12. endocrine: adrenal
TRANSCRIPT
Adrenal DiseaseAdrenal Disease
Normal AnatomyNormal Anatomy
and and
PhysiologyPhysiology
Adrenal DiseaseAdrenal DiseaseObjectives:Objectives:1. To increase students’ working 1. To increase students’ working
knowledge of adrenal anatomy, knowledge of adrenal anatomy, physiology and pathologyphysiology and pathology
2. To incorporate this working 2. To incorporate this working knowledge into patient assessment knowledge into patient assessment and clinical decision makingand clinical decision making
Adrenalglands:
cortex
medulla
Adrenal: Normal Physiology
Adrenal medulla:
- ganglion of the sympathetic nervous system
- secretes catecholamines:
epinephrine and norepinephrine
Adrenal: Normal Physiology
Adrenal medulla:
Catecholamine (epinephrine and norepinephrine) secretion in response to sympathetic stimulation: fight or flight response
Adrenal: Normal Physiology
Adrenal cortex: secretes steroid based hormones
a. sex steroids
b. mineralocorticoids
c. glucocorticoids
Adrenal: Normal physiologyAdrenal: Normal physiology
• Sex steroids (testosterone)
supplemental to gonadal
production … not crucial to life
Adrenal: Normal physiologyAdrenal: Normal physiology
b. Mineralocorticoids: control of
Na / K / H20 … blood pressure
renin / angiotensin / aldosterone
CRUCIAL TO LIFECRUCIAL TO LIFE
Adrenal: Normal physiologyAdrenal: Normal physiology
Regulation of Renin / Angiotensin / Aldosterone
• Renin secreted by JGA in response to BP or chronic Na depletion
• Renin catalyses the production of angiotensin I (a decapeptide) from a circulating protein
3. Angiotensin converting enzyme (ACE) in the lungscleaves off 2 more amino acids to formAngiotensin II (an octapeptide)
Adrenal: Normal physiologyAdrenal: Normal physiology
Renin / Angiotensin / Aldosterone
5. Angiotensin II :is a potent vasoconstrictor and it stimulates the release of aldosterone by the adrenal cortex
• Aldosterone acts on the collecting tubule to increasethe reabsorption of Na (and, therefore H2O)
Adrenal: Normal physiologyAdrenal: 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 LIFECRUCIAL TO LIFE
Adrenal: Normal physiologyAdrenal: Normal physiology
c. Glucocorticoids: control ofCHO / protein / fat metabolism
insulin antagonist ( serum glucose) hepatic glucose output
initiates lipolysis and proteolysisgluconeogenesis
Adrenal: Normal physiologyAdrenal: Normal physiology
c. Glucocorticoids:
maintenance of vascular reactivity
“primes” blood vessels to respond to catecholamine driven vasoconstriction
Adrenal: Normal physiologyAdrenal: Normal physiology
• Glucocorticoids: anti-inflammatory
inhibits lysosome, prostaglandin, eicosanoid, and cytokine release
inhibits endothelial cell adhesion
Adrenal: Normal physiologyAdrenal: Normal physiology
c. Glucocorticoids:
maintenance of homeostasis in
response to physiologic stress
(surgery, infection, starvation, etc.)
Adrenal: Normal physiologyAdrenal: Normal physiologySteroid hormone mechanism of action:
H
H H
1. cell entry2. cytoplasmic
receptor binding3. migration to
nucleus4. DNA transcription7. mRNA migration
to cytoplasm6. mRNA translation7. regulation of
receptor numberor activity
1
2
3 45 6
7
Adrenal: Normal physiologyAdrenal: 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 physiologyAdrenal: Normal physiology
c. Glucocorticoids: regulation
• Normal diurnal variation (highest in AM):
• Daily average of approximately 20 mg
Adrenal: Normal physiologyAdrenal: 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 physiologyAdrenal: Normal physiologyc. Glucocorticoids: regulation
hypothalamus
anteriorpituitary
adrenalcortex
CRH = corticotropinreleasing hormone
ACTH
cortisol
EXOGENOUSSTEROID
ORINCREASING
CORTISOL
STRESSOR
DECREASINGCORTISOL
CRH
Adrenal: DiseaseAdrenal: Disease
Hyperadrenalism
Hypoadrenalism
Patients taking or have taken oral steroids
Will have 50 in 2000 patient practice
Adrenal: Disease (hyper)Adrenal: Disease (hyper)
Hyperadrenalism: (Cushingoid)
Cushing’s disease: excess ofcortisol production (eg pituitary or adrenal tumour) with signs andsymptoms of excess steroid
Adrenal: Disease (hyper)Adrenal: Disease (hyper)
Hyperadrenalism: (Cushingoid)
Cushing’s syndrome: Signs and symptoms of excess steroid secondary to chronic use
Adrenal: Disease (hyper)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)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)Adrenal: Disease (hypo)
• Adrenal insufficiency:
Primary: Addison’s disease (loss of >90% of adrenal cortex) due toautoimmune, hemorrhage, infection, tumour, surgery, etc.
