LH;
LH
3) Secondary hypothyroidism -
deficiency of TTH;
TTH
4) Secondary hypocorticism -
deficiency of ACTH.
ACTH
• The insufficiency of STH results in
development of hypophysar dwarfisм,
or nanism :
• 1) decreased intensity of protein synthesis
that leads to delay and stop of growth (more than
30% from average) and development of bones,
internal organs, muscles. The disorders of protein
synthesis in connective tissue results in loss of its
elasticity;
• 2) decrease of inhibiting action of STH on an
absorption of glucose with predominance of
insulin effect and development of hypoglycemia;
• 3) fallout of fat mobilizing action and tendency to
obesity.
 Insufficiency of TTH
causes secondary
hypothyrosis symptoms.
Тhe administration of TTH
can restore its function.
  Insufficiency of gonadotropic hormones
results in decrease of ability of Sertoli cells
to accumulate androgens and supppression
of spermatogenesis and fertility of men.

In case of defect of LH (Luteinizing) hormone

the function of Leidig’s cells is affected, the
formation of androgens ceases and
eunuchoidism develops
 Hyperfunction of
adenohypophysis
(hyperpituitarism)
 The main reasons of
hyperpituitarism are benign tumors – adenomas
 There are  two groups of adenomas.

 1. Eosinophilic adenoma, develops from acidophilic cells

of adenohypophysis forming STH. Clinically
hyperproduction of STH appears as giantism (if adenoma
develops in children and young people before closing of
epiphysar cartilages) and acromegalia (in adult). 
Giantism is characterized by the proportional increase of
all body parts.
Gigantism
• ACROMEGALY
– a syndrome that includes:
• excessive growth of soft tissues
and bones
• high blood sugar
• high blood pressure
• heart disease
• sleep apnea
• excess snoring
• carpal tunnel syndrome
• pain symptoms (including
headache).

• Acromegaly appears by increased

growth of hands, legs, chin, nose, tongue,
liver, kyphoscoliosis.
•  increased STH -hyperglycemia, insulin
resistanse, fatty infiltration of liver .
BITEMPORAL
HEMIANOPSIA
Usually the bitemporal hemianopsia is
NOT perfectly symmeetrical. Why?
Because pituitary tumors are under no
law to grow perfectly midline.
• 2. Basophilic adenoma,
adenoma that
produce ACTH. Itsenko-Cushing
disease develops.

• а) secondary hypercorticism;
• b) increased pigmentation of the
skin.

• The increased level of ACTH is

combined with increased  level of
other products of
proopiomelanocortin.

BASOPHILIC ADENOMA OF HYPOPHYSIS

• Excess adrenocorticotropic hormone:
– causes weight gain (particularly in the body’s trunk, not
the legs or arms)
– high blood pressure
– high blood sugar
– brittle bones
– emotional changes
– Striae -stretch marks on the skin
– easy bruising.

The insufficiency of ACTH leads to secondary partial

insufficiency of adrenal cortex.
The glucocorticoid function suffers mainly.
Mineralocorticoid function practically does not vary
 Hyperfunction of neurohypophysis
• increased production vasopressin and oxytocin.

• Vasopressine (antidiuretic hormone) renders the

following influence through V1 and V2 receptors:
1) Acting on tubulus contortus distalis and collective
tubules of kidneys, increases reabsorption of water;
2) Causes contraction of smooth muscles of blood
vessels;
3) Endogenic analgetic                  
4) Stimulates consolidation of memory traces and
mobilization of  saved information (hormone of
memory);
SIADHS – syndrome of
inappropriate ADH secretion
increased secretion of vasopressin occurs in
tumors from different tissues – from
neurohypophysis, lung carcinoma and others

Its main manifestation is hypervolemia leading to

development of constant arterial hypertension.

