Alteration in Endocrine Function

Endocrine disorders
1. Hyperfunction -increased secretion/ concentration of its
hormone (s) in the blood.
2. Hypofunction - decreased secretion /concentration of its
hormone(s) in the blood.
3. Eufunction -normal secretion/concentration of its hormone
Causes:
1. Acquired causes
A. Tumors of endocrine glands.
B. Inammatory lesions of endocrine glands.
Autoimmune/ viral /bacterial infection.
C. Disorders of nutrition. Synthesis

ALTERATION IN HYPOTHALAMIC PITUITARY

FUNCTIONS
Empty sella syndrome
- pituitary gland shrinks or becomes flattened.
When the pituitary gland shrinks or becomes flattened, it
cannot be seen on MRI scans, giving the appearance of an
"empty sella." This is referred to as empty sella syndrome.
The pituitary makes several hormones that control the other
glands in the body, including the:

Adrenal glands
Ovaries

Testicles

Thyroid

Primary empty sella syndrome occurs when a hole in the

membrane covering the pituitary gland allows fluid in, which
presses on the pituitary.
Secondary empty sella syndrome occurs when the sella is
empty because the pituitary gland has been damaged by:

A tumor
Radiation therapy

Surgery

Pituitary adenoma
These benign tumors do not spread outside the skull. They
usually remain confined to the sella turcica (the tiny space in
the skull that the pituitary gland sits in). Sometimes they grow
into the walls of the sella turcica and surrounding blood
vessels, nerves, and coverings of the brain. They do not grow
very large, but they can have a big impact on a persons
health.
There is very little room for tumors to grow in this part of the
skull. Therefore, if the tumor becomes larger than about a
centimeter (about half an inch) across, it can compress and
cause damage to nearby parts of the brain and the nerves that
arise from it.
The problems pituitary adenomas can cause include:

Vision loss or double vision: The nerves that

connect the brain to the eyes (the optic nerves) and to the
muscles that move the eyes pass near the pituitary gland.
An enlarged pituitary can press on these nerves and affect
vision.

Overproduction of hormones: Many pituitary

adenomas make too much of a particular hormone, which
can cause serious symptoms

Hormone deficiency: Sometimes the pituitary

adenoma can crowd out the healthy pituitary tissue that
remains. Damage to this tissue can lead to a shortage of the
other pituitary hormones.
Microadenoma versus macroadenoma
Pituitary adenomas can be divided into 2 categories based on
size:

Microadenomas are tumors that are smaller than 1

centimeter (cm) across. Because these tumors are small,
they rarely damage the rest of the pituitary or nearby
tissues. But they can cause symptoms if they release too
much of a certain hormone into the bloodstream. Many
people may actually have small adenomas that are never
detected because they never grow large enough or secrete
enough hormones to cause a problem.

Macroadenomas are tumors 1 cm across or larger.

Macroadenomas can affect a persons health in 2 ways.
First, they can cause symptoms if they make too much of a
certain hormone. Second, they may cause symptoms by
pressing on normal pituitary tissue or nearby nerves, such
as the optic nerves.
Functional vs non-functional adenoma
Functional adenomas:

Prolactin-producing adenomas (prolactinomas),

which account for about 4 out of 10 pituitary tumors

Growth hormone-secreting adenomas, which make

up about 2 in 10 pituitary tumors

Corticotropin (ACTH)-secreting adenomas (about

7%)

Gonadotropin (LH and FSH)-secreting adenomas

(less than 1%)

Thyrotropin (TSH)-secreting adenomas (less than

1%)

Some adenomas secrete more than one type of hormone.

Non-functional adenomas: do not make any hormone They
account for about 3 in 10 of all pituitary tumors that are found.
They are usually detected as macroadenomas, causing
symptoms because of their size as they press on surrounding
structures.
Causes
Unknown, genetic changes, inherited.Exposure to cancer
causing substances like radiation.
Risk Factors
A family or personal history of multiple endocrine neoplasia,
Other disorders :acromegaly (giantism)

Symptoms
General symptoms due to size may include:

Headache

Blurred vision or tunnel vision

Prolactin Secreting Adenoma symptoms (40% of all cases)

Milk production from nonlactating females

Loss of or irregular periods

Loss of sex drive

Vaginal dryness

Low bone density or osteoporosis

circulation---increase water permeability of kidney to

water reabsorption

Symptoms from Thyrotropin-secreting Adenoma

Decreased ADH release from pituitary

Enlarged thyroid (eg goiter)

Symptoms of hyperthyroidism
Decreased renal tubular permeability to water

Tremors

Heart palpitations

Anxiety

Weight loss

Insomnia

Corticotropin-secreting Adenoma Symptoms:

Menstrual disturbance

High blood pressure

High fasting glucose

Skin changes (increased facial hair, acne, bruising,

bluish stretch marks

Buffalo hump (increased fatty tissue in back)

Obesity especially around the wrist

Round face

Growth Hormone-secreting Adenoma

Acromegaly (adult)

Gigantism (child)

High blood pressure

High fasting blood sugar

Facial features coarse

Oily skin

Excess sweating

Decreased urine osmolality(inappropriate urine dilution) and

specific gravity

Marked polyuria (5 to 20 L/d of dilute urine (water,

SG of 1.000 to 1.005, & urine osmolality of 50 to 200
mOsm/kg.)
Nocturia, fatigue, dehydration, wt loss, poor skin
turgor, dry m.m., constipation, muscle weakness,
dizziness, tachycardia, hypotension

Polydipsia ( drinks 4 to 40 L /d; craving for cold

water.

