Endocrinology Course Content

Semester (5)
Clinical Pharmacy Course
Randa AlMahdi
Course Content

 For each disease disorder there will be a

systematic approach to: Terminology of the
disease, general approach to therapeutics,
epidemiology, pathology, aetiology, clinical
manifestations, investigations
used, prevention, pharmacological treatment and non
pharmacological
treatment of diseases.
 Cases from real patients will be discussed and
solved 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: how
to 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 education
7. 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.
“1”

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: Coronary
CHEST: Chest
ABD: Abdomen
GU: Gentiurinary
WNL: Within Normal
RECTAL: Rectal
EXT: Extremities
NEURO: 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

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 and
to a lesser extent aldosterone and
androgens.
Cortisol

 Rising cortisol level inhibits the secretion of

CRF and ACTH in a negative feed back
mechanism.
Aldosterone

Renin Angiotensin Aldosterone system RAA

responses to electrolyte and volume
changes 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 cortisol from
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 adrenal
adenomas 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:

Stress
Pregnancy
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 the
morning 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/dl
Polycythemia
 WBC : Decreased lymphocytes – decreased
esinophils
 Electrolytes: Calcium -Potassium
Treatment

 Adrenocortical adenoma and adrenocortical

carcinoma: surgical removal of the involved
gland
 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 from
the 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 cause
supression 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 cortisone acetate 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
 Avoid night dose
Treatment

2) Aldosterone replacement:
By Fludrocortisone orally 0.05- 0.2 mg/ day
Or Desoxycortisoterone IM
3) Patients must be educated not to stop
corticosteroid therapy of their own and wear
bracelets or carry cards as warning.
Diabetes Milletus

Clinical Pharmacy
Services
Definition of DM

It’s a series of complex and chronic metabolic

heteroginous disorders characterized by
symptomatic 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- Exteremities
amputations
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 Age 40 or older
adulthood
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 levels
2- 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 and
storing 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, and
more 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 δ cells of the
pancreas, it reduces both insulin and
glucagon and also suppresses growth
Counter Regulatory Hormones

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.
Counter Regulatory Hormones

6. Thyroid Hormone: Increase glucose

absorption from the GIT
Clinical Presentation of DM

 The 3 Ps:
 Polydipsia  dehydration from osmotic
diuresis
 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- Diagnose
3- 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 tests
Signs 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 prevent
complications?
 Does it stop progression into end organ
damage ?
 The Diabetes Control and Complications
Trial 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 several
times/ 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 39
> 300 54
Clinical neuropathy at 5 years 60
Important measures

 Patient education :
Diet : 500- 1000 k cal/ day
Exercise
Self monitoring
Blood & urine testing
Medications
Hyperglycemic symptoms
Hypoglycemic symptoms
Complications
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 acute metabolic
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 glucose for
energy.
 Serum levels of glycerol and free fatty acids (FFAs)
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 β-hydroxybutyric acid  metabolic
acidosis.
 Acetone derived from the metabolism of
acetoacetic acid accumulates in serum and
is slowly disposed of by respiration.
Complications of Diabetes

 Diabetes is a strong risk factor for

cardiovascular diseases.
 High uncontrolled blood sugar is associated
with macrovasular and microvascular
changes.
 Macrovascular changes, no effect.
Complications of Diabetes

 Microsvascular changes: retinopathy, proteinurea &

neuropathy, these can be improved 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
β 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 long
periods: 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 evening
Recommended insulin regimens

Regimen (!) Morning Noon Evening bedtime

Regimen (1) Short acting Short acting
+ +
intermediate Intermediate
acting acting
Regimen (2) Short acting Short acting Intermediate
+ insulin acting insulin
intermediate
acting

Regimen (3) Short acting Short acting Short acting Intermediate

insulin insulin insulin acting insulin

Regimen (4) Intermediate

acting 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 until
expiry 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 keep
bottle in use at room temperature.
- When mixing 2 types withdraw soluble first.
Oral Hypoglycemic Agents

For type II only

60-70 % patients have initial response
5-20% 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 bedtime
insulin or shift to insulin