Endocrinology Flashcards
Describe the blood supply of the thyroid
Superior thyroid artery (from external carotid)
Inferior thyroid artery (from thyrocervical trunk)
What structures lie laterally to the thyroid gland?
Recurrent laryngeal nerves
Describe the tissue composition of the thyroid gland
Follicular cells producing thyroglobulin, surrounding a colloid which contains iodinated thyroglobulin
What do the C Cells of the thyroid produce?
Calcitonin
Name two molecules that thyroid hormones are bound to in the blood
Thyroxine Binding Globulin
Albumin
Describe three actions of thyroid hormones
Increase Basal Metabolic Rate
Increase Heart Rate
Children’s growth
Name two non thyroid causes that can affect TFTs
Pregnancy
Medication (Lithium, Amioderone)
What is Primary Hypothyroidism? What would the TFTs show?
Cause is the Thyroid itself (commonly autoimmune)
Low T4
High TSH
What is Secondary Hypothyroidism? What would the TFTs show?
Cause is a TSH deficiency (Pituitary problem)
Low T4
Low TSH
Describe the TFTs of Hyperthyroidism
High T3/T4
Very low TSH
What would the TFTs of high T3/T4 and high TSH show?
TSH secreting adenoma
State 4 causes of Hyperthyroidism
Graves (autoimmune)
Nodular Thyroid Disease
Thyroiditis
Ectopic Thyroid Tissue
Describe the pathophysiology of Graves disease
Thyroid stimulating immunoglobulin mimic TSH to increase T3/T4
Relapsing course triggered by stress/infection/child birth
Describe the pathophyiology of Nodular Thyroid Disease
T3/T4 release can be from a singular nodule (Toxic Adenoma) or multiple nodules
Associated with iodine deficiency
Describe the pathophysiology of Thyroiditis
Inflammation from viral infection/childbirth/medication causes release of Thyroxine
Using the mnemonic SWEATING, describe the features of Hyperthyroidism
Sweating
Weight Loss
Emotional
Appetite Increased
Tachycardia
Intolerance to heat
Nervousness
Goitre
What happens to children with Hyperthyroidism?
Accelerated growth and behavioural disturbances
There is some cross reactivity of TSH receptors in the skin and eyes. What are the resulting clinical features of this?
Lid Lag - high sympathetic tone of upper eyelid
Exopthalmos
Pretibial Myxoedema
What do the TFTs normal T3/T4 and low TSH demonstrate?
Subclinical Hyperthyroidism
Name two markers used to diagnose Hyperthyroidism
Thyroid Peroxidase Antibodies
TSH Receptor Stimulating Ab
Describe how iodine uptake assesses thyroid functionality
Increased uniform uptake - Graves
Non Uniform Increased uptake - Nodular disease
Absent Uptake - Thyroiditis
State two pharmacological managements of Hyperthyroidism, their actions and their side effects
Carbimazole and Propylthyrouracil
Reduces T3 and T4 synthesis
SE: Bone Marrow Supression (fever/sore throat is serious) and Rash
Hyperthyroidism medication can take 4-6 weeks to work, what cover could you give in the mean time for symptomatic relief?
Beta Blockers
How is Radioactive Iodine used to treat Hyperthyroidism and what are it’s disadvantages?
Radioactive iodine is taken up by cells of the thyroid which are then killed as a result
Disadvantages: Requires lifelong Levothyroxine, contraindicated in pregnancy, have to avoid pregnant women and children for a few weeks
Describe two complications of a thyroidectomy
Recurrent Laryngeal Nerve Damage
Hypoparathyroidism
Give 3 complications of Hyperthyroidism
Heart Failure
AF
Osteoporosis
State 5 causes of Primary Hypothyroidism
Autoimmune
Pregnancy
Iodine Deficiency
Genetic (Familial Thyroid Dyshormonogenesis)
Drugs (Amioderone, Lithium)
Using the mnemonic ‘MOMS SO TIRED’, describe the presentation of Hypothyroidism
Memory Loss, Obesity, Menorrhagia, Slowness, Skin and Hair Dryness, Onset Gradual, Tiredness, Intolerance to Cold, Raised BP, Energy levels fall, Depression
Name a marker for Hypothyroidism
Thyroid Peroxidase Antibodies
To treat Hypothyroidism , you would use Thyroxine replacement. What range of units is Thyroxine given in, and what marker is used to monitor?
50-100 micrograms per day
If primary hypothyroidism then TSH is used to monitor
If secondary hypothyroidism then T4 is used to monitor
Give a complication of Hypothyroidism
Myxoedema Coma
Managed with IV Thyroxine and Hydrocortisone STAT
Name two molecules that Cortisol is bound to in the blood
Cortisol Binding Globulin
Albumin
Describe the relationship between Cortisol Binding Globulin and Oestrogen and its implications
CBG production is stimulated by Oestrogen
When measuring Plasma Cortisol, it combines free cortisol and bound (with the bound level being the CBG level) therefore these levels are not reliable if the patient is on HRT
When are cortisol levels at it’s highest and lowest?
