Adrenal insufficiency and addisons disease

1. PATHOLOGY OF ADRENAL
GLANDS
Department of Internal Medicine №2
as.-prof. Martynyuk L.P.

2. P l a n o f
lecture
• Anatomy of adrenal glands
Regulation of hormone's
secretion
Biological effects of adrenal
gland hormones
• Chronic adrenal failure:
diagnostic criteria, treatment.
• Adrenal crisis
Pheochromocynoma :
diagnostic
criteria, treatment
Cushing's syndrome : diagnostic
criteria, treatment
Hypothalamic syndrome of
puberty period : diagnostic
criteria, treatment

3. Historical perspectives
• 1563: Eustachius first described
adrenal glands
• 1855: Thomas Addison noted real
importance of adrenal glands
• 1856:BrownSequard demonstrated
that adrenals are very necessary
for life (without adrenal glands animals
could not survive)

4. Anatomy
Localization: the top of
the kidney and weighting
approximately 5 g each.
Vascularization: a.
suprarenalis superior (from
a. phrenica inferior), a.
suprarenalis media (from
aorta abdominalis), a
suprarenalis inferior (from
a. renalis).
Innervation: n. splanchnicus
major (through plexus
celiacus and plexus
renalis), fibrae n. vagus
and n. phrenicus.
of adrenal
glands

6. Adrenal cortex include three zones:
• Glomerular (glomerulosa) produces
mineralocorticoids (e.g., aldosterone);
• Fascicular (fasciculata) produces
glucocorticoids (e.g., cortisol (hydrocortisone));
• Reticular (reticularis) produces cortisol and
androgens (dehydroisoandrosterone
(dehydroepiandrosterone)), which exert their
chief physiologic activity after conversion to
testosterone and dehydrotestosterone.
Adrenal medulla
• produces catecholamines.

8. Action of mineralocorticoids:
regulation of electrolyte balance in the
organism:
• increasing the level of sodium (by sodium
retention in distal nephron, colon, salivary
gland)
• decreasing the level of potassium (by
excretion).

9. Action of glucocorticoids:
• increasing of glycogen synthesis in liver
and decreasing of glucose utilization by
peripheral tissues, increasing
gluconeogenesis;
• increasing of protein synthesis in liver and
decreasing of its synthesis in muscles and
increasing of protein destruction in muscles;
• increasing of lipolisis;
• anti-inflammatory function and
immunomodulation;
• cardiovascular regulation (increasing of
blood

10. Regulation of secretion
• glucocorticoids’ and
androgens’ secretion
is regulated by
hypothalamic —
pituitary system
• mineralocodicoids’
secretion is regulated
by the renin —
angiotensin system, the
level of Na+, K+ in
blood, and to a lesser
extent of ACTH

11. Catecholamines are produced
from the t'y'rosine (organism takes it from the
meal or from the phenilalanine in the liver)
dioxyphenilalanine DOPHA) —• ad o c n e
(it goes into blood only from some neurons of
the central nervous system) —• nore ine
hrine (noradrenaline) (it goes into b oo
on y rom sympathetic teleneurons) —• e ine
hrine (adrenaline) (it goes into blood only from
adrenal medulla).
The principle urinary metabolic products of
epinephrine and norepinephrine are the
metanephrines and vanillylmandalic acid (VMA).

12. CHRONIC ADRENOCORTICAL
INSUFFICIENCY.
It is an insidious and usually progressive
disease resulting from adrenocortical
hypofunction.

13. Classification.
1. Primary
adrenocortical
insuXiciency (Addison's
disease).
2. Secondary
adrenocortical
insufficiency .

14. Etiology of adrenal insufficiency:
Primary:
• autoimmune processes (50 — 65 %);
• tuberculosis;
• neoplasm, metastatic carcinoma;
• inflammatory necrosis;
• amyloidosis; heamochromatosis;
• bilateral adrenal hemorrhage or infarction, intra —adrenal
hemorrhage (Waterhouse — Friedrichsen syndrome
following meningococcal septicemia);
• bilateral adrenalectomy;
Secondary:
• hypothalamic or pituitary disease (primary injury of these
organs leads to insufficiency of ACTH secretion that
cause the two side atrophy of adrenal
glands);
• glucocorticoid therapy.