High serum osmolality (above 295 mOsm) and high

serum sodium level (greater than 145 mEq/L).

SIADH
The syndrome of inappropriate antidiuretic hormone secretion
(SIADH)

Associated Conditions Pituitary Adenomas

Potentially life threatening condition that disturbs fluid and

electrolyte balance

Diabetes mellitus
Kidney stones
Cardiovascular disease

Causes

High blood pressure

Osteoporosis
Thyroid disease

http://www.med.nyu.edu/content?ChunkIID=96789

Diabetes Insipidus (DI)

Decreased water reabsorption

Neoplastic diseases( pancreatic, thymoma), CNS (brain tumor,

GBS)and pulmonary( pneumonia, tb) disorders, Drugs that
increase ADH production(antidepressants, NSAID)
Understanding SIADH
Excessive ADH secretion

Increased renal tubule permeability

D/O of water metabolism caused by

deficiency of ADH, also called vasopressin,
Antidiuretic hormone (ADH) prevents water loss in the
body by increasing the re-uptake of water in the kidneys
and reducing blood flow to sweat glands.
Pathophysiology and Etiology
Primary: idiopathic.
Secondary: head trauma, neurosurgery, tumors
(intracranial or metastatic), vascular disease
(aneurysms, infarct), infection (meningitis,
encephalitis).

Nephrogenic DI: long-standing renal disease,

hypokalemia, some medications.

Deficiency of ADH results in decreased renal water

reabsorption; it may be partial or complete.

Normally, ADH is synthesized in hypothalamus and

stored in posterior pituitary gland---release to

Increased water retention and expanded extracellular fluid

volume
Reduced plasma osmolality
Intracellular fluid shift\
Cerebral edema
Diminished aldosterone
secretion (regulate Na
and water)
Dilutional hyponatremia
Decreased Na
resorption
Increased
sodium secretion
Hyponatremia
Elevated glomerular filtration rate
Increased sodium secretion
Hyponatremia and electrolyte imbalance

S/sx
Thirst, anorexia, fatigue, lethargy, vomiting,
intestinal cramping, weight gain, edema, water
retention, and decreased urine output, neurologic
changes( restlessness, confusion, headache,
irritability, decreasing reflexes, and seizures)
decreased deep tendon reflexes

ALTERATION IN THYROID FUNCTION

GOITER
- enlargement of the thyroid gland and is not cancerous.
-The thyroid is a gland, shaped like a butterfly, located at the
base of the neck
-can have normal levels of thyroid hormone (euthyroidism),
excessive levels (hyperthyroidism) or levels that are too low
(hypothyroidism).
CAUSES
-lack of iodine
-imbalance in thyroid hormone
-nodules that develop in the gland
-common: females than males, all ages

Autoimmune disease (Hashimoto's

thyroiditis).
Use of radioactive iodine.

Destruction, suppression, or removal of all

or some of the thyroid tissue by
thyroidectomy.

Dietary iodide deficiency.

Subacute thyroiditis.

Lithium therapy.

Overtreatment with antithyroid drugs.

2. Secondary hypothyroidism is caused by inadequate

secretion of TSH caused by disease of the pituitary gland (ie,
tumor, necrosis).

Inadequate secretion of thyroid hormone leads to a

general slowing of all physical and mental processes.
General depression of most cellular enzyme systems
and oxidative processes occurs.
The metabolic activity of all cells of the body
decreases, reducing oxygen consumption, decreasing
oxidation of nutrients for energy, and producing less
body heat.

Types:
1. Diffuse small goiter - feels smooth.
2. Nodular goiter- feels lumpy

Clinical Manifestations
Fatigue and lethargy.
Weight gain.

Complaints of cold hands and feet.

Temperature and pulse become subnormal; patient

cannot tolerate cold and desires increased room
temperature.

Reduced attention span; impaired short-term memory.

Severe constipation; decreased peristalsis.

Generalized appearance of thick, puffy skin;

subcutaneous swelling in hands, feet, and eyelids.

Hair thins; loss of the lateral one-third of eyebrow.

Menorrhagia or amenorrhea; may have difficulty

conceiving or may experience spontaneous abortion;
decreased libido.

Neurologic signs include polyneuropathy (pins-andneedles sensation, numbness, burning pain, and loss
of vibration sense and position sense), cerebellar
ataxia(loss of coordination), muscle aches or
weakness, clumsiness, prolonged deep tendon
reflexes .

Hyperlipoproteinemia and hypercholesterolemia.

Enlarged heart on chest X-ray.

Increased susceptibility to all hypnotic and sedative

drugs and anesthetic agents.

S/SX
. swelling of the thyroid gland. Generally, painless
. Hoarseness (voice)

Coughing more frequently than usual

A feeling of tightness in the throat

Swallowing difficulties (less common)

Breathing difficulties (less common)

HYPOTHYROIDISM
-in adeq. amounts of thyroid hormone
The thyroid gland affects:
1. metabolic rate of all tissues,
2. speed of chemical reactions,
3. volume of oxygen consumed,
4. amount of heat produced.
Two hormones:
1. Levothyroxine (T4); maintains body's metabolism
in a steady state; T4 serves as a precursor of T3.
2.Triiodothyronine (T3) has a more rapid metabolic
action and utilization than T4 does.

Diagnostic Evaluation
Low T3 and T4 levels.
Elevation of serum cholesterol.

Electrocardiogram (ECG) sinus bradycardia, low

voltage of QRS complexes, and flat or inverted T
waves.

