Endocrinology Course2

8/8/2019 Endocrinology Course2

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Endocrinology Course Content

Semester (5)Clinical Pharmacy Course

Randa AlMahdi



Course Content

For each disease disorder there will be asystematic approach to: Terminology of thedisease, general approach to therapeutics,epidemiology, pathology, aetiology, clinicalmanifestations, investigations

used, prevention, pharmacological treatment and non

pharmacologicaltreatment of diseases.

Cases from real patients will be discussed andsolved as pharmaceutical care provission



Lectures topics include

1. Problem ±Oriented approach: Problem list & SOAP notes

Subjective data, Objective data, Assessment & Plan

Important abbreviations used in patients¶ records (cases: howto go through patients¶ medical records)

2. Adrenocortical Dysfunction: HPA Axis normal control, disorders& abnormalities, management

3. Adrenocortical Dysfunction: disorders.

4. Diabetes Mellitus: Type 1 pathophysiology and therapeutics ,drugs used, drugs in special populations.



Lectures topics include

5. Diabetes Mellitus: Type 2 pathophysiology and therapeutics ,drugs used, drugs in special populations.

6. Diabetes Mellitus :Monitoring parameters, patient education7. Thyroid disorders: Hyperthyroidism, drugs used in both cases,

monitoring, complications

8. Hypothyrodism, drugs used in both cases, monitoring,complications

9. Parathyroid Disorders: hyperparathyroidism &hypoparathyrodism: treatment approach.

10. Hormonal Contraception & hormonal replacement therapy.



Discussion of Endocrinology

Discussions of true endocrinology cases.

Group seminars

Assingments.



³1´

Problem Oriented

Approach



Definition

How to use, read the medical record?



Components of POM

1) Problem list

2) SOAP Note



Medical record

Chief complaint

History of present illness

Past medical history History

- Family

- Social

- Medication

Review of systems

PE

Radiography

Laboratory data

SOAP notes



Problem list

Numbered

Described as precisely as possible Arranged according to acuity

Resolved or inactive



SOAP notes

Subjective

Objective Assessment

plans



Implementation of plan

Diagnostic

Therapeutic Educational



Follow up progress

SOAP notes



Sample SOAP

Case --------------- Problem --------------------

-----------------------------------------------------------

S:

-----------------------------------------------------------

O:

-----------------------------------------------------------

A:------------------------------------------------------------

P:

------------------------------------------------------------



A: Assessment

Etiology

Indications for therapy

Assessment for therapy



P: Plan

Therapeutic plan

Drugs to be avoided Goals

Therapeutic Monitoring

Toxicity Monitoring Education plan

Future plan



Abbreviations used in medical records

VS: Vital Signs

HEENT: Head, ear, neck & trachea

COR: CoronaryCHEST: Chest

ABD: Abdomen

GU: Gentiurinary

WNL: Within Normal

RECTAL: Rectal

EXT: ExtremitiesNEURO:Neurological

BP: Blood pressure

RR: Respiratory rate

Oriented X 3: oriented to time, place & person



Adrenocortical Disorders



Contents

Normal Control of HPA Axis

Disorders include:1- Cushing¶s Syndrome

2- Addison¶s Disease

3- Hyper & Hypoaldosteronism



Regulation of Hormone Secretion

Higher control by Corticotropin Releasing

Factor CRF from the median eminence of the hypothalamus.

This stimulates secretion of

adrenocortictropic hormone from the anterior

pituitary (see the flow chart)



Hormonal control

CRF release

ACTH release

Cortisol release



CRF

From Median eminence of hypothalamus

Other neurotransmitters can stimulate as well:1) 5 hydroxytryptamine 5HT

2) Norepinephrine NE

CRF stimulates ACTH from pituitary



Anterior Pituitary

ACTH then stimulates the adrenal cortex of

the adrenal gland to secrete CORTISOL andto a lesser extent aldosterone and

androgens.



Cortisol

Rising cortisol level inhibits the secretion of

CRF and ACTH in a negative feed backmechanism.



Aldosterone

Renin Angiotensin Aldosterone system RAA

responses to electrolyte and volumechanges to either increase or decrease

aldosterone secretion.

This RAA system is stimulated or inhibited by

factors



RAA system stimulators

Low blood pressure

Salt depletion B adrenergic stimulation

CNS excitation



RAA system Inhibitors

Salt loading

Angiotensin II Vassopressin

Potassium ion

Calcium ion High blood pressure

Drugs



Cushing¶s Syndrome

Hypercortisolism

Either overproduction of endogenous cortisolfrom the gland or exogenous adminstration

of the hormone.

