Transcript adrenal & thyroid

Adrenal Disease
Normal Anatomy
and
Physiology
Adrenal Disease
Objectives:
1. To increase students’ working
knowledge of adrenal anatomy,
physiology and pathology
2. To incorporate this working
knowledge into patient assessment
and clinical decision making
Adrenal
glands:
cortex
medulla
Adrenal: Normal Physiology
1. Adrenal medulla:
- ganglion of the sympathetic
nervous system
- secretes catecholamines:
epinephrine and norepinephrine
Adrenal: Normal Physiology
1. Adrenal medulla:
Catecholamine (epinephrine
and norepinephrine) secretion
in response to sympathetic
stimulation: fight or flight
response
Adrenal: Normal Physiology
2. Adrenal cortex: secretes
steroid based hormones
a. sex steroids
b. mineralocorticoids
c. glucocorticoids
Adrenal: Normal physiology
a. Sex steroids (testosterone)
supplemental to gonadal
production … not crucial to life
Adrenal: Normal physiology
b. Mineralocorticoids: control of
Na / K / H20 … blood pressure
renin / angiotensin / aldosterone
CRUCIAL TO LIFE
Adrenal: Normal physiology
Regulation of Renin / Angiotensin / Aldosterone
1. Renin secreted by JGA in response to BP or
chronic Na depletion
2. Renin catalyses the production of angiotensin I (a
decapeptide) from a circulating protein
3. Angiotensin converting enzyme (ACE) in the lungs
cleaves off 2 more amino acids to form
Angiotensin II (an octapeptide)
Adrenal: Normal physiology
Renin / Angiotensin / Aldosterone
4. Angiotensin II :
is a potent vasoconstrictor and
it stimulates the release of aldosterone by the
adrenal cortex
5. Aldosterone acts on the collecting tubule to increase
the reabsorption of Na (and, therefore H2O)
Adrenal: Normal physiology
c. Glucocorticoids:
-control of CHO / protein / fat metabolism
-maintenance of vascular reactivity
-anti-inflammatory
-maintenance of homeostasis in response
to stress (surgery, infection, starvation, etc.)
CRUCIAL TO LIFE
Adrenal: Normal physiology
c. Glucocorticoids: control of
CHO / protein / fat metabolism
insulin antagonist ( serum glucose)
hepatic glucose output
initiates lipolysis and proteolysis
gluconeogenesis
Adrenal: Normal physiology
c. Glucocorticoids:
maintenance of vascular reactivity
“primes” blood vessels to respond
to catecholamine driven
vasoconstriction
Adrenal: Normal physiology
c. Glucocorticoids: anti-inflammatory
inhibits lysosome, prostaglandin,
eicosanoid, and cytokine release
inhibits endothelial cell adhesion
Adrenal: Normal physiology
c. Glucocorticoids:
maintenance of homeostasis in
response to physiologic stress
(surgery, infection, starvation, etc.)
Adrenal: Normal physiology
Steroid hormone mechanism of action:
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1. cell entry
2. cytoplasmic
receptor binding
3. migration to
nucleus
4. DNA transcription
5. mRNA migration
to cytoplasm
6. mRNA translation
7. regulation of
receptor number
or activity
Adrenal: Normal physiology
c. Steroid mechanism of action:
requires multiple steps for effect
therefore, requires time to have
an effect … 2 to 4 hours
Adrenal: Normal physiology
c. Glucocorticoids: regulation
• Normal diurnal variation (highest in AM):
• Daily average of approximately 20 mg
Adrenal: Normal physiology
c. Glucocorticoids: regulation
• Increased secretion in response to
physiologic stress (up to 200 mg)
• Decreased secretion in response to
exogenous steroids, eg Prednisone
Adrenal: Normal physiology
c. Glucocorticoids: regulation
EXOGENOUS
STEROID
OR
INCREASING
CORTISOL
STRESS
OR
DECREASING
CORTISOL
CRH = corticotropin
releasing hormone
hypothalamus CRH
anterior
pituitary
ACTH
cortisol
adrenal
cortex
Adrenal: Disease
Hyperadrenalism
Hypoadrenalism
Patients taking or have taken
oral steroids
Will have 50 in 2000 patient practice
Adrenal: Disease (hyper)
Hyperadrenalism: (Cushingoid)
Cushing’s disease: excess of
cortisol production (eg pituitary or
adrenal tumour) with signs and
symptoms of excess steroid
Adrenal: Disease (hyper)
Hyperadrenalism: (Cushingoid)
Cushing’s syndrome: Signs and
symptoms of excess steroid
secondary to chronic use
Adrenal: Disease (hyper)
Cushingoid side effects from excess
long term steroids:
- adrenocortical suppression
- weight gain, moon face, buffalo hump
- abdominal striae, acne
Adrenal: Disease (hyper)
Cushingoid side effects from excess
long term steroids:
- hypertension, heart failure
- osteoporosis, growth suppression
- diabetes, impaired healing, peptic ulcers
- depression, psychosis
Adrenal: Disease (hypo)
a. Adrenal insufficiency:
Primary: Addison’s disease (loss of
>90% of adrenal cortex) due to
autoimmune, hemorrhage,
infection, tumour, surgery, etc.