Pathophysiology and Etiology

1. Primary hypothyroidism (common)

HASHIMOTOS THYROIDITIS

Hashimoto's thyroiditis is a chronic progressive disease of the

thyroid gland caused by infiltration of lymphocytes; it results
in progressive destruction of the parenchyma and
hypothyroidism if untreated.
Pathophysiology and Etiology
Cause is unknown; autoimmune disease, genetically
transmitted
women in their 40s or 50s.
Clinical Manifestations
Marked by a slowly developing, firm enlargement of
the thyroid gland.
Usually no gross nodules.

Basal metabolic rate is usually low.

Periods of hyperthyroidism caused by large amounts

of T3 and T4 being released into bloodstream.

Diagnostic Evaluation``
T3 and T4 may be normal but usually become
subnormal as the disease progresses.
Antithyroglobulin antibodies and antimicrosomal
antibodies are present.

Normal or high concentration of thyroglobulinbinding protein.

Heat intolerance; profuse perspiration; flushed skin

(eg, hands may be warm, soft, moist).

Fine tremor of hands; change in bowel

habitsconstipation or diarrhea.

Increased appetite and progressive weight loss;

frequent stools.

Muscle fatigability and weakness; amenorrhea.

Atrial fibrillation possible (cardiac decompensation

common in older patients).

Bulging eyes (exophthalmos) seen only in Graves'

disease.

Thyroid gland may be palpable and a bruit may be

auscultated over gland.

Course may be mild, characterized by remissions and

exacerbations.

It may progress to emaciation, extreme nervousness,

delirium, disorientation, thyroid storm or crisis, and
death.

Thyroid storm or crisis, an extreme form of

hyperthyroidism, is characterized by hyperpyrexia,
diarrhea, dehydration, tachycardia, arrhythmias,
extreme irritation, delirium, coma, shock, and death if
not adequately treated.

Thyroid storm may be precipitated by stress (surgery,

infection) or inadequate preparation for surgery in a
patient with known hyperthyroidism.

HYPERTHYROIDISM
This hypermetabolic condition is characterized by excessive
amounts of thyroid hormone in the bloodstream.
Pathophysiology and Etiology
More common in women than in men
Graves' disease (most prevalent) diffuse
hyperfunction of the thyroid gland with autoimmune
etiology and associated with ophthalmopathy;.
TSI, an immunoglobulin found in the blood of patients with
Graves' disease, is capable of reacting with the receptor for
TSH on the thyroid plasma membrane and of stimulating
thyroid hormone production and secretion.
May appear after an emotional shock, an
infection, or emotional stress.
Toxic nodular goiter (single or multiple)more
common in older women with preexisting goiter; will
continue to be overactive unless eradicated or kept
under suppressive therapy.
o

Hyperthyroidism is characterized by hypertrophy and

hyperplasia of the thyroid gland, which is
accompanied by increased vascularity and blood flow
and enlargement of the gland.

Most of the clinical manifestations result from

increased metabolic rate, excessive heat production,
increased neuromuscular and cardiovascular activity,
and hyperactivity of the sympathetic nervous system.

Diagnostic Evaluation
Elevated T3 and T4.
Elevated serum T3 resin uptake.

131

I uptake scan may be elevated or below normal

depending on the underlying cause of the
hyperthyroidism.

GRAVES DISEASE
Graves disease, named after Robert J. Graves, MD,[1] circa
1830s, is an autoimmune disease characterized
by hyperthyroidism due to circulating autoantibodies.
Thyroid-stimulating immunoglobulins (TSIs) bind to and
activate thyrotropin receptors, causing the thyroid gland to
grow and the thyroid follicles to increase synthesis of thyroid
hormone.
Pathophysiology
Graves disease
B and T lymphocyte-mediated autoimmunity

Hyperthyroidism ranges from a mild increase in

metabolic rate to the severe hyperactivity known as
thyrotoxicosis, thyroid storm, or thyroid crisis.

directed thyroid antigens: thyroglobulin, thyroid peroxidase,

sodium-iodide symporter, and the thyrotropin
receptor(primary autoantigen of Graves disease).

Hyperthyroidism can also be the result of ingestion of

excessive amounts of thyroid hormone medication
(factitious hyperthyroidism).

The thyroid gland is under continuous stimulation by

circulating autoantibodies against the thyrotropin receptor,

Clinical Manifestations
Nervousness, emotional lability, irritability,
apprehension.
Difficulty in sitting quietly.

Rapid pulse at rest and on exertion (ranges between

90 and 160); palpitations.

pituitary thyrotropin secretion is suppressed because of the

increased production of thyroid hormones.
These thyroid-stimulating antibodies cause release of thyroid
hormone and thyroglobulin and they also stimulate iodine
uptake, protein synthesis, and thyroid gland growth.

ALTERATION IN PARATHYROID FUNCTION

DISORDERS OF THE PARATHYROID GLANDS
The parathyroid glands are small, bean-sized structures
embedded in the posterior section of the thyroid gland.
Functions include the production, storage, and release of
parathyroid hormone (PTH) in response to the serum level of
ionized calcium. PTH increases serum calcium by decreasing
elimination of calcium ions in the urine by the kidney,
increasing absorption of calcium ions from the gut, and
increasing bone contribution of calcium ions to the plasma.
HYPERPARATHYROIDISM
Hyperparathyroidism is hypersecretion of PTH.
Pathophysiology and Etiology

women older than age 50.

Primary hyperparathyroidism.

Single parathyroid adenoma (common )

Parathyroid hyperplasia accounts for

approximately 20% of cases.

Parathyroid carcinoma accounts for less than

1% of cases.

Primarily the result of renal failure.