Highest at 8am
Lowest at midnight
Give 4 causes of Addisons/Primary Adrenal Insufficiency
Genetic Abnormalities in steroid synthesis
TB
Metastases
Waterhouse Friderichson Syndrome
The symptoms of Addisons are very non specific, describe them
Fatigue
Anorexia
Nausea
Dizziness
Describe a sign of Addisons disease and the pathophysiology behind it
Increased Pigmentation
Increased stimulation of ACTH which also activates MSH
What electrolyte abnormalities will be present in Addisons?
Hyperkalaemia
Hyponatraemia
What dynamic test can be used in suspected Addisons?
Administer IV ACTH (Synacthen) and see if cortisol increases. It shouldn’t if the patient has Addisons.
What is secondary adrenal insuffiency?
Decreased ACTH production from Pituitary
Commonly due to long term steroids, or pituitary problems
How will Primary and Secondary Adrenal Insufficiency presentations differ?
Secondary will not have any increased pigmentation or reduced mineralocorticoids
Describe the management of Addisons
Glucocorticoid Replacement (Hydrocortisone)
Mineralocorticoid Replacement (Fludrocortisone)
Doses doubled in times of illness
Steroid card and Medic Alert Bracelet
Give 3 causes of an Addisonian Crisis
Infection
Trauma
Surgery
Addisonian Crisis presents like shock, describe the 2 emergency management steps
100mg IV Hydrocortisone STAT
IV Fluid Bolus
What is a Phaeochromocytoma?
Catecholamine producing tumours arising from collections of chromaffin cells
What is a Paraganglioma?
Extra adrenal version of Phaeochromocytomas, often occuring at aortic bifurcation
What is the 10% rule of Phaeochromocytoma?
10% Malignant
10% Extra-Adrenal
10% Bilateral
10% Familial
What is the triad presentation of Phaeochromocytoma?
Episodic Headaches
Sweating
Tachycardia
Name three possible investigations of Phaeochromocytoma
24hr Urinary Metanephrines
Abdo CT/MRI
MIBG Scan (radioactive imaging)
Phaeochromocytomas are generally managed with surgical excision, what medical management is used? Explain the order in which they’re given.
Alpha blockade with Doxazosin first
Beta Blockers given second
AB given first to prevent unopposed alpha adrenergic activity and hypertension. BB then given to prevent reflex tachycardia.
What is Hyperaldosteronism and when should you suspect it?
Excess production of aldosterone independent of RAAS resulting in excess sodium and water retention
Suspected if Hypertensive and Hypokalaemic(not on diuretics)
Give 3 causes of Primary Hyperaldosteronism
Conns (Aldosterone producing adenoma)
Bilateral Adrenocortical Hyperplasia
Glucocorticoid Remediable Aldosteronism (ACTH regulatory element fuses to aldosterone synthase gene, bringing it under control of ACTH)
Give 2 causes of Secondary Hyperaldosteronism
Diuretics
Renal Artery Stenosis
What is Bartter’s Syndrome?
Sodium and Chloride channel leak in the Loop of Henle causing salt wasting, then RAAS becomes activated
What are the symptoms of Hyperaldosteronism?
May be asymptomatic or have signs of hypokalaemia (weakness, cramps)
How would you manage Hyperaldosteronism?
Conns - Surgical removal and Spironolactone
Hyperplasia - Spironolactone
GRA - Dexamethasone
Describe the embryological origins of the anterior and posterior pituitary
Anterior - ectodermal in origin, upgrowth of pharyngeal roof (Rathke’s Pouch)
Posterior - neurectodermal in origin, extension of inferior forebrain
Describe the superior and lateral relations of the pituitary gland
Superior - Optic Chiasm
Lateral - Cavernous Sinus (III,IV,Va,Vb,VI)
State the 5 axis of the Pituitary Gland
Growth
Adrenal
Gonadal
Thyroid
Prolactin
Describe the Growth axis of the PG. What increases and decreases its release?
