Endocrinology Flashcards
(220 cards)
1
Q
Where is insulin and glucagon secreted from?
A
secreted from alpha and beta cells in the islets of langerhans in the pancreas
alpha cells- glucagon
beta cells- insulin
2
Q
What is type 1 diabetes mellitus?
A
autoimmune destruction of pancreatic beta cells leading to complete insulin deficiency
3
Q
When does type 1 DM usually present?
A
age 5-15
4
Q
Describe the pathophysiology of type 1 diabetes mellitus.
A
- autoantibodies attack beta cells in islets of langerhans
- leads to insulin deficiency
- hyperglycaemia
- continuous breakdown of glycogen from the liver causes glycosuria
5
Q
What is the medical term for sugar in the urine?
A
glycosuria
6
Q
Who is most at risk of T1 DM?
A
- Northern European people
- patients already suffering with autoimmune disease
7
Q
What are the signs and symptoms of T1 DM?
A
The classic triad: polydipsia, polyuria, weight loss
usually a short history of severe symptoms
may present with ketosis
8
Q
What is the medical term for extreme thirstiness?
A
polydipsia
9
Q
What is ketosis?
A
the burning of fat for energy instead of glucose
10
Q
How is T1 DM diagnosed?
A
fasting plasma glucose > 7mmol/L or random plasma glucose > 11.1mmol/L
if patient is symptomatic only need one raised plasma glucose reading
if patient asymptomatic need 2 abnormal readings on different occasions
11
Q
What is the treatment for T1 DM?
A
basal-bolus insulin treatment
basal - insulin that is injected once or twice a day always
bolus - insulin that is injected specifically before a mean
12
Q
What antibodies have been found to be associated with T1 DM?
A
anti GAD
pancreatic islet cell Ab
islet antigen-2 Ab
ZnT8
13
Q
Describe the pathophysiology of T2 DM.
A
- repeated exposure to high levels of glucose leads to repeated release of insulin which makes cells resistant to effects of insulin
- over time beta cells become fatigued and damaged from overuse and start to produce less
- continues pancreatic fatigue leads to chronic hyperglycaemia
14
Q
What are the risk factors of T2 DM?
A
obesity/ inactivity
alcohol excess
asian males
age
hypertension
family history
gestational diabetes
steroid use
Cushing’s syndrome
chronic pancreatitis
15
Q
What are the signs and symptoms of type 2 diabetes mellitus?
A
slower onset that type 1
polydipsia
polyuria
glycosuria
blurred vision
polyphagia
16
Q
What is the term for extreme hunger?
A
polyphagia
17
Q
How is T2 DM diagnosed?
A
similar to T1 except for HbA1c test
- HbA1c - GOLD STANDARD
HbA1C > 48mmol/mol - diabetes
HbA1c 42-47 mmil/mol - prediabates - Blood tests
random plasma glucose > 11.1mmol/L
fasting plasma glucose > 7 mol/L - Oral glucose tolerance test
fasting > 7 mol/L
2 hrs after glucose > 11.1 mol/L
18
Q
What is the management of type 1 diabetes?
A
1st line- lifestyle changes
- weight loss
- dietary advice (high complex carbs, low fat)
- smoking cessation
- exercise
- blood pressure control
2nd line- metformin
used if newly diagnosed patient have blood glucose above 48mmol/L after lifestyle modifications
3rd line- dual therapy of metformin with sulfonylurea/ pioglitazone/ DPP-4 inhibitor/ SGLT-2 inhibitor
4th line- if still not working, insulin
19
Q
How does metformin treat diabetes?
A
increases sensitivity to insulin
20
Q
How does sulphonylurea treat diabetes?
A
increases insulin secretion
21
Q
What is diabetic ketoacidosis?
A
complete lack of insulin results in high ketone production
medical emergency
22
Q
In which patients do we tend to see diabetic ketoacidosis?
A
it’s the most common way that children with a new diagnosis of T1 DM present
23
Q
Describe the pathophysiology of diabetic ketoacidosis.