Cortisol and Aldosterone deficiency
Adrenal: Disease (hypo)
a. Adrenal insufficiency:
Secondary: hypothalamic or pituitary
disease or exogenous steroid causing
suppression of the hypothalamic /
pituitary axis leading to atrophy of the
adrenal cortex
Cortisol deficiency only
Adrenal: Pharmacology
b. Glucocorticoids: steroids indicated
for inflammatory conditions such as:
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rheumatoid arthritis (RA)
systemic lupus erythematosis (SLE)
asthma
inflammatory bowel disease (IBD)
prevention of organ transplant rejection
many others
Adrenal: Pharmacology
b. Glucocorticoids: equivalents
Cortisol
20 mg
= Prednisone
= Solumedrol
= Decadron
5 mg
4 mg
.75 mg
Adrenal: Disease (hypo)
c. Secondary Adrenal insufficiency:
IS caused by chronic oral steroid use:
> 5 mg of Prednisone / day (> 20 mg of
cortisol) for > 2 wks within the last year
IS NOT caused by inhaled, nasal or topical
steroid use
Adrenal: Disease (hypo)
c. Secondary Adrenal insufficiency:
Strategies used to minimize suppression:
• minimize oral dosage to 20 mg/day
equivalent of cortisol or less
• every other day dosing
• tapering dosage to complete course
Adrenal: Disease (hypo)
d. Adrenal insufficiency: Problems
• impaired CHO / protein / fat metabolism
• hypoglycemia
• hypovolemia / hyperkalemia / acidosis
• hypotension
Adrenal: Disease (hypo)
d. Adrenal insufficiency: Signs and
symptoms
• excess pigmentation
• postural hypotension (dizziness)
• muscular weakness
• nausea, anorexia, weight loss
Adrenal: Disease (hypo)
d. Adrenal insufficiency: diagnosis
• Signs and symptoms
• Lab values: difficult to do and interpret
• CRH stimulation
• ACTH stimulation
• 24 hour urine cortisol
Adrenal: Disease (hypo)
d. Adrenal insufficiency: treatment
• Treat the cause (tumour / infection)
• Hormone replacement:
• mineralocorticoid
• glucocorticoid
Adrenal: Pharmacology
d. For mineralocorticoid insufficiency:
- fludrocortisone (Florinef)
- 0.05 to 0.1 mg daily
Adrenal: Pharmacology
d. For glucocorticoid insufficiency:
- Cortisol: 20 mg AM / 10 mg PM
- Prednisone: 5 mg AM / 2.5 mg PM
(divided doses to reflect normal diurnal
cycle)
Adrenal: Crisis
e. Acute Adrenal insufficiency: crisis
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medical emergency
inability to tolerate physiologic stress
acute refractory hypotension, diaphoresis
dehydration, dyspnea, hypothermia,
hypoglycemia, circulatory collapse, death
less likely with secondary AI
Adrenal: Crisis prevention
e. Acute Adrenal crisis prevention:
1. Recognition of patient at risk:
Addison’s disease
Has taken suppressive dose
Is taking low suppressive dose
(Prednisone 10 mg or less)
Adrenal: Crisis prevention
e. Acute Adrenal crisis prevention:
2. Supplement: day before / day of / day after
100 mg cortisol = 20 mg Prednisone
or
double the existing dose if
10 mg of Prednisone or less
Adrenal: Crisis treatment
e. Acute Adrenal crisis treatment:
• Hydrocortisone 100 mg IV bolus
• Hospital setting for fluid and electrolyte
replacement
• Correction of hypoglycemia
• Continued IV steroid
Adrenal: Dental concerns
1. Assess compliance with steroids
2. Assess need for supplementation:
complexity of surgery versus
degree of adrenal suppression
3. Discontinue Ketoconazole and
barbiturates if possible
Adrenal: Dental concerns
4. AM procedures
5. Anxiety reduction eg N2O / O2
6. Good intra- and post-op pain control
avoid NSAIDs (Peptic ulcers)
7. Monitor blood pressure
8. Cushingoid patients prone to fractures
Questions????
