Adrenal Flashcards
<p>Where do the adrenal glands sit?</p>
<p>Superior and medial to upper pole of kidneys</p>
<p>What zones is the adrenal cortex organised into?</p>
<p>Zona : glomerulosa, fasciculata, reticularis </p>
<p>What is the function of the zona glomerulosa?</p>
<p>Production and secretion of mineralocorticoids and aldosterone</p>
<p>What is the function of the zona fasciculata?</p>
<p>Production and secretion of glucocorticoids and cortisol</p>
<p>What is the function of the zona reticularis?</p>
<p>Production and secretion of glucocorticoids and sex steroids</p>
<p>What is the adrenal medulla innervated by?</p>
<p>Pre-synaptic fibres from sympathetic nervous system</p>
<p>What is the medulla mainly composed of, and what do they secrete?</p>
<p>Chromaffin cells-secrete catecholamines</p>
<p>What can cause adrenal hyperfunction?</p>
<p>Hyperplasia, adenoma, carcinoma</p>
<p>What can cause adrenal hypofunction?</p>
<p>Acute: Waterhouse-Friderichsen, Chronic: Addison's disease</p>
<p>What causes congenital adrenocortical hyperplasia?</p>
<p>Deficiency or lack of enzyme required for steroid biosynthesis</p>
<p>What does the altered biosynthesis in congenital adrenocortical hyperplasia result in?</p>
<p>Increased androgen production-reduced cortisol stimulates ACTH release and cortical hyperplasia (10-15x weight)-leads to masculinisation and precocious puberty</p>
<p>What causes acquired adrenocortical hyperplasia?</p>
<p>Endogenous ACTH production-pituitary adenoma (cushings), ectopic ACTH (paraneoplastic (SCLC)), bilateral adrenal enlargement, diffuse or nodular: diffuse ACTH driven, nodular usually ACTH independent</p>
<p>In what population do adrenocortical tumours usually occur?</p>
<p>Adults (can be young (Li-Fraumeni syndrome), M=F</p>
<p>How will someone with an adrenocortical tumour usually present?</p>
<p>Incidental finding, hormonal effects, mass lesion, carcinomas with necrosis can cause fever</p>
<p>How do adrenocortical adenomas appear?</p>
<p>Well circumscribed, encapsulated lesions. Usually small:2-3cm. Yellow/brown surface. Cells resemble adrenocortical cells. Well differentiated, small nuclei, rare mitoses</p>
<p>Are adrenocortical carcinomas more likely to be functional or non functional? </p>
<p>Functional </p>
<p>What can adrenocortical carcinoma resemble?</p>
<p>Adenoma- form a spectrum</p>
<p>What is the spread of adrenocortical carcinoma?</p>
<p>Local-retroperitoneum, kidney. Metastasis-usually vascular (Liver, lung, bone), peritoneum and pleura, RLN</p>
<p>What features suggest adrenocortical carcinoma?</p>
<p>Large size (>50g, often >20cm), haemorrhage and necrosis, frequent mitoses, atypical mitoses, lack of clear cells, capsular or vascular invasion</p>
<p>What is primary hyperaldosteronism also known as?</p>
<p>Conn's syndrome</p>
<p>Primary hyperaldosteronism is usually associated with what?</p>
<p>Diffuse of nodular hyperplasia of both adrenal glands (60%)</p>
<p>What percentage of primary hyperaldosteronism cases are due to adenoma?</p>
<p>35%</p>
<p>Describe adenomas causing primary hyperaldosteronism </p>
<p>Solitary, small, bright yellow and buried in gland-do not cause mass lesion. Spironolactone bodies. Do not suppress ACTH so adjacent and contralateral adrenal tissue is not atrophic. </p>
<p>What is secondary hyperaldosteronism ?</p>
<p>Increased renin-decreased renal perfusion, hypovolaemia, pregnancy</p>
<p>What are the ACTH dependent endogenous causes of hypercortisolism?</p>
<p>ACTH secreting pituitary adenoma, ectopic ACTH (SCLC). (gives ruse to adrenal hyperplasia)</p>
<p>What are the ACTH independent endogenous causes of hypercortisolism?</p>
<p>Adrenal adenoma (10%) or carcinoma (5%), non-lesional adrenal gland atrophies</p>
<p>What are some causes of acute Primary Adrenocortical Insufficiency?</p>
<p>Rapid withdrawal of steroid treatment, crisis in patient's with chronic adrenocortical insufficiency due to stress e.g. infection or not increase steroid dose. Massive adrenal haemorrhage- newborn, anticoagulant treatment, DIC, septicaemic infection-Waterhouse Friderichsen</p>
