Week 12 - Endocrine Conditions Flashcards
What type of chemical is cortisol?
Glucocorticoid steroid hormone
Where is cortisol released from?
Adrenal glands - cortex
How is cortisol produced under the HPA axis?
Hypothalamus - releases CTRH (corticotrophin releasing hormone)
This stimulates ANTERIOR pituitary to release ATCH (adrenocorticotrophic hormone)
This stimulates the adrenal glands to produce cortisol (which in turn negatively feedbacks to the hypothalamus to stop production of CRTH.
What is another name for the pituitary stalk?
What does the pituitary stalk do?
The infundibulum
Connects the posterior pituitary to the hypothalamus
What are mamillary bodies in the brain important for?
Episodic memory
Spatial navigation
Feeding reflexes (e.g. swallowing)
Damage or dysfunction of the mamillary bodies can lead to memory disorders such as Wernicke-Korsakoff syndrome, which is often associated with chronic alcoholism and characterized by severe memory impairment and confabulation (fabrication of false memories).
Which hormones are produced by the anterior pituitary gland?
ACTH
TSH
FSH & LH
Growth hormone
Prolactin
Which hormones are produced by the posterior pituitary?
ADH
Oxytocin
Which arteries supply the pituitary gland?
Superior & inferior hypophyseal a.
Originate from the internal carotids
What percentage of the adrenal glands are cortex and medulla?
What is each area responsible for?
Medulla = 10% - acute stress response + Na/glucose homeostasis
Cortex = 90% - mineralcorticoids, glucocorticoids & androgens
What are the three layers of the adrenal cortex?
What does each make?
Outer zona glomerulosa - mineralocorticoids
Middle zona fasciculata - glucocorticoids
Innermost zona reticularis - androgen precursors
How can you remember what each of the layers of the adrenal cortex are called and what they make?
GFR = Salt, Sugar, Sex
When is the secretion of ACTH at its lowest and highest in the day?
How soon after ACTH secretion will cortisol be secreted?
Highest = at the time of waking
Lowest = in the middle of the night
Cortisol follows the same pattern but 2 hours later than ACTH.
What does the Lazarus Transaction Model of Stress say?
That there is increased secretion of ACTH at times of prolonged stress -> hypercortisolaemia.
When do the levels of cortisol peak?
30-45 mins after waking
How does cortisol travel in the blood?
10% as free hormone
Rest bound to proteins - albumin (15%) and Corticosteroid binding globulin (75%)
What happens to cortisol levels in pregnancy?
They increase - as do corticosteroid binding globulin levels - this means the amount of free cortisol remains stable.
What stimulates the release of aldosterone?
RAAS
Trauma
Anxiety
Hyperkalaemia
Hyponatraemia
What inhibits the release of aldosterone?
ANP
How does aldosterone work?
It stimulates the reabsorption of Na in the DCT (lesser but also in CD, PCT and ascending LOH).
Na reabsorption occurs due to expression of intracellular receptors - these reabsorb Na in exchange for K+ (in DCT).
Finally - it also inc H+ secretion from the CD - lost in the urine.
What is another name for growth hormone?
Somatotropin
What are common features of acromegaly?
Enlarged hands, feet, forehead, jaw and nose
What is the commonest cause of acromegaly?
Pituitary adenoma (benign neoplasia)
When should ACTH levels be at their lowest?
In the middle of the night
What can cause a prolactinoma?
Pituitary tumour
What are the Sx of a prolactinoma?
Menstral cycle changes
Mood disturbances
Galactorrhoea
What can cause hypopituitarism?
Tumours
Infections
Vascular infarct
How does the cycle which produces T3 & T4 work?
Hypothalamus: The process begins in the hypothalamus, which produces thyrotropin-releasing hormone (TRH).
Pituitary Gland: TRH stimulates the anterior pituitary gland to release thyroid-stimulating hormone (TSH).
Thyroid Gland: TSH then stimulates the thyroid gland to produce and release thyroid hormones, primarily triiodothyronine (T3) and thyroxine (T4).