Water intoxication – hyponatriemia, that leads to

cell and brain edema – lifetreating condition
• Oxytocin renders the following functional
influences:
1) Stimulates secretion of milk (lactation) causing
contraction of myoepithelial cells of small-sized
ducts of mammary glands;
2) Initiates and strengthens contractions of uterus of
pregnant woman;
3) Worsens storing and mobilization of information
(amnestic hormone).
prolactinemia
Galactorrhea
Supression of gonadal axis
- supression of FSH and LH
- amenorrhea, supressed spermatogenesis,
infertility
 Hypofunction of neurohypophysis
 Insufficient production of vasopressin results in
development of diabetes insipidus.
There are two pathogenetic variants:
 central (neurogenic) during which will a little quantity of
vasopressine, is formed and
 nephrogenic during - the sensitivity of epithelial cells
receptors of distal nephron parts and collective tubules to
vasopressin action is reduced.
 The decreasing of water reabsorption in kidneys results
to poliuria and decreasing of circulatting blood volume 
(hypovolemia), falling of arterial pressure and hypoxia.

 The decreased oxytocin production appears as disorders

of lactation, weakness of labor activity.
Pathophysiology of thyroid
gland
 The synthesis in the thyroid gland takes place in the
following way:
 A. Dietary iodine (I2) is reduced to iodide (I-) in the stomach
and gut is rapidly absorbed and circulates as iodide.
 B. Follicular cells in the thyroid gland possess an active iodide
pump. Iodide is transported into the cell against an
electrochemical gradient (more than 50 mV) by a Na+-I--
symport. The iodide pump is linked to a Na+-K+-pump, . Тhe
thyroid absorption of iodide is inhibited by negative ions (such
as perchlorate, thiocyanate and nitrate), because they
compete with the iodide for the pump. In the follicular cell,
iodide passes down its electrochemical gradient through the
apical membrane and into the follicular colloid. Iodide is
instantly oxidised – with hydrogen peroxide as oxidant - by a
thyroid peroxidase to atomic or molecular iodine (I0 or I2) .
 C. The rough endoplasmic reticulum synthesises a large
storage molecule called thyroglobulin. Iodide-free
thyroglobulin is transported in vesicles to the apical
membrane, where they fuse with the membrane and finally
release thyroglobulin at the apical membrane.
 The synthesis in the thyroid gland takes place
in the following way:
 D. At the apical membrane the oxidised iodide is attached to the
tyrosine units (L-tyrosine) in thyroglobulin at one or two positions,
forming the hormone precursors mono-iodotyrosine (MIT), and di-
iodotyrosine (DIT), respectively. This and the following reactions
are dependent on thyroid peroxidase in the presence of hydrogen
peroxide -both located at the apical membrane. As MIT couples to
DIT it produces tri-iodothyronine (3,5,3`-T3), whereas two DIT
molecules form tetra-iodothyronine (T4), or thyroxine.
 E. Each thyroglobulin molecule contains up to 4 residues of T4
and zero to one T3. Thyroglobulin is retrieved back into the
follicular cell as colloid droplets by pinocytosis.
 F. Lysosomal exopeptidases break the binding between
thyroglobulin and T4 (or T3). Large quantities of T4 are released
to the capillary blood. Only minor quantities of T3 are secreted
from the thyroid gland.
 G. The proteolysis of thyroglobulin also releases MIT and DIT.
These molecules are deiodinated by the enzyme deiodinase,
whereby iodide can be reused into T4 or T3. Normally, only few
intact thyroglobulin molecules leave the follicular cells.
 H. TSH stimulates almost all processes involved in thyroid
hormone synthesis and secretion.
The hypothalamic-pituitary-thyroid feedback system, which regulates the
body levels of thyroid hormone.
Chemistry of thyroid hormone
production
 Control of thyroid gland activity
 The hypothalamic-pituitary-thyroid axis controls the thyroid
gland function and growth.
 a. The production and release of thyroid hormone is controlled
by thyroid-releasing hormone (TRH) from the hypothalamus.
 TRH reaches the anterior pituitary via the portal system, where
the thyrotropic cells are stimulated to produce thyroid-
stimulating hormone (TSH) or thyrotropin.
 TSH is the only known regulator of thyroid hormone secretion
in humans. TSH is released to the systemic blood, by which it
travels to the thyroid gland. Here, TSH stimulates the uptake
of iodide, and all other processes that promote formation and
release of T4 (and T3).
 TSH activates adenylcyclase bound to the cell membranes of
the follicular cells and increases their cAMP.
 T3 has a strong inhibitory effect on TRH secretion, as well as
on the expression of the gene for the TRH precursor.
 Control of thyroid gland activity
• b. Almost all circulating T3 is derived from T4. TSH also
stimulates the conversion of T4 to the more biologically
active T3.
• Most of the circulating thyroid hormones are bound to
plasma proteins, whereby the hormone is protected during
transport. There is an equilibrium between the pool of
protein-bound thyroid hormone and the free, biologically
active forms (T3 and T4) that can enter the body cells.
• Thyroid hormones are lipid-soluble and they can easily
cross the cellular membrane by diffusion.
• c. Inside the cell, T3 binds to nuclear receptors and
stimulates cellular metabolism and increases metabolic
rate.
 Actions of thyroid hormones
Thyroid hormones are lipid-soluble and pass through cell membranes
easily. T3 binds to specific nuclear receptor proteins with an affinity that is
tenfold greater than the affinity for T4.

