ADRENAL GLAND DISORDER

AND THERAPY
2021
Adrenal gland and it’s production
NOTES:

aldosterone synthase
(CYP11B2),

17α-hydroxylase (CYP17)
11β-hydroxylase (CYP11B1)
→ production of
glucocorticoids

C17-20 lyase →converts C21

corticosteroids to C19
androgen precursors.
In large doses:
1. ACTH causes metabolic changes:
ketosis
Lipolysis
2. hypoglycemia (immediately after
treatment)
3. resistance to insulin (later after
treatment)
Rate of corticosteroid production
Regulation of ACTH Secretion

CRF1 receptor, binding specificities for

CRH and the urocortins FOR ACTH
PRODUCTION

CRF2 receptor opposes those effects

mediated by the CRF1 receptor thereby,
providing a highly complex neural network
that modulates the adaptive response to
stress

AVP probably contributes TO full

magnitude OF CRH action to the stress
response in vivo
How corticosteroids work

 Gross (metabolic) actions:

 glucose: diabetogenic
 (glucose uptake and utilisation; gluconeogenesis)
 fat: Cushing’s syndrome
 (redistribution, lipolysis)
 protein: muscle wasting
 (catabolism, anabolism)
 minerals: hypertension (mineralocorticoid effect)
How corticosteroids work
 Cellular (nuclear)* level:
 anti-inflammatory and immunosuppressive actions:
 number and activity of leucocytes,
 proliferation of blood vessels,
 activity of mononuclear cells,
 activity of cytokine secreting cells,
 production of cytokines,
 generation of eicosanoids and PAF,
 complement components in blood,
 histamine release
 Hypercorticism: Cushing Syndrome

 ETHIOLOGY
 ACTH
overproduct
ion (70%)
 CRH
overprducti
on
Signs and symptoms
 General appearance: central obesity and facial rounding.
 SYMPTOMS About 65% and 58% of patients complain of myopathies and muscular weakness,
respectively
 SIGNS :
 Peripheral obesity and fat accumulation is found in 50% of patients.
 Facial plethora is caused by an underlying atrophy of the skin and connective tissue and is seen in
approximately 84% of patients.
 Patients often are described as having moon facies with a buffalo hump.
 Hypertension is seen in 75% to 85% of patients.
 Psychiatric changes may occur in as many as 55% of patients.
 About 50% to 60% of patients will develop Cushing’s-induced osteoporosis. Of these, 40% will present with
back pain and 20% will progress to compression fractures of the spine.
 Gonadal dysfunction is common, with amenorrhea seen in up to 75% of females.
 Excess androgen secretion is responsible for 80% of females presenting with hirsutism.
 LABORATORY TESTS
 A midnight plasma cortisol,
 24-hour urine free cortisol,
 and/or low-dose DST will establish the presence of
hypercorticalism.

 OTHER DIAGNOSTIC TESTS

 The high-dose DST,
 plasma ACTH test,
 metyrapone stimulation test, and
 CRH stimulation test will help determine the etiology.
Diagnose
TREATMENT

 The need of treatmemnt: Cushing’s syndrome is associated with a high

percentage of morbidity and mortality owing to associated disorders such as
diabetes mellitus, cardiovascular disease, and electrolyte abnormalities.
 Non harmacology treatment: surgary

 Pharmacology:
 (1) steroidogenic inhibitors;
 (2) adrenolytic agents;
 (3) neuromodulators of ACTH release; and
 (4) glucocorticoid-receptor blocking agents
TREATMENTS
HYPERALDOSTERONISM

PRIMARY ALDOSTERONISM
 adrenal adenoma (60%) or
 idiopathic adrenocortical hyperpla sia (35% bilateral and 5% unilateral).
 adrenal cortex carcinoma,
 primary adrenocortical hyperplasia,
 renin responsive adrenocortical adenoma,
 genetic mutations, (glucocorticoid-suppressible hyperaldosteronism).

SECONDARY ALDOSTERONISM
SECONDARY ALDOSTERONISM

 stimulation of the zona glomerulosa by an extra-adrenal factor, →RAS.

 Excessive potassium intake → aldosterone >,
 oral contraceptive → aldosterone
 pregnancy (10 times normal by the third trimester), and menses.
 Congestive heart failure, cirrhosis, renal artery stenosis, and Bartter’s →
aldosterone concentrations >
Signs and symptoms
Symptoms
 muscle weakness,
 fatigue,
 headache,
 though many patients are asymptomatic.

Signs
 Hypertension
 Reduced glucose tolerance is seen in 25% of patients
 Metabolic alkalosis
 Tetany/paralysis
 Polydipsia/nocturnal polyuria
LABORATORY TESTS
 serum potassium concentration of less than 3.5 mEq/L with a concurrent
urinary potassium content greater than 30 mEq per 24 hours (primary
aldosteronism)
 hypokalemia (80% to 90%),
 suppressed renin activity,
 elevated plasma aldosterone concentrations,
 hypernatremia (>142 mEq/L),
 hypomagnesemia,
 elevated bicarbonate concentration (>31 mEq/L).
 OTHER DIAGNOSTIC TESTS :
 plasma-aldosterone-to-plasma-renin-activity ratio (PA:PRA) greater than 25 is
(primary hyperaldosteronism).
Therapy
 Differentiating between an aldosterone-producing adenoma (APA) and
bilateral adrenal hyperplasia (BAH)

