Endocrine Flashcards
Does the pituitary lie outside of the dura?
Yes
How can the pituitary be accessed?
Through the sphenoid bones
Which artery supplies the posterior pituitary?
Inferior hypophyseal artery
Which vein drains the posterior pituitary?
Inferior hypophyseal vein
Which hormones are secreted by the posterior pituitary?
Vasopressin
Oxytocin
What supplies blood to the anterior pituitary?
Capillary plexus with a high concentration of releasing hormones
Which hormones are released by the anterior pituitary?
ACTH, TSH, GH, CH, FSH, PRL
What is made in the adrenal cortex?
Steroid hormones (cortisol, aldosterone and androgens)
Which histological zones are located in the cortex?
zona glomerulosa
zona fasciculata
zona reticularis
What is made in the adrenal medulla?
catecholamines e.g. adrenaline
What is the role of the HPA axis?
Maintains homeostasis in real or perceived stress
On what systems does cortisol act?
Metabolic, cardiovascular, immune, CNS
On what receptors do glucocorticoids act on?
Glucocorticoid receptors
How is glucocorticoid activity (duration and magnitude) regulated?
GR expression
How are GR distributed in the body?
Widely through the brain and peripheral tissue
What is Cushing’s syndrome?
Excess cortisol
What is the most common cause of Cushing’s syndrome?
Iatrogenic administration of steroids
What is the most common cause of Cushing’s syndrome?
Raised ACTH usually due to pituitary adenoma (Cushing’s disease)
What are potential endogenous causes of Cushing’s syndrome?
Cushing’s disease
Paraneoplastic syndromes
Adrenal adenoma/cancer
Adrenal nodular hyperplasia
How can it be told that Cushing’s syndrome is due to a paraneoplastic cause?
ACTH is not surpassed by dexamethasone
What are the symptoms of Cushing’s syndrome?
Weight gain Mood change Proximal weakness Gonadal dysfunction Tendon rupture and thickening
What are the signs of Cushing’s syndrome?
Central obesity Moon face Buffalo hump Supraclavicular fat Muscle atrophy Purple abdominal striae Osteoporosis Raised BP Raised blood glucose Infection prone and poor healing
What is the initial test if Cushing’s syndrome is suspected?
Midnight cortisol or 24 hr cortisol urine test
How is a diagnosis of Cushing’s syndrome confirmed?
Short dexamethasone suppression test - check cortisol at 8am and there is no suppression Cushing’s syndrome
48 hour dexamethasone suppression test - check midnight cortisol
What makes Cushing’s syndrome due to an adrenal tumour more likely?
If plasma ACTH is reduced by dexamethasone suppression test but patient is Cushingoid
How is an adrenal tumour investigated?
CT adrenal glands, if no mass found then do adrenal vein sampling or adrenal scintography
If the ACTH on dexamethasone suppression is low but the patient is still Cushingoid what is the differential?
Pituitary cause
Ectopic ACTH production
How do you differentiate between a pituitary cause and ectopic ACTH production?
Give high dose dexamethasone or CRH test. If cortisol is raised then there is a pituitary disease.
What is Cushing’s disease?
Excess ACTH from anterior pituitary causing Cushing’s syndrome
What is the problem when using an MRI on pituitary tumours?
Only 70 percent detected as they are very small
How is iatrogenic Cushing’s syndrome treated?
Stop steroids
How is Cushing’s disease treated?
Removal of pituitary adenoma
Bilateral adrenalectomy if the source of ACTH is undetectable or recurrent post op
How is adrenal adenoma treated?
Adrenalectomy
How is adrenal carcinoma treated?
Adrenalectomy + radiotherapy + mitotane (adrenalolytic)
How is ectopic ACTH production treated?
Surgery if tumour hasn’t spread
Metyrapone, ketoconazole and fluconzole post operatively
What is Addison’s disease?
