Endocrinology Flashcards
what are thiazolidinediones?
Thiazolidinediones are a class of agents used in the treatment of type 2 diabetes mellitus. They are agonists to the PPAR-gamma receptor and reduce peripheral insulin resistance.
e.g. pioglitazone
Adverse effects of Thiazolidinediones?
Adverse effects
weight gain
liver impairment: monitor LFTs
fluid retention - therefore contraindicated in heart failure. The risk of fluid retention is increased if the patient also takes insulin
recent studies have indicated an increased risk of fractures
bladder cancer: recent studies have shown an increased risk of bladder cancer in patients taking pioglitazone (hazard ratio 2.64)
What is Bartter’s syndrome?
Bartter’s syndrome is an inherited cause (usually autosomal recessive) of severe hypokalaemia due to defective chloride absorption at the Na+ K+ 2Cl- cotransporter (NKCC2) in the ascending loop of Henle.
Loop diuretics work by inhibiting NKCC2 - think of Bartter’s syndrome as like taking large doses of furosemide
Features of Bartter’s syndrome?
usually presents in childhood, e.g. Failure to thrive
polyuria, polydipsia
hypokalaemia
normotension
weakness
Pregnant ladies with hypothyroid - how much do they need their hypothyroid treatment increasing by?
thyroxine is safe during pregnancy
serum thyroid-stimulating hormone measured in each trimester and 6-8 weeks post-partum
women require an increased dose of thyroxine during pregnancy
by up to 50% as early as 4-6 weeks of pregnancy
breastfeeding is safe whilst on thyroxine
what may untreated severe hyponatraemia lead to?
cerebral oedema
what is considered acute or chronic hyponatraemia?
acute: develops over a period of < 48 hours
chronic: develops over a period > 48 hours
symptoms of hyponatraemia?
patients with mild hyponatraemia may be symptomatic
early symptoms may include: headache, lethargy, nausea, vomiting, dizziness, confusion, and muscle cramps
late symptoms may include: seizures, coma, and respiratory arrest
How is hypovolaemic hyponatraemia managed?
normal, i.e. isotonic, saline (0.9% NaCl)
this may sometimes be given as a trial
if the serum sodium rises this supports a diagnosis of hypovolemic hyponatraemia
if the serum sodium falls an alternative diagnosis such as SIADH is likely
what is the management of euvolemic and hypervolemic hyponatreamia?
If a euvolemic cause is suspected
fluid restrict to 500-1000 mL/day
consider medications:
demeclocycline
vaptans (see below)
If a hypervolemic cause is suspected
fluid restrict to 500-1000 mL/day
consider loop diuretics
consider vaptans
management of acute hyponatraemia?
Patients with acute, severe (<120 mmol/L) or symptomatic hyponatraemia require close monitoring, preferably in an HDU or above setting.
Hypertonic saline (typically 3% NaCl) is used to correct the sodium level more quickly than would be done in patients with chronic hyponatraemia.
complications of hyponatraemia treatment?
can occur due to over-correction of severe hyponatremia
pathophysiology:
thought to develop secondary to astrocyte (and possibly oligodendrocyte) apoptosis
astrocytes and oligodendrocytes (cells of the glial syncytium) are crucial for normal myelination
chronic hyponatraemia → loss of osmotically active organic osmolytes (such as myoinositol, glutamate, glutamine) from astrocytes. These provide protection against cerebral oedema
organic osmolytes cannot be replaced quickly enough when the brain volume begins to shrink in response to the correction of hyponatraemia
the dehydrated astrocytes and oligodendrocytes undergo apoptosis or other forms of injury → demyelination
to avoid this, Na+ levels are only raised by 4 to 6 mmol/l in a 24-hour period
symptoms usually occur after 2 days and are usually irreversible: dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confusion, and coma
patients are awake but are unable to move or verbally communicate, also called ‘Locked-in syndrome’
Physiological response to hypoglycaemia ?
hormonal response: the first response of the body is decreased insulin secretion. This is followed by increased glucagon secretion. Growth hormone and cortisol are also released but later
sympathoadrenal response: increased catecholamine-mediated (adrenergic) and acetylcholine-mediated (cholinergic) neurotransmission in the peripheral autonomic nervous system and in the central nervous system
causes of hypoglycaemia?
Causes
insulinoma - increased ratio of proinsulin to insulin
self-administration of insulin/sulphonylureas
liver failure
Addison’s disease
alcohol
causes exaggerated insulin secretion
mechanism is thought to be due to the effect of alcohol on the pancreatic microcirculation → redistribution of pancreatic blood flow from the exocrine into the endocrine parts → increased insulin secretion
nesidioblastosis - beta cell hyperplasia
Investigations for acromegaly?
