SUPRARENAL GLANDS DISEASES

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SUPRARENAL GLANDS DISEASES

• Lecturer Sakharova I.Ye. M.D.

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A Close Look at the Adrenal Glands
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Adrenal glands hyperfunction
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Adrenal glands hypofunction
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• Cushing's syndrome is a multisystem disorder
  resulting from chronic exposure to
  inappropriately elevated concentrations of free
  circulating glucocorticoids.

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Etiology of Cushing's syndrome

• Endogenous (ACTH dependent 85)
• Cushing's disease (pituitary)
• Ectopic ACTH syndrome (small cell lung carcinoma)
  
• Ectopic CRH syndrome (bronchial carcinoid
  tumours)
• ACTH independent 15
• Common Adrenal adenoma, adrenal carcinoma
• Less common Micronodular hyperplasia,
  macronodular hyperplasia
• Rare McCune-Albright syndrome, gastric
  inhibitory polypeptide

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• Exogenous
• ACTH treatment
• Glucocorticoid treatment
• Pseudo-Cushing's syndrome
• Major depressive disorder
• Alcoholism
• Obesity

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Clinical features of Cushing's syndrome

• 90 - Central (truncal) obesity. Fat deposits may
  appear in the cheeks (moon facies), in the
  dorsocervical area (buffalo hump), and the
  supraclavicular area
• 85 - Hypertension
• 65 - Presence of multiple purple striae with a
  diameter gt1 cm on the abdomen or proximal
  extremities
• 60 - Muscle wasting and weakness affect the
  proximal muscles of leg and shoulder girdle
• 40 - Easy bruising of the skin
• 40 - Osteoporosis

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• Hyperpigmentation (palmar creases and pressure
  points) in a patient with Cushing's syndrome
  strongly suggests an ACTH cause (Cushing's
  disease)
• Patients may have mild hirsutism and acne, but
  severe hirsutism and especially virilisation
  strongly suggest an adrenal carcinoma.
• Depression, lethargy, and insomnia often occur at
  the same time as other symptoms.
• In children the dominant clinical features are
  cessation of linear growth and weight gain the
  clinical course is more aggressive than in
  adults.

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Investigation of Cushing's syndrome

• Screening tests (outpatient)
• Urinary free cortisol The measurement of 24 hour
  excretion of cortisol in urine integrates the
  variations in plasma free cortisol concentrations
  seen during the entire day three consecutive 24
  hour urine specimens. There is a false negative
  rate of 5.6, with false positives of 1 in
  normal people and 5 in obese individuals.

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• Dexamethasone suppression tests
• In normal subjects, administration of a
  supraphysiological dose of glucocorticoid results
  in suppression of ACTH and hence of cortisol
  secretion (cortisol lt50 nmol/l). This is the
  basis of dexamethasone suppression tests, of
  which there are several types.

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• The 48 hour low dose test, which is the most
  sensitive and specific screening test, entails
  the administration of 0.5 mg dexamethasone at
  intervals of exactly 6 hours from 9 am on day one
  for eight doses, and measurement of serum
  concentrations of cortisol at 9 am on day three,
  exactly 6 hours after the last dose of
  dexamethasone. A negative result is indicated
  when the serum concentration of cortisol at 9 am
  on day three is suppressed to lt 50 nmol/l. Over
  98 of patients with Cushing's syndrome fail to
  "suppress" serum cortisol on the low dose test.

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Confirmatory tests

• Insulin tolerance test In normal subjects and
  those with pseudo-Cushing's, insulin induced
  hypoglycaemia (blood glucose concentration lt2.2
  mmol/l) results in a rise of ACTH and cortisol
  concentrations. This response to hypoglycaemia is
  lost in most cases of Cushing's syndrome (90).
  This test is contraindicated in anyone with a
  history of epilepsy or cardiac disease and in
  those with hypothyroidism and hypoadrenalism.

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Treatment of Cushing's syndrome

• Transsphenoidal surgery
• Pituitary radio-therapy
• Bilateral or unilateral adrenalectomy
• Medical therapy

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Medical therapy

• Metyrapone and ketoconazole are commonly used.
  Metyrapone blocks the 11-ß hydroxylase enzyme
  involved in the final step in cortisol synthesis,
  whereas ketoconazole acts at several levels and
  inhibits cortisol synthesis by a direct action on
  the P450 cytochrome enzyme. The adrenolytic
  agent, mitotane, has a cytotoxic effect on both
  normal and malignant adrenocorticol tissue. Its
  use is mainly in the management of adrenal
  carcinoma and rarely in Cushing's disease.

