BIO 329: Biochemical Endocrinology

Lecture 9

Endocrine Disorders

Dr. Olunga M.S

 Causes of Endocrine Disorders

Endocrine disorders are of two categories:

1) Hormone imbalance that results when a gland produces too much or too little of an
endocrine hormone.
2) Development of lesions (such as nodules or tumors) in the endocrine system, which
may or may not affect hormone levels.
 The endocrine's feedback system helps control the balance of hormones in the
bloodstream. If the body has too much or too little of a certain hormone, the feedback
system signals the proper gland or glands to correct the problem.
 A hormone imbalance may occur if this feedback system has trouble keeping the right
level of hormones in the bloodstream, or if the body doesn't clear them out of the
bloodstream properly.

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 Causes of Hormone imbalance

Increased or decreased levels of endocrine hormone may be caused by:

 A problem with the endocrine feedback system
 Disease
 Failure of a gland to stimulate another gland to release hormones (for example, a problem
with the hypothalamus can disrupt hormone production in the pituitary gland)
 A genetic disorder, such as multiple endocrine neoplasia (MEN) or
congenital hypothyroidism
 Infection
 Injury to an endocrine gland
 Tumor of an endocrine gland

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 Types of Endocrine Disorders

Diabetes Mellitus
Arises from defects in insulin production or action.
There are two major clinical classes of diabetes mellitus:
 type I diabetes, or insulin-dependent diabetes mellitus (IDDM),
 type II diabetes, or non-insulin-dependent diabetes mellitus (NIDDM), also called
insulin-resistant diabetes.
In type I diabetes, the disease begins early in life and quickly becomes severe. This disease
responds to insulin injection, because the metabolic defect stems from the pancreatic β-cells
and a consequent inability to produce sufficient insulin. IDDM requires insulin therapy and
careful, lifelong control of the balance between dietary intake and insulin dose.

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 Diabetes Mellitus

In type II diabetes the regulatory activity of insulin is defective: insulin is produced, but
some feature of the insulin-response system is defective. These individuals are insulin-
resistant. Type II diabetes is slow to develop (typically in older, obese individuals), and the
symptoms are milder and often go unrecognized at first.
Characteristic symptoms of type I and type II diabetes are excessive thirst and frequent
urination (polyuria), leading to the intake of large volumes of water (polydipsia) (“diabetes
mellitus” means “excessive excretion of sweet urine”). These symptoms are due to the
excretion of large amounts of glucose in the urine, a condition known as glucosuria.

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 Diabetes Mellitus

Individuals with either type of diabetes are unable to take up glucose efficiently from the
blood; insulin triggers the movement of GLUT4 glucose transporters to the plasma
membrane of muscle and adipose tissue.
Another characteristic metabolic change in diabetes is excessive but incomplete oxidation of
fatty acids in the liver. Insulin secretion reflects both the size of fat reserves (adiposity) and
the current energy balance (blood glucose level). Insulin acts on insulin receptors in the
hypothalamus to inhibit eating. Insulin also signals muscle, liver, and adipose tissues to
increase catabolic reactions, including fat oxidation, which results in weight loss.

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 Diabetes Insipidus

Diabetes insipidus occurs when the body can't properly balance the body's fluid levels.
Anti-diuretic hormone (ADH), or vasopressin, is needed for the fluid that's filtered by the
kidneys to go back into the bloodstream. ADH is produced in the hypothalamus and stored
in the pituitary gland, Conditions that cause a deficiency of ADH or block the effect of ADH
result in production of excess urine.

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 Diabetes Insipidus

Types include
• Central diabetes insipidus. Damage to the pituitary gland or hypothalamus from surgery,
a tumor, head injury or an inherited genetic disease also can cause this condition.
• Nephrogenic diabetes insipidus. Occurs when there's a defect in the structures in the
kidneys that makes the kidneys unable to properly respond to ADH.The defect may be
due to an inherited (genetic) disorder or a chronic kidney disorder. Certain drugs, such as
lithium or antiviral medications such as foscarnet (Foscavir), also can cause nephrogenic
diabetes insipidus.
• Gestational diabetes insipidus. Gestational diabetes insipidus is rare. It occurs only
during pregnancy when an enzyme made by the placenta destroys ADH in the mother.
• Primary polydipsia/dipsogenic diabetes insipidus, is a condition that can cause
production of large amounts of diluted urine from drinking excessive amounts of fluids.
Primary polydipsia can be caused by damage to the thirst-regulating mechanism in the
hypothalamus. The condition has also been linked to mental illness, such as
schizophrenia.