<p>What are the causes of chronic Primary Adrenocortical Insufficiency (Addison's)?</p>
<p>AI adrenalitis, Infections-TB, fungal (histoplasma), HIV e.g. MAI, Kaposi's, Metastatic malignancy-lung, breast. Unusual-amyloid, sarcoidosis, haemochromatosis </p>
<p>When do signs and symptoms of chronic Primary Adrenocortical Insufficiency present?</p>
<p>Once >90% of gland destroyed</p>
<p>What are the symptoms/signs of Addison's?</p>
<p>Vague-weakness, fatigue, anorexia, nausea, vomiting, weight loss, diarrhoea. Pigmentation (raised POMC- not seen in hypopituitarism), low BP, abdo pain</p>
<p>What are the biochemical changes in Addison's?</p>
<p>Decreased mineralocorticoids-K+ retention, Na+ loss, hyperkalaemia, hyponatraemia, volume depletion and hypotention. Decreased glucocorticoids-hypoglycaemia. </p>
<p>What are the adrenal medullary tumours?</p>
<p>Phaeochromocytoma, neuroblastoma</p>
<p>When is neuroblastoma usually diagnosed?</p>
<p>18 months, 40% in infancy</p>
<p>What are neuroblastomas composed of?</p>
<p>Primitive appearing cells but can show maturation and differentiation towards ganglion cells</p>
<p>What are predictors of a poor outcome in neuroblastoma patients?</p>
<p>Amplification of N-myc and expression of telomerase </p>
<p>What are phaeochromocytomas derived from and what d they secrete?</p>
<p>Chromaffin cells-secrete catecholamines</p>
<p>What are phaeochromocytomas a cause of?</p>
<p>Hypertension (up to 90%)</p>
<p>What complications are associated with phaeochromocytoma?</p>
<p>Cardiac failure, infarction, arrhythmias, CVA. </p>
<p>How is phaeochromocytoma diagnosed?</p>
<p>Lab-detection of urinary excretion of catecholamines and metabolites</p>
<p>If the phaeochromocytoma arises in the bladder, what is it associated with?</p>
<p>Micturition</p>
<p>Why are phaeochromocytomas known as the 10% tumour?</p>
<p>10% extra adrenal (paragangliomas), 10% bilateral (up to 50 in familial cases), 10% biologically malignant, 10% not associated with HT, and 25% familial </p>
<p>Where will a phaeochromocytoma likely metastasise too?</p>
<p>Skeletal metastasis-also RLN, liver and lung</p>
<p>What do phaeochromocytoma cells characteristically form?</p>
<p>Nests (zellballen)</p>
<p>What are the primary adrenal insufficiencies?</p>
<p>Addison's, congenital adrenal hyperplasia (CAH), adrenal TB/malignancy</p>
<p>What are the secondary adrenal insufficiencies?</p>
<p>Due to lack of ACTH stimulation, Iatrogenic (excess exogenous steroid), pituitary/hypothalamic disorders </p>
<p>What is Addison's disease?</p>
<p>AI destruction of adrenal cortext </p>
<p>How is adrenal insufficiency diagnosed?</p>
<p>Biochemistry-decreased Na, increased K, hypoglycaemia. Short syncthen test, ACTH levels (should be increased), renin/aldosterone levels (increased renin, decreased aldosterone), adrenal autoantibodies</p>
<p>How is a short synacthen test performed?</p>
<p>Measure plasma cortisol before and 30 mins after IV/IM ACTH injection. Normal: baseline >250nmol/l, post ACTH >550nmol/l</p>
<p>How is adrenal insufficiency managed?</p>
<p>Hydrocortisone (cortisol replacement), fludrocortisone (aldosterone replacement)-education</p>
<p>What is the commonest cause of secondary adrenal insufficiency?</p>
<p>Exogenous steroid use</p>
<p>What are some examples of exogenous steroids that may lead to 2' adrenal insufficiency?</p>
<p>High dose prednisolone, dexamethasone, inhaled corticosteroid</p>
<p>What are the differences in 2' adrenal insufficiency compared to Addison's?</p>
<p>Features similar except: skin pale (no increased ACTH), aldosterone production intact (RAAS)</p>
<p>How is 2' adrenal insufficiency treated?</p>
<p>Hydrocortisone (replacement)</p>
<p>What are the ACTH dependent causes of Cushing's?</p>
<p>Pituitary adenoma (cushings disease)68%, ectopic ACTH (carcinoid/carcinoma) 12%, ectopic CRH (</p>
<p>What are the ACTH independent causes of cushing's syndrome?</p>
<p>Adrenal adenoma 10%, adrenal carcinoma 8%, nnodular hyperplasia 1%</p>
<p>How is cushing's syndrome diagnosed?</p>
