ENDOCRINE SYSTEM

Endocrine glands include the hypothalamus, pituitary,

thyroid, parathyroids, adrenals, pancreas, ovaries, testes,
and pineal gland

Exocrine glands are not part of the endocrine system. They

secrete their substances into ducts that then empty into a
body cavity or onto a surface.

 Hormones are chemical substances produced in the

body that control and regulate the activity of
certain target cells or organs.
 Hormones act only on
cells that have
receptors specific to
that hormone, since
the shape of the
receptor determines
which hormone can
react with it.
 This is an example of the lock-and key model of
biochemical reactions.

 Lipid-soluble hormones are synthesized from

cholesterol and are produced by the adrenal
cortex, sex glands, and thyroid.
o Lipid-soluble hormones (steroids, thyroid)
are relatively small molecules that cross REGULATION OF HORMONAL SECRETION

the target cell membrane by simple  Simple Feedback

diffusion. o Negative feedback relies on the blood
 Water-soluble hormones (insulin, growth hormone level of a hormone or other chemical
[GH], and prolactin) have receptors on or in the compound regulated by the hormone (e.g.,
cell membrane. glucose).
o Water-soluble hormones circulate freely o Positive feedback is also used to regulate
in the blood to their target tissues, where hormone synthesis and release. The
they act. female ovarian hormone estradiol operates
o Water-soluble hormones are not by this type of feedback.
dependent on plasma proteins for  Nervous System Control: endocrine glands are
transport. directly affected by the activity of the nervous
system. Pain, emotion, sexual excitement, and
stress can stimulate the nervous system to
modulate hormone secretion.

CIRCADIAN RHYTHM

 This is an endogenous 24-hour rhythm that can be

driven and altered by sleep-wake or dark-light 24-
hour (diurnal) cycles.
 Hormone levels fluctuate predictably during these
cycles. For example, cortisol rises early in the day,
 declines toward evening, and rises again toward the
end of sleep to peak by morning. GH, thyroid-
stimulating hormone (TSH), and prolactin
secretions peak during sleep.
 The menstrual cycle is an example of a body
rhythm that is longer than 24 hours (ultradian).
These rhythms must be considered when
interpreting laboratory results for hormone levels.

DISORDERS OF ANTERIOR PITUITARY GLAND

ACROMEGALY

 Acromegaly is a rare condition characterized by an

overproduction of growth hormone (GH).
 Acromegaly most often occurs as a result of a
benign pituitary tumor (adenoma).
DISORDERS OF PITUITARY GLAND
 The excessive secretion of GH results in an
overgrowth of soft tissues and bones in the hands,
feet, and face.
 Because the problem develops after epiphyseal
closure, the bones of the arms and legs do not
grow longer.

Clinical Manifestations

Skeletal & Soft Tissue Changes

 Enlargement of hands and feet

 Joint pain (mild to crippling)
 Thickening and enlargement of bony and soft
tissues on the face, feet, and head
 Enlargement of the tongue → speech difficulties
 Deepened voice due to hypertrophy of vocal cords

Neurological & Sensory Effects

 Carpal tunnel syndrome

 Peripheral neuropathy
 Proximal muscle weakness
 Visual changes due to pressure on the optic nerve
from a pituitary adenoma
 Frequent headaches

Respiratory & Skin Changes

 Sleep apnea due to upper airway narrowing and

obstruction from increased pharyngeal soft tissues
  Thick, leathery, and oily skin o Used in conjunction with Pituitary
Irradiation or surgery to reduce the
Endocrine & Metabolic Effects
serum GH level
 Menstrual disturbances in women
 GH antagonizes insulin action → hyperglycemia
 Glucose intolerance leading to diabetes mellitus
 Symptoms: Polydipsia (increased thirst) and
polyuria (increased urination)
 Mobilization of stored fat → Increased free fatty
acid levels → Higher risk of atherosclerosis

Complications & Prognosis

 Reduced life expectancy by 5–10 years

Higher risk of:

 Cardiac disease
 Respiratory disease
 Diabetes mellitus
 Colorectal cancer
 Even with treatment, joint pain and deformities
often persist.