The axis operates on a negative feedback loop. High levels of T3 and T4 inhibit the release of TRH and TSH, thus regulating the production of thyroid hormones to maintain balance. When thyroid hormone levels drop, this inhibition is lifted, leading to increased production of TRH and TSH, and consequently, more thyroid hormone production
What stimulation leads to increased production of TRH?
Cold temperatures - metabolism needs to work faster => inc secretion of TRH
What stimulation can lead to decreased production of TSH?
Fasting (reduced TRH, TSH) = reduced metabolic rate
Sympathetic stimulation (anxiety, excitement) = decreased TSH
What are the proper names of T3 and T4?
T3 = triiodothyronine
T4 = thyroxine
How is T4 converted to T3?
By removal of 1 iodine molecule
Which cells in the thyroid produce calcitonin?
Thyroid C cells
Which enzyme is needed to convert T4 to T3
Iodine removal from T4 - T3 = iodothyronine deiodinase
How are T3 and T4 made?
Thyroglobulin produced by epithelial cells in the thyroid.
This then has iodine added to it (Pendrin, TPO) - then is broken down into MIT and DIT - which are combined to make T3 and T4.
Which plasma proteins do T3 and T4 bind to?
TBG (Thyroxine binding globulin)
TTR (Transthyretin)
Albumin
Which hormone acts on thyroid hormone receptors?
T3
What does T3 influence?
- Metabolic Rate and Energy Production
Basal Metabolic Rate (BMR): Thyroid hormones increase the basal metabolic rate, which is the amount of energy expended while at rest. They enhance oxygen consumption and energy expenditure in tissues.
Heat Production: By increasing metabolic activity, thyroid hormones also contribute to thermogenesis, helping to maintain body temperature. - Growth and Development
Skeletal Development: Thyroid hormones are essential for proper bone growth and development. They stimulate bone maturation and turnover.
Brain Development: These hormones are crucial during fetal and neonatal brain development, influencing neuronal differentiation, migration, and synapse formation. - Cardiovascular System
Heart Rate and Contractility: Thyroid hormones increase heart rate and the force of cardiac contractions. They enhance cardiac output by increasing the expression of beta-adrenergic receptors and other key proteins in cardiac tissue.
Blood Volume and Vascular Resistance: They affect blood pressure by regulating blood volume and decreasing systemic vascular resistance. - Nervous System
Cognitive Function: Adequate levels of thyroid hormones are necessary for maintaining normal cognitive functions, including memory and concentration. They influence mood and mental state, with imbalances potentially leading to anxiety, depression, or cognitive impairments. - Metabolism of Nutrients
Carbohydrate Metabolism: Thyroid hormones enhance gluconeogenesis (production of glucose from non-carbohydrate sources) and glycogenolysis (breakdown of glycogen into glucose), thus playing a role in blood glucose regulation.
Lipid Metabolism: They promote lipolysis (breakdown of fats) and increase the clearance of lipids from the plasma, helping regulate cholesterol levels.
Protein Metabolism: Thyroid hormones influence protein synthesis and degradation, which is essential for normal growth and tissue repair. - Reproductive System
Menstrual Cycle and Fertility: Proper thyroid function is essential for regular menstrual cycles and fertility. Thyroid imbalances can lead to menstrual irregularities and fertility issues. - Musculoskeletal System
Muscle Function: Thyroid hormones are involved in maintaining muscle strength and function. Imbalances can lead to muscle weakness or myopathy. - Digestive System
Gastrointestinal Motility: These hormones affect the motility of the gastrointestinal tract, influencing the speed at which food passes through the digestive system.
What happens to the following mechanisms in response to inc thyroid hormones?
- number of mitochondria
- Na/K ATPase activity
- glycolysis / gluconeogenesis
- insulin secretion
- plasma cholesterol
- enzyme synthesis and vitamin uptake
- respiration at cellular level
What happens to the following bodily functions in response to inc thyroid hormones?
- Growth and development
- Bone turnover
- Energy expenditure
- Metabolism
- Erythropoiesis
- HR, BF & CO
- Muscle contraction and relaxation
- Endocrine activity
- Nervous system activity
Are all increased in response to inc T3.
What is a normal functioning thyroid called?