1st line - serum IGF-1 levels
The OGTT test is recommended to confirm the diagnosis if IGF-1 levels are raised.
Serum IGF-1 may also be used to monitor disease
Oral glucose tolerance test
in normal patients GH is suppressed to < 2 mu/L with hyperglycaemia
in acromegaly there is no suppression of GH
may also demonstrate impaired glucose tolerance which is associated with acromegaly
A pituitary MRI may demonstrate a pituitary tumour
What is Gitelman’s syndrome?
Gitelman’s syndrome is due to a defect in the thiazide-sensitive Na+ Cl- transporter in the distal convoluted tubule.
what are the features of Gitelman’s syndrome?
Features
normotension
hypokalaemia
hypocalciuria
hypomagnesaemia
metabolic alkalosis
what causes thyroid eye disease?
Thyroid eye disease affects between 25-50% of patients with Graves’ disease.
Pathophysiology
it is thought to be caused by an autoimmune response against an autoantigen, possibly the TSH receptor → retro-orbital inflammation
the inflammation results in glycosaminoglycan and collagen deposition in the muscles
how do you prevent thyroid eye disease?
smoking is the most important modifiable risk factor for the development of thyroid eye disease
radioiodine treatment may increase the inflammatory symptoms seen in thyroid eye disease. In a recent study of patients with Graves’ disease around 15% developed, or had worsening of, eye disease. Prednisolone may help reduce the risk
what are the features of thyroid eye disease?
the patient may be eu-, hypo- or hyperthyroid at the time of presentation
exophthalmos
conjunctival oedema
optic disc swelling
ophthalmoplegia
inability to close the eyelids may lead to sore, dry eyes. If severe and untreated patients can be at risk of exposure keratopathy
What is the management of thyroid eye disease?
smoking cessation
topical lubricants may be needed to help prevent corneal inflammation caused by exposure
steroids
radiotherapy
surgery
complications of thyroid eye disease?
exposure keratopathy - due to eyelid retraction and proptosis - cornea becomes excessively exposed, disrupting the normal tear film → dryness, irritation, and corneal ulceration
symptoms include foreign body sensation, pain, and photophobia
Optic neuropathy - ccurs when enlarged extraocular muscles compress the optic nerve at the apex of the orbit → a reduction in visual acuity, colour vision deficits, and visual field defect
Strabismus and diplopia - fibrosis and enlargement of the extraocular muscles can result in restrictive strabismus → misalignment of the eyes → double vision (diplopia)
this not only affects visual function but can also significantly impair the quality of life.
diagnostic thresholds for gestational diabetes?
fasting glucose is >= 5.6 mmol/L
2-hour glucose is >= 7.8 mmol/L
Management of gestational diabetes?
if the fasting plasma glucose level is < 7 mmol/l a trial of diet and exercise should be offered
if glucose targets are not met within 1-2 weeks of altering diet/exercise metformin should be started
if glucose targets are still not met insulin should be added to diet/exercise/metformin
gestational diabetes is treated with short-acting, not long-acting, insulin
if at the time of diagnosis the fasting glucose level is >= 7 mmol/l insulin should be started
if the plasma glucose level is between 6-6.9 mmol/l, and there is evidence of complications such as macrosomia or hydramnios, insulin should be offered
glibenclamide should only be offered for women who cannot tolerate metformin or those who fail to meet the glucose targets with metformin but decline insulin treatment
what may be used to treat galactorrhea?
Dopamine acts as the primary prolactin releasing inhibitory factor and hence dopamine agonists such as bromocriptine may be used to control galactorrhoea.
causes of raised prolactin?
prolactinoma
pregnancy
oestrogens
physiological: stress, exercise, sleep
acromegaly: 1/3 of patients
polycystic ovarian syndrome
primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)
what drugs can cause raised prolactin?
metoclopramide, domperidone
phenothiazines
haloperidol
very rare: SSRIs, opioids
what are the antibodies in graves disease?
IgG antibodies to the thyroid-stimulating hormone (TSH) receptor
IgG Anti-thyroid peroxidase antibodies
what do non-functioning pituitary adenomas result in?
Non-functioning pituitary adenomas can result in panhypopituitarism due to infiltration of the normal pituitary tissue. Compression of the pituitary stalk can result in hyperprolactinaemia due to decreased transport of dopamine from the hypothalamus to the pituitary. Dopamine acts to suppress prolactin release
what is the mechanism of action of orlistat?
orlistat acts as a pancreatic lipase inhibitor. Orlistat works by binding reversibly to pancreatic lipase in the gastrointestinal tract, preventing the breakdown of dietary triglycerides into absorbable free fatty acids and monoglycerides. This results in approximately 30% of ingested fat passing through the gut unabsorbed, thereby reducing caloric intake and promoting weight loss.
when should orlistat be prescribed?