 Despite enlarged tissues muscle weakness is

common, and hypertrophied joints become painful
and stiff.
DISORDERS OF POSTERIOR PITUITARY GLAND
 Osteoporosis of the spine and joint pain develop.
 Many men experience erectile dysfunction, and
 The hormones secreted by the posterior pituitary,
women may have amenorrhea, increased facial hair.
antidiuretic hormone (ADH) and oxytocin, are
and deepened voices.
produced in the hypothalamus and then
DIAGNOSTICS:
transported and stored in the posterior pituitary
 Skull radiograph, MRI & CT reveals pituitary gland.
 ADH, also referred to as arginine vasopressin (AVP)
enlargement.
or vasopressin, plays a major role in the regulation
 Bone radiographs show thickened long bone and
of water balance and osmolarity.
skull.
 Radioimmunoassay shows increased plasma level of
GH. The two primary problems associated with ADH secretion
 Results of glucose tolerance test show the same or are a result of either overproduction or underproduction of
increased levels of GH. ADH.
 Overproduction or oversecretion of ADH results
MANAGEMENT: in a condition known as syndrome of inappropriate
antidiuretic hormone (SIADH).
 HYPOPHYSECTOMY removal of the Pituitary  Underproduction or undersecretion of ADH
Gland results in a condition referred to as diabetes
 Consequent destruction of the pituitary by insipidus (DI).
Radiation Therapy.
 DOC: Bromocriptine Mesylate (Parlodel)
o Inhibits the release of GH
  Urinary & Weight Changes:

o Low urine output

o Increased body weight

 Severe Symptoms (Serum Sodium < 120 mEq/L):

o Vomiting

o Abdominal cramps

o Muscle twitching

o Seizures

 Neurological Effects (Progressive Hyponatremia

& Cerebral Edema):

o Lethargy

SYNDROME OF INAPPRPRIATE ANTIDIURETIC o Confusion

HORMONE (SIADH)
o Headache
 SIADH results from abnormally high production or
o Seizures
sustained secretion of ADH.
 In SIADH, ADH is released despite normal or low o Coma
plasma osmolarity
 This disorder is characterized by fluid retention,
serum hypoosmolality, dilutional hyponatremia,
hypochloremia, concentrated urine in the presence
of normal or increased intravascular volume, and
normal renal function.

Clinical Manifestations

 Early Symptoms:

o Thirst

o Dyspnea on exertion

o Fatigue

 Fluid & Electrolyte Imbalance:

o Increased permeability of renal distal

tubule & collecting duct → water
reabsorption DIABETES INSIPIDUS

o Expansion of extracellular fluid volume  Diabetes insipidus (DI) is caused by a deficiency

of production or secretion of ADH or a decreased
o Decline in plasma osmolality
renal response to ADH.
o Increased glomerular filtration rate  The decrease in ADH results in fluid and
electrolyte imbalances caused by increased urine
o Dilutional hyponatremia (low sodium levels)
output and increased plasma osmolality
→ muscle cramping, pain, weakness
 Depending on the cause, DI may be transient or a
chronic, lifelong condition.
 Central DI (caused by head trauma, intracranial surgery,
or brain tumors):

 Acute onset with excessive fluid loss

 Triphasic pattern after intracranial surgery:
 Acute phase: Abrupt onset of polyuria
 Interphase: Temporary normalization of urine
output
 Permanent phase: Central DI becomes permanent
(occurs 10–14 days post-op)
 DI caused by head trauma is often self-limiting,
while DI from cranial surgery is more likely to be
permanent.