High ACTH ADRENAL HYPERPLASIA

(cushing¶s disease) accounts for 70% of cushings cases.

Pituitary adenomas account for 85% of these

70%.



Cushing¶s Syndrome

The remainder of cases (30%) are divided

equally as 15% each between adrenaladenomas and carcinomas and ectopic

ACTH secreting tumors.



Cushing¶s Syndrome

Diagnosis

Cushingnoid features if long standing

hypercortisolism Documentation of hypercortisolism

Elucidation of the etiology of hypercortisolism



Cortisol level Measurement

High levels are also in:

StressPregnancy

With some drugs: Heparin- Spiranolactone-

Ethanol- Lithium - Naloxone

To overcome interference measure indirectly:

urine 17 OHCH if > 12 mg/ 24 hours



Dexamethsone suppression test

1 mg dexamethasone given at the night

17 OHCH in urine is measured in themorning if suppressed to < 5



Clinical manifestations

Hyperglycemia

Obesity, moon face, baffallo Hump Myopathy

Osteoporosis

Psychological changes Hypertension

Acne

Impotence



Cusgingoid Features

Buffalo Hump

Moon face



Laboratory Investigations

Erythrocytes count > 6,000,000

hemoglobin > 18 mg/dlPolycythemia

WBC : Decreased lymphocytes ± decreased

esinophils

Electrolytes: Calcium -Potassium



Treatment

Adrenocortical adenoma and adrenocortical

carcinoma: surgical removal of the involvedgland

Inoperable patients: chemotherapy

Ectopic ACTH producing tumors: surgical

excision or radiotherapy.

Cushing¶s disease: Pituitary irradiation



Addison¶s Disease

Chronic insufficiency in the production and

secretion of cortisol and aldosterone fromthe adrenal cortex .

Destruction of the gland results from

infections

Autoimmune and infiltrative process

Or iatrogenic causes



Causes

Tuberculous infection

Ideopathic Addison¶s Iatrogenic disease: removal or irradiation

Withdrawal of chronic use exogenous

glucocorticoid

Reported cases of: Hydrocortisone 100 mg

X3 days or Prednisone 30 mg X 5 days. Or

Prednisone 20 mg X 7 days: all have induced

HPA axis suppression.



HPA axis supression

Physiologic doses of 20-30 mg

hydrocortisone or equivalent can causesupression if adminstered in the afternoon,

evening or night.

Chronic use of glucocorticoid and withdrawal

may be recovered over 10 months



Clinical manifestations

Vague no-specific symptoms: fatigue ,

malaise, nausea, dizziness and anorexia Hypotension

Diarrhea

Hyperpigmentation in body creases due to

chronic increased level of ACTH



Laboratory abnormalities

Neutropenia

Esinophilia Lymphocytosis

Hyponatremia

Hyperkalemia Sodium/ potassium ratio is < 30



Radiography

Small heart

Adrenal calcification



Acute insufficiency

Same clinical manifestations developing over

short period Percipitated by stress

Best treatment is to prevent occurance



Treatment

Replacement of the cortisol and aldosterone

1) Hydrocortisone 20-30 mg or cortisoneacetate 25- 37.5 mg , titrate dose according

to individual patient

How dosed?

Give 2/3rd of the dose early morning & 1/3rd

late afternoon.

Or 3 equally divided doses at: early morning,

noon & 4 PM



Treatment

2) Aldosterone replacement:

By Fludrocortisone orally 0.05- 0.2 mg/ dayOr Desoxycortisoterone IM

3) Patients must be educated not to stop

corticosteroid therapy of their own and wear

bracelets or carry cards as warning.



Clinical Pharmacy

Services

Diabetes Milletus



Definition of DM

It¶s a series of complex and chronic metabolic

heteroginous disorders characterized bysymptomatic glucose intolerance

All diabetic patients show abnormalities of

insulin secretion and disease complications:

Vascular & neurologic abnormalities.

Or cellular resistance to insulin in Type II DM.



Burden of the disease

Huge economic burden both direct and

indirect costs. Drugs therapy for life ± Follow ups-

Hospitalizations ± Infections- Laboratory

work-ups

Blindness- End organ damage- Exteremitiesamputations



Pathogenesis of Type I DM

10% of all diabetics

Absolute lack of insulin Develops in children or early adulthood

Patients are usually thin.

Development of ketoacidosis is common Causes: viruses, heredity (little), autoimmune

reaction.



Pathogenesis of Type II DM

90% of all diabetics

Usually obese More genetically linked than type I.