It should only be prescribed as part of an overall plan for managing obesity in adults who have:
BMI of 28 kg/m^2 or more with associated risk factors, or
BMI of 30 kg/m^2 or more
continued weight loss e.g. 5% at 3 months
orlistat is normally used for < 1 year
how do sulfonylureas work?
They work by increasing pancreatic insulin secretion and hence are only effective if functional B-cells are present. On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells.
adverse effects of sulfonylureas?
Common adverse effects
hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide)
weight gain
Rarer adverse effects
hyponatraemia secondary to syndrome of inappropriate ADH secretion
bone marrow suppression
hepatotoxicity (typically cholestatic)
peripheral neuropathy
should be avoided in breast feeding and pregnancy
management of Hirsutism and acne in PCOS?
a COC pill may be used help manage hirsutism. Possible options include a third generation COC which has fewer androgenic effects or co-cyprindiol which has an anti-androgen action. Both of these types of COC may carry an increased risk of venous thromboembolism
if doesn’t respond to COC then topical eflornithine may be tried
spironolactone, flutamide and finasteride may be used under specialist supervision
key points of levothyroxine therapy?
start on 25mcg if over 50
other patients should be started on 50-100
following a change in thyroxine dose thyroid function tests should be checked after 8-12 weeks
goal is normalisation of TSH level
iron, calcium carbonate
absorption of levothyroxine reduced, give at least 4 hours apart
side effects of thyroxine therapy ?
hyperthyroidism: due to over treatment
reduced bone mineral density
worsening of angina
atrial fibrillation
what are the features of insulinoma?
of hypoglycaemia: typically early in morning or just before meal, e.g. diplopia, weakness etc
rapid weight gain may be seen
high insulin, raised proinsulin:insulin ratio
high C-peptide
Diagnosis of insulinoma?
supervised, prolonged fasting (up to 72 hours)
CT pancreas
Whilst supervised fasting is normally the investigation of choice if this option is not given then insulin + C-peptide levels during an acute hypoglycaemic episode are useful.
what is primary hyperparathyroidism?
Primary hyperparathyroidism is caused by excess secretion of PTH resulting in hypercalcaemia. It is the most common cause of hypercalcaemia in outpatients and is often diagnosed following an incidental finding of an elevated serum calcium concentration. In 85% of cases a parathyroid adenoma is responsible.
Causes of primary hyperparathyroidism
85%: solitary adenoma
10%: hyperplasia
4%: multiple adenoma
1%: carcinoma
what are the features of primary hyperparathyroidism?
80% of patients are asymptomatic
polydipsia, polyuria
depression
anorexia, nausea, constipation
peptic ulceration
pancreatitis
bone pain/fracture
renal stones
hypertension
Investigations for primary hyperparathyroidism?
bloods
raised calcium, low phosphate
PTH may be raised or (inappropriately, given the raised calcium) normal
technetium-MIBI subtraction scan
x-ray findings
pepperpot skull
osteitis fibrosa cystica
what is the treatment for primary hyperparathyroidism?
the definitive management is total parathyroidectomy
conservative management may be offered if the calcium level is less than 0.25 mmol/L above the upper limit of normal AND the patient is > 50 years AND there is no evidence of end-organ damage
patients not suitable for surgery may be treated with cinacalcet, a calcimimetic
a calcimimetic ‘mimics’ the action of calcium on tissues by allosteric activation of the calcium-sensing receptor
what is the management of myxoedemic coma?
Myxoedemic coma is treated with thyroxine and hydrocortisone
what is hungry bone syndrome?
Hungry bone syndrome is an uncommon entity but can occur after parathyroidectomy if the hyperparathyroidism has been long-standing. The mechanism is thought to be thus: high pre-operative levels of parathyroid hormone provide a constant stimulus for osteoclast activity creating the hypercalcaemic state by de-mineralizing the bones. This process can result in x-ray changes very similar to metastatic lytic lesions if left untreated. Upon removal of the parathyroid adenoma the hormone levels fall rapidly (they have a very short half-life) and the osteoclast activity is subsequently diminished and the bones rapidly begin re-mineralisation - ‘hungry bone syndrome’. This process can be uncomfortable and also result in systemic hypocalcaemia.
What is Addison’s disease?