APA BAH
Left adrenal; (commond) bilateral
Adrenal size < 1cm hiperplasia
Hypertensive YES
hypokalemia, and higher YES
plasma and urinary
aldosterone
TREATMENT

APA
Surgary followed by spironolacton
BHA
Spironolactone, (the drug of choice)-
ANTI AHYPERTION:
calcium channel blockers, angiotensin-
converting enzyme inhibitors, and low-
dose diuretics such as
hydrochlorothiazide
SECONDARY ALDOSTERONISM

ETHIOLOGY:
 stimulation of the zona glomerulosa by an extra-adrenal factor, usually the →
renin-angiotensin system
 Excessive potassium intake
 oral contraceptive
 pregnancy (10 times normal by the third trimester),
 menses
 Congestive heart failure
 Cirrhosis
 renal artery stenosis
TREATMENT

 BASED ON ETHIOLOGY
 SPIRONOLACTON IS USED UNTIL
EXACT ETHIOLOGY IS LOCATED

ALGORITHM DIAGNOSIS OF
PRIMARY ALDOSTERONISM
ADRENAL
HYPOFUNCTION
ADDISON’S DISEASE
ADDISON SECODARY HYPOCORTISISM
HYERPIGMEMNTATION -LOW MSH AND ACTH AND
LIPOTROPIN (SYNTHESIS FROM POMC)
Weight loss, dehydration, -
 Distinguishing hyponatremia, hyperkalemia, and
Addison’s elevated blood urea nitrogen are
disease from common in Addison’s disease.
secondary Addison’s disease will have an Acth STIMULATION TEST IS NORMAL
insufficiency abnormal response to the rapid
 → → → → ACTH-stimulation test.
Plasma ACTH levels are usually 400 low (0 to 50 pg/mL; see Table 74–3)
to 2000 pg/mL in primary in secondary insufficiency
insufficiency
SYMPTOMS

 Patients commonly complain of weakness,

 weight loss,
 gastrointestinal symptoms,
 craving for salt
 headaches,
 memory impairment,
 depression,
 postural dizziness.
 Early symptoms : myalgias, malaise, and anorexia. As the situation progresses
→ vomiting, fever, hypotension, and shock.
SIGNS

 Increased pigmentation
 Hypotension (postural)
 Fever
 Decreased body hair
 Vitiligo
 Features of hypopituitarism (amenorrhea and cold intolerance)
LABORATORY TESTS :
 The short cosyntropin stimulation test

OTHER DIAGNOSTIC TESTS

 insulin hypoglycemia test,
 the metyrapone test,
 corticotropin-releasing hormone stimulation test.
Hypocortisism therapy: corticosteroid

 Factors in Successful Glucocorticoid Therapy

 Monitoring :
 Glucose concentrations
 Electrolytes (serum and urine)
 Ophthalmologic
 Stool tests for occult blood loss
 Growth and development (children and adolescents)
Counseling

 Take with food to minimize gastrointestinal discomfort

 Never discontinue medication on your own;
 gradual dose reduction is usually necessary
 Dosage increases may be necessary at times of increased stress (surgery or
emergency treatments)
 Be aware of potential side effects (i.e., visual disturbances, bruising, and
delayed wound healing)
 Be aware with drug dose:
Recognizing complications
 insomnia,
 enhanced appetite
 weight gain Common in patients with underlying risk factors:
 hypertension,
 diabetes mellitus,
 peptic ulcer disease Long-term intense treatment:
 cushingoid habitus,
 hypothalamic-pituitary-adrenal suppression,
 impaired wound healing Delayed and insidious:
 cataracts,
 atherosclerosis
 psychosis, glaucoma, pancreatitis
Avoiding unwanted effects
of corticosteroids
 Modification of dose/dose regimen
• Use short courses/low doses if possible
• Use steroid sparing drugs
• Withdraw ‘chronic’ steroids slowly
• Give dose once daily and in morning
• Give on alternate days if possible
• Give prophylactics if possible
• Give product locally
• Remember contraindications
• Enrol help of patient
Avoiding unwanted effects
of corticosteroids
 Steroid Selection: or as topical products (creams)
 remember, their effects can differ  hydrocortisone - mild
with regard to their
mineralocorticoid and anti-  clobetasone but. - moderately potent
inflammatory actions and duration  betamethasone - potent
of effect eg as parenteral products
 clobetasol prop. - very potent

AIA NaRet
Hydrocortisone 1 1
Prednisolone 5 1
Dexamethasone 35 <1
Fludrocortisone <<1 20
Giving products locally can
still cause problems!

systemic dosing can occur

local toxicity can develop -
skin: infection, thinning, bruising.
eye: viral infection, cataract, glaucoma.
inhalation: fungal infection, hoarseness
joints: infection, necrosis
Unwanted Effects

 Metabolic:
 growth suppression  hypertension

 diabetes mellitus  hypokalaemia

 muscle wasting  menstrual irregularities

 osteoporosis  adrenal suppression

 fat redistribution
 skin atrophy
 hirsutism
 acne
Unwanted Effects
 Other:
 infection
 emotional disturbances (psychosis, depression, mania)
 cataract, glaucoma
 GI bleeding, perforation
 Withdrawal
 Addisonian crisis
 raised intracranial pressure
 arthralgia/myalgia
 pustular rash
Q&A