Euthyroid
What is an enlarged thyroid called?
Goitre
When can thyroids become naturally enlarged?
Adolescence or pregnancy
When is congenital hypothyroidism screened for?
In the heel prick test after birth
Which thyroid hormones are tested for in TFTs?
TSH
FT4
FT3
How do thyroid hormones present in
- hypothyroidism?
- hyperthyroidism?
Hypo = High TSH, low FT4
Hyper = Low TSH, high T3 & T4
How long does it take for TSH levels to be reflected in blood work after a change to the pituitary gland?
About 6 weeks
Which thyroid antibody is specific to Graves disease?
What does it do?
TSH Receptor AB - stimulates the thyroid to make excessive thyroid hormone
Which thyroid antibody is more generalised and can be implicated in both hypo or hyper thyroidism?
TPO AB
How common is hypothyroidism in M & F?
x10 F : M
What are the S&S of hypothyroidism?
Cold intolerance
Facial puffiness
Dry skin
Hair loss
Hoarseness
Bradycardia
Which other AI diseases can put a P at risk of hypothyroidism?
T1DM
Coeliac disease
What percentage of Ps at 8-20 weeks postpartum will develop postpartum thyroiditis?
How is this managed?
10%
Most will recover - only a few will need replacement
What is the difference between primary and secondary hypothyroidism?
Primary = damage to the thyroid itself
Secondary = problem is in hypothalamus or pituitary glandWha
What are the main causes of primary hypothyroidism?
What is the commonest cause of these?
Commonest = AI
Also = infection, drugs, congenital, I deficiency, damage
What is damage to the pituitary during childbirth called (haemorrhage can suffer infarct pituitary gland)?
Sheehan’s syndrome
What are the main causes of secondary hypothyroidism? (Rare!)
Tumours
Sheehan syndrome
TRH resistance / deficiency
Lymphocytic hypophysitis
Radiotherapy
How can you differentiate between primary and secondary hypothyroidism on bloods?
Primary - TSH high, T4 & T3 low
Secondary - all low
How is hypothyroidism treated?
Levothyroxine - 1.6 mcg/kg
Repeat TSH in 4-6w - aim for range of 2
Take 1 hour before a meal or 4 hours after the last meal (empty stomach). If you miss a dose, take an extra dose.
What is the emergency presentation of hypothyroidism known as?
Myxoedema
What are the Sx of myxoedema?
Decreased mental status
Hypothermia
Bradycardia
Hypotension
Hypoglycaemia
Facial oedema
Peripheral oedema
How is myxoedema managed?
ICU admission
Levothyroxine, poss T3 as well
IV Hydrocortisone - 200-400mg/day
What are the RF for hyperthyroidism?
Other AI disease
What is more common - hypo or hyperthyroid?
Hypothyroid
What are the Sx of hyperthyroidism?
What are the causes of hyperthyroidism? (Thyrotoxicosis)
Which drugs can cause thyrotoxicosis?
Lithium
Amiodarone
What blood results would make you suspect thyrotoxicosis?
Transaminitis - high AST & ALT
High bone turnover - high ALP, hypercalcaemia
Pancytopenia or neutropenia
What causes Grave’s disease?
TSH receptor AB binds and stimulates the receptor => excess production of thyroid hormones
What is a common sign of Grave’s disease?
Goitre
How can you tell a P has Grave’s disease on radioiodine uptake test?
The gland is uniformly lit up with radioisotope
What is TED?
Inflammation of all orbital tissues except eye
Itchy, dry eyes
Prominent eyes
Can get diplopia, loss of sight, loss of colour vision, redness and swelling of conjunctiva, inability to close eyes, aching and pain behind the eyes.
What percentage of Ps with Graves can get TED?
Up to 20%
What are the two types of hyperthyroid nodules?
Single nodule = toxic adenoma
Multiple nodules = toxic multi-nodular goitre
What test can be used to differentiate between different nodules and Graves disease?
Radioiodine uptake test - can differentiate between causes of thyrotoxicosis
- Graves disease - will be increased uptake uniformly across the gland
- Toxic adenoma - one part highlighted
Toxic multi-nodular goitre - multiple parts highlighted
What can cause thyroiditis (inflammation of thyroid gland)?