Excess secretion of PTH results in increased serum

calcium levels

Clinical Manifestations
Decalcification of bones (Ca removal).
o Skeletal pain, backache, pain on weightbearing, pathologic fractures, deformities,
formation of bony cysts.

Formation of bone tumors overgrowth of

osteoclasts(break).

Formation of calcium-containing kidney

stones.

Malignancy or metastasis from a cancer to the

parathyroid glands.

Resistance to PTH action.

With inadequate PTH secretion, there is decreased

resorption of calcium from the renal tubules,
decreased absorption of calcium in the GI tract, and
decreased resorption of calcium from bone.

Blood calcium falls to a low level, causing symptoms

of muscular hyperirritability, uncontrolled spasms,
and hypo-calcemic tetany.

In response to decreased serum calcium levels and

lack of PTH, the serum phosphate level rises and
phosphate excretion by the kidneys decreases.

Clinical Manifestations
Tetany general muscular hypertonia; attempts at
voluntary movement result in tremors and spasmodic
or uncoordinated movements; fingers assume classic
tetanic position.
o Chvostek's sign a spasm of facial muscles
that occurs when muscles or branches of
facial nerve are tapped.

The patient may trip, drop objects, show

general fatigue, lose memory for recent
events, experience emotional instability,
have changes in level of consciousness, with
stupor and coma.

Cardiac arrhythmias, hypertension, cardiac

standstill.

Serum calcium and alkaline phosphatase levels are

elevated and serum phosphorus levels are decreased.

Skeletal changes are revealed by X-ray.

Early diagnosis typically is difficult. (Complications

may occur before this condition is diagnosed.)
computed tomography (CT) will disclose parathyroid
tumors more readily than X-ray.

HYPOPARATHYROIDISM

Trousseau's sign carpopedal spasm within 3

minutes after a BP cuff is inflated 20 mm Hg
above the patient's systolic pressure.

Laryngeal spasm.

Severe anxiety and apprehension.

Renal colic is usually present if the patient has

history of stones; preexisting stones loosen and
migrate into the ureter.

Depression of neuromuscular function.

Diagnostic Evaluation
Persistently elevated serum calcium (11 mg/100 mL);
test is performed on at least two occasions to
determine consistency of results.
PTH levels are increased.

Secondary hyperparathyroidism.
o

Hypoparathyroidism results from a deficiency of PTH and is

characterized by hypocalcemia and neuromuscular
hyperexcitability.
Pathophysiology and Etiology
The most common cause is accidental removal or
destruction of parathyroid tissue or its blood supply
during thyroidectomy or radical neck dissection for
malignancy.
Decrease in gland function (idiopathic
hypoparathyroidism); may be autoimmune or familial
in origin.

Diagnostic Evaluation
Phosphorus level in blood is elevated.
Decrease in serum calcium level to a low level (7.5
mg/100 mL or less).

PTH levels are low in most cases; may be normal or

elevated in pseudohypoparathyroidism.

ALTERATIONS IN ADRENAL GLAND FUNCTION

The adrenal medulla two hormones:
Epinephrine (adrenalin) increase contractility and
excitability of heart muscle, --- increased cardiac
output; --- blood flow to muscles, brain, and viscera;
enhances blood sugar by stimulating conversion of
glycogen to glucose in liver;
inhibits smooth muscle contraction.

Norepinephrine (noradrenaline) increase

peripheral vascular resistance ---increases in diastolic
and systolic BP.

The adrenal cortex secretes adrenocortical hormones

synthesized from cholesterol.

Buffalo hump (fat pad) in neck and supraclavicular

area.

Glucocorticoids (cortisone and hydrocortisone)

enhance protein catabolism and inhibit protein
synthesis;
antagonize action of insulin and increase blood sugar;

Rounded face (moon face); plethoric, oily.

increase synthesis of glucose by liver;

GI changes

influence defense mechanism of body and its

reaction to stress;

Increased gastric secretion and pepsin production- peptic

ulcer, abdominal pain, increased appetite, weight gain

influence emotional reaction.

Mineralocorticoids (aldosterone and

desoxycorticosterone)
regulate reabsorption of sodium; regulate excretion of
potassium by renal tubules.
Adrenosterones (adrenal androgens) exert minimal
effect on sex characteristics and function.

CUSHING'S SYNDROME
-plasma cortisol levels are elevated, causing signs and
symptoms of hypercortisolism.
-excessive anterior pituitary hormone corticotropin

Cardiovascular changes
Sodium and secondary fluid retention- hypertension, heart
failure, left ventricular hypertrophy
Protein loss- capillary weakness, bleeding, ecchymosis
Other changes
Altered neurotransmission-Mental disturbances mood
changes, irritability, psychosis,
Decreased lymphocyte production and suppressed
antibody formation- increased susceptibility to infection

Increased susceptibility to infections.

Cortisol(stress hormone)
Pathophysiology and Etiology
10 times more frequently in women than in men.
Cushing's syndrome are the result of excess
hormones (glucocorticoids, mineralocorticoids, and
adrenal androgens).

Excessive Androgen production

Women experience virilism (masculinization).
o Hirsutism excessive growth of hair on the
face and midline of trunk.

Prolonged exposure to pharmacologic doses of

exogenous glucocorticoids
Secretory adrenocortical tumors stimulating adrenal
cortex to increase corticotrophin production
---excessive levels of glucocorticoids
---adrenal hyperplasia, suppression of pituitary
corticotropin, and reduced hypothalamic secretion of
corticotropin releasing hormone

Clinical Manifestations
Excessive Glucocorticoids
Endocrine and metabolic changes
Cortisol induced insulin resistance and increased
glucogeneogenesis- DM, Decreased glucose tolerance, fasting
hyperglycemia, glucosuria

Musculoskeletal changes
Hypokalemia- muscle weakness

Breasts atrophy, amenorrhea,

oligomenorrhea

Clitoris enlargement.