Nephrogenic DI (caused by renal insensitivity to ADH):

 Clinical manifestations similar to central DI

 Less dramatic onset and lower fluid loss compared
to central DI

Complications of Severe DI

 If oral fluid intake cannot compensate for urine

loss:
 Severe dehydration:
o Poor skin turgor
o Hypotension
o Tachycardia
o Hypovolemic shock

Neurological Symptoms (due to hypernatremia &

increased serum osmolality):

 Irritability
 Mental dullness
 Coma
Clinical Manifestations:

 Polydipsia (excessive thirst) DISORDERS OF THYROID GLAND

 Polyuria (excretion of large amounts of urine, 2–20
L/day)  Alterations in thyroid function are among the most
 Compensatory Mechanism: common endocrine disorders.
o Most patients drink large amounts of  The thyroid hormones, thyroxine (T4) and
water, helping maintain normal or triiodothyronine (T3), regulate energy metabolism
moderately elevated serum osmolality and growth and development.
 Disorders of the thyroid gland include goiter,
General Symptoms: benign and malignant nodules, inflammation,

 Fatigue (due to nocturia) hyperthyroidism, and hypothyroidism

 Generalized weakness
 Clinical Manifestations

General Effects of Excess Thyroid Hormone

 Increased metabolism

 Enhanced tissue sensitivity to sympathetic nervous

system stimulation

Thyroid Gland Examination Findings

 Goiter:

o Palpable enlargement of the thyroid gland

o May be visible if excessively large

 Bruits on auscultation:

o Indicates increased blood supply to the

thyroid
HYPERTHYROIDISM
Ophthalmopathy (Eye Abnormalities)

 Hyperthyroidism is hyperactivity of the thyroid  Exophthalmos (Classic in Graves’ Disease):

gland with sustained increase in synthesis and
release of thyroid hormones. o Bilateral protrusion of the eyeballs
 The most common form of hyperthyroidism is
o Due to increased fat deposits and fluid
Graves’ disease.
(edema) in orbital tissues and muscles
 Other causes include toxic nodular goiter,
thyroiditis, excess iodine intake, pituitary tumors, o Increased pressure forces the eyeballs
and thyroid cancer. outward
 The term thyrotoxicosis refers to the physiologic
 Eye-Related Complications:
effects or clinical syndrome of hypermetabolism
that results from excess circulating levels of T4, o Upper eyelid retraction and elevation →
T3, or both. visible sclera above the iris
 Hyperthyroidism and thyrotoxicosis usually occur
o Incomplete eyelid closure → dry and
together, as seen in Graves’ disease.
irritated corneas

o Risk of corneal ulcers and vision loss

o Ocular muscle changes → muscle

weakness and diplopia (double vision)

Early & Systemic Symptoms

 Early signs:

o Weight loss

o Increased nervousness

 Cardiovascular & Neuromuscular Symptoms:

o Palpitations

o Tremors
Advanced & Severe Symptoms SECONDARY & TERTIARY HYPERTHYROIDISM

 Acropachy: Clubbing of the digits (advanced  A pituitary tumor that secretes TSH, amiodarone
disease) toxicity, and struma ovarii, an ovarian tumor that
secretes thyroid hormone.
Complications
 Other causes include toxic nodular goiter,
Thyrotoxicosis (also called Thyrotoxic Crisis or Thyroid thyroiditis, excess iodine intake, pituitary tumors,
Storm) and thyroid cancer.
 Thyrotoxicosis refers to the physiologic effects
 Is Acute, severe, and rare condition caused by
or clinical syndrome of hypermetabolism that
excessive thyroid hormone release
results from excess circulating levels of T4, T3, or
 Life-threatening emergency but rarely fatal if both.
treated early
HYPOTHYROIDISM
 Common triggers (stressors):
 Hypothyroidism is a deficiency of thyroid
o Infection hormone that causes a general slowing of the
metabolic rate.
o Trauma
 Hypothyroidism is more common in women than
o Surgery (especially thyroidectomy, due to men.
gland manipulation)  Hypothyroidism can be classified as primary or
secondary
PRIMARY HYPERTHYROIDISM
PRIMARY HYPOTHYROIDISM
 A toxic nodule is a thyroid nodule that becomes
independent of the pituitary and secretes excess  Primary hypothyroidism is caused by
thyroid hormone. destruction of thyroid tissue or defective
 Graves' disease is an autoimmune disorder that hormone synthesis.
causes hyperthyroidism. In autoimmune disorders,  A Hashimoto's Thyroiditis is an autoimmune
the body produces antibodies against some part of disease. It occurs with other autoimmune
itself. disease.
 Iodine Deficiency causes hypothyroidism
because Iodine is necessary for thyroid
hormone synthesis.
SECONDARY & TERTIARY HYPOTHYROIDISM manifestations of severe, pounding headache;
tachycardia with palpitations; profuse sweating;
 Secondary hypothyroidism can result from
and unexplained abdominal or chest pain.
pituitary pathology such as infection,
inflammation, infiltration. hemorrhage, or
tumor (either a non-functioning tumor within
the pituitary or a brain tumor impinging upon
it).
 Tertiary hypothyroidism can be caused by
hypothalamic under-activity or tumor.