Viral infection (De Quervains) or Bacterial infection
AI (Postpartum thyroiditis)
Drugs
Radiation
How can post partum thyroiditis present in terms of hormone levels?
Initially - they go really high - as all the hormones are released. May then stop producing T4 and go into a hypothyroid state.
What is first line Rx for hyperthyroidism?
Medicine
- Carbimazole
- Propylthiouracil
Symptom control = propanolol
Otherwise think radioiodine or surgery
What are the risks if hyperthyroidism is not treated?
AF
Osteoporosis
How do Carbimazole and Propylthiouracil work?
What side effect of these medications do you need to be wary of? What do Ps need to keep an eye out for?
Both inhibit TPO = dec T3 and T4.
Can cause agranulocytosis => drop in WCC.
Tell Ps to seek medical advice if sore throat, mouth ulcer or infection lasts longer than 2 weeks.
Which nerve in the neck can be damaged during thyroid surgery?
Recurrent laryngeal nerve - can cause vocal cord palsy
What medical emergency can occasionally be seen in Ps with Grave’s disease?
Thyroid storm (thyrotoxic crisis)
What are the Sx of thyrotoxic crisis?
Hyperpyrexia
Tachycardia, Arrythmias, HF
Low GCS, agitation, delirium
N&V
Deranged LFTs
How is thyroid storm managed?
What percentage of the population have thyroid nodules?
65% of general pop - most are benign and insignificant
What can cause goitre?
Which disease causes an excess of cortisol?
Cushing’s disease
When is CRH released from the hypothalamus?
In response to stress
What are cortisol, androgens & aldosterone all originally made from?
What does knowledge of this pathway allow you to do?
Cholesterol
If you work out which product you are deficient in - your can determine which enzyme is causing the problem.
GFR - glomerulosa, then fasciulata and then reticularis (Salt, Sugar, Sex)
What are the effects of glucocorticoids (cortisol)?
When do you suppress and when do you stimulate in terms of dynamic testing?
If you have excess levels of a hormone - need to do suppression test
If you have deficient levels of a hormone - need to do a stimulation test
What is the difference between Cushing’s disease and Cushing’s syndrome?
Cushing syndrome = signs and symptoms of prolonged elevated cortisol - can be from any cause
Cushing’s disease = pituitary adenoma which secretes XS ACTH.
What are the potential causes of Cushing’s syndrome?
Cushing’s disease
Paraneoplastic Cushings - secretes ACTH - e.g. SCLC
ACTH will be high in both of these
Exogenous steroids
Adrenal adenoma (XS cortisol released)
ACTH will be low in these
Which is the first line test for Cushing’s syndrome?
How does it work?
Dexamethasone suppression test
Give dexamethasone at 10pm - measure cortisol and ACTH at 9am. Does the dexamethasone suppress their morning spike of cortisol?
What other test can be done for Cushing’s syndrome?
24 urinary cortisol collection
What can cause primary adrenal insufficiency?
Vascular - haemorrhage / infarct
Inflammation/Infective/Infiltrative (sarcoidosis, amyloidosis, TB, fungal infection, opportunistic infection)
Trauma
AI (ABs to adrenal gland)
Iatrogenic
Neoplasia - metastatic deposition
Congenital = adrenoleucodystrophy, congenital adrenal hyperplasia
Drugs = Rifampicin, ketoconazole
What does primary adrenal insufficiency cause?
Deficiencies in glucocorticoids, mineralocorticoids and androgens
What is the most common cause of primary adrenal insufficiency?
AI Adrenalitis (AB to 21-hydroxylase in 85% of cases)
If you have an adrenal tumour producing excess aldosterone, how can this affect bloods?
Can cause hypokalaemiaW
Following suppression testing, what investigations can you do to confirm:
- Pituitary adenoma
- SCLC
- Adrenal tumour
Pituitary adenoma = MRI brain
SCLC = chest XR
Adrenal tumour = abdo CT
What is the difference between primary, secondary and tertiary adrenal insufficiency?