Voice masculine.

Loss of libido.

If exposed in utero possible hermaphrodite.

Males loss of libido.

Excessive Mineralocorticoids
Hypertension.
Hypernatremia, hypokalemia.

Weight gain.

Expanded blood volume.

Edema.

Diagnostic Evaluation
Excessive plasma cortisol levels.
An increase in blood glucose levels and glucose
intolerance.

Decreased serum potassium level.

Reduced eosinophils.

Elevation of plasma ACTH in patients with pituitary

tumors.

Skin Changes

Low plasma ACTH levels with adrenal tumor.

Decreased collagen and weakened tissues

X-rays of the skull detect erosion of the sella turcica

by a pituitary tumor.

CT scan and ultrasonography detect location of

tumor.

Increased catabolism- loss of muscle mass

Decreased bone mineral ionization, osteopenia,
osteoporosis characteristic kyphosis, backache, skeletal
growth retardation- pathologic fractures

Fragile and thin skin, striae and ecchymosis, acne.

Heavy trunk; thin extremities.

A profound decline in blood levels of potassium

(hypokalemia) and hydrogen ions (alkalosis) results
in muscle weakness and inability of kidneys to
acidify or concentrate urine, leading to excess
volume of urine (polyuria).

A decline in hydrogen ions (alkalosis) results in

tetany, paresthesia.

An elevation in blood sodium (hypernatremia) results

in excessive thirst (polydipsia) and arterial
hypertension.

Normal responses to stress lacking.

Hyperpigmentation.

Adrenal Crisis
Primary adrenal hypofunction
Mineralocorticoid or glucocorticoid deficiency
Weakness, fatigue, weight loss, nausea, vomiting,
anorexia, decrease tolerance to stress, cardiovascular
abn (orthostatic hypotension, decreased cardiac size
and output, weak, irregular pulse) craving for salty
food lead to sodium retention

ADRENOCORTICAL INSUFFICIENCY (ADDISONS

DISEASE)
Adrenocortical insufficiency occurs with
-inadequate secretion of the hormones of the adrenal cortex,
primarily the glucocorticoids, mineralocorticoids and
androgens.
-impaired pituitary secretion of corticotrophin, decreased
glucocorticoid secretion although aldosterone secretion is
unaffected
Adrenal crisis (Addisonian crisis) adrenal hypofunction and
involves critical deficiency of mineralocorticoids and
glucocorticoids occurs after acute stress, sepsis, trauma,
surgery or omission of steroid therapy (life threatening)
Pathophysiology and Etiology
Primary adrenocortical insufficiency (Addison's disease) destruction and subsequent hypofunction of the
adrenal cortex, usually caused by autoimmune
process.
Secondary adrenocortical insufficiency ACTH
deficiency from pituitary disease or suppression of
hypothalamic-pituitary axis by corticosteroid
treatment for nonendocrine disorders causes atrophy
of adrenal cortex.

Decreased cortisol levels and simultaneous secretion

of excessive corticotrophin and melanocyte
stimulating hormone
Bronze skin coloring (hand and finger, elbows and
knees) darkening of scars. Absence of
pigmentation(vitiligo)
Decreased glucogenesis
Fasting hypoglycemia
Secondary adrenal crisis
Low corticotropin and melanocyte stimulating
hormone
Same with primary hypofunction but without
hyperpigmentation

Adrenal gland hypofunction

Absent or low cortisol levels
Liverdec. hepatic glucose outputhypoglycemia
Stomachreduced levels of digestive enzymes
vomiting, cramps, and diarrhea

Cortisol deficiency produces abnormal fat, protein,

and carbohydrate metabolism;

Absent or very low aldosterone levels

Kidneys -- sodium and water loss with potassium
retention-hypovolemia---shock
Heart--- arrhythmias and decreased cardiac output--hypotension---shock

Diagnostic Evaluation
Blood chemistry decreased glucose, decreased
sodium, increased potassium.
Increased lymphocytes on complete blood count.

PHEOCHROMOCYTOMA
Pheochromocytoma is a catecholamine-secreting neoplasm
associated with hyperfunction of the adrenal medulla.
Pathophysiology and Etiology
Pheochromocytoma can occur at any age, but is most
common between the ages of 30 and 60; it is
uncommon in people older than age 65.
Most pheochromocytoma tumors are benign; 10% are
malignant with metastasis.

Tumors located in the adrenal medulla produce both

increased epinephrine and norepinephrine; those
located outside the adrenal gland tend to produce
epinephrine only.

May occur as component of multiple endocrine

neoplasia II, an autosomal-dominant syndrome
characterized by pheochromocytoma, thyroid cancer,
hyperparathyroidism, and Cushing's syndrome with
excess ACTH.

Clinical Manifestations
Hyponatremia and hyperkalemia.
Water loss, dehydration, and hypovolemia.

Muscular weakness, fatigue, weight loss.

GI problems anorexia, nausea, vomiting, diarrhea,

constipation, abdominal pain.

Hypotension, hypoglycemia, low basal metabolic

rate, increased insulin sensitivity.

Mental changes depression, irritability, anxiety,

apprehension caused by hypoglycemia and
hypovolemia.

Low fasting plasma cortisol levels; low aldosterone

levels.

Clinical Manifestations
Variation in signs and symptoms depends on the
predominance of norepinephrine or epinephrine
secretion and on whether secretion is continuous or
intermittent.