 Important cellular constituents are stimulated by T3: The mitochondria,

the Na+-K+-pump, myosin ATPase, adrenergic b-receptors, many
enzyme systems and proteins for growth and maturation including CNS
development.
 Thyroid hormones stimulate oxygen consumption in almost all cells.
 Thyroid hormones stimulate the rate of:
1) hepatic glucose output and peripheral glucose utilisation;
2) hepatic metabolism of fatty acids, cholesterol and triglycerides;
3) the synthesis of important proteins (the Na+-K+-pump, respiratory
enzymes, erythropoietin, b-adrenergic receptors, sex hormones, growth
factors etc);
4) the absorption of carbohydrates in the intestine and the gut excretion of
cholesterol;
5) the modulation of reproductive function.
 Actions of thyroid hormones
 The many rate-stimulating effects are summarized in an
overall increase in oxygen consumption. This slow - but long
lasting - calorigenic and thermogenic effect is confined to the
mitochondria.
 Regulates protein, fat and carbohydrate catabolism in all cells
 Insulin antagonist
 Maintains growth hormone secretion, skeletal maturation
 The thyroid hormones and the catecholamines work together
in metabolic acceleration.
 Thyroid hormones increase cardiac rate and output as well as
ventilation.
 The high basal metabolic rate raises the core and shell
temperature, so that the peripheral vessels dilatate. This
vasodilatation forces the cardiac output to increase. A
circulatory shock develops, if the rise in cardiac output is
insufficient to match the vasodilatation – so called high output
failure.
Affects CNS development
Necessary for muscle tone and vigor
Maintains secretion and motility of GI tract
Maintains calcium mobilization
Affects RBC production
Stimulate lip[id turnover, free fatty acid release and
cholesterol synthesis
Lowers serum calcium levels by opposing
Disorders of the Thyroid Gland

• Goiter is enlargement of thyroid gland

• Simple goiter
• Adenomatous or nodular goiter
• Hypothyroidism
• Infantile hypothyroidism (cretinism)
• Myxedema
• Hyperthyroidism
• Graves disease
• Thyroid storm
• Thyroiditis
• Hashimoto disease
Hypothyroidism (Hashimoto’s
disease, Goiter) and
Hyperthyroidism (Graves’ disease)
 Hyperthyroidism
 The classical hyperthyroidism or thyrotoxicosis (Graves
thyroiditis, Basedows disease) is a condition characterized by
an abnormal rise in basal metabolic rate, struma and eye signs
(thyroid eye disease). The eyes of the patient typically bulge (ie,
exophtalmus). Patients with thyrotoxicosis have high metabolic
rates.
 Neuromuscular system
 Tremors, hyperactivity, emotional lability, anxiety, inability to
concentrate, insomnia
 Thyroid myopathy – proximal muscle weakness with decrease
muscle mass
 Ocular changes
 Wide, staring gaze and lid lag
 Thyroid ophthalmopathy
 Gastrointestinal system
 Hypermotility, malabsorption, and diarrhea
 Skeletal system
 Stimulates bone resorption (inc. porosity of cortical bone and
reduced volume of trabecular bone)
 Osteoporosis and increased risk of fractures
 Graves Disease