Primary adrenocorticoid insufficiency so not enough corticosteroids and adrenocorticoids (e.g. aldosterone) are made
What are main causes of Addison’s?
80 percent autoimmune
TB
Adrenal mets
Adrenal haemorrhage -Waterhouse Friederichsen syndrome
How do Addison’s symptoms develop?
Gradually
What are the symptoms of Addison’s?
Nausea, vomiting, diarrhoea and sweating Salt cravings due to sodium loss in urine Fatigue, light headedness, dizziness Hyper pigmentation Muscle weakness and pain Weight loss Changes in mood/ personality Darkening of palmar crease/recent scars (not seen in secondary or tertiary adrenal insufficiency)
How does aldosterone work?
Regulates BP by acting on distal tubes to enhance sodium and water reabsorption and secrete potassium into urine
Which hormone has the opposite function to aldosterone?
ANP
Which organ releases ANP?
The heart
What the signs of Addison’s?
Low BP +/- orthostatic hypotension
Hyper pigmentation
Other autoimmune conditions such as T1DM, Hashimoto’s thyroiditis and vitiligo
Why is there hyper pigmentation in Addison’s?
Melanocyte stimulating hormone (MCH) and ACTH have the same precursor molecule (POMC). POMC gets cleaved in the anterior pituitary to get MSH, ACTH and beta lipotrophin.
What is autoimmune polyendocrine syndrome?
Addison’s plus at least one of: T1DM, Hashimoto’s thyroiditis or vitiligo
What is the maintenance therapy of Addison’s?
Lifelong hydrocortisone/prednisolone tablets in a dosing regimen that mimics physiological release
+/- fludrocortisone (to replace aldosterone)
Which features suggest hypoaldosteronism?
Hyponatremia and hyperkalemia
Which signs are suggestive of Addison’s disease?
Hypercalcaemia Hypoglycaemia Eospinophila and lymphocytosis Metabolic acidosis due to hydrogen ion retention Signs of hypoaldosteronism
On which receptor does aldosterone act?
Na/K pump in the collecting tubule
How is Addison’s diagnosed?
Synacthen test (ACTH stimulation test) - cortisol levels should not rise when tetracosactide is given
What is an Addisonian crisis?
Severe acute adrenal insufficiency
What the signs of an Addisonian crisis?
Confusion Lethargy Syncope Hyponatremia Hypercalcaemia Severe vomiting and diarrhoea leading to dehydration low BP Hypokalemia Convulsions Fever Penetrating lower body pain
What is the management of an Addisonian crisis?
Fluids
Emergency stat cortisol
Fludrocortisone can be given
Give emergency pack
What is diabetes incipidus?
Extreme thirst due to lack of renal vasopressin (ADH) production
How does ADH work?
Increases water reabsorption in the distal tubule and collecting duct by increasing sodium reabsorption across the loop of Henle
How is hyponatremia treated?
Fluid restrict and give saline
At what point does hyponatremia become severe?
Na
What is the link between sodium levels and dehydration?
ECF volume is determined by sodium levels
Salt loss presents earlier than water loss
What is an isolated high urea suggestive of?
Upper GI bleed
What is an isolated high urea suggestive of in the absence of an upper GI bleed?
ECF depletion
What the key clinical signs in hyponatremia?
Postural hypotension
Normal JVP
Oedema
What are the clinical signs of SIADH?
Euvolemic
Truly hypotonic plasma
Very concentrated urine
What is the pathogenesis of SIADH?
Excess ADH from posterior pituitary so excess water retention and dilution of plasma solutes
How is SIADH treated?
No saline - already excess H2O
Fluid restrict
Can give steroids if needed
Stop drugs if needed
How can you tell there is not renal loss of sodium (and only gut loss) in hyponatremia?
No sodium in the urine
What is the diagnosis if the patient has no sodium in the urine with hyponatremia?
SIADH
What potential conditions may be present with renal loss of sodium in hyponatremia?