Excess secretion of norepinephrine and epinephrine

produces hypertension, hypermetabolism, and
hyperglycemia.

Etiology: autoimmunity, viral, and certain

histocompatibility antigens as well as a genetic
component.

Hypertension may be paroxysmal (intermittent) or

persistent (chronic).

Usual presentation is rapid with classic symptoms of

polydipsia, polyphagia, polyuria, and weight loss.

Most commonly seen in patients under age 30 but can

be seen in older adults.

Chronic form mimics essential hypertension;

however, antihypertensives are not effective.

Headaches and vision disturbances are

common.

The hypermetabolic and hyperglycemic effects

produce excessive perspiration, tremor, pallor or face
flushing, nervousness, elevated blood glucose levels,
polyuria, nausea, vomiting, diarrhea, abdominal pain,
and paresthesia.

Emotional changes, including psychotic behavior,

may occur.

Symptoms may be triggered by allergic reactions,

physical exertion, emotional upset, or may occur
without identifiable stimulus.

Diagnostic Evaluation
Epinephrine and norepinephrine in urine and blood
are elevated while patient is symptomatic.
CT scan and magnetic resonance imaging (MRI) of
the adrenal glands or of the entire abdomen are done
to identify tumor.

Etiology: strong hereditary component, commonly

associated with obesity.

Usual presentation is slow and typically insidious

with symptoms of fatigue, weight gain, poor wound
healing, and recurrent infection.

Found primarily in adults over age 30; however, may

be seen in younger adults and adolescents who are
overweight.

Patients with this type of diabetes, but who

eventually may be treated with insulin, are still
referred to as having type 2 diabetes.

Clonidine suppression test is used to distinguish

essential hypertension from pheochromocytoma.

Diabetes Mellitus
INSULIN SECRETION AND FUNCTION
Insulin is a hormone secreted by the beta cells of the
islet of Langerhans in the pancreas.
Increased secretion or a bolus of insulin, released
after a meal, helps maintain euglycemia.

Type 2 Diabetes Mellitus

known as noninsulin dependent diabetes mellitus or adult
onset diabetes mellitus.
Caused by a combination of insulin resistance and
relative insulin deficiency some individuals have
predominantly insulin resistance, whereas others
have predominantly deficient insulin secretion, with
little insulin resistance.
Approximately 90% of diabetic patients have type 2.

blood glucose levels are maintained at a normal range

of 60 to 110 mg/dL.
Insulin is essential for the utilization of glucose for
cellular metabolism as well as for the proper
metabolism of protein and fat.
o

Carbohydrate metabolism insulin affects the

conversion of glucose into glycogen for
storage in the liver and skeletal muscles, and
allows for the immediate release and
utilization of glucose by the cells.
Protein metabolism amino acid conversion
occurs in the presence of insulin to replace
muscle tissue or to provide needed glucose
(gluconeogenesis).
Fat metabolism storage of fat in adipose
tissue and conversion of fatty acids from
excess glucose occurs only in the presence
of insulin.

Glucose can be used in the endothelial and nerve

cells without the aid of insulin.

Without insulin, plasma glucose concentration rises

and glycosuria results.

CLASSIFICATION OF DIABETES
Type 1 Diabetes Mellitus
known as insulin dependent diabetes mellitus and juvenile
diabetes mellitus.
Little or no endogenous insulin, requiring injections
of insulin to control diabetes and prevent
ketoacidosis.
Five to 10% of all diabetic patients have type 1.

Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is defined as
carbohydrate intolerance occurring during pregnancy.
Occurs in approximately 4% of pregnancies and
usually disappears after delivery.

Women with GDM are at higher risk for diabetes at a

later date.

GDM is associated with increased risk of fetal

morbidity.

Screening for GDM for all pregnant women other

than those at lowest risk (under age 25, of normal
body weight, have no family history of diabetes, are
not a member of an ethnic group with high
prevalence of diabetes) should occur between the
24th and 28th weeks of gestation.

DIABETES MELLITUS
Diabetes mellitus is a metabolic disorder characterized by
hyperglycemia and results from defective insulin production,
secretion, or utilization.
Pathophysiology and Etiology
Clinical Manifestations
Hyperglycemia
Weight loss, - prevention of normal metabolism of
carbo, protein, fats
Polyuria, polydipsia - high serum osmolality caused
by high serum glucose level

Polyphagia - to depleted cellular storage of

carbohydrates, fats and protein due to lack of insulin

Blurred vision- glucose induced swelling

Numbness and tingling- neural tissue damaged

Fatigue, headache, lethargy, reduced energy levellow intercellular glucose level

Muscle cramps, irritability, emotional labilityelectrolyte imbalance

of the pancreas supports exocrine function, and the remaining

20% is involved with endocrine function.

Abdominal discomfort and pain, nausea, diarrhea,

constipation- dehydration, electrolyte imbalance

Digestive enzymes are produced within the pancreatic acinar

cells, packaged into storage vesicles called zymogens, and
then released via the pancreatic ductal cells into the pancreatic
duct, where they are secreted into the small intestine to begin
the metabolic process.

Altered Tissue Response

Poor wound healing
Recurrent infections, particularly of the skin

Premature activation of pancreatic enzymes within the

pancreas leads to organ injury and pancreatitis

skin itching. Vaginal pruritus

Zymogen granules have an acidic pH and a low calcium

concentration, which are factors that guard against premature
activation until after secretion has occurred and extracellular
factors have triggered the activation cascade. Under various
conditions, disruption of these protective mechanisms may
occur, resulting in intracellular enzyme activation and
pancreatic autodigestion leading to acute pancreatitis.

