Adrenal Flashcards
Where are mineralocorticoids produced?
Zona glomerulosa
Where are glucocorticoids produced?
Zona fasciculata
regulated by ACTH
Where are androgens produced?
Zona reticularis
Wehere are catecholamines produced?
Medulla
What regulates aldosterone?
Renin-angiotensin system and plasma potassium
What does angiotensin II do?
Causes vasoconstriction and stimulates release of aldosterone from adrenals
Name a vitamin which is a steroid?
Vitamin D is a steroid
Immunological effects of cortisol?
Increases capillary permeability
Increases macrophage activity
Increases inflammatory cytokine production
Increases leucocyte migration
Metabolic effects of cortisol?
Increases lipolysis, central redistribution
Increases break down of carbohydrate (increases blood sugar)
Increases proteolysis
Circulatory/renal effects of cortisol
Increases cardiac output
Increases blood pressure
Increases renal blood flow and GFR
Cortisol effects on bone/connective tissue
Accelerates osteoporosis
Decreases serum calcium
Decreases collagen formation
Decreases wound healing
Aldosterone and Na+?
Aldosterone increases reabsorption of Na+
21 year old female ‘unwell’ for few months Weight loss Amenorrhoea Acutely unwell over past 48 hours with vomiting and diarrhoea On examination: Dark skin Dehydrated Hypotensive Decreased Na Increased K
Addisons
Commonest cause of secondary adrenal insufficiency?
Exogenous steroid use
e.g. high dose prednisolone
inhaled corticosteroid
dexamethasone
Aldosterone replacement?
Fludrocortisone
Cortisol replacement
Hydrocortisone
Might you see acne amenhorrea and hypertension in Cushing’s?
Yes
Main cause of Cushing’s?
-Taking too much steroid (= chronic suppression of pituitary ACTH and adrenal atrophy)
Pituitary adenoma
(then ectopic ACTH e.g. in carcinoid/carcinoma)
Types of cancer that produced ACTH?
Carcinoid/carcinoma
Possible complications of long term steroid and ACTH suppression?
Body is unable to respond to stress (illness/surgery)
Need extra doses of steroid when ill/surgery
Hypertension and hypokalaemia?
Could be primary aldosteronism
Difference between primary and secondary hyperaldosteronism
Primary hyperaldosteronism = excessive levels of aldosterone independent of renin-angiotensin system
Secondary hyperaldosteronism = excessive levels of aldosteronism because of high renin levels
Cardiovascular effects of aldosterone
Altered endothelial function Increase in ROS and cytokine synthesis Increased cardiac collagen Increased blood pressure Sodium retention Increased sympathetic outflow
Commonest secondary cause of hypertension?
Primary aldosteronism (essential hypertension is most common primary cause)
Somebosy presents with hypertension, hypokalaemia and cramps (because of alkalosis) what might they have?
Hyperaldosteronism
Con’s syndrome
Adrenal adenoma (produces aldosterone)
Causes of hyperaldosteronism?
Conns syndrome (adrenal adenoma) Bilateral adrenal hyperplasia --> MOST COMMON CAUSE (unilateral is rare)
KCNJ5 mutations?
May lead to primary aldosteronism
=allows more sodium into cell and depolarisation etc
Management of primary aldosteronism?
Surgical Unilateral laparoscopic adrenalectomy Only if adrenal adenoma (and excess confirmed in adrenal vein sampling) Cure of hypokalaemia Cures hypertension in 30-70% cases Medical In bilateral adrenal hyperplasia Use MR antagonists (spironolactone or eplerenone)
CAH
Congenital adrenal hyperplasia
21 a hydroxylase
Autosomal recessive
Management of hypercalcemia?
Fluids
Frusemide
Bisphosphonates
Where do papillary thyroid cancers occur?
In iodine rich areas
Do follicular adenoma and carcinoma share the same architecture?
Yes, difficult to distinguish
Excisional biopsy may be required
Which type of thyroid cancer are related with MEN?
Medullary carcinomas are related with MEN
They originate from parathyroid follicular C cells and secrete calcitonin
Which type of thyroid cancers originate from parathyroid follicular C cells and secrete calcitonin?
Medullary
How do follicular thyroid cancers spread
Via blood
Can phaechromoctyoma lead to diabetes?
Yes
Most common cause of death in acromegalics?
Cardiovascular disease
Is acne common in acromegaly?
Yes
Cardiovascular disease seen in acromegaly?