Addisons
Kidney disease causing sodium loss
What is Conns syndrome?
Excess ADH production from the adrenal glands (primary aldosteronism)
What is the main cause of Conn’s?
66 percent - adrenal gland hyperplasia
33 percent adrenal adenoma
How is Conn’s diagnosed?
High aldosterone to renin ratio and then do a CT to look for adrenal masses
How is Conn’s treated?
Spironolactone or eplerenone that blocks ADH function
Adrenalectomy if this doesn’t work
How does PTH work?
Upregulates osteoclast activity to release calcium into blood from bones
How does PTH stimulate osteoclasts?
Indirectly, PTH binds to osteoblasts to increase RANKL expression and inhibit osteoprotegrin expression (that normally inhibits the binding of RANKL to RANK). RANKL binding stimulates osteoclast precursors to turn into osteoclasts
What role does PTH have in regards to vitamin D?
Activates vitamin D in the kidneys
Increases calcium absorption in the gut through this binding via calbindin
How does PTH increase renal absorption of calcium?
Acts on distal tubules and collecting tubules to enhance calcium reabsorption
How does PTH influence phosphate reabsorption in the kidney?
Decreases phosphate reabsorption in tubular fluid so more lost in urine
Why is there only a small drop in phosphate with a rise in PTH?
When bones are broken down some phosphate is released
PTH increases phosphate reabsorption from the kidneys
How is PTH secretion stimulated?
Low serum calcium (negative feedback)
High phosphate has some inhibitory effect
How is the serum calcium sensed in regard to PTH secretion?
Specific calcium sensing receptors on chief cells
Can even slight changes in serum calcium cause maximum PTH secretion?
Yes
What is primary hyperparathyroidism?
Hyper function of parathyroid glands themselves causing raised PTH
What can cause primary hyperparathyroidism?
Parathyroid adenoma, parathyroid hyperplasia, parathyroid carcinoma (rare)
What do bloods tests show in primary hyperparathyroidism?
Raised calcium/ raised PTH/ raised Alk phos/ raised phosphate (unless in renal failure)
What would urine tests show in primary hyperparathyroidism?
Raised calcium
What symptoms characterise the symptoms of primary hyperparathyroidism?
Stones, moans, groans and psychiatric overtones (kidney stones, hypercalcaemia, constipation, peptic ulcers and depression)
What are the less common signs of primary hyperparathyroidism?
Thirst and dehydration Abdo pain Pancreatitis Osteoporosis and osteopenia (maybe pathological fractures) Raised BP
What percentage of primary hyperparathyroidism cases are adenomas?
80 percent
What percentage of primary hyperparathyroidism cases are hyperplasia?
20 percent
What may be seen on imagining with primary hyperparathyroidism?
Subperiosteal cysts Erosions Browns tumours of the phalanges \+/- acrosteolysis \+/- pepper pot skull
Which scan is used to diagnose osteoporosis?
DEXA
What is the treatment for primary hyperparathyroidism?
Mild - raise fluid intake to prevent stones + avoid thiazide diuretics + reduce intake of calcium and vitamin D
Severe - surgical removal or adenoma or parathyroidectomy - done if high urine or serum calcium, osteoporosis, bone disease, renal stones, decreased GFR and less than 50 years old
What are the complications of parathyroid surgery?
Hypoparathyroidism
Hoarse voice to recurrent laryngeal nerve damage
Low calcium symptoms (hungry bones syndrome)
How do blood results look with secondary hyperparathyroidism?
Low calcium and raised PTH
What is the treatment for secondary hyperparathyroidism?
phosphate binders and vitamin D +/- cincalet
How does cincalet work?
Raises the sensitivity of parathyroid cells to calcium so there is decreased PTH secretion
How doe blood results look with tertiary hyperparathyroidism?
Raised calcium with a very high PTH
What is the pathogenesis of tertiary hyperparathyroidism?