Diagnostic Evaluation
o FBS of greater than or equal to 126 mg/dL
o Random blood glucose of greater than or
equal to 200 mg/dL with classic symptoms
(polyuria, polydipsia, polyphagia, weight
loss)

Capillary blood glucose values obtained by finger

stick samples tend to be higher than values in venous
samples.
o

Pathogenesis of acute pancreatitis

Predisposing factors

Pancreatitis

Extracellular: neural and vascular response(alcohol use,

gallstones, and certain drugs)

Signs and symptoms

Intracellular: intracellular digestive enzyme activation,

increased calcium signaling, and heat shock protein activation

Abdominal pain (cardinal symptom):

Characteristically dull, boring, and steady; usually sudden
in onset and gradually becoming more severe until reaching
a constant ache; most often located in the upper abdomen
and may radiate directly through to the back

Nausea and vomiting, sometimes with anorexia

Diarrhea
Patients may have a history of the following:

---injury to the acinar cell --- impairs the secretion of zymogen

granules

Recent operative or other invasive procedures

Family history of hypertriglyceridemia
Previous biliary colic and binge alcohol consumption
(major causes of acute pancreatitis)

Activated neutrophils then exacerbate the problem by

releasing superoxide (the respiratory burst) or proteolytic
enzymes. Finally, macrophages release cytokines that further
mediate local inflammatory responses.

Clinical manifestations:

Fever (76%) and tachycardia (65%); hypotension

Abdominal tenderness, muscular guarding (68%),
and distention (65%); diminished or absent bowel sounds
Jaundice (28%)
Dyspnea (10%); tachypnea; basilar rales, especially
in the left lung
In severe cases, hemodynamic instability (10%) and
hematemesis or melena (5%); pale, diaphoretic, and listless
appearance
Occasionally, extremity muscular spasm secondary to
hypocalcemia

These mediators of inflammation cause an increased

pancreatic vascular permeability, leading to hemorrhage,
edema, and eventually pancreatic necrosis. As the mediators
are excreted into the circulation, systemic complications can
arise, such as bacteremia due to gut flora translocation, acute
respiratory distress syndrome (ARDS), pleural effusions,
gastrointestinal (GI) hemorrhage, and renal failure.
The systemic inflammatory response syndrome (SIRS) can
also develop, leading to the development of systemic shock.
Eventually, the mediators of inflammation can become so
overwhelming to the body that hemodynamic instability and
death ensue.

Uncommon physical findings are associated with severe

necrotizing pancreatitis:

Diagnosis

Cullen sign (bluish discoloration around the

umbilicus resulting from hemoperitoneum)

Grey-Turner sign (reddish-brown discoloration along

the flanks resulting from retroperitoneal blood dissecting
along tissue planes); more commonly, patients may have a
ruddy erythema in the flanks secondary to extravasated
pancreatic exudate

Erythematous skin nodules, usually no larger than 1

cm and typically located on extensor skin surfaces;
polyarthritis
Pathophysiology
Normal pancreatic function
The pancreas is a gland located in the upper posterior
abdomen. It is responsible for insulin production (endocrine
pancreas) and the manufacture and secretion of digestive
enzymes (exocrine pancreas) leading to carbohydrate, fat, and
protein metabolism. Approximately 80% of the gross weight

Lysosomal and zymogen granule compartments fuse,

enabling activation of trypsinogen to trypsin
Intracellular trypsin triggers the entire zymogen
activation cascade
Secretory vesicles are extruded across the basolateral
membrane into the interstitium, where molecular fragments
act as chemoattractants for inflammatory cells

Serum amylase and lipase

Liver-associated enzymes
Blood urea nitrogen (BUN), creatine, and electrolytes
Blood glucose
Serum cholesterol and triglyceride
Diabetes Mellitus
INSULIN SECRETION AND FUNCTION
Insulin is a hormone secreted by the beta cells of the
islet of Langerhans in the pancreas.
Increased secretion or a bolus of insulin, released
after a meal, helps maintain euglycemia.

blood glucose levels are maintained at a normal range

of 60 to 110 mg/dL.

Insulin is essential for the utilization of glucose for

cellular metabolism as well as for the proper
metabolism of protein and fat.
o

Carbohydrate metabolism insulin affects the

conversion of glucose into glycogen

Protein metabolism amino acid conversion

occurs in the presence of insulin to replace
muscle tissue or to provide needed glucose
(gluconeogenesis).

Fat metabolism storage of fat in adipose

tissue and conversion of fatty acids from
excess glucose occurs only in the presence
of insulin.

CLASSIFICATION OF DIABETES
Type 1 Diabetes Mellitus
insulin dependent diabetes mellitus and juvenile diabetes
mellitus.
Etiology: autoimmunity, viral, and certain
histocompatibility antigens as well as a genetic
component.
polydipsia, polyphagia, polyuria, and weight loss.

Muscle cramps, irritability, emotional labilityelectrolyte imbalance

Abdominal discomfort and pain, nausea, diarrhea,

constipation- dehydration, electrolyte imbalance

Altered Tissue Response

Poor wound healing
Recurrent infections, particularly of the skin

skin itching. Vaginal pruritus

Diagnostic Evaluation
o FBS of greater than or equal to 126 mg/dL
o Random blood glucose of greater than or
equal to 200 mg/dL with classic symptoms
(polyuria, polydipsia, polyphagia, weight
loss)

Capillary blood glucose values obtained by finger

stick samples tend to be higher than values in venous
samples.
ALTERATION IN PANCREATIC
FUNCTION

under age 30 but can be seen in older adults.

