Endocrinology: Pathology - Adrenal cortex and medulla Flashcards
List six causes of Cushing syndrome. Which of these are ACTH-dependent and which are ACTH-independent? Which is most common?
- Exogenous glucocorticoids (most common)
ACTH-dependent:
2. ACTH-secreting pituitary adenomas (most common ACTH-dependent, 70%; “Cushing disease”)
3. Corticotroph cell hyperplasia (primary or secondary due to hypothalamic dysfunction with raised CRH)
4. Ectopic ACTH secretion by non-pituitary tumours
ACTH-independent:
5. Primary adrenal neoplasm
6. Primary cortical hyperplasia (rare)
What is the most common non-pituitary tumour to secrete ACTH?
Small cell lung Ca
Which primary adrenal neoplasm causes more marked hypercortisolism?
Carcinoma
What are the four morphological patterns seen in the adrenal gland in the setting of hypercortisolism, and what causes each?
- Focal atrophy: due to exogenous glucocorticoids
- Diffuse hyperplasia: due to ACTH-dependent causes
- Micronodular and macronodular hyperplasia: primary hyperplasia
- Pituitary adenoma or carcinoma
What derangements in serum ACTH and response to dexamethasone suppression test are seen in the setting of pituitary causes of Cushing syndrome vs ectopic ACTH syndromes vs adrenal tumours?
Pituitary causes:
- Increased ACTH
- No change in ACTH or urinary cortisol excretion with low doses
- Reduced ACTH and suppression of urinary cortisol excretion with higher doses
Ectopic ACTH:
- Increased ACTH
- No change in ACTH or urinary cortisol excretion with low or high doses
Adrenal tumours:
- Decreased ACTH (due to negative feedback)
- No change in ACTH or urinary cortisol excretion with low or high doses
List three causes of primary hyperaldosteronism. Which of these is most common?
- Bilateral idiopathic hyperaldosteronism (most common, 60%)
- Adrenocortical neoplasm (aldosterone-producing adenoma, adrenocortical carcinoma)
- Primary familial hyperaldosteronism (including glucocorticoid-suppressible)
What is Conn syndrome?
Hyperaldosteronism caused by aldosterone-secreting adenoma
Describe three broad causes of secondary hyperaldosteronism with specific examples of each
- Decreased renal perfusion (e.g. renal artery stenosis, arteriolar nephrosclerosis)
- Arterial hypovolaemia and oedema (e.g. CCF, cirrhosis, nephrotic syndrome)
- Pregnancy
What is the pathogenesis of pregnancy-induced hyperaldosteronism?
Due to oestrogen-induced increase in plasma renin
What is the difference in plasma renin activity between primary and secondary causes of hyperaldosteronism?
Primary: decreased plasma renin activity with increased aldosterone:renin activity ratio (must be confirmed with aldosterone suppression test)
Secondary: increased plasma renin activity
Describe the clinical presentation of primary and secondary hyperaldosteronism
Both present with HTN, and Na+ and fluid retention
Primary hyperaldosteronism may also present with hypokalaemia
Describe two broad causes of primary adrenocortical insufficiency with specific examples of each
- Loss of cortex (e.g. congenital hypoplasia, AI adrenalitis, infection, systemic AI conditions such as sarcoidosis and amyloidosis, metastatic carcinoma)
- Failure of metabolism (e.g. congenital hyperplasia, drug- or steroid-induced ACTH inhibition)
Describe two broad causes of secondary adrenocortical insufficiency with specific examples of each
- Hypothalamic-pituitary disease (e.g. neoplasm, infection, infiltrative disease such as sarcoidosis, inflammation)
- Hypothalamic-pituitary suppression (e.g. long-term steroid administration, steroid-producing neoplasms)
What are the three syndromes that adrenocortical insufficiency may present as?
- Primary acute adrenocortical insufficiency
- Primary chronic (Addison disease) adrenocortical insufficiency
- Secondary adrenocortical insufficiency
Give three causes of primary ACUTE adrenocortical insufficiency
- Acute stress (e.g. surgery, infection) in setting of chronic adrenocortical insufficiency
- Rapid withdrawal of exogenous steroids after prolonged treatment
- Massive adrenal haemorrhage (e.g. in newborns, Waterhouse-Friderichsen syndrome)
What is Waterhouse-Friderichsen syndrome? Who does it most commonly affect?
Acute adrenal failure due to adrenal haemorrhage secondary to severe bacterial infection
More common in children
What is the usual causative organism in Waterhouse-Friderichsen syndrome? What are some other implicated organisms?
