Pathophysiology

Diseases of endocrine system

 Diseases of Endocrine System

Pituitary Gland (Anterior Lobe)

1. Hypopituitarism: (Diminished secretion of Anterior Pituitary Hormones)

Predisposing to various clinical manifestations

Diminished Growth Hormone Secretion Result in DWARFISM

Etiology of Hypopituitarism:
Pituitary Adenoma destroying glandular epithelium.
Pituitary adenomas are tumors that occur in the pituitary gland,
and account for about 15% of intracranial neoplasms.

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Hypopituitarism is the decreased (hypo) secretion of one or more of
the eight hormones normally produced by the pituitary gland at the
base of the brain

Too little GH during childhood makes an individual a

pituitary dwarf.
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2. Hyperpituitarism ( Excessive secretions of anterior pituitary hormones)

1. Excess (GH) leading to Gigantism & Acromegaly

2. Excess (ACTH) leading to Cushing Syndrome

Etiology:

…………Pituitary Adenoma

Growth H ACTH

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Clinical Manifestations of Hyperpituitarism
1. Gigantism: Excess Secretion of (GH) in Childhood

2. Acromegally: Excess Secretion of (GH) after puberty

Clinical Presentation of Acromegally:

1. Skin Thickening

3. Enlarged Lips, Nose & Tongue

4. Visceromegaly as Cardiomegaly

5. Large Hands, Feet & Lower Jaw

Visceromegaly is enlargement of the internal

organs in the abdomen

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 Too much forms a giant; life expectancy is less because GH
affects blood glucose levels and promotes diabetes mellitus.
 The overproduction of GH in adults results in acromegaly; since
long bone growth is no longer possible, only the feet, hands, and
face grow.
 Diseases of Posterior Pituitary
Diabetes Insipidus
Defective Secretion of ADH
Resulting in Inability of Kidneys to Concentrate Urine
Clinical Picture:
1. Polyuria (as excessive or abnormally large production and/or passage of urine (at
least 2.5 or 3 L over 24 hours in adults). )
2. Polydipsia : is a medical symptom in which the patient displays excessive thirst
3. Hypernatremia: is an electrolyte disturbance that is defined by an elevated
sodium level in the blood. Hypernatremia is generally not caused by an excess of
sodium, but rather by a relative deficit of free water in the body.
3. Diluted Urine of fixed specific gravity at 1010
Etiology:
A. Neurogenic (ADH) Deficiency (Hypothalamic Disorders)
B. Nephrogenic ( Tubular Insensitivity to ADH )
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 Diseases of Thyroid Gland
Hyperthyroidism : ( overproduction of Thyroxine )

Clinical Picture:
1. Weight loss & fatigue + increased appetite
2. Tachycardia
3. Heat intolerance & excessive sweating
4. Anxiety & Tremor
5. visible enlargement of thyroid gland
6. sleeplessness & restlessness
7. Exophthalmos goiter (protrusion of eye ball The eyes protrude because of
edema in the eye socket tissue; )
A tremor is an involuntary, somewhat rhythmic, muscle contraction
and relaxation involving to-and-fro movements (oscillations or
twitching) of one or more body parts. It can affect the hands, arms,
eyes, face, head, vocal folds, trunk, and legs.
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Etiology of Hyperthyroidism

Diffuse Active Thyroid Hyperplasia (Grave's Disease)

occurs when the thyroid gland is enlarged or overactive.

Simple Goiter
Lack of iodine
Toxic Multi-Nodular Goiter (Thyroxine (T4)
contains four
iodine atoms)
causes
enlargement of
the thyroid

Toxic Adenoma (Hormone – Producing Tumor )

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 Hypothyroidism
Definition: chronic disease caused by Diminished Secretion of Thyroxine
Resulting in ………………………Cretinism (Mental Retardation) in Infancy
Myxedema in Adult
Etiology : Auto Immune Disease ( Hashimoto`s Disease )

Hashimoto's thyroiditis or chronic lymphocytic

Non-Pitting Edema thyroiditis is an autoimmune disease in which the
thyroid gland is gradually destroyed by a variety of cell-
and antibody-mediated immune processes. It was the
first disease to be recognized as an autoimmune
disease. It was first described by the Japanese specialist
Hashimoto Hakaru in Germany in 1912.
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Cretinism (congenital hypothyroidism)
occurs in individuals who have suffered
from low thyroid function since birth.