Pancreatitis

Type 2 Diabetes Mellitus

noninsulin dependent diabetes mellitus or adult onset diabetes
mellitus.
Caused by insulin resistance and relative insulin
deficiency
90% of diabetic patients have type 2.

Etiology: strong hereditary, associated with obesity.

slow and typically insidious with symptoms of

fatigue, weight gain, poor wound healing, and
recurrent infection.

adults over age 30; however, may be seen in younger

adults and adolescents who are overweight.

Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) is defined as
carbohydrate intolerance occurring during pregnancy.
Occurs in approximately 4% of pregnancies and
usually disappears after delivery.

GDM is associated with increased risk of fetal

morbidity.

Screening for GDM should occur between the 24th

and 28th weeks of gestation.

Inflammation of the pancreas (acute and chronic)

Good prognosis when associated with biliary tract disease;
poor when associated with alcoholism
Mortality is high 60%
Causes
Acute pancreatitis
Cholelithiasis, alcohol abuse, abnormal organ structure,
metabolic or endocrine disorder, pancreatic cyst or tumors,
penetrating peptic ulcer, blunt trauma or surgical trauma,
drugs(glucocorticoids), kidney failure
Chronic pancreatitis
Alcohol abuse, Malnutrition, Heredity (rare)

Pathophysiology
Normal pancreatic function

DIABETES MELLITUS
Diabetes mellitus is a metabolic disorder characterized by
hyperglycemia and results from defective insulin production,
secretion, or utilization.

The pancreas is responsible for insulin production (endocrine

pancreas) and the manufacture and secretion of digestive
enzymes (exocrine pancreas) leading to carbohydrate, fat, and
protein metabolism.

Pathophysiology and Etiology

Digestive enzymes are produced within the pancreatic acinar

cells, packaged into storage vesicles called zymogens, and
then released via the pancreatic ductal cells into the pancreatic
duct, where they are secreted into the small intestine to begin
the metabolic process.

Clinical Manifestations
Hyperglycemia
Weight loss, - prevention of normal metabolism of
carbo, protein, fats
Polyuria, polydipsia - high serum osmolality caused
by high serum glucose level

Polyphagia - to depleted cellular storage of

carbohydrates, fats and protein due to lack of insulin

Blurred vision- glucose induced swelling

Numbness and tingling- neural tissue damaged

Fatigue, headache, lethargy, reduced energy levellow intercellular glucose level

Premature activation of pancreatic enzymes within the

pancreas leads to organ injury and pancreatitis
Zymogen granules have an acidic pH and a low calcium
concentration, which are factors that guard against premature
activation disruption of these protective mechanisms may
occur, resulting in intracellular enzyme activation and
pancreatic autodigestion leading to acute pancreatitis.
Pathogenesis of acute pancreatitis
Predisposing factors

Extracellular: neural and vascular response(alcohol use,

gallstones, and certain drugs)
Intracellular: intracellular digestive enzyme activation,
increased calcium signaling, and heat shock protein activation
---injury to the acinar cell --- impairs the secretion of zymogen
granules

Lysosomal and zymogen granule compartments fuse,

enabling activation of trypsinogen to trypsin
Intracellular trypsin triggers the entire zymogen
activation cascade
Secretory vesicles are extruded across the basolateral
membrane into the interstitium, where molecular fragments
act as chemoattractants for inflammatory cells
Activated neutrophils release proteolytic enzymes.
Macrophages release cytokines that further mediate local
inflammatory responses.
These mediators of inflammation cause an increased
pancreatic vascular permeability,
leading to hemorrhage, edema, and eventually pancreatic
necrosis.
As the mediators are excreted into the circulation, systemic
complications can arise, such as bacteremia due acute
respiratory distress syndrome (ARDS), pleural effusions,
gastrointestinal (GI) hemorrhage, and renal failure.
The systemic inflammatory response syndrome (SIRS) can
also develop, leading to the development of systemic shock.
Eventually, the mediators of inflammation can become so
overwhelming to the body that hemodynamic instability and
death ensue.
Change
Inflammation

Sign and symptoms

Low grade fever
Mid epigastric abdominal
pain (cardinal symptom)dull, boring, and steady;
usually sudden in onset and
gradually becoming more
severe until reaching a
constant ache; most often
located in the upper abdomen
and may radiate directly
through to the back
Muscle guarding

Hypermotility or paralytic
Diarrhea
ileus secondary to
pancreatitis or peritonitis
Nausea and persistent
vomiting,anorexia and
abdominal distention,
diminished or absent bowel
sounds
Heart failure

Crackles at lung bases

Circulating pancreatic
enzymes

Left pleural effusion, basilar

rales, dyspnea, tachypnea

Dehydration and possible

hypovolemia

Tachycardia, hypotension,
hemodynamic instability, pale,
diaphoretic, listless

Malabsorption

Extreme malaise, jaundice,

muscular spasm(hypocalcemia)

Uncommon physical findings are associated with severe

necrotizing pancreatitis:

Cullen sign (bluish discoloration around the

umbilicus resulting from hemoperitoneum)
Grey-Turner sign (reddish-brown discoloration
along the flanks resulting from retroperitoneal blood
dissecting along tissue planes); more commonly, patients
may have a ruddy erythema in the flanks secondary to
extravasated pancreatic exudate
Erythematous skin nodules, usually no larger than 1
cm and typically located on extensor skin surfaces;
polyarthritis
Diagnosis

Serum amylase and lipase

Liver-associated enzymes
Blood urea nitrogen (BUN), creatine, and electrolytes
Blood glucose
Serum cholesterol and triglyceride