Download Chapter 20 outline

Chapter 20:
Other Hormones
Copyright © 2011, 2007 Mosby, Inc., an affiliate of Elsevier. All rights reserved.
Chapter 20 Outline

Other hormones

Pituitary hormones
 Thyroid hormones
 Pancreatic hormones
 Female sex hormones
 Male sex hormones
 Other agents that affect sex hormone systems
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2
Other Hormones



Haveles (p. 249)
Hormones are secreted by endocrine glands
and transported by blood to target tissues,
where they are biologically active
Endocrine glands include the pituitary, thyroid,
parathyroids, pancreas, adrenals, gonads, and
placenta

Help maintain homeostasis by regulating body
functions and are controlled themselves by feedback
systems
cont’d…
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3
Other Hormones


In most systems, the hormone released has a
negative feedback effect on the secretion of the
hormone-stimulating substance
Drugs that affect the endocrine system include
the hormones secreted by the endocrine glands,
synthetic hormone agonists and antagonists,
and substances that influence the synthesis and
secretion of hormones

Used in replacement therapy such as treatment of
diabetes mellitus (insulin) and hypothyroidism
(levothyroxine)
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4
Pituitary Hormones



Haveles (pp. 249-251)
Anterior pituitary
Posterior pituitary
cont’d…
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5
Pituitary Hormones


Haveles (p. 249)
The pituitary gland (master gland) is located at
the base of the brain; “master gland” due to its
regulatory effect on other endocrine glands and
organs of the body


Secretes peptide hormones that regulate the thyroid,
adrenal, and sex glands; the kidney and the uterus;
and growth
Also has a trophic effect; without gonadotropins, the
entire reproductive system fails; without growth
hormone and thyrotropin, normal growth and
development are impossible
cont’d…
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6
Pituitary Hormones


Pituitary deficiency can produce loss of secondary
sex characteristics, decreased metabolism,
dwarfism, diabetes insipidus, hypothyroidism,
Addison disease, loss of pigmentation, thinning
and softening of the skin, decreased libido, and
retarded dental development


Haveles (pp. 249-250)
Hypersecretion of pituitary hormones can produce
sexual precocity, goiter, Cushing disease, acromegaly,
and giantism
The two parts to the pituitary gland are the anterior
lobe (adenohypophysis) and the posterior lobe
(neurohypophysis)
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7
Anterior Pituitary


Haveles (pp. 250-251) (Fig. 20-2)
Secrets growth hormone (somatotropin),
luteinizing hormone (LH); follicle-stimulating
hormone (FSH); thyroid-stimulating hormone
(TSH) or thyrotropin, adrenocorticotropic
hormone (ACTH) or corticotropin, and
prolactin

β-Lipotropin is a precursor to β-endorphin
cont’d…
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8
Anterior Pituitary

Human growth hormone is used medically to
treat children who lack it



Pharmaceutical gonadotropin-releasing hormone
(GnRH) is a synthetic analogue
Leuprolide stimulates pituitary function and is used
to treat infertility
GnRH agonists are used to treat prostate cancer
and endometriosis
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9
Bromocriptine


Haveles (p. 251)
Inhibits pituitary function


Not a hormone; it is a dopamine agonist that
suppresses prolactin levels
Used to treat prolactin-secreting adenomas,
acromegaly, and Parkinson disease
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10
Posterior Pituitary


Haveles (p. 251)
Secretes vasopressin (antidiuretic hormone
[ADH]) and oxytocin

vasopressin (Pitressin) has vasopressor and
antidiuretic hormone activity and is used to treat
transient diabetes insipidus
• Synthetic vasopressin analogues (desmopressin [DDAVP,
Stimate] and lypressin [Diapid]) are used for chronic
treatment of pituitary diabetes insipidus and for certain
clotting disorders (hemophilia A and von Willebrand
disease)

oxytocin (Pitocin, Suntocinon) is used to induce
labor, control postpartum hemorrhage, and induce
postpartum lactation
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11
Thyroid Hormones




Haveles (pp. 251-252)
Iodine
Hypothyroidism
Hyperthyroidism
cont’d…
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12
Thyroid Hormones


Haveles (p. 251)
The thyroid gland secretes two iodinecontaining thyroid hormones—triiodothyronine
(T3) and tetraiodothyronine (thyroxine [T4]); in
addition, calcitonin regulates calcium
metabolism