GH released in a pulsatile manner from anterior pituitary and acts on Growth Factor and IGF Receptors
GH released increased by GHRH
GH release decreased by Somatostatin
Describe the Adrenal axis of the PG
CRH from Hypothalamus stimulates ACTH to be released from anterior pituitary which subsequently causes Cortisol release
Describe the Gonadal axis of the PG in Women
GnRH from the Hypothalamus causes LH and FSH release
FSH - Ovarian Follicle Development, targetting granulosa cells
LH - Targets Theca cells to produce androgens and oestrogen precursors
Describe the Gonadal axis of the PG in Men
GnRH from the Hypothalamus causes LH and FSH release
FSH - Targets Sertoli cells to increase sperm production
LH - Targets Leydig cells to produce Testosterone
Describe the Thyroid Axis of the PG
TRH is released from the Hypothalamus which then causes TSH to be released from the Anterior Pituitary
TRH also mildly stimulates Prolactin
Describe the Prolactin Axis of the PG
TRH causes mild release of Prolactin from Anterior Pituitary
Dopamine inhibits release of Prolactin from Anterior Pituitary
Prolactin goes on to cause lactation
Prolactin inhibits FSH and LH
State the four different assessments of the PG
Clinical
Biochemical
Dynamic
Imaging
Describe the timings of PG hormone level testing
Prolactin and TSH can be checked at any hour
Cortisol checked at 9am
LH and FSH checked within first 5 days of Menstruation in Women, or fasted at 9am in Men
One of the dynamic tests for the PG is the Synacthen test, describe it
Tests for Primary Adrenal Failure
Administering synthetic ACTH doesn’t correspond to a rise in Cortisol
One of the dynamic tests for the PG is the Insulin Tolerance test, describe it
Used to test Pituitary reserves
Administering Insulin induces frank hypoglycaemia causing physiological stress and subsequent ACTH and GH release
What imaging technique is used for the PG? If a tumour is found, how is it classified?
MRI with Contrast
Microadenoma<1cm
Macroadenoma>1cm
Give 4 causes of Hyperprolactinaemia
Prolactinoma
Pregnancy
Compression of pituitary stalk
Dopamine Antagonists (Haloperidol, Metaclopramide)
Give 3 symptoms for Women and Men respectively of Hyperprolactinaemia
W - Amenorrhoea, Low Libido, Galactorrhoea
M - ED, Decreased facial hair, Galactorrhoea
Hyperprolactinaemia is managed medically first line, What is the risk?
Dopamine Agonists such as Cabergoline (weekly) or Bromocriptine (daily)
If a tumour, reducing the size may cause a CSF leak and subsequent meningitis
Give 3 serum investigations that might be relevant in Hyperprolactinaemia
Basal Prolactin
Pregnancy Test
TFTs
Acromegaly is normally caused by a GH secreting tumour, what happens if it is left untreated?
Disfiguring
Increased Bowel Cancer Risk
Risk of premature death from CVD
Give 4 features of Acromegaly
Increased size of hands/feet
Coarsening of facial features
Soft tissue swelling (carpal tunnel/snoring)
Headache (HTN)
As GH is pulsatile, it is not a reliable investigation in Acromegaly. What dynamic test could you use instead and why?
Glucose causes insulin release, and insulin and GH are antagonistic. Physiologically OGTT should supress GH release, however in Acromegaly GH remains high.
What surgical approach would you take to surgically remove a tumour causing Acromegaly?
Transphenoidal
Give two pharmacological options to treat Acromegaly
Octreotide - Somatostatin Anologues
Pegvisomant - GH Antagonists
What are NFPAs?
Non Functioning Pituitary Adenomas
May present with Headache/Hypopitutarism/Visual Field Loss
What are the 3 levels of Hypopituiarism? Give two causes of each.
Hypothalamus - Infection, Tumour
Stalk - Surgery, Carotid Artery Aneurysm
Pituitary - Radiation, Ischaemia
State the order that hormones are affected in Hypopituitarism
GH, FSH/LH, TSH, ACTH, PRL
Hypopituitarism in adulthood presents quite non specifically, but in childhood how will it present?
Short Stature
Describe the difference between Cushing’s Disease and Cushing’s Syndrome
Syndrome - collection of symptoms caused by excess cortisol
Disease - when the excess cortisol is caused by an ACTH secreting pituitary adenoma
Name two tumours that could cause Cushing’s Disease
Pituitary Adenoma
SCC of the Lung
Name two causes of Cushing’s Syndrome
Excess steroid use
Adrenal Adenoma
Give 3 symptoms and 3 signs of Cushing’s
Symptoms - Weight gain, weakness, irritability
Signs - Moon face, Buffalo hump, Abdominal Striae
State one static and one dynamic test for Cushings
Static - 24hr Urinary Free Cortisol
Dynamic - Dexamethasone Supression Test
How does the High Dose Dexamethasone Supression Test work?
Dexamethasone is given at 10pm at night, and cortisol levels are measured at 9am the next morning
Exogenous - high cortisol, low ACTH
Pituitary Adenoma - low cortisol, low ACTH
Ectopic ACTH - high cortisol, high ACTH
Give 3 possible managements of Cushings
Stop steroid medication if possible (GRADUALLY TAPER)
Removal of tumours
Metyrapone - inhibits cortisol production
What might Hypocalcaemia be an artefact of?