15. Pathogenesis.
Deficiency of adrenal hormones contributes to
the hypotension and produces disturbances in
carbohydrate, fat, and protein metabolism, and
severe insulin sensitivity.

16. Symptoms and signs.
Presentation may be acute and chronic. Frequently
clinical signs of the primary chronic adrenocortical
insufficiency are manifested in that time when
adrenocortical tissue is destroyed on 70-90 %.
The most common complaints are:
- weakness,
- malaise,
- weight loss,
- anorexia,
- Depression,
- Hyperpigmentation of the skin

19. Objective examination:
1. Hypotension or postural hypotension
2. Tachycardia.
3. Weight loss
4. Anorexia, nausea, vomiting, abdominal
pain, diarrhea are often. Gastritis, ulcer
disease can occur.
5. Decreased cold tolerance, with
hypometabolism may be noted.
6. Sexual disorders.
7. Neurologic and psychiatric disorders:
8. Hypoglycemia.

20. Laboratory findings.
1. A low serum Na level and a hi;/h serum P level
2. Adrenal insufficiency can be specifically diagnosed by:
• low levels of lasma lucocorticoids
and mineralocorticoids, or urinary 17 —
hydroxycorticosteroid (17 — OHCS) or 17
— ketogenic steroid (17 — KGS);
• demonstrating failure to increase plasma cortisol
levels, or urinary 17 — OHCS or 17 — K
G
S
excretion, upon administration of ACTH
• To distinguish between primary and secondary adrenal
insufficiency, me have to find the level of laSl+la
ACTH: primary shows increased, and secondary shows
decreased
level.

21. Instrumental findings
1. The ECG may decreased voltage
and
prolonged P — R and Q — T intervals.
2. The shows alized slowing of
the a rhythm.

22. Treatment.
I. Etiologic: appropriate treatment of
complicating infections (e.g., tuberculosis).
II. Pathogenic:
1. Diet (enough quantity of proteins, vitamins,
salt and water).
2. Glucocorticoids
Average dosage is:
• cortisol: 20
25 mg
daily;
• prednisolone 5

23. 3. Mineraloocorticoids.
DOCSA 5 mq orally daily should be used in
patients with severe and moderate duration or
fludrocortisone 0.1 — 0.2 mq orally once a day
is recommended
4. Intercurrent illnesses (e.g., infections)
should be regarded as potentially serious
and the patient should double his dosage
until he is well.
5. If nausea or vomiting preclude oral
therapy, medical attention should be sought
immediately and parental therapy started.

24. Adrenal crisis -
is a medical emergency caused by sudden
marked insufficiency of adrenocortical
hormones.

25. Precipitating factors
1. stress (infection (especially with
septicemia), trauma, surgery, prolonged
fasting, salt loss due to excessive
sweating during hot weather);
2. sudden withdrawal of adrenocortical
hormone therapy in patients with
chronic insufficiency.

26. Clinical features.
An adrenal crisis is characterized by
- profound asthenia,
severe pains in the abdomen, lower back
or legs;
- nausea, vomiting diarrhea;
peripheral vascular collapse;
- renal shutdown with azotemia.
Body temperature may be subnormal,
through severe hyperthermia due to
infection is often seen.

27. Treatment.
Therapy should be instituted
immediately once a provisional
diagnosis of adrenocortical failure
has been made.
• Substitution therapy
• Rehydration
• Treatment of complications (hyperpyrexia,
psychotic reactions).

28. PHEOCHROMOCYTOMA.
It is a tumor of chromaffin
cells
secrete catecholamines

29. Clinical features
- hypertension,
Tachycardia, diaphoresis, postural hypotension,
tachypnea,
flushing,
cold and clammy skin, severe headache,
angina, palpitation,
visual disturbances, dyspnea,
parasthesias
- nausea, vomiting, epigastric pain, constipation
or diarrhea and a sense of impending doom are
common; some or all of these symptoms and
signs may occur in any patient.

30. Investigations
1. An increased 3-h
(24-h) urinary excretion of
epinephrine,
norepinephrine and their
metabolic products (VMA or
metanephrines). ,
.
,
2. Increased plasma
epinephrine, norepinephrine.
’
3. CT scanning of the
abdomen for the localization
of the tumor.
-

31. Treatment
1. Surgical removal of the tumor is the
treatment of choice.
2. During crisis a combination of a- and
§-adrenergic blocking agents
- phentolamine (tropaphen) 2 - 4 mg
every
5 -10 min till stopping of the crisis,
phenoxybenzamine 10 20 mg 3 —
4 times daily,
propranolol 30 60 mg/day

32. Cushing's syndrome
is a constellation of signs and
symptoms caused by prolonged
excessive amounts of circulating
cortisol.