A
occurs when body does not have enough insulin to use and process glucose
- complete absence of insulin
- unrestrained production of glucose and decreased peripheral glucose uptake
- hyperglycaemia
- osmotic diuresis
- dehydration
- peripheral lipolysis for energy
- increased free fatty acids
- fatty acids oxidised to acetyl coA
- production of ketones leads to acidosis
24
Q
What is the direct effect of ketones on the body?
A
anorexia and vomiting
25
What are the causes/ risk factors of diabetic ketoacidosis?
- untreated T1DM/ interruption of insulin therapy
- undiagnosed DM
- infection/ illness
- myocardial infarction
26
What is the presentation of diabetic ketoacidosis?
extreme diabetes symptoms plus:
- nausea and vomiting
- weight loss
- confusion/ drowsiness, potential coma
- Kussmaul's breathing
- 'pear drop' breath
- abdo pain
27
What is Kaussmaul's breathing?
an abnormal breathing pattern characterised by rapid, deep breathing at a consistent pace
characteristic of diabetes-related ketoacidosis (DKA)
28
How is diabetic ketoacidosis diagnosed?
blood test:
hyperglycaemia (blood glucose > 11mmol/L)
ketosis (blood ketones > 3mmol/L)
arterial blood gas:
acidosis (pH < 7.3 and/or bicarbonate < 15 mmol/L) - ABG
urine dipstick:
glycosuria, ketonuria
U+Es:
raised urea + creatinine
29
What is the treatment for diabetic ketoacidosis?
- immediate abc management
- replace fluid loss with IV 0.9% saline
- IV insulin
- restore electrolytes
30
What are the potential complications of diabetic ketoacidosis?
cerebra oedema (leading to coma, death)
31
Why can insulin treatment for DKA cause hypokalaemia and why is it dangerous?
insulin decreases potassium levels in the blood by redistributing K+ into cells via increased sodium potassium pump activity
causes low serum K+ levels - hypokalaemia
low levels of K+ can cause arrhythmia and weakness
31
Why can insulin treatment for DKA cause hypokalaemia and why is it dangerous?
insulin decreases potassium levels in the blood by redistributing K+ into cells via increased sodium potassium pump activity
causes low serum K+ levels - hypokalaemia
low levels of K+ can cause arrhythmia and weakness
32
Why is polyphagia a symptom/ sign of diabetes mellitus?
although glucose is high in blood it cannot enter cells
cells are starved of energy
body undergoes lipolysis and proteolysis which leaves patients hungry
32
Why is polyphagia a symptom/ sign of diabetes mellitus?
although glucose is high in blood it cannot enter cells
cells are starved of energy
body undergoes lipolysis and proteolysis which leaves patients hungry
33
What is HHS?
hyperosmolar hyperglycaemia state
marked hyperglycaemia and hyperosmolality
serious complication of T2 DM- medical emergency
usually no ketosis
34
Describe the pathophysiology of hyperosmolar hyperglycaemic state.
- insulin levels are sufficient to inhibit hepatic ketogenesis BUT insufficient to inhibit hepatic glucose production
- hyperglycaemia results in osmotic diuresis with loss of sodium and potassium
- severe volume depletion results in a significant raised serum osmolarity resulting in hyper viscosity of blood
35
What causes hyperosmolar hyperglycaemic state?
untreated/ undiagnosed T2DM
36
What are the signs and symptoms of HHS?
Extreme diabetes symptoms plus...
- fatigue/ lethargy
- nausea and vomiting
- altered consciousness
- headaches
- papilloedema
- dehydration
- hypotension
- tachycardia
37
How is HHS diagnosed?
severe hyperglycaemia:
random plasma glucose > 30mmol/L
glycosuria on dipstick
hyperosmolality
unlike DKA- no significant acidosis or ketosis
38
What is the treatment for HHS?
fluid replacement with 0.9% saline
VTE prophylaxis (high risk due to dehydration) - LMW heparin e.g. enoxaprin
IV insulin if high levels of ketones or treatment not working
39
What are the complications of HHS?
hyperviscosity may cause:
stroke
MI
PE
high dose insulin therapy may cause:
insulin related hypoglycaemia
treatment related hypokalaemia
40
What is hypoglycaemia?
blood glucose levels below 3 mmol/L
41
Describe the pathophysiology of hypoglycaemia.