Thyroid Disease
Normal Anatomy
and
Physiology
Thyroid Disease
Objectives:
1. To increase students’ working
knowledge of thyroid anatomy,
physiology and pathology
2. To incorporate this working
knowledge into patient assessment
and clinical decision making
Thyroid
gland:
Thyroid: Normal Physiology
Thyroid gland produces 3 hormones:
T3: triiodothyronine
T4: thyroxine
Calcitonin: controls Calcium levels in
conjunction with parathyroid hormone
and Vitamin D
Thyroid: Normal Physiology
T3: triiodothyronine: more potent form of
thyroid hormone … 20% formed by
the thyroid, 80% by deiodination in
the periphery
T4: thyroxine: produced in the thyroid
Thyroid hormone formation is iodine
dependant
The Great Lakes
area is
endemically
deficient in
iodine, for this
reason iodine
is added to the
table salt.
Thyroid: Normal Physiology
Thyroid hormone … distribution:
produced and stored (3 to 4 month
reserve) in the thyroid gland
secreted and transported bound to
thyroid globulin
Thyroid: Normal Physiology
Thyroid hormone … effects:
controls oxidative metabolism and basic
metabolic rate
growth and maturation of tissues
Thyroid: Normal physiology
Thyroid hormone mechanism of action:
7
H
1
H
2
3
H
4
5
6
1. cell entry
2. cytoplasmic
receptor binding
3. migration to
nucleus
4. DNA transcription
5. mRNA migration
to cytoplasm
6. mRNA translation
7. regulation of
receptor number
or activity
Thyroid: Normal physiology
Thyroid hormone: regulation
• Increased secretion in response to
physiologic stress (cold, illness, etc)
• Decreased secretion in response to
increased thyroid hormone levels
Thyroid: Normal physiology
Thyroid hormone: regulation
INCREASING
THYROID
HORMONE
STRESS / COLD
OR
DECREASING
THYROID
HORMONE
TRH = thryroid
releasing hormone
hypothalamus TRH
anterior
pituitary
TSH
Thyroxine
thyroid
gland
Thyroid: Assessment
Serum TSH
• Elevated in hypothyroidism
• Decreased in hyperthyroidism
• Most commonly performed screening
test
Thyroid: Disease
Hyperthyroidism
Hypothyroidism
Thyroid masses:
benign / malignant
Hyperthyroidism (thyrotoxicosis)
Causes:
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autoimmune (Graves’ disease)
multinodular goitre
thyroid adenoma
subacute thyroiditis
ingestion of TH (OD / factitial / food)
anterior pituitary disease
Hyperthyroidism (thyrotoxicosis)
Graves’ disease: autoimmune
- stimulatory anti-TSH receptor antibodies resulting in continual
stimulation of thyroid hormone
production
- 7:1 female to male ratio
Hyperthyroidism (thyrotoxicosis)
Signs and symptoms:
- nervousness, irritability, tremour
fatigue, heat intolerance,
weight loss, rosy complexion
- tachycardia, palpitations, atrial
fibrillation, angina
Hyperthyroidism (thyrotoxicosis)
Signs and symptoms:
- myxedema…red, raised, puffy areas
- dyspnea due to muscle weakness
- diarrhea
- wide stare, lid lag
Hyperthyroidism (thyrotoxicosis)
Signs and symptoms:
- Graves’ ophthalmopathy:
- edema and inflammation of the extraocular muscles
- increase in orbital connective tissue
and fat
- may be persistent and lead to loss
of vision
Hyperthyroidism (thyrotoxicosis)
Treatment:
- Medical: propylthiouracil … blocks
hormone synthesis in the thyroid
and conversion of T4 to T3 in
the periphery
- B-blocker (propranolol) to control
adrenergic symptoms
Hyperthyroidism (thyrotoxicosis)
Treatment:
- Radioiodine ablation
- Surgery: thyroidectomy
Radio ablation will and surgery might
make the patient hypothyroid
Thyrotoxic crisis (thyroid storm)
Acute hyperthyroid crisis: risk factors