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• Conn's syndrome is a disease of the adrenal
  glands involving excess production of a hormone,
  called aldosterone.
• Another name for the condition is primary
  hyperaldosteronism.

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Epidemiology of Conn's syndrome

• Represents under 1 of hypertension causes
• Peak age 30-50 years
• Most patients are women

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• Primary Hyperaldosteronism
• (Conn's syndrome)
• Solitary adrenal adenomas (80-90)
• Bilateral adrenal hyperplasia (10-20)
• 3. Adrenal Carcinoma (rare)
• 4. Unilateral Adrenal Hyperplasia (very rare)

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Clinical features of Conn's syndrome

• Often asymptomatic
• Frontal headache
• Muscle weakness to flaccid paralysis decreased
  muscle strength (because of low potassium level)
• Polyuria and Polydipsia (carbohydrate
  intolerance)
• Hypertension

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Investigation of Conn's syndrome

• Serum Electrolytes
• Serum Potassium decreased
• Serum Sodium increased (Mild)
• Metabolic Acidosis
• B. Increased serum level of aldosterone
• C. Greatly decreased serum level of renin
• Blood may also be taken directly from the
  adrenal veins (via a catheter passed through a
  vein in the inguinal region) to determine whether
  both adrenals are over-secreting aldosterone.

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Treatment of Conn's syndrome

• Adrenal Adenoma
• Surgical excision (unilateral adrenalectomy)
• B. Adrenal Hyperplasia
• Spironolactone (Aldactone)

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• Congenital adrenal hyperplasia (CAH) is a group
  of inherited autosomal-recessive disorders in
  which a genetic defect results in the deficiency
  of an enzyme essential for synthesis of cortisol
  and, at times, aldosterone.

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• The incidence of CAH is 0.06 to 0.08 in 1,000
  live births. There are several forms of CAH, the
  most common of which is 21-hydroxylase (21-OH)
  deficiency, occurring in over 90 of all cases
  (AAP, 2000).

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Pathophysiology

• In a child with CAH, cortisol synthesis is
  blocked by the lack of the enzyme 21-OH. This
  reduction of cortisol leads ton increased ACTH
  production by the anterior pituitary. Prolonged
  oversecretion of ACTH causes enlargement or
  hyperplasia of the adrenal glands and excess
  production of androgens.

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Clinical features of CHA

• The enzyme deficiency of 21-OH exposes the fetus
  to excessive production of androgens. In the male
  fetus, this causes no physical changes however,
  in the female, excessive androgens will virilize
  (to develop sexual characteristics of a male) the
  external genitalia, resulting in an enlarged
  clitoris (possibly to the extent of resembling
  the male phallus), fusion of the labial folds,
  and a rugated appearance to the labia. This is
  known as ambiguous genitalia or
  pseudohermaphrodism. The ovaries, fallopian
  tubes, and uterus are normal.

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• Approximately 75 of cases of 21-OH deficiency
  have salt wasting from a defect in ability to
  synthesize aldosterone. If not diagnosed at
  birth, the neonate with 21-OH deficiency and salt
  wasting will develop a life-threatening
  hyponatremia, hyperkalemia, and hypovolemia by
  day 10-14 of life. This is known as adrenal
  crisis.

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Acute adrenal (addisonian) crisis

• Clinical features fever, dehydration, nausea,
  vomiting, hypotension, that evolves rapidly to
  circulatory shock.

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Treatment of acute adrenal (addisonian) crisis

• Hydrocortison (Cortef) IV 100 mg as a bolus
• Intravenous saline and glucose
• Hydrocortison 10-15 mg/kg as a continuous
  infusion for 24 hours Decrease one third of the
  hydrocortison daily dose every day until a
  maintenance dosage is reached within 5 days

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• Children with atypical 21-OH deficiency will
  present later (often in the toddler or preschool
  years) with premature adrenarche (pubic hair
  development), accelerated growth velocity,
  advanced bone age, acne, and hirsutism (excessive
  body hair in a masculine distribution pattern).

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Investigation of CAH

• Molecular genetics
• Increased level of 17-hydroxyprogesteron in serum
  
• Increased level of 17-ketosteroids in urine
• Positive reaction to the glucocorticoid-therapy

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THANKS FOR ATTENTION