Fibrosis, hypertrophy, carditis
VALVE DISEASE IS NOT COMMON
Growth in children with Cushing’s?
Growth is often arrested due to excess steroid
Causes of SIADH?
C, C, C
Chest: pneumonia, TB, carcinoma, abscess
Cranial causes: head injury, intracranial bleed, meningoencephalitis, space occupying lesions
CHLORPROPRAMIDE and other drugs
Drugs which could cause gynaecomastia?
Sprionolactone
Methyldopa
Visual field loss, sweaty greasy skin, large tongue, difficulty with dentures (because of jaw or something), spade shaped hands. Who am I
Acromegaly
Congenital heart disease can cause growth retardation?
Pastest says yes
Diabetic nephropathy and death?
Responsible for 25% of diabetic deaths under the age of 30
Is diabetic nephropathy commonly associated with coronary artery disease?
yes
Drug which you should give to diabetics, can help slow down proteinuria etc
ACE INHIBITOR OMG
Amylase levels in diabetic ketoacidosis
Usually raised
Hypothyroidism and Down Syndrome?
Hypothyroidism is common in people with Down Syndrome
Salt wasting form of CAH
Weight loss, extreme tiredness, dehydration, vomitting
Virilising form of CAH
-Recognised at 2-4 years
Early virilisation
Penis enlargement
Growth of hair
Non-classical form of CAH
Less severe Develop sexually at an early age -Hirsutis -Acne -Oligomenorrhea -Precocious puberty -Infertility or subfertility
Diagnosis of CAH?
Basal or stimulated 17-OH-Progeseterone
Genetic being used more
Sources of phaeochromocytoma
Phaechromocytoma in adrenal medulla
rarely = sympathetic chain –> paraganglioma
Chromaffin cell reaction colour
Chromaffin cells reduce chrome salts to metal chromium resulting in a brown colour reaction
Phaechromocytoma symptoms?
Classic triad: sweating, hypertension, headache Labile hypertension Postural hypotension Paroxsymal sweating, headache, pallor, tachycardia (chromaffin cells reduce chrome salts to metal chromium resulting in a brown colour reaction) -Try to diagnose Phaechromocytoma! Risks in pregnancy and other risks for everyone relating to arrythmia and ischemia --> could cause death etc Palpitations Breathlessness Constipation Anxiety/Fear Weight loss Hypertension Postural hypotension in 50% cases Pallor Bradycardia and Tachycardia Pyrexia Signs of complications Left ventricular failure Myocardial necrosis Stroke Shock Paralytic ileus of bowel
Differentials for Phaeochromocytoma
Angina Anxiety Carcinoid Thyrotoxicosis Insulinoma Menopause Arrhythmia( eg. SVT) Migraine Drug toxicity Alcohol withdrawal Pregnancy Hypoglycaemia Mastocytosis Autonomic neuropathy Factitious
Biochemical Abnormalities in Phaeochromocytoma
Hyperglycaemia – adrenaline secreting tumours
May have low potassium level
High haematocrit – i.e. raised Hb concentration
Mild hypercalcaemia
Lactic acidosis – in absence of shock
The 10% tumour
Phaeochromocytoma 10% malignant 10% extra-adrenal [probably 20-30%] 10% bilateral 10% associated with hyperglycaemia 10% in children 10% familial (but probably 25%)
Hypertension and hyperglycemia?
Consider phaeochromocytoma
Diagnosis of Phaeochromocytoma/catecholamine excess
-2 x 24 hour urine catecholamine/metanephrine
-Plasma: ideally at time of symptoms
Identify source of catecholamines:
-MRI
-MIBG
-PET
Clinical Syndrome Associations (phaechromocytoma)
Multiple Endocrine Neoplasia II Von-Hippel-Lindau syndrome Succinate dehydrogenase mutations Neurofibromatosis Tuberose sclerosis
MEN II
Autosomal dominant Activating mutation in tyrosine kinase receptor (RET proto-oncogene) Associations: Medullary thyroid cancer Parathyroid hyperplasia Bilateral phaeochromocytomas
What is MENII associated with?