 The disease is named for Robert Graves who in

1835 first identified the association of goiter,
palpitations, and exophthalmos.
 Most common cause of endogenous
hyperthyroidism
 Triad:
– Hyperthyroidism
– Infiltrative ophthalmopathy with resultant
exophthalmos
– Localized, infiltrative dermopathy (pretibial
myxedema)
 Hyperthyroidism (Graves Disease)
 Thyroid eye disease (with exophtalmus) is not confined to
Graves’s hyperthyroidism only. Some exophtalmus patients are
euthyroid or hypothyroid.
 Common to all types of thyroid eye diseases are specific
antibodies that cause inflammation of the retro-orbital tissue
with swelling of the extraocular eye muscles, so they cannot
move the eyes normally.
 Proptosis and lid lags are typical signs, and conjunctivitis and
scars on the cornea follow due to lack of protective cover.
 The oedematous retro-orbital tissue may force the eye balls
forward and press on the optic nerve to such an extent that
vision is impaired or blindness results.
 The best treatment is to normalise the accompanying
thyrotoxicosis. Other therapeutic measures are palliative.
Lid lag in Graves disease
 Hyperthyroidism (Graves Disease)
TSH receptor antibody (IgG antibodies) release causes Graves’s disease
from activated B-cells. A genetic deficiency is involved, which is shown by
the 50% concordance in monozygotic twins. Trigger mechanisms are
presumed to be bacterial or viral infections producing autoimmune
phenomena in genetically deficient individuals.
The immune system can produce the following autoantibodies:
1.   TSH-receptor antibodies against
receptors on the surface of the
thyroid follicular cells, which they
stimulate just like TSH itself, causing
thyroid hypersecretion. These IgG
antibodies are also termed long-
acting thyroid stimulator.
2.   Specific autoantibodies causing
retro-orbital inflammation and thyroid
eye disease.
3.   Thyroglobin antibodies against the
storage molecule, thyroglobin.
4.   Microsomal antibodies against
thyroid peroxidase.
These autoantibodies can be found in
the plasma of most patients with
Grave’s disease.
 The pathogenesis of Graves disease, and the clinical
manifestations of Graves’s disease.
 The increased metabolic rate and sympatho-adrenergic activity dominate
 The patient is anxious with warm and sweaty skin,
 tachycardia,
 palpitations,
 fine finger tremor,
 pretibial myxoedema (ie, accumulation of mucopolysaccharides).
 Typically is a symmetrical, warm pulsating goitre. Lean hyperthyroid
females - like female distance runners - have small fat stores and greatly
reduced menstrual bleedings (oligomenorrhoea) or even amenorrhoea.
 The high T3 level increases the density of -adrenergic receptors on the
myocardial cells. The cardiac output is high even at rest and arrhythmias
are frequent (eg, atrial fibrillation).
 Elderly patients may present with an apathetic hyperthyroidism, they
complain of tiredness and somnolence.
 Erroneous treatment with thyroid hormone can kill the patient by causing
vasodilatation and cardiac output failure.
 A suppressed serum TSH confirms the diagnosis of hyperthyroidism, and
the serum T3 or T4 is raised.
 Toxic goiter and toxic solitary adenoma
(Plummers disease) are cases of secondary
hyperthyroidism just as inflammation in acute
thyroiditis and chronic thyroiditis. The cells
secrete thyroid hormone without inhibition from
the hypothalamo-pituitary axis.

Thyroid scintigraphies. A. Graves’ Disease. Diffuse thyroid uptake.

B. Plummer’s Disease. Nodular uptake on left thyroid lobe
with suppression of the gland.
 Hypothyroidism

 Primary hypothyroidism is an abnormally low activity of the

thyroid gland with low circulating thyroid hormone levels
caused by thyroid disease.
 Secondary hypothyroidism results from hypothalamic-pituitary
disease.
 Primary hypothyroidism is caused by microsomal
autoantibodies precipitated in the glandular tissue. Lymphoid
infiltration of the thyroid may eventually lead to atrophy with
abnormally low production of T4. Another clinical form starts
out as Hashimotos thyroiditis, often with hyperthyroidism and
goiter.
• When hypothyroidism is congenital both physical and
mental development is impaired and cretinism is the
result. Also iodide deficiency in childhood may also result
in a cretin or a mentally retarded hypothyroid dwarf.