- blood glucose is taken up by cells, leading to drop in blood glucose levels
- this stimulated alpha cells to produce glucagon and reduce production of insulin from beta cells
- decreased blood glucose increases production of adrenaline, GH and cortisol
- all of these mechanism act to rapidly increase blood glucose
the pathophysiology of hypoglycaemia depends on its cause and an interruption to one of the above mechanisms
42
What does the thyroid gland secrete?
thyroxine (T4)
triiodothyronine (T3)
43
What is hypothyroidism?
a clinical effect of lack of thyroid hormones
44
What is the difference between primary and secondary hypothyroidism?
primary:
abnormally reduced thyroid function
secondary:
pituitary fails to produce enough TSH
45
What are the causes of primary hypothyroidism?
most common cause: Hashimoto's thyroiditis
radiotherapy
de quervain's thyroiditis
dietary iodine deficiency
46
Which conditions are associated with hypothyroidism?
downs syndrome
turners syndrome
coeliac disease
47
How do patients with hypothyroidism present?
weight gain
lethargy
cold intolerance
menorrhagia
constipation
dry scalp
48
What investigations confirm a diagnosis of hypothyroidism?
1st line: thyroid function tests (TFTs)
primary - high TSH, low T4
secondary - low TSH, low T4
elevated antithyroid peroxidase antibodies
49
How is hypothyroidism treated?
levothyroxine
50
What is Hashimoto's thyroiditis?
an autoimmune disease in which the thyroid gland is attacked causing primary hypothyroidism
51
Describe the pathophysiology of Hashimoto's thyroiditis.
antithyroid antibodies attack thyroid tissue causing progressive fibrosis (low T4, high TSH)
52
What is the treatment for Hashimoto's thyroiditis?
levothyroxine
53
What is hyperthyroidism?
the clinical effect of excess thyroid hormone
54
What is the difference between primary and secondary hyperthyroidism?
primary- abnormal increased thyroid function
secondary- abnormal increased TSH production
55
What is the main cause of hyperthyroidism?
Graves' disease- accounts for approx. 70% of cases
56
What are the causes of hyperthyroidism?
- Graves' disease (most common)
- toxic multi nodular goitre
- iodine excess
- thyroiditis
- amiodarone use
57
How does hyperthyroidism present?
weight loss
heat intolerance
palpitations
sweating
pretibial myxoedema
diarrhoea
oligomenorrhoea
anxiety
tremor
58
How is hyperthyroidism diagnosed?
1st line: thyroid function tests (TFTs)
will show high T4 and low TSH
antibodies present: TSH-receptor antibodies
59
What is the treatment for hyperthyroidism?
Depends on the cause
1. Drug management
- 1st line: carbimazole (blocks synthesis of T4)
- 2nd line: propylthiouracil (prevents T4 to T3 conversion)
- beta blockers (rapid symptom relief of tremor etc)
2. Radioiodine treatment (beta particles used to cause ionisation of thyroid cell, may exacerbate thyroid eye disease)
3. Surgery (thyroidectomy)
60
What is Graves' disease?
autoimmune destruction of the thyroid gland resulting in hyperthyroidism
61
What causes Graves' disease?
autoimmune disease
can be caused by MS drug alemtuzumab
62
Describe the pathophysiology of Graves' disease.
IgG autoantibodies are directed against the thyrotropin (TSH) receptor
they bind and activate the receptor, causing autonomous production of thyroid hormones
63
How does Graves' disease present?
All symptoms of hyperthyroidism plus:
thyroid eye disease:
- bulging eyes (exophthalmos)
- extra ocular muscle palsy (ophthalmoplegia)
- eyelid retraction
thyroid acropatchy (triad of digital clubbing, soft tissue swelling of hands and feet, periosteal new bone formation)
64
How is Grave's disease diagnosed?