Autoimmune destruction of the adrenal glands is the most common cause of primary hypoadrenalism in the UK, accounting for 80% of cases. This is termed Addison’s disease and results in reduced cortisol and aldosterone being produced.
features of Addison’s disease?
lethargy, weakness, anorexia, nausea & vomiting, weight loss, ‘salt-craving’
Hyperpigmentation (especially in palmar creases)
vitiligo
loss of pubic hair in women
hypotension
hypoglycaemia
hyponatraemia and hyperkalaemia may be seen
crisis: collapse, shock, pyrexia
Why do you get hyperpigmentation in Addison’s disease?
ACTH is derived from a larger precursor molecule called proopiomelanocortin (POMC). When POMC is cleaved to produce ACTH, other melanocyte-stimulating hormones (MSH) are also produced. These MSHs have the effect of stimulating melanocytes in the skin to produce more melanin, the pigment responsible for skin colour
primary Addison’s is associated with hyperpigmentation whereas secondary adrenal insufficiency is not
Causes of hypoadrenalism?
Primary causes
tuberculosis
metastases (e.g. bronchial carcinoma)
meningococcal septicaemia (Waterhouse-Friderichsen syndrome)
HIV
antiphospholipid syndrome
Secondary causes
pituitary disorders (e.g. tumours, irradiation, infiltration)
Exogenous glucocorticoid therapy
What is Liddle’s syndrome?
Liddle’s syndrome is a rare autosomal dominant condition that causes hypertension and hypokalaemic alkalosis. It is thought to be caused by disordered sodium channels in the distal tubules leading to increased reabsorption of sodium.
Treatment is with either amiloride or triamterene
How is Familial hypercholesterolaemia inherited?
Familial hypercholesterolaemia (FH) is an autosomal dominant
FH is caused by mutations in the gene which encodes the LDL-receptor protein.
How is familial hypercholesterolaemia managed?
Clinical diagnosis is now based on the Simon Broome criteria:
in adults total cholesterol (TC) > 7.5 mmol/l and LDL-C > 4.9 mmol/l or children TC > 6.7 mmol/l and LDL-C > 4.0 mmol/l, plus:
for definite FH: tendon xanthoma in patients or 1st or 2nd degree relatives or DNA-based evidence of FH
for possible FH: family history of myocardial infarction below age 50 years in 2nd degree relative, below age 60 in 1st degree relative, or a family history of raised cholesterol levels
Diagnosis of diabetes?
If the patient is symptomatic:
fasting glucose greater than or equal to 7.0 mmol/l
random glucose greater than or equal to 11.1 mmol/l (or after 75g oral glucose tolerance test)
If the patient is asymptomatic the above criteria apply but must be demonstrated on two separate occasions.
When HbA1c is used for the diagnosis of diabetes:
a HbA1c of greater than or equal to 48 mmol/mol (6.5%) is diagnostic of diabetes mellitus
a HbAlc value of less than 48 mmol/mol (6.5%) does not exclude diabetes (i.e. it is not as sensitive as fasting samples for detecting diabetes)
in patients without symptoms, the test must be repeated to confirm the diagnosis
it should be remembered that misleading HbA1c results can be caused by increased red cell turnover (see below)
In what conditions can HbA1c not be use for diagnosis?
haemoglobinopathies
haemolytic anaemia
untreated iron deficiency anaemia
suspected gestational diabetes
children
HIV
chronic kidney disease
people taking medication that may cause hyperglycaemia (for example corticosteroids)
How does alcohol lead to hypoglycaemia?
causes exaggerated insulin secretion
mechanism is thought to be due to the effect of alcohol on the pancreatic microcirculation → redistribution of pancreatic blood flow from the exocrine into the endocrine parts → increased insulin secretion
causes of hypoglycaemia?
insulinoma - increased ratio of proinsulin to insulin
self-administration of insulin/sulphonylureas
liver failure
Addison’s disease
alcohol
nesidioblastosis - beta cell hyperplasia
physiological response to hypoglycaemia?
hormonal response: the first response of the body is decreased insulin secretion. This is followed by increased glucagon secretion. Growth hormone and cortisol are also released but later
sympathoadrenal response: increased catecholamine-mediated (adrenergic) and acetylcholine-mediated (cholinergic) neurotransmission in the peripheral autonomic nervous system and in the central nervous system
Features of hypoglycaemia?
blood glucose levels and the severity of symptoms are not always correlated, especially in patients with diabetes.
blood glucose concentrations <3.3 mmol/L cause autonomic symptoms due to the release of glucagon and adrenaline (average frequency in brackets):
Sweating
Shaking
Hunger
Anxiety
Nausea
blood glucose concentrations below <2.8 mmol/L cause neuroglycopenic symptoms due to inadequate glucose supply to the brain:
Weakness
Vision changes
Confusion
Dizziness
Severe and uncommon features of hypoglycaemia include:
Convulsion
Coma
Complications of HRT?