• Myxoedema in the adult is severe thyroid gland

hypothyroidism with a puffy swollen face due to a hard,
non-pitting oedema (called myxoedema or tortoise skin).
The skin is dry and cold; there is bradycardia, often
cardiomegaly (ie, myxoedema heart), hair loss,
constipation, muscle weakness and anovulatory cycles in
females.

• A high TSH level and a low total or free T4 in plasma

confirms the diagnosis primary hypothyroidism. Thyroid
autoantibodies are usually demonstrable in the plasma.
Hypercholesterolaemia and increased concentrations of
liver and muscle enzymes (aspartate transferase, creatine
kinase) in the plasma is typical.
 Secondary hypothyroidism is caused by reduced
TSH (Thyroid stimulating hormone) drive due to
pituitary or hypothalamic insufficiency. A test dose of
TRH (Thyroid releasing hormone) to a myxoedema
patient with hypothalamic or pituitary insufficiency will
result in a normal TSH response.
 HYPO-THYROIDISM
 Cretinism
• Severe retardation
• CNS/Musc-skel
• Short stature
• Protruding tongue
• Umbilical hernia
• Maternal iodine defic.
 Myxedema (coma)
• Sluggishness
• Cold skin
 This 1 year old baby
was diagnosed with Cretinism
Cretinism.

APGAR score of early suspicion of hypothyroidism

 H → Hypotonia → 1
Y → Yellow (icterus >3) →1
P → Pallor, cold, hypothermia →1
O → Open post. fontanel →1
T → Tongue enlarged →1
H → Umbilical hernia →2
Y → absent Y (female) →1
R → Rough dry skin →1
O → Edematous typical face →2
I.D.→ Inactive defecation → 2
Birth weight > 3.5 kg →1
Post.mature > 40w →1
Total = 15.
If score > 5 suggest hypothyroidism,
must investigate.
These four brothers work at a salt
factory in Pakistan. Two of them suffer
from cretinism, caused by iodine
deficiency. All the brothers ensure
they use iodized salt in their
households to prevent cretinism in the
next generation and give their children
the iodine they need for intellectual
development.
 Simple Mnemonics for Clinical
picture of cretinism
at birth & early neonatal :
1- Feeding difficulty, choking & anorexia

2- Constipation, abdomenal distention,

umbilical hernia, delayed passage of
meconium
3- Heavy birth weight (Over weight).
4- Hypothermia, cold skin.
5- Open posterior fontanel.
6- Less activity, always sleep, little cry
hoarse voice.
7- Prolonged physiological jaundice.
8- Bradycardia: ↓ HR (Slow Pulse) .
9- Apneic attacks: ↓ Respiratory rate.
10- X- Ray knee: absent ossific centers
at birth of the lower end of the femur.
 Myxedema
 Hypothyroidism developing in the older child or
adult
 Characterized by slowing of physical and mental
activity
 Accumulation of matrix substances
(glycosaminoglycans and hyaluronic acid) in the
skin, subcutaneous tissues, and visceral sites 
edema, broadening and coarsening of facial
features, enlargement of the tongue, and
deepening of the voice
 Measurement of serum TSH level is the most
sensitive screening test
 Primary
hypotyrioidism

Myxedema
 Myxedematous Coma.
• Myxedematous coma is a lifethreatening, end-stage
expression of hypothyroidism.

• It is characterized by coma, hypothermia, cardiovascular

collapse, hypoventilation, and severe metabolic disorders that
include hyponatremia, hypoglycemia, and lactic acidosis. It
occurs most often in elderly women .