Same as hyperthyroidism
TFTs- high T4 and low TSH
65
How is Graves' disease treated?
The same as hyperthyroidism:
1. Drug management
- 1st line: carbimazole (blocks synthesis of T4)
- 2nd line: propylthiouracil (prevents T4 to T3 conversion)
- beta blockers (rapid symptom relief of tremor etc)
2. Radioiodine treatment (beta particles used to cause ionisation of thyroid cell, may exacerbate thyroid eye disease)
3. Surgery (thyroidectomy)
66
What is De Quervain's thyroiditis?
aka subacute granulomatous thyroiditis
inflammation of thyroid gland resulting in the rapid swelling of the thyroid gland, painful and uncomfortable
67
What causes De Quervain's thyroiditis?
often occurs following a viral infection
68
Describe the pathophysiology of De Quervain's thyroiditis.
4 phases:
phase 1 - lasts 3-6 weeks
hyperthyroidism, painful goitre, raised ESR
phase 2- lasts 1-3 weeks
euthyroid (normal function)
phase 3- weeks to months
hypothyroidism
phase 4
thyroid structure and function returns to normal
69
How does De Quervain's thyroiditis present?
neck/ jaw/ ear pain
difficulty eating
tend, firm, enlarged thyroid
fever
palpitations
70
What investigations confirm a diagnosis of De Quervain's thyroiditis?
Elevated:
total T4
T3
T3 resin uptake
free thyroxine index
CRP
71
What is the treatment of De Quervain's thyroditis?
hyperthyroid phase: NSAIDS and corticosteroids for pain
hypothyroid phase: usually not treatment but if severe hypothyroidism occurs may give small dose of levothyroxine
72
What is an acute diagnosis for a patient with an episode of hyperthyroidism followed by an episode of hypothyroidism?
De Quervain's thyroiditis
73
What are the four main types of thyroid cancer?
papillary
follicular
anaplastic
medullary
74
What are the risk factors of thyroid cancer?
head and neck radiation exposure
female sex
75
How does thyroid cancer present?
palpable thyroid nodule
76
How is thyroid cancer diagnosed?
1st line: ultrasound neck
fine needle biopsy
laryngoscopy
77
What is the treatment for thyroid cancer?
total thyroidectomy followed by radioactive iodine ablation and suppression of TSH
78
What are the possible complications of total thyroidectomy?
increased risk of recurrent laryngeal nerve damage or hypoparathyroidism
thyroid storm
79
What type of thyroid cancer has the best and worst prognosis?
Best: papillary
Worst: anaplastic, median survival 3-8 months
80
What is a thyroid storm?
AKA thyrotoxic crisis
the severe end of the spectrum of thyrotoxicosis and is characterised by compromised organ function
81
What are the potential causes of a thyroid storm?
Graves' disease
post thyroidectomy
infection/ trauma
MI
DKA
pregnancy
iodine
abrupt cessation of thyroid drugs
82
How does a thyroid storm present?
fever
cardiovascular disfunction
profuse sweating
tachyarrhythmias
nausea and vomiting
83
Describe the pathophysiology of a thyroid storm.
clinical syndrome that results when tissues are exposed to high levels of circulating thyroid hormones, usually caused by hyperthyroidism
84
How is a thyroid storm diagnosed?
completely suppressed TSH and high thyroxine
diagnosed with clinical presentation
85
How is a thyroid storm treated?
1st line: antithyroid treatment- carbimazole
hydroscortisone- treats possible relative adrenal insufficiency, decreased T4 to T3 conversion
gold standard: thyroidectomy
86
Describe the basic anatomy of the thyroid gland.
two lobes (left and right) connected by the central isthmus
wrapped around the cricoid cartilage
butterfly shape
blood supply from the inferior and superior thyroid artery
87
What hormones are secreted by the anterior pituitary?