Patients may have: High insulin, normal

insulin or low insulin levels.

Insulin receptors may be inactive,

desensitized or inadequate insulin action.

May be further classified to insulin sensitive

or resistant.



Difference between the two types

Characteristic Type I Type II

Age of onset Childhood- early

adulthood

Age 40 or older

Rapidness of onset Usually abrupt Usually gradual

Family history Little Usually +ve

Etiology Unknown(

postulations)

High heredity

association

Body weight Usually thin Usually obese

Insulin Diminished ± absent Low- normal or high

Ketosis Common Uncommon (stress)

Symptoms 3 Ps + weight loss Asymptomatic (3 Ps

may or may not show)



Other types of DM

Secondary DM:

1- Increased ACTH or increased Cortisol levels2- Drug induced: Thiazide diuretics

3- Gestational DM: 24- 28 weeks gestation.

4- Impaired glucose tolerance test: high blood

glucose level but not diagnostic of DM.

Have 40% increased risk of developing DM in

10 years time.



Normal metabolism & utilization

of carbohydrates

Carbohydrates CHO glucose

Processes of taking glucose into blood andstoring glucose in liver as glycogen and as

triglycerides and fat in adipose tissue

facilitated by insulin.

Insulin is secreted at a 0.5- 1 U / hour, andmore is secreted at a blood glucose level of >

100 mg/ dl



Normal metabolism & utilization

of carbohydrates

Insulin is cleaved (metabolized by the liver ,

peripheral tissue and the kidneys. Glucose in blood is maintained at 60- 160

mg/dl Normal metabolism & utilization of

carbohydrates



Counter Regulatory Hormones

1. It increases glycogenolysis and

gluconeogenesis in the liver.2. Growth Hormone: Secreted from the

anterior pituitary , it interferes with body¶s

ability to utilize glucose.

3. Somatostatin: Secreted by the cells of thepancreas, it reduces both insulin and

glucagon and also suppresses growth




hormone and hence decrease blood glucose ,

reduces absorption of glucose from the gut.4. Epinephrine : from the adrenal medulla , it

stimulates conversion of glycogen to glucose

in liver, (same action like ephedrine and

phenylprapronalamine)5. Glucorticoides: increase gluconeogenesis

and liver glycogen.




6. Thyroid Hormone: Increase glucose

absorption from the GIT



Clinical Presentation of DM

The 3 Ps:

Polydipsia dehydration from osmoticdiuresis

Polyurea from osmotic diuresis

Polphagia due to hunger from low blood

sugar (more in type I).



To assess a diabetic patient

1- Screen those at risk

2- Diagnose3- Classify type



Screening tests

+ve family history (more with type II)

Markedly obese Women who gave birth to 9 pounds babies.

All pregnant ladies at 24- 28 weeks gestation

All patients with recurrent urinary tact, skin

or genital infections

Elderly > 65 years age in places where DM

is highly prevalent (Sudan)



Diagnosis

OGTT

Positive screening testsSigns and symptoms of high blood sugar

High random blood sugar

OGTT:

Fasting blood glucose < 115

1 hour postprandial: < 200

2 hours postprandial: < 140



Treatment of DM



Goals of treatment

Answering the questions:

Does tight sugar control preventcomplications?

Does it stop progression into end organ

damage ?

The Diabetes Control and ComplicationsTrial DCCT



DCCT

Large clinical trial 1440 subjects treated for

6.5 years Results have shown important findings

which had great impact on treatment plans

Trial had compared tight sugar control to

conventional one



DCCT

Treatment parameter Conventional Intensive

Insulin 1-2 day injections 3 or >, pump

Testing Daily, urine or blood Blood tests severaltimes/ day

Diet + exercise Quarterly Monthly

Follow up exam Quarterly Monthly

Care contact PRN by patient Weekly b y nurse



Results of DCCT

Complications Reduction %

> Step sustained retinopathy 63

Macular edema 26

Severe retinopathy 47

Laser treat5ment 51

Urinary albumin excretion mg/ day

40

> 300

39

54

Clinical neuropathy at 5 years 60



Important measures

Patient education :

Diet : 500- 1000 k cal/ dayExercise

Self monitoring

Blood & urine testing

Medications

Hyperglycemic symptoms

Hypoglycemic symptoms

Com lications



Monitoring glucose level

Plasma glucose levels are 15% less than

whole blood glucose Conversion of mmol/ l to mg/dl?