Hypoalbuminaemia
Give 2 causes of Hypocalcaemia with high phosphate
CKD
Hyperparathyroidism
Give 2 causes of Hypocalcaemia with low phosphate
Osteomalacia
Acute Pancreatitis
Using the mnemonic SPASMODIC, describe the features of Hypocalcaemia
Spasms
Perioral Paraesthesia
Anxious
Seizures
Muscle tone increased (smooth)
Orientation impaired
Dermatitis
Impetigo Herpetiformes
Chvostek’s Sign
What is Trosseau’s Sign?
A sign of Hypocalcaemia
Shows Carpopedal Spasm when you inflate cuff above systolic for 3 minutes
What is Chvostek’s Sign?
A sign of Hypocalcaemia
Twitching of facial muscles in response to tapping over facial nerve distribution
How do you treat mild and severe Hypocalcaemia respectively?
Mild - Calcium PO every 6 hours
Severe - 10ml 10% Calcium Gluconate over 30 mins
Give five causes of Hypercalcaemia
Malignancy
Hyperparathyroidism
Sarcoidosis
Thyrotoxicosis
Lithium
Give four symptoms of Hypercalcaemia
Bone pain
Renal Stones
Depression
Constipaton
If the cause of Hypercalcaemia was malignancy what would the blood tests show?
Low Albumin
Low Chloride
Low Potassium
High Phosphate
Alkalosis
Describe a three step management plan of Hypercalcaemia
1) Correct Dehydration (IV 0.9% Saline)
2) Bisphosphonates (Inhibit Osteoclast activity)
3) Chemo if malignancy, Steroids if Sarcoidosis
Describe 3 actions of the parathyroid gland
Increase Osteoclast activity
Increase Calcium reabsorption from the kidney
Increase Calcitriol production
What is Primary Hyperparathyroidism?
Overactivity causes HIGH calcium
80% Solitary Adenoma
20% Gland Hyperplasia
Associated with MEN syndrome
What is Secondary Hyperparathyroidism?
Low Calcium and appropriately raised PTH
Causes - CKD, Low Vit D
What is Tertiary Hyperparathyroidism?
Occurs after prolonged Secondary Hyperparathyroidism, the gland becomes autonomous
Inappropriate raised PTH (or normal) and raised Ca2+
Name 3 tumours that can produce PTHrP
SCC of lung
Breast carcinomas
RCC
Give 2 causes of Primary Hypoparathyroidism
Autoimmune
Congenital (DiGeorge)
Give 2 causes of Secondary Hypoparathyroidism
Myeloma
Sarcoidosis
What is Pseudohypoparathyroisism? How will it present?
Target cells fail to respond to PTH
Round face
Short Stature
Short Metacarpals
Hirsutism is male pattern hair growth in women, give 3 causes
PCOS
Cushings
Familial
Give 3 pharmacological options for Hirsutism
COCP
Metformin
Spironolactone
Describe the pathophysiology of PCOS
LH increases relative to FSH causing increased testosterone relative to oestrogen
Link with hyperinsulinaemia
Describe 5 features of the classical presentation of PCOS
Oligomenorrhoea
Sub/Infertility
Hirsutism
Obesity
Acanthosis Nigracans (demonstrates insulin resistance)
What is the diagnostic criteria of PCOS called? What does it include?
Rotterdam Criteria
Polycystic Ovaries (12 or more follicles)
Oligo/Anovulation
Clinical/Biochemical signs of Hyperandrogenism
Women with PCOS are often given the IUS, why?
Counteracts the endometrial hyperplasia caused by oligo-ovulation
Give 4 pharmacological managements for PCOS
Co-Cyprindriol - Hirsutism and Acne (COCP)
Metformin
Orlistat (Lipase Inhibitor)
What is a Plethora?
Describes the facial appearance in Cushing
How do you treat ectopic ACTH production?
Metyrapone
What is Bartters Syndrome
Congenital salt wasting from LoH causing RAAS activation
What is Nelson’s Syndrome?
occurs when an adrenocorticotrophic hormone (ACTH) secreting tumour develops following therapeutic total bilateral adrenalectomy for Cushing’s disease.
What Cortisol level in a Dexamethasone Supression test would exclude Cushing?
<50 nmol /l
What static test is first line in Acromegaly?
Serum IFG1
How would you manage a myxoedema coma?
IV Thyroxine
IV fluids
And IV hydrocortisone as can’t distingush from addisons
What is Pseudocushings, and how will you investigate?
Mimics Cushing’s, often caused by excess alcohol
Differentiated by insulin stress