N. meningitidis
May also be caused by Pseudomonas, streptococcus, Haemophilus influenzae, staphylococci
Four features of Waterhouse-Friderichsen syndrome
- Sepsis
- Hypotension -> shock
- DIC with widespread purpura
- Acute adrenocortical insufficiency
What causes >90% of cases of Addison disease?
Autoimmune adrenalitis
Tuberculosis
AIDS
Metastatic cancers
What is the most common cause of Addison disease?
Autoimmune adrenalitis
Which two autoantibodies are implicated in autoimmune adrenalitis?
Antibodies to 21-hydroxylase and 17-hydroxylase
What are the two underlying syndromes which cause autoimmune adrenalitis and what are their other features?
- APS1: with polyendocrinopathy and skin changes (due to AIRE mutation)
- APS2: with autoimmune thyroiditis or T1DM, no skin changes
What are the most common infectious causes of Addison disease?
Tuberculosis
Fungi (e.g. Histoplasma capsulatum)
How does AIDS cause adrenal insufficiency?
May be due to opportunistic infection (e.g. CMV, MAC) or malignancy (e.g. Kaposi sarcoma)
Which two metastatic cancers most commonly cause Addison disease?
Lung
Breast
Describe five clinical features of Addison disease
- Non-specific progressive weakness and fatigue
- GI disturbances: anorexia, nausea and vomiting, diarrhoea, weight loss
- Hyperpigmentation
- Hypoaldosteronism: hyperkalaemia, Na+ and fluid loss leading to volume depletion and hypotension
- Acute crisis if stressed
Three clinical features of acute adrenal crisis
- Intractable vomiting
- Abdominal pain
- Cardiovascular collapse
What causes the hyperpigmentation seen in Addison disease?
Due to increased production of POMC, precursor to ACTH but also MSH -> stimulates melanocytes
Which clinical feature of Addison disease differentiates it from secondary causes of adrenocortical insufficiency?
Hyperpigmentation not seen in secondary adrenocortical insufficiency (because ACTH release is decreased)
What is phaeochromocytoma?
Adrenal medullary neoplasm composed of chromaffin cells which secrete catecholamines (but may also secrete peptide hormones or other steroids, including cortisol)
What is the “rule of 10s” of phaeochromocytoma?
- 10% extra-adrenal (“paragangliomas”)
- 10% sporadic cases are bilateral (50% if familial)
- 10% malignant
- 10% not associated with HTN
- Now 25% (previously thought to be 10%) associated with germline mutations (e.g. von Hippel-Lindau, NF1, Sturge-Weber, MEN)
Describe the clinical presentation of phaeochromocytoma
90% have HTN
Two-thirds present with paroxysmal catecholamine release, characterised by episodic diaphoresis, headache, anxiety, tremor, visual disturbance, abnormal pain and nausea
List three malignancies associated with MEN-1. Which of these are most common?
3 (+1) P’s:
1. Parathyroid (most common)
2. Pancreas (endocrine)
3. Pituitary (usually Prolactinoma)
List three malignancies associated with MEN-2
- Phaeochromocytoma
- Medullary carcinoma
- Parathyroid hyperplasia
What is pre-eclampsia and how does it present?
Systemic syndrome characterised by widespread maternal endothelial dysfunction, likely due to placental ischaemia
Presents with HTN, oedema and proteinuria (usually in third trimester)
In which demographic is pre-eclampsia more common?
Primiparas
Five symptoms which suggest severe pre-eclampsia (with likelihood of transition to eclampsia)
- Hypercoagulability
- AKI
- Pulmonary oedema
- Headache
- Visual disturbances
What is eclampsia?
Severe form of pre-eclampsia characterised by seizures
What is HELLP syndrome? How common is it?
Occurs in 10% of women with eclampsia
Characterised by:
- Haemolysis
- Elevated Liver enzymes
- Low Platelets
Describe the three pathogenic factors involved in pre-eclampsia
- Abnormal placental vasculature -> placental ischaemic
- Endothelial dysfunction
- Coagulation abnormalities: decreased PGI2, increased thromboxane
Six morphological features seen in the placenta in pre-eclampsia
- Placental infarcts and villous ischaemia with hypovascularity
- Fibrinoid necrosis
- Retroplacental haemorrhage
- Intramural lipid deposition
- Prominent syncytial knots
- Thickened trophoblastic basement membrane