Clinical Manifestations

 Fatigue, lethargy
 Impaired memory, slowed speech, decreased
initiative
 Somnolence (excessive sleepiness)
 Depression
 Weight gain due to a decreased metabolic rate
 Decreased cardiac contractility & output DISORDERS OF ADRENAL CORTEX

 Low exercise tolerance  Adrenal cortex steroid hormones have three main
 Shortness of breath on exertion classifications: glucocorticoids, mineralocorticoids,
 Risk of cardiovascular complications, especially in and androgens.
patients with preexisting heart disease  Glucocorticoids regulate metabolism, increase
 Anemia (low or normal erythropoietin levels) blood glucose levels, and are critical in the
 Easy bruising physiologic stress response.
 Increased serum cholesterol & triglycerides →  The primary glucocorticoid is cortisol.
Risk of coronary atherosclerosis  Mineralocorticoids regulate sodium and potassium
 Myxedema (Severe Hypothyroidism) balance.
o Physical changes:  The primary mineralocorticoid is aldosterone.
o Puffiness  Androgens contribute to growth and development
o Facial & periorbital edema in both genders and to sexual activity in adult
o Masklike appearance women.
 The term corticosteroid refers to any one of

DISORDERS OF ADRENAL MEDULLA these three types of hormones produced by the

adrenal cortex.
PHEOCHROMOCYTOMA

 Pheochromocytoma, which is a rare condition

caused by a tumor in the adrenal medulla affecting
the chromaffin cells, results in an excess
production of catecholamines (epinephrine,
norepinephrine).
 The most dangerous immediate effect of the
disease is severe hypertension.
 If left untreated, it may lead to hypertensive
encephalopathy, diabetes mellitus, cardiomyopathy,
and death.
 The most striking clinical features of
pheochromocytoma are severe, episodic
hypertension accompanied by the classic
 CUSHING SYNDROME

 Cushing syndrome is a
clinical condition that
results from chronic
exposure to excess
corticosteroids,
particularly
glucocorticoids.
 Several conditions can
cause Cushing syndrome.
 The most common cause is
iatrogenic administration
of exogenous corticosteroids (e.g., prednisone).
 Other causes of Cushing syndrome include adrenal OTHER Causes:
tumors and ectopic ACTH production by tumors (usually
of the lung or pancreas) outside of the hypothalamic-  Over-stimulation of the adrenal glands by an

pituitary-adrenal axis. ectopic ACTH producing tumor.

 Cushing disease and primary adrenal tumors are more  The most common site of ectopic production is a

common in women in the 20- to 40-year-old age-group. small cell lung cancer, though other cancers can

 Ectopic ACTH production is more common in men. produce ACTH as well.

 Cushing's syndrome is any state which creates
Clinical Manifestations pathologic hypercortisolism. Cushing's disease is
the specific case of hypercortisolism resulting
 The first indication of Cushing syndrome may be the
from an ACTH-secreting pituitary adenoma.
clinical presentation, including
 (1) centripetal (truncal) obesity or generalized obesity;
 (2) “moon face” (fullness of the face) with facial
plethora;
 (3) purplish red striae (usually depressed below the
ADDISON’S DISEASE
skin surface) on the abdomen, breast, or buttocks
 (4) hirsutism in women;  Adrenocortical insufficiency (hypofunction of the
 (5) menstrual disorders in women; adrenal cortex) may be from a primary cause
 (6) hypertension; and (Addison’s disease) or a secondary cause (lack of
 (7) unexplained hypokalemia. pituitary ACTH secretion).
 In Addison’s disease, all three classes of adrenal
corticosteroids (glucocorticoids,
mineralocorticoids, and androgens) are reduced.
 In secondary adrenocortical insufficiency,
corticosteroids and androgens are deficient but
mineralocorticoids rarely are.
 ACTH deficiency may be caused by pituitary
disease or sup pression of the hypothalamic-
pituitary axis because of the administration of
exogenous corticosteroids.
 • Decreased ACTH secretion in either scenario
decreases cortisol secretion from the adrenal
gland, but the rest of the adrenal still functions
normally. Thus, there is no hyperkalemia in
secondary and tertiary adrenal insufficiency.

