ADRENAL GLANDS

DISORDERS

RPh. Dr. Sana Mukhtar

Clinical Pharmacy - 702

LEARNING OBJECTIVES
Define the different disorders of adrenal
gland.
Discuss these disorders with its etiology,
features.
Enlist the diagnostic techniques for these
disorders.
Make a therapeutic plan.

Adrenal cortex

ADRENAL DYSFUNCTION
Decrease function
Adrenal insufficiency
Eg Addison disease

Increase function
Cushing syndrome
Hyperaldosteronism
Pheochromocytoma

CUSHINGS SYNDROME

CLINICAL PRESENTATION
Central obesity
Face , trunk , neck, abdomen
involvement
Moon face with plethora
Peripheral obesity and fat
accumulation
Buffalo hump
Myopathies or muscular
weakness
Striae along lower abdomen, red
to purple colour
Hypertension
Exophthalmus
CHF
Osteopenia & osteoporosis

Glucose intolerance
Psychiatric changes
Gonadal dysfunction with
amenorrhea
Malaise
Hirsuties
Striae, acne, skinthinning, bruising
Polyuria, nocturia
decreased libido and
impotence in males

Cushing's syndrome

Frequency of signs and symptoms

in Cushings syndrome
Sign
or
symptom

Occurrence
%

Sign
or
symptom

Occurrence
%

Central obesity

94

Easy bruisability

60

Hypertension

82

Osteoporosis

60

Glucose intolerance

80

Personality changes

55

Hirsutism

75

Acne

50

Amenorrhea or impotency

75

Edema

50

Purple striae

65

Headache

40

Plethoric faces

60

Poor wound healing

40

DIAGNOSIS

Hypercortisolism
24 hour urinary free cortisol test UFC
Night time salivary cortisol test (>0.25 g/dl )
Low dose dexamethasone suppression test.
Plasma ACTH , CRH test.
CT scans
MRI

THERAPEUTIC PLAN
Depends on etiology.
Symptoms resolve over several weeks to months with
rational therapy.
Iatrogenic dose tapering.
Transphenoidal adenectomy.
ACTH production decreases temporarily after surgery.
Glucocorticoid replacement therapy for 3 12 months.
Pituitary irradiation.
Ectopic ACTH secreting tumors , adrenal adenomas
surgery / radiation / chemotherapy

Cushing's syndrome

SURGERY
RADIATION
CHEMOTHERAPY
CORTISOL-INHIBITING DRUGS

PHARMACOTHERAPY
Steroidogenic inhibitors
Neuromodulators of ACTH secretion
Glucocorticoid receptor antagonist.

STEROIDOGENIC
INHIBITORS
Ketoconazole

Inhibits 11 deoxycortisol to cortisol

Inhibit ACTH secretion.
Highly effective in lowering cortisol.
200 mg PO OD - increased to 600 800 mg OD
Interactions with many drugs.
Antacids, histamine 2 antagonist, sucralfate, isoniazzid ,
rifampin.
Drug levels are required in certain conditions.
ADR- gynocomastia, GI upset , elevated reversible
transaminase level

 Metyrapone

Blocks final step inhibit 11 hydroxylase.

Used when ketoconazole has limited use
Used in combination.
Initial dose 250 mg upto 2 gm/day
ACTH increased due to drop of cortisol.
Increase in androgen and mineralocorticoids HTN, acne,
hirsutism.

 Aminoglutethimide
Inhibits conversion of cholesterol to pregnelone.
Short term effects due to compensatory rise in ACTH.
Effects are long lasting when given in combination.

Combination therapy with metyrapone &

aminoglutethemide
Beneficial when used in combination.
Promising results in lowering cortisol.

ADRENOLYTIC AGENTS
Mitotane
Inhibits 11 hydroxylation in adrenal cortex.
Reduced synthesis of cortisol.
Cell degeneration of all zones except glomerulosa in acute
therapy .

NEUROMODULATORS
Not very efficacious when used alone.
Combination therapy is sometimes effective.
Cyproheptadine
Lower ACTH secretion
For non surgical patients.
Relapse can occur.

Bromocriptine
Valproic acid
Octreotide
Roseglitazone

GLUCOCORTICOID
RECEPTOR BLOCKER

Mifepristone
Progesterone , androgen glucocorticoid receptor blocker
Inhibits Dexamethsone suppression
Increases endogenous cortisol & ACTH

Pre treatment

Post treatment

ADRENAL
INSUFFICIENCY

ADDISONS DISEASE
Adrenal insufficiency
Autoimmune mediated destruction of
adrenal cortex.
Primary and secondary adrenal
insufficiency.

 PRIMARY
destruction of adrenal
cortex
- autoimmune disorders
- chronic infection

CORTISOL
ALDOSTERONE

SECONDARY
Lack of ACTH
- drugs
- tumors and
infections of
pituitary gland

CORTISOL

CLINICAL FEATURES
Weight loss
Muscle weakness
Fatigue
Hyperpigmentation of skin
Alopecia . vitiligo
hypotension
Hyponatremia
Salt craving

Hypoglycemia
Elevated creatinine
Elevated ESR
hyperkalemia

DIAGNOSIS
Basal serum cortisol < 3 g/dl
Cosyntropin stimulation test (>19 g/dl ruled out)
Metyrapone test (plasma cortisol <8 g/dl & plasma 11
deoxycortisol <7 g/dl )
Insulin induced Hypoglycemia test
2 day ACTH Stimulation test (<18 g/dl serum cortisol)
Plasma aldosterone
Adrenal CT
MRI

PHARMACOTHERAPY

Dexamethasone - 0.5 mg od
Hydrocortisone 15 mg
Cortisone 20 mg
Prednisone 2.5 - 5 mg
Follow up in 6 8 weeks
Fludricortisone acetate 0.05 mg po od
For hyperkalemia deoxycorticosterone trimethylacetate
in oil
Stress related dose adjustment 5 10 mg hydrocort.
Alternative therapy licorice may be harmful

ADDISONIAN CRISIS
ACUTE ADRENAL INSUFFICIENCY

Sudden penetrating pain in lower back , abdomen or legs

Severe vomiting diarrhea with dehydration

Hypotension

Loss of consciousness

ADDISONIAN CRISIS

Establish IV access.
Serum electrolytes, glucose, cortisol, ACTH
Rapidly infuse 2 3 l N/S or 5% dextrose.
Inject hydrocortisone 100 mg IV Q6h.
Taper the dose over next 2 3 days if patient stable.
Start fludricortisone 0.1 mg daily
Pregnancy continue the usual glucocorticoid and mineralocorticoids ,
some women need high doses in third trimester.
Unable to take orally dexamethasone IM
daily
1 2 mg deoxycorticosterone
25 mg IV hydrocort Q6h
Adequate saline hydration
During labor increase the dose

For hospitalized severly ill patients

hydrocort 100 mg IV Q8h then taper

REFERENCES
Dipiro clinical practice
Herfindal clinical pharmacy and
therapeutic.
Roger walker
Davidson clinical medicine