Thyroid hormones are important for energy
metabolism, growth, and development
Thyroid hormones are synthesized from iodine and
tyrosine and stored as complex protein until TSH
stimulates their release
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13
Iodine


The thyroid gland requires intake of adequate
iodine; if iodine intake is deficient, normal
amounts of thyroid hormones cannot be
made


Haveles (p. 251)
TSH is secreted in excess, and the thyroid
hypertrophies (simple or nontoxic goiter)
Marine life is the only common food that is
naturally rich in iodine; iodized salt has
decreased the incidence of simple goiter
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14
Hypothyroidism


In the small child, hypothyroidism is called
cretinism; in an adult, it is called myxedema or
simple hypothyroidism


Haveles (p. 251) (Box 20-1)
Patients are usually drowsy, weak, and listless and
exhibit an expressionless, puffy face with edematous
tongue and lips
Thyroid hypofunction is treated with exogenous
thyroid hormones

The most common is levothyroxine
cont’d…
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15
Hyperthyroidism


Haveles (pp. 251-252)
Two forms of thyroid hyperfunction

Diffuse toxic goiter (Graves disease) is characterized
by a diffusely enlarged, highly vascular thyroid gland
• Common in young adults and considered a disorder of the
immune response

Toxic nodular goiter (Plummer disease) is
characterized by nodules that secrete excessive
hormone while the rest of the glandular tissue is
atrophied
• Occurs primarily in older patients
cont’d…
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16
Hyperthyroidism

Excess levels of circulating thyroid hormone
produce thyrotoxicosis



Adverse effects include excess production of heat,
increased sympathetic activity, increased
neuromuscular activity, increased sensitivity to pain,
ophthalmopathy, exophthalmos, and anxiety
Oral manifestations include accelerated tooth
eruption, marked loss of alveolar process, diffuse
demineralization of jawbone, and rapidly progressive
periodontitis
Direct inotropic effect in cardiovascular system
cont’d…
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17
Hyperthyroidism


Haveles (p. 252) (Box 20-2)
Treatment: the two most common treatments
are radioactive iodine (131I) and thyroidectomy

Either treatment usually results in hypothyroidism
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18
Antithyroid Agents


Haveles (p. 252)
Antithyroid drugs such as propylthiouracil
(PTU) and methimazole (Tapazole) are used
in patients who cannot tolerate surgery or
treatment with 131I

These drugs interfere directly with the synthesis of
thyroid hormones by inhibiting the iodination of
tyrosine moieties and the coupling of iodotyrosines
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19
Pancreatic Hormones


Haveles (pp. 252-262)
Diabetes mellitus (DM)

Types of diabetes
 Complications of diabetes
 Dental issues
 Cautions and contraindications
 Systemic complications of diabetes
 Effect of drugs on complications of diabetes
 Evaluation of the dental patient with diabetes
 Treatment of hypoglycemia
 Drugs used to manage diabetes
cont’d…
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20
Pancreatic Hormones


Haveles (p. 252)
Two primary hormones secreted by islets of
Langerhans of the pancreas are insulin and
glucagon


Insulin promotes fuel storage (glucose out of blood)
Glucagon promotes fuel mobilization (glucose into
the blood)
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21
Diabetes Mellitus


A group of metabolic disorders characterized
by persistent hyperglycemia



Haveles (pp. 252-253) (Fig. 2-3; Table 20-1)
Type I (insulin-dependent DM [IDDM])
Type II (non–insulin-dependent DM [NIDDM])
Symptoms and complications result, usually
from inadequate or poorly timed secretion of
insulin from the pancreas and/or insulin
resistance of the cells
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22
Types of Diabetes


Haveles (pp. 253-254)
Type I: usually develops in persons younger
than age 30 years and results from
autoimmune destruction of pancreatic beta
cells



Associated with a complete lack of insulin secretion,
increased glucagon secretion, rapid onset of
disease, ketosis, and severe symptoms
Without insulin, type I DM is fatal
Must be treated with injections of insulin
cont’d…
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23
Types of Diabetes


Haveles (pp. 253-254) (Box 20-3)
Type II: usually develops in persons older than
age 40 years, but more and more cases are
being reported in persons younger than age
20 years; attributed to lack of exercise

The pancreas can secrete enough insulin to
prevent ketoacidosis but not enough to normalize
plasma glucose
• Insulin secreted does not reduce glucose levels in serum
to normal levels
 Insulin
resistance develops and the
pancreas gives out
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24
Complications of Diabetes


