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Chapter 18: Alterations of Hormonal Regulation
Mechanisms that can cause target cells to fail to respond to hormones include:
1. Cell surface receptor-associated disorders
o
Most commonly caused by interruption of the connection between the hypothalamus and pituitary,
the pituitary stalk (infundibulum).
Antidiuretic hormone - controls serum osmolality, increases permeability of the renal tubules to
water, and causes vasoconstriction when administered pharmacologically in high doses.
Hypersecretion of ADH
High ADH levels interfere with renal free water clearance, leading to abnormally concentrated
urine, and dilute blood plasma (hypoosmolality), especially sodium (hyponatremia).
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o
2. Diabetes insipidus
o
Insufficiency of ADH
Low ADH levels cause formation of large quantities of dilute urine, and increased plasma
concentration (hyperosmolality). Dehydration results.
Three types:
1. Neurogenic - caused by insufficient amounts of ADH
Due to damage to the hypothalamus or pituitary.
2. Nephrogenic - caused by an inadequate response to ADH
Due to diseases that damage renal tubules (example pyelonephritis) or drugs such as
methoxyflurane anesthesia, lithium, or demeclocycline.
3. Psychogenic (primary polydipsia) caused by excessive intake of fluids
Due to psychological disorders
2. Hyperpituitarism
o
Manifestations:
Headache and fatigue
Visual changes
Hyposecretion of neighboring anterior pituitary hormones due to pressure atrophy
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1. Hypersecretion of growth hormone (GH)
Acromegaly - hypersecretion of GH during adulthood (after closure of epiphyseal plates)
Proliferation of connective tissue and bony matrix creates course facial features, large
hands and feet, etc.
Long term hypersecretion of GH causes hypertension, renal, thyroid, and reproductive dysfunction.
2. Hypersecretion of prolactin
Caused by prolactinomas most common hormone-secreting pituitary tumor
Manifestations:
Increase in metabolic rate and heat production (causes flushed skin and perspiration)
Increased heart rate and cardiac dysrhythmias; heart failure (in extreme cases)
Weight loss
2. Graves disease
o
Ocular symptoms - infiltration of the orbital contents causes orbital edema, which produces
protruding eyes (exophthalmos), muscle palsies, and damage to the optic nerve.
Pretibial myxedema - caused by infiltration of subcutaneous tissues of the anterior lower leg
which results in a doughy edema.
Treatment includes partial thyroidectomy or ablation of the gland with radioactive iodine.
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3. Thyrotoxic crisis (thyroid storm)
o
Rare but dangerous worsening of the thyrotoxic state, in which death occurs within 48 hours
without treatment.
Usually occurs in individuals who have undiagnosed or partially treated Graves disease and are
subjected to excessive stress, Including:
Surgery, infection, pulmonary or cardiovascular disorders, emotional distress, physical stress.
Manifestations:
B. Hypothyroidism
Size of thyroid gland varies, depending on cause; may be small, normal or enlarged.
Weaker, more sluggish muscle contractions, which cause constipation and decreased
cardiac contractility
Myxedema
Characteristic sign of severe of long-standing hypothyroidism.
Altered composition of the dermis and other tissues.
Produces a nonpitting, boggy edema, especially around the eyes, hands, and feet.
1. Primary hypothyroidism
o
Loss of thyroid tissue leads to decreased production of TH (low T3 and T4), increased secretion of
TSH, and goiter.
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a. Acute thyroiditis - inflammation of the thyroid gland, often caused by a bacterium, that can result
in hypothyroidism.
b. Subacute thyroiditis - self-limiting nonbacterial inflammation of the thyroid gland.
Inflammatory process damages follicular cells, causing leakage of T3 and T4.
Hyperthyroidism then is followed by transient hypothyroidism, which is corrected by cellular
repair and a return to normal levels in the thyroid.
c.
2. Secondary hypothyroidism
o
3. Myxedema coma
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4. Congenital hypothyroidism
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C. Thyroid carcinoma
Relatively rare.
Typically discovered as a small thyroid nodule or metastatic tumor in the lungs, brain, or bone.
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IV. Alterations of Parathyroid Function
Parathyroid hormone (PTH) helps to maintain normal serum calcium levels by stimulating the
breakdown of bone and by increasing renal and gastric absorption of calcium.
A. Hyperparathyroidism
1. Primary hyperparathyroidism
o
Manifestations:
Very high serum levels of calcium cause neurologic, gastric, and muscular dysfunction.
Bone resorption leads to osteopenia, osteoporosis, bone fragility, and pathologic fractures.
Hypercalcemia and hypercalciuria can contribute to the formation of renal calculi.
2. Secondary hyperparathyroidism
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B. Hypoparathyroidism
Abnormally low PTH level causes inability to maintain normal serum calcium levels.
Lack of PTH causes depressed serum calcium levels, increased serum phosphate levels, decreased
bone resorption, and eventual hypocalciuria.
Lowered threshold for nerve and muscle excitation, causing muscle spasms, hyperreflexia,
clonic-tonic convulsions, laryngeal spasms, and, in severe cases, death by asphyxiation.