• more likely in patients who have long
standing or poorly treated disease and
in patients with goiter and eye signs
• precipitated by trauma, infection
or surgery
Thyrotoxic crisis (thyroid storm)
Acute hyperthyroid crisis: S & S
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extreme restlessness
nausea, vomiting, abdominal pain
fever, diaphoresis
tachycardia, arrythmia
pulmonary edema, congestive
heart failure
• stupor, coma, hypotension … death
Thyrotoxic crisis (thyroid storm)
Acute hyperthyroid crisis: treatment
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propylthiouracil (Propyl-Thyracil)
potassium iodide (Thyro-Block)
propranolol (Inderal)
glucorticoids
IV glucose, Vitamin B complex
wet packs, ice packs, fans
Hyperthyroidism (thyrotoxicosis)
Dental concerns:
- be aware of signs and symptoms
- assess compliance with medications
- in poorly controlled or newly diagnosed:
- avoid epinephrine
Hyperthyroidism (thyrotoxicosis)
Dental concerns:
- refer to MD if concerns exist
- prevent and manage infection
- be alert to S&S of thyroid storm
- treat as normal if well controlled
Hypothyroidism
Causes:
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congenital agenesis or hypoplastic
autoimmune (Hashimoto’s thyroiditis)
iodine deficiency with goitre
iodine excess
post-radio ablation
post-surgical ablation
anterior pituitary disease
Hypothyroidism
Signs and symptoms:
- Congenital: Neonatal cretinism
- Slowing of mental and physical
activity, weakness
- Cold intolerance
- Constipation, weight gain
Hypothyroidism
Signs and symptoms:
- Dry skin, dry and brittle hair
- Loss of outer 1/3 of the eybrows
- Puffy eyelids
- Hoarse voice
- Myxedema
Hypothyroidism
Treatment:
- T4 (L-thyroxin, Synthroid)
- Titrated until patient has
normal TSH
Hypothyroid crisis
Myxedematous Coma: risk factors
- Seen in untreated or non-compliant
patients
- Precipitated by cold, trauma, surgery,
infections and CNS depressants
- More common in winter
Hypothyroid crisis
Myxedematous Coma: S & S
- severe myxedema
- bradycardia
- severe hypotension
Hypothyroid crisis
Myxedematous Coma: treatment
- IV T4
- Steroids
- CPR
Hypothyroidism
Dental Concerns:
- be aware of signs and symptoms
- assess compliance with medications
- in poorly controlled or newly diagnosed:
- use CNS depressants (sedatives
and narcotics) with caution
Hypothyroidism
Dental Concerns:
- refer to MD if concerns exist
- prevent and manage infection
- be alert to S&S of myxedematous coma
- treat as normal if well controlled
Thyroid masses
Benign:
-
goitre due to iodine deficiency
enlargement due to Graves’ disease
thyroiditis
thyroglossal duct cyst
benign adenoma
Thyroid masses
Malignant
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follicular carcinoma
papillary carcinoma
anaplastic carcinoma
other carcinomas
Thyroid masses
Malignant: increased risk for cancer if
nodule is found
- in patients of a young age
- in a male
- with a history of radiation exposure
- with concommitant dysnea, dysphagia
or dysphonia (hoarseness)
Thyroid masses
Malignant: increased risk for cancer if
nodule is found to
- be a hard fixed lump
- be a single nodule
- have demonstrated rapid growth
Thyroid masses
Assessment:
- history
- clinical examination
- thyroid function tests
- thryroid scan
- fine needle aspiration biopsy
Thyroid cancer
Treatment:
- radio ablation with 131I *
- thyroidectomy +/- neck dissection
- external beam radiotherapy for
persistent disease *
* Does not cause osteoradionecrosis
of the jaws
Questions????