• It occurs more frequently in the winter months, which suggests

that cold exposure may be a precipitating factor. The severely
hypothyroid person is unable to metabolize sedatives,
analgesics, and anesthetic drugs, and buildup of these agents
may precipitate coma.
Diffuse and Multinodular Goiters
• Reflect impaired synthesis of thyroid hormones
• Diffuse nontoxic (simple) goiter
– Diffusely involves the entire gland without producing
nodularity
– Enlarged follicles are filled with colloid = colloid goiter
• Multinodular goiter
– Irregular enlargement of the gland
– Produce the most extreme enlargement and are most
mistaken for neoplastic process than any other form
of thyroid disease
GOITER
CAUSE :
• IODINE DEFICIENCY
• INTAKE OF GOITROGENIC SUBSTANCES/
DRUGS:
– CASSAVA,
– CABBAGE,
– CAULIFLOWER,
– CARROTS
– RADDISH
– TURNIPS
– RED SKIN OF PEANUTS
– IODINE
– COBALT
– LITHIUM
Many vegetables are goiterogens, fruits are NOT.
 NON-TOXIC GOITER
IODINE DEFICIENCY OR
INTAKE OF GOITROGENIC SUBSTANCES

IMPAIRED THYROID HORMONE SYNTHESIS

SERUM THYROXINE

PITUITARY SECRETE TSH

THYROID GLAND ENLARGES

TO COMPENSATE FOR THE REDUCED LEVEL OF THYROXINE
Multinodular
goiter
 Hashimoto Thyroiditis
 Chronic lymphocytic thyroiditis
 Struma lymphomatosa
 Most common cause of
hypothyroidism in areas of the
world where iodine levels are
sufficient
 Pathogenesis:
 CD8+ cytotoxic T-cell mediated
cell death
 Cytokine mediated cell death
 Binding of anti-thyroid Ab’s 
ADCC
 Anti-TSH receptor Ab’s,
antithyroglobulin, antithyroid
peroxidase Ab’s
A woman presenting with an enlarged
thyroid who has Hashimoto's thyroiditis
 It may be associated with other endocrine organ
deficiencies such as diabetes mellitus or Addison's disease. 

It produces atrophic changes with regeneration. This can

lead to a goiter forming. Patients with Hashimoto’s thyroiditis
are usually hypothyroid or euthyroid. However, they may
have an initial thyrotoxic phase
Specific helper-T lymphocytes are activated in this
condition . This activation may be triggered by a viral
infection.
 Level of Organization Hypothyroidism Hyperthyroidism

Basal metabolic rate Decreased Increased

Sensitivity to catecholamines Decreased Increased

Myxedematous features Exophthalmos

General features Deep voice Lid lag
Impaired growth (child) Decreased blinking

Blood cholesterol levels Increased Decreased

Mental retardation (infant) Restlessness, irritability, anxiety

General behavior Mental and physical sluggishness Hyperkinesis
Somnolence Wakefulness

Cardiovascular function Decreased cardiac output Increased cardiac output

Bradycardia Tachycardia and palpitations

Gastrointestinal function Constipation Diarrhea

Decreased appetite Increased appetite

Respiratory function Hypoventilation Dyspnea

Adrenal cortex
- secretes several classes of steroid hormones (glucocorticoids and
mineralocorticoids)
- with three concentric zones of cells that differ in the major steroid
hormones they secrete.

Adrenal medulla
- source of the catecholamines epinephrine and norepinephrine.
- chromaffin cell is the principle cell type.
- The medulla is rich innervated by preganglionic sympathetic fibers and
is, in essence, an extension of the sympathetic nervous system.
 Adrenal cortex

Adrenal
gland
Kidney

Adrenal cortex
Glucocorticoids –
glucose from noncarb Effects of Effects of
mineralocorticoids: glucocorticoids:
sources, such as
muscles
Mineralocorticoids 1. Retention of sodium 1. Proteins and fats broken down
ions and water by and converted to glucose, leading
(aldosterone) –
kidneys to increased blood glucose
induces kidneys to
reabsorb water and 2. Increased blood 2. Possible suppression of
salts volume and blood immune system
Both of them deal with pressure
long-term stress
 Actions of Cortisol
Major Influence Effect on Body

Increase blood sugar

Stimulates gluconeogenesis
Glucose metabolism Decreases glucose using by the tissues
Antagonize insulin