• 1) Affected individuals are short and stocky

and have had hypothyroidism since infancy.
• 2) Thyroid treatment helps but unless it is
begun in the first two months, mental
retardation can occur.
• Myxedema is hypothyroidism in
adults; thyroid hormones can
restore normal function.
 Parathyroid gland
Parathyroid is a regulator of plasma calcium & phosphate.
Homeostasis of plasma calcium regulated as follows:
A. Parathormone RAISES Plasma Calcium to Normal level

B. Calcitonin of thyroid gland LOWERS Plasma Calcium to Normal Level

______________________________
Diseases of Parathyroid Glands
Hypoparathyroidism: a state of Deficient Secretion of PTH Predisposing to
HYPOCALCEMIA
Causes : 1. Congenital absence. 2. Acquired causes as Surgery, Autoimmunity ,
Neoplasia…..
Clinical Picture:
Increased Neuromuscular excitability due to hypocalcaemia
resulting in Tetany, or Convulsions.
A convulsion is a medical condition where body muscles contract and relax rapidly and
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repeatedly, resulting in an uncontrolled shaking of the body
• Tetany is a medical sign consisting of the involuntary
contraction of muscles, which may be caused by
disease or other conditions that increase the action
potential frequency.
• The terms "tetany" and "tetanus" are distinct. Muscle
cramps that are caused by the disease tetanus are not
classified as tetany; rather, they are due to a blocking
of the inhibition to the neurons that supply muscles.

• If PTH is not produced in response to low blood Ca2+,

tetany results because the Ca2+ plays an important
role in both nerve conduction and muscle contraction.
• In tetany, the body shakes from continuous muscle
contraction due to the increased excitability of nerves
that fire spontaneously and without rest; this condition
may be due to hypoparathyroidism.

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Hyperparathyroidism :
Definition : Over Activity due to Excess Secretions of Parathormone
Etiology :
1. Parathyroid Hyperplasia
2. Functioning Adenoma of Parathyroid gland

Clinical Picture : Hypercalcemia predisposing to:

1. Renal Stones
2. Gall Stones
3. Bone Resorption predisposing to bone fracture
In hyperparathyroidism, the abnormally high blood
calcium levels can cause the bones to be soft and
fragile, and the individual to be prone to kidney stones.
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 Recall Physiology
• The hypothalamus uses ACTH-releasing hormone to
control the anterior pituitary’s secretion of ACTH.
Glucocorticoids: Cortisol is a biologically significant
glucocorticoid.
• Cortisol breaks down fatty acids rather than
carbohydrates; cortisol therefore raises blood glucose
levels.
• The adrenal cortex secretes two types of hormones:
glucocorticoids and mineralocorticoids.
• 1) Glucocorticoids help regulate blood glucose levels.
• 2) Mineralocorticoids regulate the levels of minerals in
the blood.
 Diseases of Adrenal Gland
Adrenal Insufficiency

Addison's Disease

Definition: Adrenal Insufficiency of Steroid Hormones

Causes:
1. Tuberculosis
2. Autoimmune disease
Clinical Picture:
1. Weight Loss, Hypotension, Hypoglycemia, HYPOnatremia & HYPER kalemia.
2. Skin hyper pigmentation

Hyponatremia is a metabolic condition in which there is not enough

sodium (salt) in the body fluids outside the cells.
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 Recall Physiology
• Hyperkalemia (hyperkalaemia hyper- high;
kalium, potassium; -emia, "in the blood")
refers to the condition in which the
concentration of the electrolyte potassium
(K+) in the blood is elevated. Extreme
hyperkalemia is a medical emergency due
to the risk of potentially fatal abnormal
heart rhythms (arrhythmia).
• Normal serum potassium levels are
between 3.5 and 5.0 mEq/L at least 95% of
the body's potassium is found inside cells,
with the remainder in the blood. This
concentration gradient is maintained
principally by the Na+/K+ pump.

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 Addison’s disease
• (Also called chronic adrenal insufficiency,
hypocortisolism, and hypoadrenalism)
• is a rare, chronic endocrine disorder in which
the adrenal glands do not produce sufficient
steroid hormones (glucocorticoids and often
mineralocorticoids).
• caused by damage by the body's own immune
system, certain infections or various rarer
causes.
Malfunction of the Adrenal Cortex

1) Low levels of adrenal cortex hormones

(hyposecretion) result in Addison disease.

2) The lack of cortisol results in low glucose levels; a

stressed person has insufficient energy.