Classic signs and symptoms are often present as well (polyuria, polydipsia, polyphagia).
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1. Type 1 Diabetes Mellitus
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Results from a severe, absolute lack of insulin caused by loss of pancreatic beta cells.
Manifestations:
Hyperglycemia, polydipsia, polyuria, polyphagia, weight loss, and fatigue.
Exercise allows uptake of glucose without insulin, so can cause hypoglycemia or reduce insulin
requirement.
Triggered by environmental factors, including obesity, poor diet, and lack of exercise.
Pathophysiology:
In the obese, insulin has a diminished ability to influence glucose uptake and metabolism
(insulin resistance of target tissues).
Some insulin production continues in type 2 diabetes mellitus, but the size and number of
beta cells decrease. Initially insulin secretion may be high, but it declines with time.
Low insulin and high glucagon causes hyperglycemia, but usually not ketoacidosis.
Increased lipid metabolism results in high levels of circulating lipids; risk of atherosclerosis.
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3. Gestational diabetes
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Occurs when a woman not previously diagnosed with diabetes shows glucose intolerance
during pregnancy.
Can cause potentially life threatening complications for both mother and fetus.
Insulin shock
Decreased blood glucose (45 to 60mg/dl) causes pallor, tremor, anxiety, tachycardia,
palpitations, sweating, headache, dizziness, irritability, fatigue, poor judgment, confusion,
visual disturbances, hunger, seizures, and ultimately coma.
Occurs when the body cannot use glucose as a fuel source because the body has no insulin or
not enough insulin, and fat is used instead.
This leads to severe metabolic acidosis that, in association with hyperglycemia and
dehydration, can result in coma, shock, and even death.
Occurs more often in the elderly, or those with infections or cardiovascular or renal disease.
Poor glucose control results in high levels of glucose (more than 500mg/dl) and high osmotic
pressures that lead to severe dehydration, low blood volume, and low perfusion pressures.
Ketosis is uncommon because there is enough insulin to prevent lipolysis and protein catabolism.
Glycation - attachment of glucose to proteins, lipids, and nucleic acids in blood vessels,
nerves, lenses, and other tissues, forming advanced glycation end products (AGEs).
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b. Induction of the polyol pathway
o
Sorbitol increases intracellular osmotic pressure, causing cellular edema and tissue dysfunction.
This process is especially important in renal cells, red blood cells, eye lens, and nerves.
Usually due to an adenoma of adrenal cortex (ACTH independent; low ACTH levels).
Manifestations:
Obesity with fat deposition in face (moon face), neck and abdomen (truncal obesity).
Protein breakdown for gluconeogenesis causes muscle weakness, bone loss, and bruising.
High levels of glucocorticoids cause insulin insensitivity and impaired glucose tolerance.
At high levels, glucocorticoids mimic aldosterone, causing sodium and water retention
(hypertension) and potassium excretion.
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2. Hyperaldosteronism
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Aldosterone causes increased renal sodium and water retention with excess potassium
secretion.
Manifestations:
Hypertension - can lead to an increased risk for atherosclerosis and congestive heart failure.
Hypernatremia
Hypokalemia - can be severe enough to cause cardiac dysrhythmias and muscle weakness.
Due to either:
Primary adrenal insufficiency - inability of the adrenals to produce and secrete the
adrenocortical hormones.
Associated with other autoimmune diseases such as Hashimoto thyroiditis and pernicious anemia.
Manifestations:
Addisonian crisis in response to an acute stressor, the patient experiences fever, nausea,
vomiting, hyponatremia, hyperkalemia, hypotension, and dehydration, which could result
in circulatory shock.
In individuals with primary Addison disease, the lack of feedback on the pituitary results in
increased compensatory secretion of ACTH which can cause hyperpigmentation of the skin.
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C. Disorders of the Adrenal Medulla
Most are benign, although 10% are malignant and may metastasize.
Symptoms of catecholamine excess are related to their sympathetic nervous system effects:
Hypertension
Tachycardia, palpitations
Glucose intolerance
Excessive sweating
Constipation
Weight loss
With exposure to certain foods (containing tyrosine) or excessive physiologic stress (e.g.,
surgery), episodes of extreme hypertension can occur with potential for cerebral and
cardiovascular complications.
Gland
Hypothalamus
Thyroid gland
Adrenal cortex
Prolactin
Mammary gland
Kidney
Oxytocin
Calcitonin
Primarily bone
Insulin
Glucagon
Liver
Thyroid Gland
Parathyroid hormone
parathormone
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Gland
Hormone
Target Tissue
Primary Actions
Adrenal Medulla
Epinephrine, norepinephrine
Adrenal Cortex
Mineralocorticoids (aldosterone)
Kidney
Glucocorticoids (cortisol)
Testis
Testosterone
Ovaries
Estrogens
Progesterone
Pineal Gland
Melatonin
Hypothalamus
Thymus
Thymosin
Stomach mucosa
Gastrin
Gastric glands
Small intestine
Secretin
Pancreas
Cholecystokinin
Heart
Kidneys
Kidney
Erythropoietin
Bone marrow