Primary = Addison’s disease - adrenal glands are damaged (often AI cause) = reduced secretion of cortisol and aldosterone
Secondary = inadequate ACTH released from pituitary (damaged)
Tertiary = inadequate CRH released from hypothalamus - normally as a result of P being on LT steroids.
What are the Sx of adrenal insufficiency?
Fatigue
Nausea
Cramps
Abdo pain
Reduced libido
Pigmentation of skin - especially creases - due to ACTH stimulating melanocytes to produce melanin.
Hypotension - esp postural hypotension - due to decreased aldosterone.
What blood results can indicate primary adrenal insufficiency?
Low Na and poss high K+ - signs of low aldosterone
Raised ACTH - can indicated that the adrenal gland is not responding
Low cortisol
pH - looking for metabolic acidosis
What is the first line test for adrenal insufficiency?
Short synacthen test (synthetic ACTH) - make sure all steroid medications are stopped prior to test!
Give synacthen and then measure cortisol - to see it inc (a) rapidly, (b) slowly or (c) not at all.
What is the emergency presentation of adrenal insufficiency?
Adrenal crisis
Treatment for adrenal insufficiency is to give titrated replacement steroids. Which steroids are given to replace:
- cortisol
- aldosterone
Cortisol = hydrocortisone
Aldosterone = fludrocortisone
What should Ps do to their steroid doses during times of acute illness?
Double the dose
How does adrenal crisis present?
Reduced GCS
Hypotension, hypoglycaemia, hyponatremia & hyperkalaemia
Very unwell
How is adrenal crisis managed?
IV HCS - 100mg stat + 100 mg every 6 hours
IV fluid resuscitation
Correct hypoglycaemia
If primary adrenal sufficiency - need to give fludrocortisone 100mcg OD
What are the sick day rules for adrenal insufficiency?
For moderate illness - double dose of steroids = Rule 1
For severe illness or surgery - give IV HCS 100mg + continuous infusion of 200mg every 24hours
Which part of the adrenal gland is affected by exogenous steroids?
Get atrophy of fasciculata + reticularis (glomerulosa is spared due to RAAS)
What is AI Polyglandular Syndrome?
Means that in some Ps AI conditions may result in more than one disease manifestation - e.g. Addisons and T1DM
What does AI Polyglandular Syndrome mean in practice?
That when one AI condition exists consider screening for others - e.g. check cortisol, coeliac screen and TFTs.
Which arteries supply the adrenal gland?
Superior adrenal artery (from inferior phrenic a.)
Middle adrenal artery (from AA)
Inferior adrenal a. (from renal a.)
What are the three endocrine causes of hypertension?
Adrenal dysfunction
Acromegaly
Thyroid dysfunction
What causes primary hyperaldosteronism? (Conn’s)
Adrenal glands themselves produce too much aldosterone.
Caused by
= Adrenal adenoma
= Bilateral adrenal hyperplasia
= Familial hyperaldosteronism (T1 and T2) - RARE
= Adrenal carcinoma - RARE
What is the difference between primary hyperaldosteronism and secondary hyperaldosteronism?
Primary hyperaldosteronism = caused by adrenal gland producing too much aldosterone due to defects with the adrenal gland.
Secondary hyperaldosteronism = caused by excess renin stimulating the adrenal gland to produce excess aldosterone (renal a. stenosis / obstruction or HF).
What investigations can you do for hyperaldosteronism?
Check renin:aldosterone ratio (both high = secondary, renin low = primary)
BP
Serum electrolytes - Na and K
Blood gas - alkalosis?
Saline suppression test
Which dynamic test can be done to investigate hyperaldosteronism?
Saline suppression test = give 2L of saline over 4h. In a normal physiological response, the increased blood volume from the saline infusion should suppress aldosterone production. If aldosterone levels remain elevated despite the saline infusion, it indicates that the adrenal glands are producing aldosterone autonomously. This lack of suppression suggests primary hyperaldosteronism.
Which drugs are aldosterone antagonists?
Spironalactone
Eplerenone
What is the second most common cause of hypertension?
Hyperaldosteronism
What is a tumour of chromaffin cells of the medulla called?