DISORDERS OF PARATHYROID GLANDS

HYPERPARATHYROIDISM

 Hyperparathyroidism is a condition involving an

increased secretion of parathyroid hormone (PTH).
 PTH helps regulate serum calcium and phosphate
levels by stimulating bone resorption of calcium,
renal tubular reabsorption of calcium, and
activation of vitamin D.
PRIMARY ADRENAL INSUFFICIENCY

• Autoimmune Disease

• Polyglandular autoimmune syndrome Type 1

(HAM: hypoparathyroidism, adrenal insufficiency,
mucocutaneous candidiasis)
• Polyglandular autoimmune syndrome Type 2:
(Adrenal insufficiency with either autoimmune
thyroid disease or insulin-dependent diabetes
mellitus with possible vitiligo, premature ovarian
failure, and/or pernicious anemia)

• Waterhouse Friedrichsen Syndrome

PRIMARY HYPERPARATHYROIDISM

• Excess secretion of PTH by the parathyroid glands.

Increase PTH will raise blood Calcium level.

• Because PTH induces release of calcium from bone,

alkaline phosphatase can be elevated, as in any cause of
bone breakdown.

SECONDARY & TERTIARY HYPERPARATHYROIDISM

SECONDARY & TERTIARY ADRENAL INSUFFICIENCY  The parathyroid glands are not under control of
the pituitary. PTH secretion is regulated entirely
• Pituitary lesions or tumors can lead to secondary
by calcium con centration. So secondary
adrenal insufficiency due to decreased ACTH
hyperparathyroidism is not related to the pituitary
secretion.
as with other secondary endocrine diseases, but
• Hypothalamic lesions or tumors can cause
rather to blood calcium concentration.
tertiary adrenal insufficiency due to decreased
 Vitamin D deficiency or renal failure (which causes
CRII stimulation of ACTII release from the
hypocalcemia secondary to decreased vitamin D
pituitary.
activation.
 Tertiary Hyperparathyroidism occurs when VITAMIN D DEFICIENCY
secondary hyperparathyroidism persists
inappropriately after the resolution of the renal
failure or after renal transplantation.

HYPOPARATHYROIDISM

 Hypoparathyroidism is an uncommon condition

associated with inadequate circulating PTH. It is
characterized by hypocalcemia resulting from a
lack of PTH to maintain serum calcium levels.
 PTH resistance at the cellular level may also occur
(pseudohypoparathyroidism). This is caused by a
genetic defect resulting in hypocalcemia in spite of
normal or high PTH levels and is often associated
with hypothyroidism and hypogonadism.
 Surgical damage I removal of the parathyroids,
for example from thyroid surgery
 Magnesium (a 2+ ion like calcium), which affects
the parathyroids' secretion of PTH; hypo- or
hypermagnesemia can lead to hypocalcemia.
 Infiltrative disease of the parathyroids (e.g.,
Wilson's disease)
 Metastases to the parathyroids

HUNGRY BONE SYNDROME

 Congenital absence of the parathyroids (e.g.,

DiGeorge Syndrome is a problem with the third
and fourth branchial pouches in which the thymus
and parathyroids are absent).
 Autoimmune destruction of the parathyroids in
rare diseases such as HAM (hypoparathyroidism,
adrenal insufficiency, mucocutaneous candidiasis)
and APECED (autoimmune polyendocrinopathy
candidiasis, ectodermal dystrophy).
 Familial (i.e., genetic) hypoparathyroidism.