Prolonged secondary hyperparathyroidism causes the glands to act autonomously after undergoing hyper plastic or adenomatous change
In which patients is tertiary hyperparathyroidism more common?
CKD patients
What do blood tests show in malignant hyperparathyroidism?
Raised calcium with low PTH
What is the pathogenesis of malignant hyperparathyroidism?
PTH-rp produced by some squamous cell lung cancers, breast and renal cell carcinomas - this mimics PTH
PTH is low as PTH-rp not detected by assay.
What can cause elevated prolactin levels?
Micro/macro prolactinoma, anti emetics, anti psychotics, hypothyroidism, pregnancy, lactation, pituitary stalk compression
What symptoms may be present in a prolactinoma?
Amenorrhoea, infertility, galactorrhoea and impotence
What are the signs of prolactinoma?
Galactorrhoea
Visual field defects due to compression of optic chiasm
What do blood tests show in prolactinoma?
Very high prolactin levels
Rule out thyroid involvement with TSH (high TSH raises prolactin)
MRI of pituitary (MRI more sensitive)
Which imaging modality is used to diagnose prolactinoma?
MRI pituitary
How is a prolactinoma treated?
Dopamine agonist -bromocriptine, cabergoline, peroglide
Surgery - if pharmacological treatment unsuccessful
What symptoms are present in acromegaly?
Headaches Arthralgia Sweating Increased ring or shoe size Weakness Diabetes Carpal tunnel syndrome
What signs are present in acromegaly?
Prognathism, spade hands, prominent supraorbital ridge, bitemporal hemaniopia, hypertension
What is the pathogenesis of acromegaly?
Increased growth hormone from pituitary
Usually due to somatotroph derived prolactinoma
What makes acromegaly hard to diagnose?
Slow progression and onset of symptoms makes it hard to diagnose early
How is a diagnosis of acromegaly made?
IGF 1 screening
Glucose tolerance test - GH levels not suppressed enough indicates acromegaly to confirm
MRI pituitary
How is acromegaly treated?
Somatostatin analogue - octreotide
Surgery
What is the blood supply to the thyroid?
Superior and inferior thyroid arteries
What is the normal weight of the thyroid?
10 - 20g
What is the cellular structure of the thyroid?
Follicular cells around a colloid pool
What is the role of C cells in the thyroid?
To produce calcitonin
Where is T4 made?
In the thyroid gland - deiodinated in the periphery to T3
How does T3 enter cells?
Diffuses through cell membranes
How does T3 work?
Binds to nuclear receptors to alter gene transcription
What are the roles of T3?
To raise BMR
Increase sensitivity to catecholamines
Important role in fetal neural development
How does thyrotoxicosis affect tendon reflexes?
Brisk reflexes
How does hypothyroidism affect tendon reflexes?
Slow relaxing reflexes
What heart conditions may be precipitated by thyrotoxicosis?
AF
Palpitations
What may be present in the history with thyrotoxicosis?
Other autoimmune conditions
What drugs can lead to thyrotoxicosis?
Amiodarone
Lithium
Interferon
Retrovirals
What is the first line investigation in thyrotoxicosis and what does it show?
TFTs show high T4/T3 and low TSH
What test can be used to confirm a diagnosis of Grave’s disease?
Thyroid stimulating immunoglobulin
TPO antibodies
Which antibodies are often a marker of autoimmune disease, including Grave’s?
Gastric parietal antibodies
What is the most common cause of thyrotoxicosis?
Grave’s disease
Other than Grave’s, what else can cause thyrotoxicosis?
Toxic multi nodular goitre Toxic adenoma Restrictive thyroiditis Excess iodine (Jod-Basedow) Drugs Thyroid hormone resistance TSH producing tumour (rare)
What bloods results are seen in thyrotoxicosis due to a TSH producing tumour?
Raised T3/T4 AND raised TSH
What is Grave’s disease?
