Pathology of Adrenal Gland Flashcards
What is the cause of Cushing Syndrome ( Hypercortisolism)
- Endogenous
1) ACTH dependent
i. Hypothalamus CRH producing tumour
ii. Cushing disease ACTH secreting pituitary adenoma, hyperplasia
iii. Ectopic ACTH Paraneoplastic syndrome, cancer of lung, thyroid, pancreas
2) ACTH independent Adrenal adenoma, carcinoma - Exogenous Corticosteroid Rx common cause
Explain pathogenesis pituitary, adrenal, paraneoplastic & iatrogenic Cushing syndrome.
Rujuk gambar page 6 lecture note
explain gland enlargement
How Cushing syndrome can cause hyperglycemia, glycosuria, polydipsia and DM?
Gluconeogenesis
Anti insulin action: inhibit glucose uptake by cell —–> Hyperglycaemia, glycosuria, and polydipsia
Continuous stimulation of insulin production ——> beta cell exhaustion ——–>Diabetes mellitus (type 2 DM)
Increased protein breakdown in skin, connective tissue, muscle & bone in Cushing syndrome cause?
- Loss of collagen -> thin skin
- Weak capillaries -> easily bruised skin
- Stretching of the skin -> cutaneous striae *common in abdomen
- Delayed wound healing
- Decreased muscle mass & proximal limb weakness
- Bone resorption -> osteoporosis -> backache & increased risk of fracture
Increased protein breakdown in skin, connective tissue, muscle & bone in Cushing syndrome cause?
- Loss of collagen -> thin skin
- Weak capillaries -> easily bruised skin
- Stretching of the skin -> cutaneous striae *common in abdomen
- Delayed wound healing
- Decreased muscle mass & proximal limb weakness
- Bone resorption -> osteoporosis -> backache & increased risk of fracture
Clinical feature of Cushing syndrome that can be seen physically?
1) Moon face Redness of the face - Thin skin - Polycythaemia 2) Redistribution of free fatty acids from adipose tissue to truncal area truncal ( obesity) 3) Accumulation of fat in posterior neck back (buffalo hump) 4)Thin limbs reduced fat muscle wasting
Excess Androgen cause?
Hirsutism, Impotency and acne vulgaris, amenorrhea
How mineralocorticoid lead to hypertension?
- Increased sensitive to catecholamine in blood vessels—->increased peripheral resistance
- Glucocorticoid increase cardiac muscle contraction
- Renal Na & water reabsorption
How Hyperpigmentation in mucous membranes of the mouth,
pressure points like the elbows occur in ACTH dependent Cushing syndrome?
High level of POMC
Increase ACTH and MSH
hyperpigmentation
How to investigate Cushing syndrom?
Dexamethasone suppression test.
- Administration of exogenous glucocorticoid dexamethasone —-> Measure urinary steroid excretion
given Higher dose of dexamethasone reduce ACTH secretion in pituitary Cushing syndrome so Reduce urinary steroid secretion
Low dose or high doses of dexamethasone do not suppress in ectopic (cortisol and ACTH) and adrenal (cortisol) Cushing syndrome
Explain Primary Hyperaldosteronism.
• Inhibit RAA: decreased Renin
- Bilateral idiopathic hyperaldosteronism
- Aldosterone secreting adenoma (Conn’s syndrome)- the most common cause
- Adrenocortical carcinoma rare
- Familial hyperaldosteronism about 5% of cases
Explain Secondary Hyperaldosteronism
• Activate RAA: increased Renin
- Decreased renal perfusion: arteriolar nephrosclerosis, renal artery stenosis
- Arterial hypovolemia and edema: congestive heart failure, cirrhosis, nephrotic syndrome
- Pregnancy: oestrogen induced increases in plasma renin substrate
Clinical Features of Hyperaldosteronism?
- Renal Na water reabsorption: Hypertension, oedema
* Renal K loss Hypokalemia: Neuromuscular manifestations - muscle weakness, paresthesia, visual disturbances tetany
Laboratory Investigations of Hyperaldosteronism?
• Primary hyperaldosteronism elevated ratio of plasma aldosterone
concentration to plasma renin activity
• Confirmation aldosterone suppression test (high salt diet)
Normal person- high salt diet suppress aldosterone level
What is Adrenogenitalor Virilizing Syndrome and what are the cause?
Excess androgen
Causes
- Primary gonadal disorder
- Primary adrenal disorder
- Adrenocortical tumour
- Congenital adrenal hyperplasia
Clinical Features of Adrenogenital Syndrome
Virilization effect
• Masculinization in ♀: ambiguous genitalia, oligomenorrhea, hirsutism
• Precocious puberty in ♂
Cause of Primary Chronic Adrenocortical Insufficiency (Addison Disease)?
- Genetic causes of adrenal insufficiency: congenital adrenal hypoplasia (adrenal hypoplasia congenita) and adrenoleukodystrophy
- Autoimmune adrenalitis
- Infections: HIV, TB, fungi
- Metastatic carcinoma
Cause of Secondary Adrenocortical Insufficiency?
1) Hypothalamic pituitary disease
• metastatic cancer, infection, infarction, or irradiation
2) Hypothalamic pituitary suppression
• Long term steroid administration
Clinical Features of Adrenocortical Insufficiency?
- 90% of adrenal cortex is compromised
- Insidious onset
• Progressive weakness & fatigue
• GI disturbances. Anorexia, nausea, vomiting, diarrhea, weight loss
• Hypoglycaemia - Reduced aldosterone : hyperkalaemia, hyponatremia, hypovolaemia, hypotension
Primary adrenocortical insufficiency cause hyperpigmentation.
Laboratory Investigations of Adrenocortical Insufficiency
1) Decreased plasma cortisol
2) Plasma ACTH
Primary adrenocortical insufficiency: increased plasma ACTH
Secondary adrenocortical insufficiency: decreased plasma ACTH
cause of Primary Acute Adrenocortical Insufficiency
Adrenal Crisis
1) Stress ( trauma, surgery) can precipitate chronic
adrenocortical insufficiency
2) Rapid withdrawal of prolong corticosteroids Rx
3) Failure to increase steroid dose in response to acute stress
4 Massive adrenal haemorrhage
• Newborns after prolonged difficult delivery with
considerable trauma hypoxia
• Anticoagulant therapy
• Postsurgical patients with DIC
•Waterhouse Friderichsen syndrome Neisseria meningitis, Pseudomonas, Pneumococci, Haemophilus influenzae
Clinical Features Primary Acute Adrenocortical Insufficiency (Adrenal Crisis)
- Severe hypotension, hyponatraemia, hyperkalaemia
- Hypoglycaemia
- Hypercalcemia muscle cramps
- Nausea, intractable vomiting, diarrhoea unexplained fever, abdominal pain, coma, vascular collapse, and circulatory shock
The most important disease Diseases of Adrenal Medulla?
- Pheochromocytoma
- Neuroblastic tumour
Clinical Features of Pheochromocytoma
- Paroxysmal episode of acute onset of hypertension with tachycardia, palpitations, headache, sweating, tremor, & a sense of apprehension
- Pain in abdomen or chest, nausea, vomiting
- Precipitated by emotional stress, exercise, posture changes palpate tumour region