increased risk of breast cancer
increased by the addition of a progestogen
in the Women’s Health Initiative (WHI) study there was a relative risk of 1.26 at 5 years of developing breast cancer
the increased risk relates to the duration of use
the risk of breast cancer begins to decline when HRT is stopped and by 5 years it reaches the same level as in women who have never taken HRT
increased risk of endometrial cancer
oestrogen by itself should not be given as HRT to women with a womb
reduced by the addition of a progestogen but not eliminated completely
the BNF states that the additional risk is eliminated if a progestogen is given continuously
increased risk of venous thromboembolism
increased by the addition of a progestogen
transdermal HRT does not appear to increase the risk of VTE
NICE state women requesting HRT who are at high risk for VTE should be referred to haematology before starting any treatment (even transdermal)
increased risk of stroke
increased risk of ischaemic heart disease if taken more than 10 years after menopause
What is androgen insensitivity syndrome?
Androgen insensitivity syndrome is an X-linked recessive condition due to end-organ resistance to testosterone causing genotypically male children (46XY) to have a female phenotype. Complete androgen insensitivity syndrome is the new term for testicular feminisation syndrome
Features of androgen insesntivity syndrome?
‘primary amenorrhoea’
little or no axillary and pubic hair
undescended testes causing groin swellings
breast development may occur as a result of the conversion of testosterone to oestradiol
Diagnosis and management of androgen insenstivity syndrome?
Diagnosis
buccal smear or chromosomal analysis to reveal 46XY genotype
after puberty, testosterone concentrations are in the high-normal to slightly elevated reference range for postpubertal boys
Management
counselling - raise the child as female
bilateral orchidectomy (increased risk of testicular cancer due to undescended testes)
oestrogen therapy
What is Kallmann’s syndrome?
Kallmann’s syndrome is a recognised cause of delayed puberty secondary to hypogonadotropic hypogonadism. It is usually inherited as an X-linked recessive trait. Kallmann’s syndrome is thought to be caused by failure of GnRH-secreting neurons to migrate to the hypothalamus.
The clue given in many questions is lack of smell (anosmia) in a boy with delayed puberty
Features of Kallmann’s syndrome?
‘delayed puberty’
hypogonadism, cryptorchidism
anosmia
sex hormone levels are low
LH, FSH levels are inappropriately low/normal
patients are typically of normal or above-average height
Management of Kallmann’s syndrome
testosterone supplementation
gonadotrophin supplementation may result in sperm production if fertility is desired later in life
Pathophysiology of Osmotic demyelination syndrome?
pathophysiology:
thought to develop secondary to astrocyte (and possibly oligodendrocyte) apoptosis
astrocytes and oligodendrocytes (cells of the glial syncytium) are crucial for normal myelination
chronic hyponatraemia → loss of osmotically active organic osmolytes (such as myoinositol, glutamate, glutamine) from astrocytes. These provide protection against cerebral oedema
organic osmolytes cannot be replaced quickly enough when the brain volume begins to shrink in response to the correction of hyponatraemia
the dehydrated astrocytes and oligodendrocytes undergo apoptosis or other forms of injury → demyelination
to avoid this, Na+ levels are only raised by 4 to 6 mmol/l in a 24-hour period
symptoms usually occur after 2 days and are usually irreversible: dysarthria, dysphagia, paraparesis or quadriparesis, seizures, confusion, and coma
patients are awake but are unable to move or verbally communicate, also called ‘Locked-in syndrome’
What is Primary hyperparathyroidism?
Primary hyperparathyroidism is caused by excess secretion of PTH resulting in hypercalcaemia. It is the most common cause of hypercalcaemia in outpatients and is often diagnosed following an incidental finding of an elevated serum calcium concentration. In 85% of cases a parathyroid adenoma is responsible.
Causes of primary hyperparathyroidism
85%: solitary adenoma
10%: hyperplasia
4%: multiple adenoma
1%: carcinoma
Investigations in primary hyperparathyroidism?
bloods
raised calcium, low phosphate
PTH may be raised or (inappropriately, given the raised calcium) normal
technetium-MIBI subtraction scan
x-ray findings
pepperpot skull
osteitis fibrosa cystica
Treatment for primary hyperparathyroidism?
the definitive management is total parathyroidectomy
conservative management may be offered if the calcium level is less than 0.25 mmol/L above the upper limit of normal AND the patient is > 50 years AND there is no evidence of end-organ damage
patients not suitable for surgery may be treated with cinacalcet, a calcimimetic
a calcimimetic ‘mimics’ the action of calcium on tissues by allosteric activation of the calcium-sensing receptor
Mechanism of action on sulfonylureas?