- adrenocorticotropic hormone (ACTH)
- growth hormone (GH)
- luteinising hormone (LH)
- follicle-stimulating hormone (FSH)
- prolactin
- thyroid-stimulating hormone (TSH)
88
What hormones are secreted by the posterior pituitary?
- anti-diuretic hormone (ADH)
- oxytocin
89
What hormone is secreted from the pars intermedia of the pituitary gland?
melanocyte-stimulating hormone
90
What is the function of ACTH?
stimulates the adrenal glands to secrete steroids (e.g. cortisol)
91
What is the function of GH?
regulates growth, metabolism and body composition
92
What is the function of LH and FSH?
These are the gonadotropins
act on ovaries/ testes to stimulate sex hormone production and egg/ sperm maturity
93
What is the function of prolactin?
stimulates milk production in mammary glands
94
What is the function on TSH?
stimulates thyroid gland to secrete thyroid hormones
95
What is the function of ADH/ vasopressin?
controls water balance and blood pressure
96
What is the function of oxytocin?
stimulates uterine contractions during labour and milk secretion during breast feeding
97
What is the function of melanocyte-stimulating hormone?
acts on cells in the skin to stimulate the production of melanin
98
Where are posterior pituitary hormones made?
hypothalamus
99
What is a pituitary adenoma?
a benign growth on the pituitary gland
100
What are the 3 categories of pituitary adenoma?
prolactinoma
acromegaly
Cushing's syndrome
101
What is Cushing's syndrome?
long term exposure to excessive cortisol hormone released by adrenal glands
102
What are causes of Cushing's syndrome?
2 classes:
ACTH dependent (rare):
- ACTH secretion from pituitary adenoma
- ectopic ACTH production from small cell lung cancer
ACTH independent:
- Iatrogenic- steroid use (e.g. prednisolone)
- adrenal adenoma
103
What is the difference between Cushing's syndrome and Cushing's disease?
Cushing's syndrome that occurs as a result of a pituitary tumour is called Cushing's disease
104
How does Cushing's disease present?
round moon face
central obesity
abdominal striae
buffalo hump
proximal limb muscle wasting
mood change
ammenorhea/ irregular periods
acne
hirsutism
105
What is ammenorhea?
absence of a period in women
106
What is hirsutism?
when women have excessive dark/ coarse hair in a male-like pattern (face/ chest/ back)
107
How is Cushing's syndrome diagnosed?
1st line: raised random plasma cortisol
gold standard: dexamethasone suppression test- cortisol will not be suppressed in Cushing's
other tests:
24hr urinary free cortisol
MRI brain (for pit. adenoma)
chest CT (for small cell lung cancer)
abdominal CT (for adrenal tumour)
108
Why can you not make a diagnosis of Cushing's off the random plasma cortisol alone?
can be misleading as cortisol is raised depending on illness, time of day, stress etc and will influence results
109
What is the treatment for Cushing's syndrome?
depends on the underlying cause
if cause is:
- iatrogenic- stop steroids
- Cushing's disease- trans-sphenoidal surgery to remove pituitary adenoma
- adrenal adenoma- adrenalectomy
- ectopic ACTH production- surgery to remove neoplasm is can be located and hasn't metastasised
cortisol synthesis inhibition drugs: metyrapone, ketoconazole
110
What are the potential complications of Cushing's syndrome?
hypertension
cardiovascular diasease
osteoporosis
diabetes mellitus
111
What is acromegaly?
release of excess growth hormone (GH) causing overgrowth of all systems
112
What are the causes of acromegaly?
- 99% due to pituitary adenoma
- (rarely) secondary to a malignancy that secretes ectopic GH (e.g. lung cancer)
113
Describe the pathophysiology of acromegaly.
GHRH is released from the hypothalamus and stimulates release of GH from anterior pituitary
this results in excessive production of insulin-like growth factor (IGF-1) which is responsible for inappropriate growth
this stimulates bone and soft tissue growth
114
How does acromegaly present?
large spade-like hands a feet
prominent forehead and brow
large tongue
increased jaw size- "prognathism"
bitemporal hemianopia
acroparaesthesia (tingling and numbness of arms/ legs)
arthralgia (joint pain)
profuse sweating
headache
115
What inhibits the release of GH?
somatostatin
high levels of glucose
dopamine
116
How is acromegaly diagnosed?