<p>Establish cortisol excess: overnight dexamethasone suppression test, 24 hr urinary free cortisol, late night salivary control, low dose dexa test, repeat</p>
<p>What is the commonest cause of cortisol excess?</p>
<p>Prolonged high dose steroid therapy</p>
<p>What does prolonged high dose steroid therapy lead to?</p>
<p>Iatrogenic cushing's syndrome-chronic suppression of pituitary ACTH production and adrenal atrophy</p>
<p>What is primary aldosteronism?</p>
<p>Autonomous production of aldosterone independent of its regulators (AT2, K)</p>
<p>What are the CV actions of aldosterone?</p>
<p>Increase cardiac collagen, cytokine and ROS synthesis, sodium retention, altered endothelial function, increased pressor response, increased sympathetic outflow</p>
<p>What are the clinical features of primary aldosteronism?</p>
<p>Significant hypertension, hypokalaemia (in around 30%), alkalosis</p>
<p>What is step 1 in PA diagnosis?</p>
<p>Confirm aldosterone excess (measure plasma aldosterone and renin and express as ratio (ARR), if raised investigate further with saline suppression test, failure of aldosterone to suppress by >50% with 2l of normal saline:confirms PA)</p>
<p>What is step 2 in PA diagnosis?</p>
<p>Confirm subtype- adrenal CT to demonstrate adenoma, sometimes adrenal vein sampling to confirm adenoma is true source of aldosterone excess</p>
<p>What is the surgical management of PA?</p>
<p>Unilateral laparoscopic adrenalectomy (only if adrenal adenoma, and vein sampling confirmed), cure of hypokalaemia and HT in 30-70%</p>
<p>What is the medical management of PA?</p>
<p>In bilateral adrenal hyperplasia- use MR antagonists (spironolactone or eplerenone)</p>
What are the congenital adrenal hyperplasias?
Rare conditions associated with enzyme defects in the steroid pathway
What is the commonest CAH?
21alpha hydroxylase deficiency (95%)
How is 21a hydroxylase deficiency diagnosed?
Basal (or stimulated) 17-OH progesterone-supported by genetic analysis
What is the presentation of classical CAH?
Males-adrenal insufficiency (2/3wks), poor wt gain, biochemical pattern (Addison’s). Females-genital ambiguity
What is the presentation of non-classical CAH?
Hirsute, acne, oligomenorrhoea, precocious puberty, infertility or sub-fertility
What are the principles of treatment of CAH?
Glucocorticoid replacement, mineralocorticoid replacement in some, surgical correction, control androgen excess, restore fertility
What are some clinical features that can be indicative of a phaeochromocytoma?
Labile HT, postural hypotension, paroxysmal sweating, headache, pallor, tachycardia, or none of above!
What is the classical triad of features in phaeochromocytoma?
HT (50% paroxysmal), headache, swelling
What are the symptoms of phaeochromocytoma other than the classical triad?
Palpitations, breathlessness, constipation, anxiety/fear, wt loss, flushing-uncommon, incidental finding on imaging, family tracing
What are the signs of phaeochromocytoma?
HT, postural HT in 50%, pallor, bradycardia, tachycardia, pyrexia
What are the signs of complications in phaeochromocytoma?
LVF, myocardial necrosis, stroke, shock, paralytic ileus of bowel
What biochemical abnormalities may you see in phaeochromocytoma?
Hyperglycaemia (adrenaline secreting tumours), low K, high haematocrit (i.e. raised Hb concentration), mild hypercalcaemia, lactic acidosis
How is phaeochromocytoma diagnosed initially?
Confirm Catecholamine excess-urine :2x24hr catecholamine/metanephrins, plasma: ideally at time of symptoms
How do you identify the source of catecholamine excess in phaeochromocytoma?
MRI scan-abdo, whole body. MIBG (meta-iodobenzylguanidine), PET scan
How is phaeochromocytoma managed medically?
Full alpha/beta blockade (A before B)-phenoxybenzamine (alpha blocker), beta blocker. Fluid and/or blood replacement, anaesthetic assessment
How is phaeochromocytoma managed surgically?
Laparoscopic-total excision where possible
How is phaeochromocytoma managed if malignant?
Chemotherapy- radio-labelled MIBG
What clinical syndromes are phaeochromocytoma associated with?
MEN2, VHL syndrome, succinate dehydrogenase mutations, NF, tuberose sclerosis