Xerostomia: pronounced susceptibility to caries;
the xerostomia is secondary to an increase in
urination



Haveles (p. 254)
Dry, cracking oral mucosa with presence of
mucositis, ulcers, infections, and an inflamed painful
tongue
Periodontal disease: patients with uncontrolled
or undiagnosed diabetes are more prone to
periodontal disease
Advanced glycation end-products (AGEs):
collagen becomes cross-linked; thickening of
blood vessels is associated with elevated AGEs
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25
Dental Issues


Haveles (p. 254)
Dental appointments should not interfere with
meals and should involve minimal stress


Patients with diabetes have fragile blood vessels,
delayed wound healing, and a tendency to
develop infections
Surgical therapy should be approached with
caution
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26
Cautions and Contraindications


Haveles (p. 254)
Drugs that may decrease insulin release or
increase insulin requirements, such as
epinephrine, glucocorticoids, or opioid
analgesics, should be used with caution in
patients with diabetes
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27
Systemic Complications of
Diabetes






Haveles (pp. 254-255)
Cardiovascular system: incidence of problems is
higher in patients with diabetes
Retinopathy: microvascular disease affects the
blood supply to the retina
Neuropathy: leads to reduced and sometimes
absent feelings, especially in the lower extremities
Infections: gangrene can occur in the peripheral
extremities due to depressed immunity, less
effective white blood cells, microvascular changes,
and neuropathy
Healing: slower healing
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28
Effect of Drugs on Complications
of Diabetes


Haveles (pp. 255-256)
Intensive treatment of patients with IDDM can
substantially reduce the onset and
progression of diabetic retinopathy,
nephropathy, and neuropathy

The risk of hypoglycemia is increased three times,
and the increase in weight gain tends to be
greater
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29
Evaluation of the Dental Patient
With Diabetes


Haveles (p. 256)
Two laboratory tests useful in evaluating a
patient’s glucose control are serum glucose
and glycosylated hemoglobin


Serum glucose is a measure of the patient’s
glucose control at the time that the blood is
sampled
Glycosylated hemoglobin (HbA1C) reflects glucose
control over a 2- to 3-month period
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30
Treatment of Hypoglycemia


Haveles (p. 256)
When patient is conscious, treatment consists
of any source of sugar: fruit juice, cake icing,
glucose gel, or soluble carbohydrate

If the patient is unconscious and lacks a swallowing
reflex, treatment consists of intravenous dextrose
(50%)
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31
Drugs Used to Manage Diabetes





Haveles (pp. 256-262)
Insulins
Oral antidiabetic agents
Other new drugs
Glucagon
cont’d…
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32
Drugs Used to Manage Diabetes


Haveles (pp. 256-257) (Fig. 20-4; Table 20-4)
Insulins



Usually administered by subcutaneous injection,
large molecular size prevents it from being
absorbed from the gastrointestinal tract
Differ in onset and duration of action
Human insulin is prepared by recombinant DNA
synthesis and by modifying porcine insulin
cont’d…
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33
Drugs Used to Manage Diabetes

Insulins



Recently, an inhaled dose form was approved to
treat both type 1 and type 2 diabetes
Can be used in place of short-acting injectable
insulin that is used at mealtime for patients with
type 1 diabetes
It is added to regimens that also include longacting insulin
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34
Selected Insulin Preparations


Rapid acting




Haveles (p. 256) (Table 20-4)
insulin aspart (Novolog)
insulin lispro (Humalog)
insulin gallisin (Apidra)
Short acting

insulin regular (Novolin R, Humulin R)
cont’d…
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35
Selected Insulin Preparations


Intermediate acting



Haveles (p. 256) (Table 20-4)
insulin NPH (Humulin N, Novolin N)
Humulin L Lente
Long acting


insulin detemir (Levimir)
insulin glargine (Lantus)
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36
Drugs Used to Manage Diabetes


Haveles (pp. 257) (Box 20-4)
Hypoglycemia is the most common adverse
reaction to insulin



May be caused by unintentional overdose (insulin
shock), failure to eat, or increased exercise or
stress
Symptoms are explained by increased release of
epinephrine from the adrenals, include sweating,
weakness, nausea, and tachycardia
Symptoms from glucose deprivation of the brain
include headache, blurred vision, mental confusion,
incoherent speech, and eventually coma,
convulsions, and death
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37
Oral Antidiabetic Agents