1st line: insulin-like growth factor (IGF-1) raised
gold standard: oral glucose tolerance test, no suppression of GH (as there usually would be in this test)
MRI brain for pituitary adenoma to assess size and extent
117
How is acromegaly treated?
gold standard- trans-sphenoidal surgery of pituitary tumour if present/ surgical removal of other cancer if causing acromegaly
if surgery not possible, use medications to block GH:
2nd line: somatostatin analogue e.g. ocreotide
3rd line: GH receptor analogue e.g. pegvisomant
4th line: dopamine agonist e.g. cabergoline/ bromocriptine
118
What are the potential complications of acromegaly?
erectile dysfunction
type 2 diabetes
heart disease
hypertension
arthritis
119
Who generally has high prolactin levels?
pregnant women and new mothers
120
What is a prolactinoma?
benign adenoma of the pituitary gland producing excess prolactin
121
What cells make prolactin?
lactotrophs
122
What are the risk factors for prolactinoma?
female
20-40 years old
123
What are the causes of hyperprolactinaemia OTHER THAN prolactinoma?
non-functioning pituitary tumour- compresses pituitary stalk and stops inhibition of prolactin release
antidopaminergic drugs
124
Describe the pathophysiology of prolactinoma.
hypersecretion of prolactin causes secondary hypogonadism
this is due to its inhibitory effects on gonadotropin-releasing hormone
125
What are the two types of prolactinoma?
micro:
tumour < 10mm diameter on MRI
most common - 90% of cases
macro:
tumour > 10mm diameter on MRI
126
How does prolactinoma present in males and females?
males:
- low testosterone
- erectile dysfunction
- reduced facial hair
- low libido
females:
- amenorrhoea
- oligomenorrhoea
- infertility
- galactorrhea
- low libido
127
Why does prolactinoma cause infertility in women?
high prolactin inhibits ovulation in women due to its effect on GnRH
128
What investigations are used to diagnose prolactinoma?
1st line- serum prolactin levels
(elevated if prolactinoma)
2nd line- pituitary MRI
(to detect adenoma)
129
What is the treatment of prolactinoma?
medical approach more efficient than surgical approach unlike other pituitary adenomas
1st line- dopamine agonists, oral cabergoline/ bromocriptine
2nd line- HRT e.g. oestrogen
130
Why are dopamine agonists used to treat prolactinoma?
dopamine inhibits prolactin release, so we want to stimulate the release of dopamine to shrink the prolactinoma
131
What type of molecule is aldosterone?
mineralocorticoid
132
What does aldosterone do to the kidney?
it acts on the kidney to:
- increase sodium reabsorption from the distal tubule
- increase potassium excretion from the distal tubule
133
Where are Sertoli cells found?
the testes
134
What is Conn's syndrome?
primary hyperaldosteroneism due to an aldosterone producing adenoma of the adrenal gland
135
What is primary hyperaldosteroneism?
when the adrenal glands are directly responsible for producing too much aldosterone
136
What is secondary hyperaldosteroneism?
when excessive renin stimulates the adrenal glands to produce more aldosterone
137
How can you differentiate between primary and secondary hyperaldosteroneism?
by measuring serum renin levels
primary- serum renin will be low as it is suppressed by high BP
secondary- serum renin will be high
138
What are the causes of primary hyperaldosteroneism?
bilateral adrenal hyperplasia (70%)
Conn's syndrome- aka adrenal adenoma
139
What are the signs and symptoms of Conn's syndrome?
often asymptomatic but can present with:
hypertension
headaches
hypokalaemia
nocturia, polyuria, polydipsia
140
What are the investigations for Conn's syndrome?