Phaechromocytoma
What are the clinical features of phaeochromocytoma?
Which genetic diseases are phaeochromocytomas associated with?
MEN 2
NF 1
How are phaechromocytomas diagnosed?
24 hour urinary catecholamines
Plasma levels of free metanephrines
Can also do MRI, CT, MIBG
What is a metanephrine?
A breakdown product of adrenaline - longer half life, less fluctuations.
Which drugs are
= α receptor blockers
= β receptor blockers?
α = doxazocin, phenoxybenzamine
β = propanolol
What is the management of phaechromocytomas?
What is the rule of 10 regarding phaeochromocytoma?
10% are bilateral
10% are metastatic
10% are extra-adrenal
How can you differentiate between a benign nodule and phaeochromocytoma on imaging?
Benign nodules - contain a lot of fat
What is congenital adrenal hyperplasia?
Metabolic disorder - deficit in enzymes needed to make cortical steroids.
Most commonly 21-hydroxylase deficiency.
Enzyme deficiency -> inc ACTH required -> enlarged adrenal glands and pituitary gland
What is the role of calcium in the body?
How is calcium found in the extra cellular fluid?
3 forms
- Complexed to anions
- Protein bound
- Ionised
Why do we use corrected calcium levels?
Because it is corrected for the patient’s protein level - which can vary depending on the physiological status of the patient.
Corrected calcium provides a more accurate reflection of the physiologically active calcium by adjusting the total calcium level based on the albumin concentration. This adjustment helps clinicians better assess the true calcium status of the patient and avoid misinterpretation of calcium levels.
Where is 99% of the body’s calcium found?
Bones
Which vitamin is important for calcium absorption?
Vitamin D
Which diuretics
- increase calcium absorption
- decrease calcium absorption
Furosemide increases Ca absorption
Thiazide diuretics decrease Ca absorption
Which hormones are involved in increasing calcium levels?
Parathyroid hormone
Vitamin D
If Ca is low, PTH is released
How does PTH work?
If Ca is low, parathyroid cells sense this and release PTH.
Effects of PTH =
- stimulates osteoclasts and inhibits osteoblasts = release of Calcium into the blood
- increases calcium reabsorption in the kidney tubules (LOH, DCT & CD) and decreases phosphate absorption (meaning less phosphate available to bind to calcium to form complexes) (in the proximal tubule)
- stimulates conversion of calcidiol to calcitriol (Vit D) in the kidneys - this inc absorption of Ca from the GIT
Which mineral is required for PTH to work?
Magnesium
If P has low magnesium - PTH will not be released - may then present with low serum Ca.
Why can cancer cause hypercalcaemia?
Malignant tumours can produce PTHrP (parathyroid hormone related protein) - similar action to PTH - will inc calcium levels.
Which receptors on osteoclasts are involved with initiating them into active osteoclasts?
RANK-L
M-CSF
Which cells produce PTH?
Chief cells in PTH gland
Which cells produce calcitonin?
Parafollicular C cells of thyroid gland
What is Calcitonin secretion stimulated by?
A decrease of calcium in the blood
Release of gastrin can also stimulate release of calcitonin
What does calcitonin do?
Inhibits osteoclasts
Reduces reabsorption of Ca and P in the kidney => moderate excretion of both
What is raised calcitonin in the blood indicative of?
Medullary carcinoma of the thyroid gland
What are the causes of hypercalcaemia?
Primary hyperparathyroidism
Hypercalcaemia of malignancy
What are the Sx of hypercalacaemia?
Stones (renal stones), bones (bone pain), moans (abdominal pain and constipation) and groans (psychiatric – lethargy, depression)
How can very high levels of calcium affect the heart?
Can cause shortened QT & arrhythmias.
Which tests should you for suspected hypercalcaemia?
How does the PTH level help determine what is causing the hypercalcaemia?
If Ca high, but PTH low - is not primary hyperparathyroidism - source is coming from somewhere other than the parathyroid gland
What types of hyperparathyroidism are there?
Primary - Problem with parathyroid gland
Secondary - chronic stimulus of the PT gland = e.g. Vit D deficiency
Tertiary - au
Why does chronic renal failure cause high calcium?