Protein metabolism Increases breakdown of proteins

Increases plasma protein levels

Fat metabolism Increases mobilization of fatty acids

Increases use of fatty acids

Stabilizes lysosomal membranes of the inflammatory cells, preventing the

release of inflammatory mediators
Decreases capillary permeability to prevent inflammatory edema
Depresses phagocytosis by white blood cells to reduce the release of
inflammatory mediators
Anti-inflammatory action Suppresses the immune response
 Causes atrophy
(pharmacologic levels) of lymphoid tissue
 Decreases eosinophils
 Decreases antibody formation
 Decreases the development of cell-mediated immunity
Reduces fever
Inhibits fibroblast activity
 Other effects

Inhibit bone formation – osteoporosis

Inhibit ADH and ACTH secretion
Stimulate gastric acid secretion
Promote maturation of fetal lungs
 Disorders of adrenal gland function

1) Hypofunction of adrenal cortex - hypocorticism

Addison disease;
2) Hyperfunction of fascicular zone - syndrome of
Itsenko-Cushing – Hypersecretion of cortisol;
3) Hyperfunction of glomerulose zone –
hyperaldosteronism – Hyperfunction of adrenal
cortex resulting in excess secretion of aldosterone;
4) Dysfunction of adrenal cortex - adrenogenital
syndrome
 Insufficiency of adrenal cortex
• According to etiology there are primary and secondary
types of adrenal cortex insufficiency.
• Primary insufficiency arises as a result of adrenals injury,
• secondary is connected with the defeat of hypotalamus
(deficiency of corticoliberin), or with hypofunction of
adenohypophysis (deficiency of ACTH).
• Insufficiency of corticosteroids can be total when all
hormones are affected, and partial fall down of activity of one
adrenal hormone.
• Insufficiency of adrenal cortex can be acute and chronic.
chronic
• Examples of acute insufficiency are: are
а) state after removal of adrenals;                
b) hemorrhage in adrenals which arises during sepsis,
meningococci infection (syndrome Waterhouse-Friderixan);
c) syndrome of interruption of glucocorticoid treatment.
• Fast ceasing of the adrenal function causes collaps and the
patients can die during the first day.
• The chronic insufficiency of
adrenals cortex is Adison’s disease
(bronzed disease).
• The most often reasons of it are:
а) tuberculose destruction of adrenals;
b) autoimmune process.
Tuberculose of
adrenal gland.
Adison’s
disease
Skin hyperpigmentation in case of Adison’s disease
 І. Manifestation of mineralocorticoids deficit :
• 1) dehydration develops owing to loss of sodium ions (decreases
rearbsortion) with the  loss of water (poliuria);
• 2) arterial hypotension is caused by decrease of circulating
blood volume;
•   
• 3) hemoconcentration is connected with fluid loss, results in
disorders of microcirculation and hypoxia;
hypoxia

• 4) decreasing of kidney blood circulation is caused by

decrease of arterial pressure with diminishing of glomerular
filtration and development of azotemia

• 5) hyperkaliemia
• 6) distal tubular acidosis. It is connected with disorders of
acidogenesis in distal nephron canales;
• 7) gastro-intestinal disorders (nausea, vomiting, diarrhea). Loss
of sodium (osmotic diarrhea) and intoxication have significant role.
This disorders without appropriate correction result to death.
 ІІ. decrease of glucocorticoid function

• 1) hypoglycemia          
• 2) arterial hypotension (permissive action for catecholamines);
• 3) decrease reaction of fat tissue to lipotropic stimulus;
• 4) decrease immunity
• 5) decrease of ability to remove water during water load (water
intoxication);
• 6) muscular weakness and fast tiredness;
• 7) emotional disorders (depression);
• 8) delay of growth and development of children;
• 9) sensor disorders - loss of ability to distinguish shades of
gustatory osmotic acoustical sensations;
• 10) distress-syndrome of a newborn (hyalin membrane disease). It
is caused by disorders  of surfactant formation
 HYPOADRENALISM
Caused by any anatomic or metabolic lesion of the adrenal
cortex that impairs output of the cortical steroids.
Primary Acute Adrenal Insufficiency
- Waterhouse Friderichsen Syndrome
due to overwhelming septicemic infection caused by
meningococci, but occasionally other virulent
organism such as gonococci, pneumococi and
staphylococci.
morphology: massive bilateral adrenal hemorrhage
 Increase of adrenals cortex function
•  Hyperaldosteronism.
There are primary and secondary hyperaldosteronism.
hyperaldosteronism
•  Primary hyperaldosteronism (Conn syndrome)syndrome - adenoma of  zona
glomerulosa, :
1) arterial hypertension. It is connected with increase of sodium  contents  in
blood and in wall of blood  vessels, the sensitivity of their smooth muscles to
action of pressor factors,  particularly catecholamines, is increased. 
2) hypokaliemia -disorders of heart activity, miostenia, paresis
3) metabolic alkalosis.