Haveles (pp. 257-259, 260-261) (Table 20-6)
Currently four groups of oral agents


The oldest is sulfonylureas; oral hypoglycemic
agents
Antihyperglycemic agents: lower elevated blood
sugar but do not produce hypoglycemia
• Biguanides
• Nonsulfonurea secretagogues
• α-Glucosidase inhibitors
• Thiazolidinediones
cont’d…
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38
Oral Antidiabetic Agents


Haveles (p. 257)
Biguanides: metformin (Glucophage)
increases hepatic and peripheral insulin
sensitivity
cont’d…
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39
Oral Antidiabetic Agents


Haveles (pp. 257-258) (Fig. 20-6)
Sulfonylureas: the only orally active agents
used to manage diabetes for many years


Mechanism of action includes stimulation of
release of insulin from the beta cells of the
pancreas, reduction of glucose from the liver,
reduction in serum glucagon levels, and increase
in sensitivity of target tissues to insulin
Indicated for patients with NIDDM who cannot be
treated with diet and exercise alone
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40
Oral Diabetic Agents




Haveles (p. 259)
Nonsulfonylurea secretagogues
α-Glucosidase inhibitors: acarbose (Precose)
slows down the breakdown of ingested fat,
thus postprandial hyperglycemia is reduced
Thiazolidinediones: increase insulin
sensitivity of adipose tissue, skeletal muscle,
and the liver
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41
Other New Drugs



Haveles (p. 259)
exenatide (Byetta): an incretin mimetic that has
an amino acid sequence similar to human
glucagon-like peptide-1 (GLP-1) and in the
presence of glucose acts to stimulate insulin
secretion
pramlintide (Symlin): an amylinomimetic agent
responsible for modulation of gastric emptying,
prevention of postprandial rise in plasma
glucagon, and satiety, which leads to decreased
caloric intake and potential weight loss
cont’d…
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42
Other New Drugs



Haveles (p. 262)
Colesevelam: a bile-acid sequestrant used to
lower low-density lipoprotein (LDL) cholesterol
Dipeptidyl-peptidase-4 inhibitors: sitagliptin
(Januvia) is an oral medication approved for
use in the treatment of type II diabetes as
monotherapy or in combination with metformin,
a sulfonylurea, or a thiazolidinedione
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43
Glucagon


A polypeptide hormone produced by α cells of
the pancreas


Haveles (p. 262)
Increases liver glycogenolysis by stimulating cyclic
adenosine monophosphate (cAMP) synthesis and
increasing phosphorylase kinase activity
An antagonist to insulin

May be used parenterally for emergency treatment
of hypoglycemia, glucose is usually preferred
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44
Female Sex Hormones




Haveles (pp. 262-266)
Estrogens
Progestins
Hormonal contraceptives
cont’d…
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45
Female Sex Hormones


There are both male and female sex hormones


Haveles (pp. 262-263)
Most sex hormones occur in both sexes but in
different proportions
The two major female sex hormones are
estrogens and progestins


The are secreted primarily by the ovaries but also by
the testes and placenta
They are largely responsible for producing female sex
characteristics, developing the reproductive system,
and preparing the reproductive system for conception
cont’d…
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46
Female Sex Hormones

Estrogen and progesterone levels vary daily


Changes are dependent on the pituitary
gonadotropic hormones FHS and LH
On day 1 of an average 28-day cycle,
secretions of FSH and LH begin to increase

This release is caused by a reduction in the blood
levels of estrogen and progesterone, which normally
inhibit their release
cont’d…
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47
Female Sex Hormones

An ovarian egg matures in response to
increased FSH


The follicle in which it is contained grows in size
and begins to secrete estrogen
On approximately day 12, the rate of
secretion of FSH and LH increases markedly
to cause a rapid swelling of the follicle

This culminates in ovulation on day 14
cont’d…
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48
Female Sex Hormones


Haveles (p. 263) (Fig. 20-7)
After ovulation, LH causes secretory cells of
the follicle to develop into a corpus luteum
that secretes large quantities of estrogen and
progesterone

This causes a feedback decrease in the secretion
of both FSH and LH
cont’d…
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49
Female Sex Hormones

The corpus luteum completely degenerates on
approximately day 26


The decrease in estrogen and progesterone leads to
menstruation and increased release of FSH and LH
The FSH initiates growth of new follicles to begin a
new cycle
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50
Estrogens