They work by increasing pancreatic insulin secretion and hence are only effective if functional B-cells are present.
On a molecular level they bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells.
Adverse effects of sulfonylureas?
Common adverse effects
hypoglycaemic episodes (more common with long-acting preparations such as chlorpropamide)
weight gain
Rarer adverse effects
hyponatraemia secondary to syndrome of inappropriate ADH secretion
bone marrow suppression
hepatotoxicity (typically cholestatic)
peripheral neuropathy
Sulfonylureas should be avoided in breastfeeding and pregnancy.
What are the threee main types of multiple endocrine neoplasia?
What oncogener is associated with medullary thyroid cancer?
Medullary thyroid cancer is associated with the RET oncogene
what are dynamic pituitary function tests?
A dynamic pituitary function test is used to assess patients with suspected primary pituitary dysfunction
Insulin, TRH and LHRH are given to the patient following which the serum glucose, cortisol, growth hormone, TSH, LH and FSH levels are recorded at regular intervals. Prolactin levels are also sometimes measured
*dopamine antagonist tests using metoclopramide may also be used in the investigation of hyperprolactinaemia. A normal response is at least a twofold rise in prolactin. A blunted prolactin response suggests a prolactinoma
A normal dynamic pituitary function test has the following characteristics:
GH level rises > 20mu/l
cortisol level rises > 550 mmol/l
TSH level rises by > 2 mu/l from baseline level
LH and FSH should double
primary, secondary and tertiary hyperparathyroidism?
Primary hyperparathyroidism
PTH over-secretion usually from a parathyroid adenoma
both PTH and calcium are elevated
surgery to remove the adenoma is the most effective treatment
conservative measures such as bisphosphonates can be used
Secondary hyperparathyroidism
occurs in chronic kidney disease typically
can be secondary to vitamin D deficiency
PTH released due to low calcium, high phosphate and lack of vitamin D activation by diseased kidneys
PTH level high with calcium levels being low or normal
medical management primarily: phosphate binders, calcium and vitamin D supplementation
Tertiary hyperparathyroidism
autonomous hypersecretion of PTH due to hypertrophied parathyroid glands
occurs after a period of long standing secondary hyperparathyroidism
treatment involves parathyroidectomy
What may cause Pseudohperkalaemia?
haemolysis during venipuncture (excessive vacuum of blood drawing, prolonged tourniquet use or too fine a needle gauge)
delay in the processing of the blood specimen
abnormally high numbers of platelets, leukocytes, or erythrocytes (such as myeloproliferative disorders)
familial causes
What is Pseudohyperkalaemia?
Pseudohyperkalaemia is a rise in serum potassium that occurs due to excessive leakage of potassium from cells, during or after blood is taken. It is a laboratory artefact and does not represent the true serum potassium concentration. The majority of potassium is intracellular and thus leakage from cells can significantly impact serum levels. In this case the potassium is released as the large numbers of platelets aggregate and degranulate.
Hashimoto vs Graves disease?
** Anti-TPO with features of Hyperthyroid (Low TSH, High T3/T4) –> Grave’s Disease
** Anti-TPO with features of Hypothyroid (High TSH, Low T3/T4) –> Hashimoto Thyroiditis
How do Sulfonylureas act?
Sulfonylureas - bind to an ATP-dependent K+(KATP) channel on the cell membrane of pancreatic beta cells
They work via mimicking the role of ATP on potassium-ATP channels from the outside. They act to block these channels causing membrane depolarisation and thus opening of voltage-gated calcium channels. This process results in the stimulation of insulin release.
Management of acromegaly?
Trans-sphenoidal surgery is the first-line treatment for acromegaly in the majority of patients.
If a pituitary tumour is inoperable or surgery unsuccessful then medication may be indicated:
somatostatin analogue
directly inhibits the release of growth hormone
for example octreotide
effective in 50-70% of patients
pegvisomant
GH receptor antagonist - prevents dimerization of the GH receptor
once daily s/c administration
very effective - decreases IGF-1 levels in 90% of patients to normal
doesn’t reduce tumour volume therefore surgery still needed if mass effect
dopamine agonists
for example bromocriptine
the first effective medical treatment for acromegaly, however now superseded by somatostatin analogues
effective only in a minority of patients
What treatment may be used as an adjunct to surgery in acromegaly?
octreotide, a somatostatin analogue which is often used as an adjunct to surgery resulting in reduced growth hormone levels and reduction in tumour size
Features of hypoclacaemia?
As extracellular calcium concentrations are important for muscle and nerve function many of the features seen in hypocalcaemia seen a result of neuromuscular excitability
Features
tetany: muscle twitching, cramping and spasm
perioral paraesthesia
if chronic: depression, cataracts
ECG: prolonged QT interval
What two clinical signs are seen in hypocalcaemia and what percentage of people are they seen in?