• Secondary hyperaldosteronism is a result of renin-angiotensin  system

activation. This state appears by:
a) arterial hypertension;
b) edemas;                                   
c) hypokaliemia;
d) metabolic alkalosis.
• There are two clinical forms of
hypercorticism with
hyperproduction of
glucocorticoides:
1. Cushing’s disease – basophil
adenoma of anterior
hypophysis .
2. Cushing’s syndrome:
syndrome
• а) tumor – adenoma of zona
fasciculata of adrenal cortex;
• b) ectopic production of
АCТH by some malignant
tumors (pulmonar cancer);        
• c) iatrogenic – introduction of
glucocorticoides for medical
purposes.
 BUFFALO
HUMP

STRIAE
MOON
FACIES
 Glucocorticoid
hypercorticism appears by:
1) arterial hypertension;    
2) hyperglycaemia – steroid
diabetes mellitus;
3) obesity;
4) development of infectious
diseases without signs of
an inflammation;
5) gastric hypersecretion and
formation of ulcers in
stomach and duodenum;
6) osteoporosis;
7) muscular weakness;
8) slow wound healing.
• Adrenogenital syndrome results from the
hereditary determined blockade of cortisole
synthesis  and incerased production of androgens
• Depending on the level of blockade of cortisole
 synthesis there are three variants of adrogenital
syndrome.
• І. Disorders of early stages of synthesis –
deficiency of glucocorticoides, mineralcorticoides Adrenogenital 
and androgens hyperproduction. Manifestations:
signs of insufficiency of gluco- and syndrome
mineralocorticoidal functions of adrenal cortex
features of early sexual maturing in males,
virilization in women (appearance of man's sexual
features).
• ІІ. Disorders of intermediate stages – deficiency
of glucocorticoides, excess of androgens, formation
of mineralocorticoides is not affected (classical
androgenic syndrome). Manifestations are the
same, as in the first case, only without signs of
insufficiency of mineralocorticoidal function.
• ІІІ. Disorders at final stages of cortirol synthesis
– deficiency of glucocorticoides, hyperproduction of
androgens and mineralocorticoide. Features of
hyperaldosteronism are connected with
manifestations of classical androgenital syndrome.
 Disorders of adrenal medulla function
 Hypofunction of adrenal medulla happens
rarely
 Hyperfunction of adrenal medulla arises from
tumors of chromaphine cells –
pheochromocytome. Appears with arterial
hypertension, tachycardia, extrasystole, flatering
of atriums, hyperglycaemia, hyperlipidaemia,
hyperthermia.  Development of moderately
expressed diabetes, thyreotoxicosis is possible. In
time of paroxism vertigo, headache,
hallucinations, increased excitability of the
nervous system, cramps appear.
 T
N

 This large adrenal neoplasm

has been sectioned in half.
Note the grey-tan color of the
tumor compared to the yellow
cortex stretched around it and
a small remnant of remaining
adrenal at the lower right.
This patient had episodic
hypertension. This is a tumor
arising in the adrenal medulla
- a pheochromocytoma.
 Cardiovascular: Coronary artery
disease, hypertension, stroke, arrhythmia.
 Muscles: Tension headaches, backache
 Connective tissues: Rheumatoid arthritis
 Pulmonary: Asthma.
 Immune: Immunosuppression, deficiency,
autoimmunity
 Gastrointestinal: Ulcer, irritable bowel syndrome,
diarrhea, nausea and vomiting, ulcerative colitis
 Integumetary: Eczema, neurodermatitis, acne
 Endocrine: Diabetes mellitus, amenorrhea
 Central nervous: Fatigue and lethargy, type A
behavior, overeating, depression, insomnia.