3) The lack of aldosterone drops blood sodium levels; a

person then has low blood pressure and dehydration
and coma
4) Left untreated, Addison disease can be fatal.
Addison disease
Cushing Syndrome (Excess Cortisol Production)

Causes:
1. Excess ACTH production ( Hyperpituitarism) pituitary adenoma
2. Functioning Adrenal Neoplasm ( Hormone Producing Tumor)

Clinical Picture:
1. Buffalo neck
2. Moon Face
3. Hirsutism is the excessive hairiness on women in those parts of the body where
terminal hair does not normally occur or is minimal - for example, a beard or chest hair.
4. Hypertension
5. Menstrual Disturbances & Impotence
6. Impaired Glucose Tolerance Test (Glucose Intolerance) resulting in Hyperglycemia
7. Muscle wasting

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 Hirsutism

High levels of adrenal cortex hormones from

hypersecretion result in Cushing syndrome.
• 1) Excess cortisol causes a tendency toward
diabetes mellitus.
• 2) Muscular protein then decreases and
subcutaneous fat forms an obese trunk but
normal arms and legs.
 Cushing Syndrome Treatment

• Treatment of a pituitary adenoma would

probably involve surgery (hypophysectomy).
 Homeostasis of Plasma Glucose

Insulin (Beta Cells) Lowers Plasma Glucose to Normal Level by Glycolysis

Glucagon (Alpha Cells) Raises Plasma Glucose to Normal Level by Glycogenolysis

Hormones secreted into blood

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 Diabetes Mellitus
Hyperglycemia due to Insulin Deficiency
Resulting in Disturbed Metabolism of Carbohydrate, Fat & Protein
Etiology: Destruction of Beta Cells by various Environmental & Genetic Familial
Factors
DIAGNOSTIC CRITERIA

Test Normal Diabetic

Fasting Blood Glucose 60 - 120 mg/dl 150 mg/dl
2 hours after 75 g glucose 120 mg/dl 250 mg/dl

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Glucose Tolerance Test

Impaired Tolerance

Normal Tolerance

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 Types of Diabetes Mellitus
A. Insulin Dependent Diabetes Mellitus (IDDM)
B. Non Insulin Dependent Diabetes Mellitus (NIDDM)

Parenteral Insulin Enteral Medicine

A B

Gastrointestinal tract

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Enteral
1- Enteral administration is administration that involves any part of the
gastrointestinal tract and has systemic effects:
A. by mouth (orally), many drugs as tablets, capsules, or drops
B. by gastric feeding tube, duodenal feeding tube, or gastrostomy, many
drugs and enteral nutrition
C. rectally, various drugs in suppository
Parenteral
1. intravenous (into a vein), e.g. many drugs, total parenteral nutrition
2. intra-arterial (into an artery), e.g. vasodilator drugs in the treatment of
vasospasm and thrombolytic drugs for treatment of embolism
3. intraosseous infusion (into the bone marrow) is, in effect, an indirect
intravenous access because the bone marrow drains directly into the
venous system. This route is occasionally used for drugs and fluids in
emergency medicine and pediatrics when intravenous access is difficult.
4. intra-muscular
5. intracerebral (into the brain parenchyma)
6. intracerebroventricular (into cerebral ventricular system)
7. subcutaneous (under the skin)
 Diabetes mellitus type 1
• (Type 1 diabetes, T1DM, IDDM, or, formerly,
juvenile diabetes) is a form of diabetes mellitus
that results from autoimmune destruction of
insulin-producing beta cells of the pancreas.

• The subsequent lack of insulin leads to increased

blood and urine glucose. The classical symptoms
are polyuria (frequent urination), polydipsia
(increased thirst), polyphagia (increased hunger),
and weight loss.
 Diabetes mellitus type 2
• Formerly non-insulin-dependent diabetes
mellitus (NIDDM) or adult-onset diabetes – is a
metabolic disorder that is characterized by high
blood glucose in the context of insulin resistance
and relative insulin deficiency.

• Diabetes is often initially managed by increasing

exercise and dietary modification.