Trousseau’s sign
carpal spasm if the brachial artery occluded by inflating the blood pressure cuff and maintaining pressure above systolic
wrist flexion and fingers are drawn together
seen in around 95% of patients with hypocalcaemia and around 1% of normocalcaemic people
Chvostek’s sign
tapping over parotid causes facial muscles to twitch
seen in around 70% of patients with hypocalcaemia and around 10% of normocalcaemic people
Causes of Hypokalaemia with acidosis, with alkalosis, with HTN without HTN?
Hypokalemia with alkalosis= CCTV=> cushing’s, Conn’s, thiazide n loop, vomiting
Hypokalemia with acidosis=DRAP=> Diarrhea, RTA, Acetazolamide, Partially rx dka
Hypokalemia with Hypertension= CCL11=> Cushing’s, Con’s, Liddle’s,11-beta hydroxylase deficiency
Hypokalemia without Hypertension: DR BiL Gates=> Diuretics, RTA 1 n 2, Barterr’s, giteLman’s and GI loss
what is 11-beta hydroxylase deficiency?
a form of congenital adrenal hyperplasia (CAH) characterised by impaired cortisol synthesis and accumulation of 11-deoxycorticosterone (DOC), which has mineralocorticoid activity. The excess DOC leads to sodium retention, volume expansion, and hypertension. Additionally, the condition causes hypokalaemia due to increased potassium excretion driven by the mineralocorticoid excess.
Management of hyperthyroidism in pregnancy?
Propylthiouracil is used in the first trimester of pregnancy in place of carbimazole, as the latter drug may be associated with an increased risk of congenital abnormalities. At the beginning of the second trimester, the woman should be switched back to carbimazole, as propylthiouracil has been associated with a small risk of severe hepatic injury.
What is sick euthyroid syndrome?
In sick euthyroid syndrome (now referred to as non-thyroidal illness) it is often said that everything (TSH, thyroxine and T3) is low. In the majority of cases however the TSH level is within the >normal range (inappropriately normal given the low thyroxine and T3).
Changes are reversible upon recovery from the systemic illness and hence no treatment is usually needed.
Causes of sick euthyroid?
Causes of sick euthyroid include: myocardial infarctions, starvation, burns, trauma, surgery, malignancy, diabetic ketoacidosis, any organ failure and inflammatory conditions.
Pathophysiology of SIADH?
Pathophysiology
SIADH involves an excessive release of antidiuretic hormone (ADH), also known as vasopressin, which leads to water retention, volume expansion, and dilutional hyponatraemia
ADH is produced by the hypothalamus and stored in the posterior pituitary gland. Its primary function is to regulate the body’s water balance
It does this by increasing water reabsorption in the collecting ducts of the kidneys, thereby decreasing the volume of urine produced
In SIADH, there is an inappropriate and continuous release of ADH that is not inhibited by normal physiological mechanisms, such as adequate or excess body fluid levels
As a result, the kidneys reabsorb more water, leading to decreased urine output, and expansion of extracellular fluid volume.
Importantly, this increase in body fluid volume does not lead to the expected signs of fluid overload, such as oedema or hypertension, because the excess fluid is uniformly distributed throughout all body fluid compartments.
However, as water is retained in the body, the concentration of electrolytes in the blood, particularly sodium, becomes diluted, leading to hyponatraemia.
Causes of SIADH
Investigations for SIADH?
Urine osmolality: Urine osmolality is inappropriately high (>100 mOsm/kg) in relation to serum osmolality, as the kidneys should normally dilute urine in the setting of low serum osmolality.
Urine sodium concentration: Urine sodium concentration is typically high (>40 mmol/L) due to the action of ADH on the renal tubules.
management of SIADH?
correction must be done slowly to avoid precipitating central pontine myelinolysis
fluid restriction
demeclocycline: reduces the responsiveness of the collecting tubule cells to ADH
ADH (vasopressin) receptor antagonists have been developed
What thyroid disorder is associated with MALT lymphoma?
Hashimoto’s
What is subclincial hyperthyroidism?
Subclinical hyperthyroidism is an entity which is gaining increasing recognition. It is defined as:
normal serum free thyroxine and triiodothyronine levels
with a thyroid stimulating hormone (TSH) below normal range (usually < 0.1 mu/l)
Causes of Subclinical hyperthyroidism?
multinodular goitre, particularly in elderly females
excessive thyroxine may give a similar biochemical picture
why is it important to recognise subclinical hyperthyroidism?