Medullary thyroid carcinoma
Bilateral phaeochromocytoma
Parathyroid carcinoma
Von Hippel Lindau Syndrome
Mutation in HIF 1-a
Autosomal dominant
Range of vascular tumours
Family screening vital
Succinate Dehydrogenase
SDH – B, C & D
Inactivating mutations – stabilise HIF-1a
50% extra-adrenal
SDH-D = head & neck PGL; > 70% penetrance
SDH-B = malignant PGL; < 50% penetrance
Pitfalls in Phaeochromocytoma
catecholamines raised in heart failure
episodic catecholamine secretion - levels in plasma + urine may be normal
malignant and extra-adrenal tumours less efficient at catecholamine synthesis Dopamine > Norepinephrine >Adrenaline
remember genetic syndromes
Permanent agranulocytosis is a serious side effects of which drugs?
Agranulocytosis - big decrease in WBC, particularly neutrophils
Carbimazole and propylthiouracil (drugs for hyperthyroidism)
Someone presents insidiously with diastolic hypertension…
Phaeochromocytoma
What is a dermoid cyst?
Contains mature material like skin, hair follicles and sweat glands
(i. e. material usually found on the outside)
- usually present in teenage years
Cystic hygroma
Posterior triangle swelling Contains lots of watery fluid ALMOST ALWAYS FOUND IN CHILDREN -present from birth -often large and disfiguring -just below angle of mandible -lymph fluid -transilluminate
congenital epithelial cysts, which arise on the lateral part of the neck from a failure of obliteration of the second branchial cleft in embryonic development
Branchial cysts
Level of carotid bifurcation?
Level of the superior border of the thyroid cartilage
vertebral body C4
What does a branchial cyst contain on fine needle aspiration?
Cholesterol crystals
“half filled hot water bottle”
Branchial cyst
Branchial cyst and cystic hygroma, anterior or posterior swellings?
Branchial cyst : anterior triangle
Cystic hygroma: posterior swelling
FNA thyroid and when you should re do aspiration?
inadequate Thy 1- repeat FNA
benign Thy 2 – repeat FNA 6/12
suspicious Thy 3 – thyroid lobectomy
malignant Thy 4-5 – total thyroidectomy
How is ADH assessed?
Urine osmolarity
Low sodium but volume stats unremarkable, what should you think about?
SIADH
-diagnosis of water excess as the cause is often done as diagnosis of exclusion
Talk to me about hypovolemia
Hypovolaemia implies water deficit. If it is present when [Na] is low, then there must be an even bigger sodium deficit. This is important:
hypovolaemia in hyponatraemia → too little sodium.
Hypervolaemia is most often seen as oedema. This too is useful as it gives useful information about sodium and water balanc
What does hypovolemia in hyponatremia mean?
Too little sodium
What is derived from Rathke’s pouch?
Anterior pituitary
Acidophils
Somatotrophs
Mammotrophs
(GH and PRL)
anterior pituitary
Basophils
Corticotrophs
Thyrotrophys
Gonadotrophs
Location of mineralocorticoid receptors?
Kidneys
Salivary glands
Gut
Sweat glands
- sodium/potassium balance
- blood pressure regulation
- control of extracellular volume
Loosers zones
Osteomalacia
Adrenal crisis
Extreme fatigue V v. low serum sodium, high serum K Dehydration Vascular collapse (because of low BP) Renal shut down
Which autoimmune diseases are associated with Addisons?
T1Dm
Pernicious anemia
Autoimmune thyroid disorders
Normal results of short SynACTHen test?
Normal: cortisol = baseline >250nmol/L, post : >480
Hydrocortisone as cortisol replacement
If unwell, give intravenously first
Usually 15-30mg daily in divided doses
Try to mimic diurnal rhythm
Which kind of tumour will take up MIBG?
Phaechromocytoma
What might someone with a phaeochromocytoma die from?
Arrhythmia
Ischemia
Carcinoid syndrome
Abdominal pain that comes and goes
Bright red flushing of the face, neck, or upper chest
Diarrhea
Heart palpitations
Low blood pressure
Skin lesions on the face called telangiectasias
Wheezing
Advice you should give patients if they are taking long term steroids?
- Know how to increase steroid replacement dose for intercurrent illness
- Carry a ‘steroid’ card
- Wear a Medic-Alert bracelet (gives details of their condition so tat emergency replacement therapy can be given if found unconscious)
Hirsutism developing before puberty is suggestive of what?
CAH
Biochemistry classical of Addisons?
Classically hyponatremia, hyperkalaemia, high urea (although biochem may be normal)
Severe hypotension and dehydration precipitated by intercurrent illness, accident or operation?
ADDISONIAN CRISIS
Most common cause of ambiguous genitalia?
CAH