Cortisol and Aldosterone deficiency
Adrenal: Disease (hypo)Adrenal: Disease (hypo)
• Adrenal insufficiency:
Secondary: hypothalamic or pituitarydisease or exogenous steroid causingsuppression of the hypothalamic / pituitary axis leading to atrophy of theadrenal cortex
Cortisol deficiency only
Adrenal: PharmacologyAdrenal: Pharmacology
b. Glucocorticoids: steroids indicated for inflammatory conditions such as:
- rheumatoid arthritis (RA)- systemic lupus erythematosis (SLE)- asthma- inflammatory bowel disease (IBD)- prevention of organ transplant rejection- many others
Adrenal: PharmacologyAdrenal: Pharmacology
b. Glucocorticoids: equivalents
Cortisol 20 mg
= Prednisone 5 mg= Solumedrol 4 mg = Decadron .75 mg
Adrenal: Disease (hypo)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)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)Adrenal: Disease (hypo)
d. Adrenal insufficiency: Problems
• impaired CHO / protein / fat metabolism
• hypoglycemia
• hypovolemia / hyperkalemia / acidosis
• hypotension
Adrenal: Disease (hypo)Adrenal: Disease (hypo)
d. Adrenal insufficiency: Signs and symptoms
• excess pigmentation
• postural hypotension (dizziness)
• muscular weakness
• nausea, anorexia, weight loss
Adrenal: Disease (hypo)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)Adrenal: Disease (hypo)
d. Adrenal insufficiency: treatment
• Treat the cause (tumour / infection)
• Hormone replacement:• mineralocorticoid• glucocorticoid
Adrenal: PharmacologyAdrenal: Pharmacology
d. For mineralocorticoid insufficiency:
- fludrocortisone (Florinef)
- 0.05 to 0.1 mg daily
Adrenal: PharmacologyAdrenal: 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: CrisisAdrenal: Crisis
e. Acute Adrenal insufficiency: crisis
• 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 preventionAdrenal: Crisis prevention
e. Acute Adrenal crisis prevention:
1. Recognition of patient at risk:
Addison’s diseaseHas taken suppressive doseIs taking low suppressive dose
(Prednisone 10 mg or less)
Adrenal: Crisis preventionAdrenal: Crisis prevention
e. Acute Adrenal crisis prevention:
2. Supplement: day before / day of / day after
100 mg cortisol = 20 mg Prednisoneor
double the existing dose if 10 mg of Prednisone or less
Adrenal: Crisis treatmentAdrenal: 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 concernsAdrenal: Dental concerns
• Assess compliance with steroids
2. Assess need for supplementation:complexity of surgery versusdegree of adrenal suppression
3. Discontinue Ketoconazole and barbiturates if possible
Adrenal: Dental concernsAdrenal: Dental concerns
4. AM procedures
5. Anxiety reduction eg N2O / O2
6. Good intra- and post-op pain controlavoid NSAIDs (Peptic ulcers)
7. Monitor blood pressure
8. Cushingoid patients prone to fractures
Questions????
Thyroid DiseaseThyroid Disease
Normal AnatomyNormal Anatomy
and and
PhysiologyPhysiology
Thyroid DiseaseThyroid DiseaseObjectives:Objectives:1. To increase students’ working 1. To increase students’ working
knowledge of thyroid anatomy, knowledge of thyroid anatomy, physiology and pathologyphysiology and pathology
2. To incorporate this working 2. To incorporate this working knowledge into patient assessment knowledge into patient assessment and clinical decision makingand clinical decision making
Thyroidgland:
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 Lakesarea isendemically deficient in iodine, for thisreason 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 physiologyThyroid: Normal physiologyThyroid hormone mechanism of action:
H
H H
1. cell entry2. cytoplasmic
receptor binding3. migration to
nucleus4. DNA transcription7. mRNA migration
to cytoplasm6. mRNA translation7. regulation of
receptor numberor activity
1
2
3 45 6
7
Thyroid: Normal physiologyThyroid: 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 physiologyThyroid: Normal physiologyThyroid hormone: regulation
hypothalamus
anteriorpituitary
thyroidgland
TRH = thryroidreleasing hormone
TSH
Thyroxine
INCREASING THYROID
HORMONE
STRESS / COLDOR
DECREASINGTHYROID
HORMONE
TRH
Thyroid: AssessmentThyroid: Assessment
Serum TSH
• Elevated in hypothyroidism
• Decreased in hyperthyroidism
• Most commonly performed screeningtest
Thyroid: DiseaseThyroid: Disease
Hyperthyroidism
Hypothyroidism
Thyroid masses: benign / malignant
Hyperthyroidism (thyrotoxicosis)Hyperthyroidism (thyrotoxicosis)
Causes:
• autoimmune (Graves’ disease)• multinodular goitre• thyroid adenoma• subacute thyroiditis• ingestion of TH (OD / factitial / food)• anterior pituitary disease
Hyperthyroidism (thyrotoxicosis)Hyperthyroidism (thyrotoxicosis)
Graves’ disease: autoimmune
- stimulatory anti-TSH receptor anti- bodies resulting in continual
stimulation of thyroid hormone production
- 7:1 female to male ratio
Hyperthyroidism (thyrotoxicosis)Hyperthyroidism (thyrotoxicosis)
Signs and symptoms:
- nervousness, irritability, tremour fatigue, heat intolerance, weight loss, rosy complexion
- tachycardia, palpitations, atrial fibrillation, angina
Hyperthyroidism (thyrotoxicosis)Hyperthyroidism (thyrotoxicosis)
Signs and symptoms:
- myxedema…red, raised, puffy areas
- dyspnea due to muscle weakness
- diarrhea
- wide stare, lid lag
Hyperthyroidism (thyrotoxicosis)Hyperthyroidism (thyrotoxicosis)
Signs and symptoms:
- Graves’ ophthalmopathy:
- edema and inflammation of the extra-ocular muscles
- increase in orbital connective tissue and fat
- may be persistent and lead to loss of vision
Hyperthyroidism (thyrotoxicosis)Hyperthyroidism (thyrotoxicosis)
Treatment:
- Medical: propylthiouracil … blockshormone synthesis in the thyroidand conversion of T4 to T3 in the periphery
- B-blocker (propranolol) to controladrenergic symptoms
Hyperthyroidism (thyrotoxicosis)Hyperthyroidism (thyrotoxicosis)
Treatment:
- Radioiodine ablation
- Surgery: thyroidectomy
Radio ablation will and surgery mightmake the patient hypothyroid
Thyrotoxic crisis (thyroid storm)Thyrotoxic crisis (thyroid storm)
Acute hyperthyroid crisis: risk factors
• more likely in patients who have longstanding or poorly treated disease andin patients with goiter and eye signs
• precipitated by trauma, infection or surgery
Thyrotoxic crisis (thyroid storm)Thyrotoxic crisis (thyroid storm)
Acute hyperthyroid crisis: S & S
• extreme restlessness• nausea, vomiting, abdominal pain• fever, diaphoresis• tachycardia, arrythmia• pulmonary edema, congestive
heart failure• stupor, coma, hypotension … death
Thyrotoxic crisis (thyroid storm)Thyrotoxic crisis (thyroid storm)
Acute hyperthyroid crisis: treatment
• propylthiouracil (Propyl-Thyracil)• potassium iodide (Thyro-Block)• propranolol (Inderal)• glucorticoids• IV glucose, Vitamin B complex • wet packs, ice packs, fans
Hyperthyroidism (thyrotoxicosis)Hyperthyroidism (thyrotoxicosis)
Dental concerns:
- be aware of signs and symptoms
- assess compliance with medications
- in poorly controlled or newly diagnosed:- avoid epinephrine
Hyperthyroidism (thyrotoxicosis)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
HypothyroidismHypothyroidism
Causes:
• congenital agenesis or hypoplastic• autoimmune (Hashimoto’s thyroiditis)• iodine deficiency with goitre• iodine excess• post-radio ablation• post-surgical ablation• anterior pituitary disease
HypothyroidismHypothyroidism
Signs and symptoms:
- Congenital: Neonatal cretinism
- Slowing of mental and physicalactivity, weakness
- Cold intolerance
- Constipation, weight gain
HypothyroidismHypothyroidism
Signs and symptoms:
- Dry skin, dry and brittle hair
- Loss of outer 1/3 of the eybrows
- Puffy eyelids
- Hoarse voice
- Myxedema
HypothyroidismHypothyroidism
Treatment:
- T4 (L-thyroxin, Synthroid)
- Titrated until patient has normal TSH
Hypothyroid crisisHypothyroid 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 crisisHypothyroid crisis
Myxedematous Coma: S & S
- severe myxedema
- bradycardia
- severe hypotension
Hypothyroid crisisHypothyroid crisis
Myxedematous Coma: treatment
- IV T4
- Steroids
- CPR
HypothyroidismHypothyroidism
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
HypothyroidismHypothyroidism
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 massesThyroid masses
Benign:
- goitre due to iodine deficiency- enlargement due to Graves’ disease- thyroiditis- thyroglossal duct cyst- benign adenoma
Thyroid massesThyroid masses
Malignant
- follicular carcinoma- papillary carcinoma- anaplastic carcinoma- other carcinomas
Thyroid massesThyroid 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 massesThyroid 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 massesThyroid masses
Assessment:
- history
- clinical examination
- thyroid function tests
- thryroid scan
- fine needle aspiration biopsy
Thyroid cancerThyroid cancer
Treatment:
- radio ablation with 131I *
- thyroidectomy +/- neck dissection
- external beam radiotherapy for persistent disease *
* Does not cause osteoradionecrosisof the jaws
Questions????