The importance in recognising subclinical hyperthyroidism lies in the potential effect on the cardiovascular system (atrial fibrillation) and bone metabolism (osteoporosis). It may also impact on quality of life and increase the likelihood of dementia
Management of subclinical hyperthyroidism?
TSH levels often revert to normal - therefore levels must be persistently low to warrant intervention
a reasonable treatment option is a therapeutic trial of low-dose antithyroid agents for approximately 6 months in an effort to induce a remission
Which type of renal tubular acidosis will cause renal stones?
Distal renal tubular acidosis can cause calcium phosphate renal stones and is linked to Sjogrens syndrome
Type 1 RTA (distal)
inability to generate acid urine (secrete H+) in distal tubule
causes hypokalaemia
complications include nephrocalcinosis and renal stones
causes include idiopathic, rheumatoid arthritis, SLE, Sjogren’s, amphotericin B toxicity, analgesic nephropathy
What happens to the hormones in the follicular phase?
A rise in FSH results in the development of follicles which in turn secrete oestradiol
When the egg has matured, it secretes enough oestradiol to trigger the acute release of LH. This in turn leads to ovulation
What are the phases of the menstrual cycle?
What happens to the hormones in the luteal phase?
Progesterone secreted by corpus luteum rises through the luteal phase.
If fertilisation does not occur the corpus luteum will degenerate and progesterone levels fall
Oestradiol levels also rise again during the luteal phase
What may happen when paient recieve radioiodine treatment for Graves disease?
Radioiodine treatment may lead to the development / worsening of thyroid eye disease in up to 15% of patients with Grave’s disease
treatment for diabetic peripheral neuropathy?
first-line treatment: amitriptyline, duloxetine, gabapentin or pregabalin
if the first-line drug treatment does not work try one of the other 3 drugs
tramadol may be used as ‘rescue therapy’ for exacerbations of neuropathic pain
topical capsaicin may be used for localised neuropathic pain (e.g. post-herpetic neuralgia)
pain management clinics may be useful in patients with resistant problems
Management of Gastroparesis secondary to diabatic autonomic neuropathy?
management options include metoclopramide, domperidone or erythromycin (prokinetic agents)
what is the first hormone secreted in response to hypogkycaemia?
Glucagon is the first hormone secreted in response to hypoglycaemia
Glucagon promotes gluconeogenesis in an attempt to raise blood glucose levels.
What are the different types of thyroid cancer?
Papillary
Follicular
Medullary
Anaplastic
Lymphoma
What is Phaeochromocytoma?
Phaeochromocytoma is a rare catecholamine secreting tumour. About 10% are familial and may be associated with MEN type II, neurofibromatosis and von Hippel-Lindau syndrome
Basics
bilateral in 10%
malignant in 10%
extra-adrenal in 10% (most common site = organ of Zuckerkandl, adjacent to the bifurcation of the aorta)
Features of Phaeochromocytoma?
Features are typically episodic
hypertension (around 90% of cases, may be sustained)
headaches
palpitations
sweating
anxiety
Tests for phaeochromocytoma?
24 hr urinary collection of metanephrines (sensitivity 97%*)
this has replaced a 24 hr urinary collection of catecholamines (sensitivity 86%)
Managment of phaeochromocytoma ?
Surgery is the definitive management. The patient must first however be stabilized with medical management:
alpha-blocker (e.g. phenoxybenzamine), given before a
beta-blocker (e.g. propranolol)
what karyotype is associated with Klinefelter’s syndrome?
karyotype 47, XXY
Features of Klinefelter’s syndrome?
Features
often taller than average
lack of secondary sexual characteristics
small, firm testes
infertile
gynaecomastia - increased incidence of breast cancer
elevated gonadotrophin levels but low testosterone
Diagnosis is by karyotype (chromosomal analysis).
causes of raised prolactin?
Causes of raised prolactin - the p’s
pregnancy
prolactinoma
physiological
polycystic ovarian syndrome
primary hypothyroidism
phenothiazines, metoclopramide, domperidone
Causes of raised prolactin
prolactinoma
pregnancy
oestrogens
physiological: stress, exercise, sleep
acromegaly: 1/3 of patients
polycystic ovarian syndrome
primary hypothyroidism (due to thyrotrophin releasing hormone (TRH) stimulating prolactin release)
Drug causes of raised prolactin
metoclopramide, domperidone
phenothiazines
haloperidol
very rare: SSRIs, opioids
what is the target fasting glucose for gestational diabetes?
The target for fasting blood glucose in gestational diabetes is <5.3 mmol/L. The target for blood glucose two hours after an oral glucose tolerance test is <6.4 mmol/L.
what is the most common cause of ectopic ACTH production
small cell lung cancer