Kidneys fail - less P excreted - so more Ca binds to P = hypocalcaemia. Also - less calcitonin made in the kidneys also => hypocalcaemia.
The parathyroid glands respond to hypocalcemia by increasing the secretion of parathyroid hormone (PTH) to try to raise calcium levels. PTH increases calcium reabsorption from the kidneys, releases calcium from bones, and stimulates the conversion of vitamin D to its active form (though this last effect is limited in renal failure).
Chronic stimulation of the parathyroid glands due to ongoing hypocalcemia and hyperphosphatemia leads to hyperplasia (enlargement) of the parathyroid glands, resulting in secondary hyperparathyroidism.
What is the commonest cause of primary hyperparathyroidism?
Adenoma of the parathyroid gland = 85%
What does serum Ca, PTH and P look like in primary hyperparathyroidism?
Ca inc
PTH inc
Low P
What is the typical age of discovering primary hyperparathyroidism in Ps?
50-60 yo
What investigations can be done for primary hyperparathyroidism?
USS
Nuclear medicine scan
MRI
CT
Renal USS and DEXA scan - for complications
What is the common bone manifestation of primary hyperparathyroidism?
Where is this often seen first?
Osteitis Fibrosa Cystica (bone pain, path fracture, proximal muscle weakness + hyperreflexia)
Often seen in the distal 1/3 of the forearm
How is primary hyperparathyroidism treated?
Surgery
or Medical Rx if surgery unsuitable - Cinacalcet
GH deficiency - relatively common but Sx vague
What do we use to measure GH?
Use IGF-1 instead of GH (this is too pulsatile to be measured)
If worried about whether the pituitary is working properly - what blood tests can you do?
Prolactin
FSH/LH
Testosterone (M)
Oestrogen (F)
TSH, FT4, FT3
IGF-1
9am cortisol
What is hyponatremia?
Serum Na <135
What types of hyponatremia are there?
Hypovolaemic hyponatremia
Euvolaemic hyponatremia
Hypervolaemic
What causes hypovolaemic hyponatremia?
Prolonged D&V
What causes euvolaemic hyponatremia?
SIADH
What causes hypervolaemic hyponatremia?
Odema due to water and sodium retention - heart/liver/kidney failure
How many hyponatremia manifest neurologically?
How can you determine the cause of hyponatremia?
Look at the urine sodium and osmolality
Low urine osmolality = too much fluid intake or too little salt intake
High urine osmolality but low Na in urine = oedematous causes - HF, portal hypertension, nephrotic syndrome, hypoalbuminuria, GI loss
High urine osmolality & high Na in urine = SIADH, drugs, salt wasting, vomiting
What is SIADH?
Excessive ADH produced - stimulated water reabsorption in the CD - dilutes the sodium in the blood (hyponatremia) but not enough to cause overload => euvolaemic hyponatremia.
Urine becomes conc as less water is excreted by the kidneys - therefore have high urine osmolality and high urine sodium.
What is the diagnostic criteria for SIADH?
What can cause SIADH?
Post-op complication
Infection (esp atypical pneumonia, lung abscesses)
Head injury
Meds - thiazide diuretics, cabamazepine, vincristine, cyclophosphamide, APs, SSRIs and
NSAIDs.
Malignancy - esp SCLC
Meningitis
How is SIADH managed?
Discontinue causative meds if applicable
Determine cause & treat
Fluid restriction - 500ml - 1L
Which formula determines whether fluid restriction is likely to work for SIADH?
Furst formula
Which drug is licensed to treat SIADH first line?
Tolvaptan (V2 receptor antagonist = ADH receptor blocker)
Very powerful - can inc Na levels in 6 hours
Which drug is licensed to treat SIADH second line?
Demeclocycline
What complication can arise from long term severe hyponatremia being treated too quickly?
Central pontine myelinolysis
As blood Na falls - water moves from the blood into the brain cells (from area of low conc to high). Brain adapts by reducing solutes in the cells making them low osmolality. If we therefore correct the blood to quickly - water will leave the cells of the brain rapidly -> encephalopathy and confusion (poss headache, N&V), followed by demyelination of neurons - esp in pons -> spastic quadriparaesis, psuedobulbar palsy and cognitive and behavioural changes. Sig risk of death.