• If the condition progresses, medications may be

needed. Often affecting the obese, diabetes
requires patients to routinely check their blood
sugar.
Clinical Picture :
Polyuria
Polydipsia
polyphagia
General weakness
Skin Sepsis ( pruritis of external genitalia )
Poor wound healing

Pruritus ani (also known as anusitis or "the swamps") is the irritation of the skin
at the exit of the rectum, known as the anus, causing the desire to scratch.
The intensity of anal itching increases from moisture, pressure, and rubbing
caused by clothing and sitting. At worst, anal itching causes intolerable
discomfort that often is accompanied by burning and soreness. The irritation
can be caused by intestinal parasites, anal perspiration, frequent liquid
stools, diarrhea, residual stool deposits, or the escape of small amounts of
stool as a result of incontinence or flatulence. Another cause is yeast
infection or Candidiasis. Some diseases increase the possibility of yeast
infections, such as diabetes mellitus or HIV infection. 34
 Complications of Uncontrolled DM

1-Atheroma is an accumulation and swelling in artery walls that is

made up of (mostly) macrophage cells, or debris, that contain
lipids (cholesterol and fatty acids), calcium and a variable
amount of fibrous connective tissue. Atheroma occurs in
atherosclerosis.

Atheroma predisposing to vascular occlusion (Coronary, Cerebral &

Retinal arteries)
Retinopathy

2-Unconsciousness: A coma is a profound state of unconsciousness

wherein a person will not wake up or respond normally to pain
or light, lacking normal sleep and wake cycles, and cannot do
voluntary actions.
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Complications of Uncontrolled DM
• (Retinopathy),
• Kidney disease (nephropathy), and
• Nerve damage (neuropathy)
 Diabetic Retinopathy (damage to the retina) caused by complications
of diabetes mellitus

Atheroma Leads to Papilledema + Hemorrhage + Retinal Detachment

??? Blindness
Papilledema (or papilloedema) is optic disc (swelling that is caused by increased
intracranial pressure.

The optic disc or optic nerve head is the location where ganglion cell axons exit
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the eye to form the optic nerve.
A. Hyperglycemic Coma (Ketoacidosis ) Ketoacidosis is a
metabolic state associated with high concentrations of
ketone bodies, formed by the breakdown of fatty acids and
the deamination of amino acids. The two common ketones
produced in humans are acetoacetic acid and β-
hydroxybutyrate. (lack of insulin)

B. Hypoglycemic Coma: problems arise from an inadequate

supply of glucose to the brain. Hypoglycemia coma is
triggered by the abject destruction of neurons in the
hippocampus and cerebral cortex areas of the brain, which
are parts that are essential to memory and cognition.
Hyperglycemic Coma

Definition: A State of Unconsciousness Due to Hyperglycemia

Caused by Insufficient Insulin
Clinical Features:
• Unconsciousness
• Smell of Acetone from mouth
• Hyperglycemia (Blood Glucose ? 500 mg/dl)
• Glycosuria
• Ketonuria

The main aims in the treatment of diabetic ketoacidosis are

replacing the lost fluids and electrolytes while suppressing
the high blood sugars and ketone production with insulin.
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• Hyperglycemic Coma: Diabetic ketoacidosis arises because of a
lack of insulin in the body.
• The lack of insulin and corresponding elevation of glucagon leads
to increased release of glucose by the liver (a process that is
normally suppressed by insulin) from glycogen and through
gluconeogenesis.
• High glucose levels spill over into the urine, taking water and
solutes (such as sodium and potassium) along with it in a process
known as osmotic diuresis. This leads to polyuria, dehydration,
and compensatory thirst and polydipsia.
• The absence of insulin also leads to the release of free fatty acids
from adipose tissue (lipolysis), which are converted, again in the
liver, into ketone bodies (acetoacetate and β-hydroxybutyrate).
• The ketone bodies, turn the blood acidic (metabolic acidosis). The
body initially buffers the change with the bicarbonate buffering
system, but this system is quickly overwhelmed and other
mechanisms must work to compensate for the acidosis.
Hypoglycemic Coma

Definition : A State of Unconsciousness due to Hypoglycemia caused by

Excess Insulin
Clinical Features:
1. Hunger Feeling
2. Excessive Sweating
3. Nausea & Headache
4. Tiredness & Anxiety
5. Speech Difficulty
6. Hypoglycemia (Blood Glucose ? 10mg/dl)
7. Confusion & ?? Coma

Acute Hypoglycemia During Sleep is Dangerous & Might be Fatal.

The most common forms of hypoglycemia occur as a complication of

treatment of diabetes mellitus with insulin or oral medications.

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• Hypoglycemia is treated by restoring the
blood glucose level to normal by the ingestion
or administration of dextrose or carbohydrate
foods.
• In more severe circumstances it is treated by
injection or infusion of glucagon.
• Recurrent hypoglycemia may be prevented by
reversing or removing the underlying cause,
by increasing the frequency of meals, with
medications like diazoxide, octreotide, or
glucocorticoids.