Autoimmune condition causing one of: thyroid dysfunction (through thyroid stimulating antibodies) opthalmopathy pre tibial myxoedema acropatchy
How may a goitre appear in Grave’s?
Diffuse, smooth goitre with a bruit
What are the features of Grave’s opthalmopathy?
Diplopia Exophthalmos Reduced acuity Tearfulness and grittiness Proptosis Lid lag Loss of colour vision Retraction
How should Grave’s be investigated?
TFTs and MRI orbit (look for periorbital oedema)
How is Grave’s disease treated?
Steroids
Surgery/radiotherapy may be needed
What is the first line treatment for thyrotoxicosis?
Carbimazole (+/- propylthiouracil)
What the side effects of carbimazole?
Rash - 1 in 100
agranulocytosis -1 in 1000
sore throat
What is the second line therapy for thyrotoxicosis?
Radioiodine abalation
What are the potential side effects of using radio iodine?
Radioactivity
Hypothyroidism
Thyroid eye disease
When should surgery be done in thyrotoxicosis?
In the presence of a large goitre
What are the potential risks of a thyroidectomy?
Hoarseness of voice due to damage to the recurrent laryngeal nerve
Hypothyroidism (+/- hypoparathyroidism)
What are common features in a hypothyroid history?
Tired Cold Weight gain Dry skin and hair Myxoedema coma
How do TFTs appear in primary hypothyroidism?
Raised TSH and low T3/T4
Which other blood test may appear low in hypothyroidism other than TFTs?
Cortisol
Which blood test can confirm Hashimoto’s?
TPO antibody positive
What are the causes of hypothyroidism?
Congenital (1 in 400) Iodine deficiency Hashimoto's Iatrogenic Post partum thyroiditis
What is the treatment for hypothyroidism?
Levothyroxine (synthetic T4)
How does poor levothyroxine compliance show on TFTs?
High TSH with normal T3/T4
What are the clinical features of a toxic multi nodular goitre?
Thyrotoxicosis Fast growing lump in the neck with sudden enlargement or pain May have retrosternal extension Dysphagia Cough/dyspnoea/stridor
What primary investigations are relevant in toxic multi nodular goitre?
TFTs
Lung function to assess airway compromise
CXR (maybe with thoracic inlet views)
How is the diagnosis of a toxic multi nodular goitre confirmed?
Ultrasound scan with fine needle aspiration
CT (without contrast)
What is the first line treatment in toxic multi nodular goitre?
Watch and wait (especially if comorbidities present)
What secondary treatment options for toxic mulitnodular goitre?
Surgery or radioiodine
What the specify signs and symptoms of thyroid cancer/neoplasia?
Slowly enlarging mass Unilateral Soft and fluctuant mass Asymptomatic History of radiation exposure
Which investigations should be done in suspected thyroid malignancy?
CXR
Calcitonin (raised in medullary thyroid cancer - rare)
USS with fine needle aspiration
How is thyroid cancer treated?
Near total thyroidectomy with adjuvant iodine 131 abalation (+/- external beam radiotherapy)
Which treatment in thyroid cancer will help to confirm the histology?
Near total thyroidectomy
What is the post operative treatment following thyroidectomy in thyroid cancer?
High does thyroxine to suppress TSH and therefore recurrence
What acts a good tumour marker in thyroid cancer?
Rising serum thyroglobulin
What is the role of an iodine tracer in thyroid cancer?
Monitoring
What is a non-malignant form of thyroid neoplasia?
Follicular adenoma
How is papillary thyroid cancer spread?
Lymphatics
How is follicular thyroid cancer spread?
Blood
Which thyroid cancer is linked to MEN2?
Medullary
In which is it rare to have manifestations in the thyroid?
Lymphoma
Which thyroid cancer has the worst prognosis?
Aplastic
What is the 10 year disease free rate in papillary and follicular thyroid cancers?
Over 90 percent