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 Adrenal insufficiency

Hormones produced in the adrenal glands include cortisol, adrenaline and aldosterone.
Production that is too much or too little can result in adrenal disorders that affect the way
the body functions.
• Addison’s disease, also called adrenal insufficiency. In this disorder, the adrenal gland
does not produce enough cortisol and/or aldosterone.
Signs and symptoms may include:
• Extreme fatigue, Weight loss and decreased appetite, Darkening of your skin
(hyperpigmentation), Low blood pressure, even fainting, Salt craving, Low blood sugar
(hypoglycemia), Nausea, diarrhea or vomiting (gastrointestinal symptoms), Abdominal
pain, Muscle or joint pains, Irritability, Depression or other behavioral symptoms, Body
hair loss or sexual dysfunction in women.

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 Adrenal insufficiency

• Cushing’s disease. Overproduction of a pituitary gland hormone leads to an overactive

adrenal gland In this disorder, the levels of cortisol are too high. This term can be applied
when large doses of steroids are given to treat certain medical conditions.
Symptoms of high levels of cortisone (Cushing’s disease) include:
Upper body obesity, while arms and legs stay thinner. (A common trait called a Buffalo
hump refers to a lump in between the shoulders.), Being tired and confused, Developing
high blood pressure and diabetes, Skin that bruises easily, Wide purplish streak marks on
the abdominal skin.

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 Adrenal insufficiency

• Congenital adrenal hyperplasia, refers to genetic condition in which the adrenal glands
are not able to make cortisol well. As a result ACTH is elevated. Depending on the defect
higher levels of male hormone might be made.
• Adrenal gland suppression. This is a type of adrenal insufficiency that is related to
outside sources of cortisol or related synthetic hormones such as prednisone or
dexamethasone.
• Hyperaldosteronism. In this condition, the body produces too much aldosterone which
can lead to blood pressure elevation and potassium loss.
• Virilization. This condition happens when the body produces too much of the male sex
hormones and is only apparent in females or boys before puberty

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 Adrenal gland related tumors

These include:
• Adrenal gland tumors. Tumors can disrupt hormone output, but are usually
noncancerous.
• Adrenocortical carcinoma. This rare condition refers to cancer forming in the adrenal
gland’s outer layer.
• Pheochromocytoma. In this condition, the glands makes too much epinephrine and
norepinephrine which can raise blood pressure.
• Pituitary tumours. Abnormal growth on the pituitary gland can cause adrenal gland
conditions by disrupting the amount of hormones made by the adrenal glands. ACTH
producing tumors cause Cushing’s disease. If tumors are large enough, they may press on
the normal pituitary cells and cause deficiency of ACTH and secondary adrenal
insufficiency.

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 Types of Endocrine Disorders

Gigantism (acromegaly) and other growth hormone problems. If the pituitary gland
produces too much growth hormone, a child's bones and body parts may grow abnormally
fast. If growth hormone levels are too low, a child can stop growing in height.
Hyperthyroidism. The thyroid gland produces too much thyroid hormone, leading to
weight loss, fast heart rate, sweating, and nervousness. The most common cause for an over
active thyroid is an autoimmune disorder called Grave's disease.
Hypothyroidism the thyroid gland does not produce enough thyroid hormone, leading to
fatigue, constipation, dry skin and depression. The underactive gland can cause slowed
development in children. Some types of hypothyroidism are present at birth.

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 Types of Endocrine Disorders

Hypopituitarism. The pituitary gland releases little or no hormones. It may be caused by a

number of different diseases. Women with this condition may stop getting their periods.
Multiple endocrine neoplasia I and II (MEN I and MEN II). These rare, genetic conditions
are passed down through families. They cause tumors of the parathyroid, adrenal, and
thyroid glands, leading to overproduction of hormones.
Polycystic ovary syndrome (PCOS). Overproduction of androgens interfere with the
development of eggs and their release from the female ovaries. PCOS is a leading cause of
infertility.
Precocious puberty. Abnormally early puberty that occurs when glands tell the body to
release sex hormones too soon in life.

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