Multiply by 18



Glycosylated hemoglobin

Offered accurate assessment of glucose

control over a period of time Must be kept at 6.5 ± 7 %



Management of Diabetes Mellitus



Complications of Diabetes

Diabetic ketoacodosis

Diabetic ketoacidosis (DKA) is an acutemetabolic complication of diabetes

characterized: hyperglycemia,

hyperketonemia, and metabolic acidosis.

DKA occurs mostly in type 1 diabetes.It causes nausea, vomiting, and abdominal

pain and can progress to cerebral edema,

coma, and death.



Pathophysiology of DKA

Insulin deficiency the body to metabolize

triglycerides and muscle instead of glucosefor energy.

Serum levels of glycerol and free fatty acids

(FF As) rise because of lipolysis as does

alanine from muscle catabolism. Glycerol and alanine provide substrate for

hepatic gluconeogenesis, which is stimulated

by the excess of glucagon that accompanies

insulin deficiency.



Pathophysiology of DKA

ketogenesis proceeds in the absence of

insulin. The major ketoacids produced, acetoacetic

acid and -hydroxybutyric acid metabolic

acidosis.

Acetone derived from the metabolism of acetoacetic acid accumulates in serum and

is slowly disposed of by respiration.




Diabetes is a strong risk factor for

cardiovascular diseases. High uncontrolled blood sugar is associated

with macrovasular and microvascular

changes.

Macrovascular changes, no effect.




Microsvascular changes: retinopathy,

proteinurea & neuropathy, these can beimproved by glycemic control.

Tight control of blood pressure in diabetic

patients reduces mortality

Other risk factors include: smoking,hypertension, obesity & hyperlipidemia.

Use of Aspirin + lipid lowering agent + ACEI

are recommended



Insulin

Is a polypeptide hormone of complex

structure synthesized and secreted by the cells of the islets of Langerhans in the

pancreas

Is a vital hormone essential to life.



Insulin Types

Three basic types:

- Short acting with rapid onset: Soluble insulin,Insulin Lispro & Insulin aspart.

- Intermediate acting Insulins: isophane

insulin & Insulin zinc suspension.

- Those with slower onset and last for longperiods: Insulin zinc suspension.



Insulin Therapy

Duration of a particular type varies from

patient to another. Doses must be individualized for each

patient

Gradually the dose is increased avoiding

hypoglycemic reactions



Insulin Indications

All patients with diabetic ketoacidosis

Patients with rapid onset of symptoms Weakness

Ketonurea

All children with diabetes

Type II diabetics when other methods fail to

achieve good control

Pregnant diabetics

Peri-operatively.



Injection technique



Examples of recommended

regimens

Short acting + Intermediate acting twice daily

before meals

Short acting + Intermediate acting before

breakfast, short acting before evening meal

& intermediate acting at bed time.

Short acting three times before meals +intermediate acting at bed time

Type II may need intermediate acting with

or without short acting in morning or

evenin



Recommended insulin regimens

Regimen (!) Morning Noon Evening bedtime

Regimen (1) Short acting

+intermediate

acting

Short acting

+Intermediate

acting


+

intermediate

acting

Short acting

insulin

Intermediate

acting insulin


insulin

Short acting

insulin

Short acting

insulin

Intermediate

acting insulin

Regimen (4) Intermediate

actin insulin



Insulin use

Insulin requirements may be increased

during stress, infection

Insulin injection techniques may include:

syringes, pens & insulin pumps

Dose may be given by: IM ± IV (soluble only),

SC IV route is reserved for urgent cases, surgery

or seriously ill



Insulin injections sites

Arms

Thighs Buttocks

Abdomen

Hypertrophy at injection site is a common side

effect





Insulin delivery devices



Insulin delivery devices



Pharmaceutical Issues

Insulin storage

- Must be kept in refrigerator to stay untilexpiry date shown on bottle. Do not freeze.

- Once punctured a vial is stable for one

month at room temperature.

- Cold insulin is painful when injected keepbottle in use at room temperature.

- When mixing 2 types withdraw soluble first.



Oral Hypoglycemic Agents

For type II only

60-70 % patients have initial response5-20% experience secondary failure?



Oral Hypoglycemic Agents

Sulfonylureas

Biguanides Thioguaine triodinase inhibitors

Alpha glucosidase inhibitors.



Oral tretment measures

Fasting blood sugar > 150, Hgb A1c> 8%

Acarbose or sulfonylurea or metformin If FBS < 110 & Hgb A1c <7 monotherapy

adequate

If FBS > 150 & Hgb A1c > 8% sulfonylurea

+ Metformin

If FBS < 110 & Hgb A1c <7 continue

If still FBS > 150 & Hgb A1c > 8% adding

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Endocrinology Course2