If Ps present with hyponatremia & severe Sx - what can be given to them?
Hypertonic NaCl fluid
What is the limit to increasing Na in a time period?
Dont inc more than 6mmol in 6 hours!
If overcorrection of SIADH occurs - what Rx can be given?
Desmopressin 2-4 micrograms SC 8hr + replace water or give dextrose
What correction rate should you aim for in low risk Ps with chronic SIADH?
4-8 mmol/L/day - unless at high risk of ODS(CPM) - then aim for 4-6/day
What are the common causes of hypercalcaemia?
Hyperparathyroidism
Malignancy
What are the Sx of hypercalcaemia?
Bones, Stones, Abdominal Groans and Psychiatric Moans
How is severe hypercalaemia managed?
Rehydration - 0.9% 4-6L in 24 hours (monitor for overload)
Loop diuretics only used if fluid overload develops - are not effective for reducing serum calcium.
Can think about bisphosphonates
What are the Sx of hypocalcaemia?
Inc neuromuscular excitability -> tingling, numbness, cramps, seizures
What is the most common cause of hypocalcaemia?
Renal failure - dec Ca, inc P and PTH
What is pituitary apoplexy?
What are the clinical features of pituitary apoplexy?
What causes primary hypothyroidism?
How do you know if it is primary hypothyroidism?
AI hypothyroidism
Thyroiditis
Drugs
Iodine deficiency
Get raised TSH, low T4 & T3
What causes secondary hypothyroidism?
How do you know if it is secondary hypothyroidism?
Disease of the hypothalamus or pituitary
Get low TSH, T4 & T3
What can cause primary hyperthyroidism?
How can you tell if it is primary hyperthyroidism?
AI
Thyroiditis
Drugs
Gestational
Toxic Nodule
Get low TSH and high T4 and T3
What can cause secondary hyperthyroidism?
How can you tell if it is secondary hyperthyroidism?
Disease of hypothalamus or pituitary
Get inc TSH, T4 and T3
What are the treatment options for hyperthyroidism?
Medication
Radioiodine
Surgery
What are the risks of not having treatment for hyperthyroidism?
AF
Osteoporosis
What is the rare complication of Ps with Grave’s disease?
What is it triggered by?
How does it present?
Thyroid storm
Triggered = surgery, pregnancy, acute severe illness
Presents - hyperpyrexia, tachycardia, arrhythmia, HF, low GCS, agitation, delirium, N&V, deranged LFTs
How is thyroid storm managed?
β blocker
PTU (better at converting peripheral T3 to T4)
Iodine solution
Steroids
Bile acid sequestrant
How does the thyroid affect bile acids?
Thyroid hormones play a crucial role in regulating bile acid metabolism, influencing their synthesis, secretion, and enterohepatic circulation. Hyperthyroidism typically enhances these processes, leading to an increased bile acid pool, while hypothyroidism typically diminishes these processes, leading to a decreased bile acid pool.
Which drugs can affect thyroid function?
How does adrenal insufficiency present in routine bloods? Why?
Hyponatremia + Hyperkalaemia
Primarily due to Aldosterone deficiency - dec Na reabsorption and K remains in the blood.
How do you do a 9am cortisol test?
Dont forget = results can be distorted if P is a shift worker
What is the management of adrenal crisis?
IV HCS
IV Fluids
Hypoglycaemia management
If primary adrenal insufficiency - give mineralcorticoid and glucocorticoids.
What crisis can a non-functioning pituitary adenoma present with?
Pituitary apoplexy - shows as a large white mass on CT - due to the bleeding inside the tumour.
How do we manage pituitary apoplexy?
IV Saline
Steroids (IV Hydrocortisone) initially & replace other hormones later
Commencement of levothyroxine can precipitate an adrenal crisis - this P is already presenting with adrenal crisis - therefore give 3 days of steroid therapy before commencing hormone therapy for the other axis deficiencies.