Haveles (pp. 263-264) (Table 20-8)
Overview
Estrogens are largely responsible for the
changes that take place during puberty


Synthetic estrogens can be used for therapy and
conception
The most common side effects of estrogen therapy
are nausea and vomiting
• Other side effects include uterine bleeding, vaginal
discharge, edema, thrombophlebitis, weight gain, and
hypertension
cont’d…
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51
Estrogens


Haveles (pp. 263-264)
Estrogen therapy may also promote endometrial
carcinoma in postmenopausal women

This risk may be cancelled out by administration of a
progestin
cont’d…
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52
Estrogens



Effect on oral tissues
Changes in sex hormone levels are related to




Haveles (p. 264)
Gingivitis at puberty
During pregnancy
After menopause
The increase in gingival inflammation may
occur even with a decrease in the amount of
plaque
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53
Progestins


Haveles (p. 264)
The corpus luteum is the primary source of
progesterone during the normal female sexual
cycle

Progesterone promotes secretory changes in the
endometrium and prepares the uterus for implantation
of the fertilized ovum
• If implantation does not occur, progesterone secretion declines
and menstruation occurs
• If implantation takes place, the trophoblast secretes chorionic
gonadotropin, which sustains the corpus luteum, maintaining
progesterone and estrogen levels and preventing menstruation
cont’d…
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54
Progestins


Haveles (p. 264)
Progestins are used in a variety of dose forms



Parenteral medroxyprogesterone (Depo-Provera)
is administered every 3 months as a contraceptive
Progestin-only “minipills” are used orally
A progestational agent can be administered as an
intrauterine device (IUD) or implant under the skin
of the arm
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55
Hormonal Contraceptives


Oral contraceptives are the most common dose
forms of hormonal contraceptives and consist of
estrogens and progestins in various
combinations


Haveles (pp. 264-265) (Box 20-5)
These are the most common birth control pills and are
more than 99% effective
The combination type of oral contraceptive is
taken for 21 days of each month

The seven pills in the fourth week contain no active
ingredient
cont’d…
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56
Hormonal Contraceptives


Seasonale is the newest in combination oral
contraceptives



Haveles (p. 265)
An extended cycle contraceptive
The contraceptive vaginal ring is a new dose
form that introduces hormonal contraception
into the body
An injectable contraceptive is also available
cont’d…
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57
Hormonal Contraceptives



Haveles (p. 265)
Hormonal contraceptives are associated with a
significant increase in the frequency of dry
sockets after extractions
Contraindications for use of oral contraceptives
include thromboembolitic disorders, significant
dysfunction of the liver, known or suspected
carcinoma of the breast or other estrogendependent neoplasm, and undiagnosed genital
bleeding
cont’d…
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58
Hormonal Contraceptives


Haveles (p. 265) (Table 20-9)
Certain antibiotics have been said to reduce the
effectiveness of hormonal contraceptives


They are thought to do so by indirectly suppressing
the intestinal flora and thus diminishing the
availability of hydrolytic enzymes to regenerate the
parent steroid molecule
Consequently, plasma concentrations of steroids are
said to be abnormally low, and the steroid is cleared
more rapidly from the body than under normal
circumstances
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59
Male Sex Hormones




Haveles (p. 266) (Box 20-6; Table 20-10)
Androgens
Testosterone, the main androgen, has both
androgenic and anabolic effects
Androgens are responsible for the
development of secondary male sex
characteristics
cont’d…
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60
Male Sex Hormones


Androgens are used illicitly for muscle mass
gain


Haveles (p. 266)
Androgenic steroids are schedule III controlled
substances because of their abuse
Side effects of androgenic steroids include
nausea, cholestatic jaundice, hepatocellular
neoplasms, increased serum cholesterol,
habituation, and depression and excitation
cont’d…
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61
Other Agents that Affect Sex
Hormone Systems






Haveles (pp. 266-267) (Table 20-11)
Clomiphene has the ability to induce ovulation in
some anovulatory women
Leuprolide is used in the management of
endometriosis and to treat infertility
Tamoxifen is indicated in the palliative treatment
of breast cancer in postmenopausal women
Danazol is used to treat endometriosis and
fibrocystic disease in women
Aromatase inhibitors reduce almost the entire
amount of estrogen made in the bodies of
postmenopausal women
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62