12. endocrine: adrenal

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????