33. Clinical feafnres
• Obesity
Typically the distribution of fat
involves the trunk, particularly the
cervicodorsal region (buffalo
hump), supraclavicular area, and
abdomen. The face is round and
plethoric (moon face). The
extremities are thin in relation to
the rest of the body.

34. • The skin of patients with
Cushing's syndrome is thin
and fragile, ecchymoses and
hematomas results from a
combination of thin skin and
capillary fragility.
• Striae, when present, are
usually located on the
abdomen, breast, and axillae.
Occasionally, they may be
found on the back and on
the extremities. They are pink
or purplish in color and wider
than 1 cm

35. Clinical features
• Hypertension
• Proximal muscular weakness affecting
predominantly the muscles of the pelvic girdle
• Acne, hirsutism, and menstrual
irregularities
• Osteoporosis, compression fractures and
persistent back pain
• Peripheral edema
• psychiatric manifestations, including anxiety,
depression, and even frank psychosis

36. Diagnosis.
There are two phases of investigation:
• confirmation of the presence or absence of
Cushing's syndrome;
• differential diagnosis of its case.

37. 1. Glucose intolerance, glucosuria is
often seen, but ketoacidosis or the
chronic complications of hyperglycemia
are very uncommon
2. The level of cortisol and ACTH
3. Dexamethasone suppression test
4. Radiologic diagnosis includes X-ray
examination for a pituitary tumor
, and
computed tomography which is the most
popular procedure for visualizing the
adrenals in patients with Cushing's
syndrome

38. Treatment.
1) Suręery:
the transfrontal exploration,
transphenoidal hypophysectomia
adrenalectomy
2)pituitary irradiation.
3) pharmacoIoś;ic therapy
peritol (4 mg 2 3 times a day, which is increased to a
maximum dose of 4 mg every 4 h over 2 to 4 — 6 — 12
weeks the dopamine agonist bromocriptine the usual dose is
2.5 mg
three times a day. But the therapy has to be began from the
1/•of a tablet (2.5 mg) at a bedtime for 3 to 4 days (because of
its side effect such as somnolence), then it has to be
increased on 1
/4of a tablet each 3 days to 7.5 mg.
symptomatic therapy

39. Hypothalamic syndrome
pubertal period.
Particularities.
• Obesity is not cushingoid
(not central).
• Striae (pink and not
very large).
• Hypertension (constant
or
permanent).
• Glucose intolerance.

40. 1. Diet 8.
2. Parlodel (2.5 — 5 mg for 3 — 6 month).
3. Peritol (4 mg 2 times a day for 1 month).
4. Dehydration therapy (hypothiasid 50 — 100 mg/day
MgSO4 25 % solution intramuscular 10 — 15
times).
5. Nonsteroid anti-inflammatory drugs (indometacine).
6. Biogenic stimulators (aloe, plasmol).
7.
Treatment.
Increasing of microcirculation of the blood in the brain
(cavinton, piracetam).
8. Vitamintherapy.
9. Symptomatic therapy (hypotensive therapy).
10. Physiotherapy.

41. References
• The,Merck Manual of Diagnosis and Therapy (fourteenth
Edition)/ Robert Berkow and others. — published by
Merck Sharp & Dohme Research Laboratories, 1982.
P. 1014 — 1019,1025 — 1028, 1021 — 1024.
• Manual of Endocrinology and Metabolism (Second
Edition)/ Norman Lavin. — Little, Brown and Company.-
Boston-New York-Toronto-London, 1994. - P
. 111
142, 173 - 180..
Endocrinology (A Logical Approach for Clinicians
(Second Edition)). William Jubiz.-New York: WC Graw-
Hill Book, 1985. - P
. 38 — 42, 144 —164, 198 —205.
(Third Edition). Mohammad mam Danish.
2002. — P.459 — 462, 504 — 505.
P*a*kistan
,
• Short Textbook of Medical Diagnosis and Ma en
t