FBC/ U+E/ LFT:
low plasma potassium
aldosterone- renin ratio - high
CT/ MRI to locate adrenal lesions
gold standard- selective adrenal venous sampling
141
What is selective adrenal venous sampling?
a test used to determine whether autonomous hormone production is unilateral or bilateral
only unilateral can be treated with surgery
142
What is the treatment for Conn's syndrome?
1st line: aldosterone antagonists
SPIRONOLACTONE/ eplerenone
controls BP and K+ levels
laparoscopic adrenalectomy
143
What is the aim of treatment of Conn's syndrome?
lower blood pressure, decrease aldosterone levels and resolve electrolyte imbalance
144
What is Addison's disease?
primary adrenal insufficiency
the adrenal glands are damaged which results in reduced cortisol and aldosterone
145
What are the causes of Addison's disease?
autoimmune adrenalitis - most common in developed countries
TB - most common worldwide
146
What causes secondary adrenal insufficiency?
loss/ damage of the pituitary gland
147
What is tertiary adrenal insufficiency?
results from inadequate CRH released from the hypothalamus, usually due to long term oral steroid use causing suppression of the hypothalamus
148
How does adrenal insufficiency present?
non-specific symptoms
fatigue
weight loss
nausea
vomiting
abdo pain
hypotension
key symptoms: hyperpigmentation especially in palmar crease for Addison's
149
How is adrenal insufficiency diagnosed?
1st line: U+E's
low sodium- due to low aldosterone
high potassium- due to low aldosterone
low cortisol
ACTH- high in Addison's, low in secondary insufficiency
Addisons: high renin, low aldosterone
Gold standard: short synacthen test (ACTH stimulations test) gives low cortisol and high ACTH
150
How is adrenal insufficiency managed?
hydrocortisone to replace cortisol
fludrocortisone to replace aldosterone
151
What is the potential complications of Addison's disease?
Addisonian Crisis (AKA adrenal crisis)
152
Why is it dangerous to stop steroids abruptly?
causes adrenal insufficiency
153
What is SIADH?
syndrome of inappropriate ADH
inappropriately large amount of ADH secretion causes water to be reabsorbed in the collecting duct
154
What are the causes of SIADH?
- idiopathic
- post-operative from major surgery
- infection (atypical pneumonia and lung abscesses)
- iatrogenic (thiazide diuretics, antipsychotics, SSRIs, NSAIDS)
- malignancy (particularly small cell lung cancer)
155
What is the pathophysiology of SIADH?
- ADH is produced in the hypothalamus and secreted by the posterior pituitary
- it stimulates water reabsorption from the collecting ducts in the kidneys
- excessive ADH results in excessive water reabsorption in the collecting ducts
- this dilutes sodium in the blood causing hyponatraemia
- this is usually not significant enough to cause a fluid overload therefore you end up with "euvolaemic hyponatraemia"
- the urine becomes more concentrated and less water is excreted by the kidneys, therefore patients with SIADH have a "high urine osmolality" and "high urine sodium"
156
How does SIADH present?
symptoms largely due to hyponatraemia:
headache
fatigue, confusion
muscle aches and cramps
if hyponatraemia severe- seizures and reduced consciousness
157
How is SIADH diagnosed?
usually a diagnosis of exclusion
- U+E: hyponatraemia
- urine sodium and osmolality: high
- negative short synachen test: excludes adrenal insufficiency
- no diarrhoea/ vomiting
- no history of diuretic use
- no AKI/ CKD
158
How is SIADH managed?
establish and treat underlying cause
most common iatrogenic so stop causative medications if possible
fluid restriction to correct hyponatraemia
vasopressin receptor agonist for chronic SIADH, e.g. tolvapan
159
What are the types of diabetes insipidus?
cranial and nephrogenic
160
What is diabetes insipidus?
a disease characterised by either the decreased secretion of ADH from the posterior pituitary (cranial DI) or an insensitivity to ADH (nephrogenic DI)
161
What type of diabetes insipidus is most common?
cranial
162
What are the causes of cranial diabetes insipidus?
idiopathic
brain tumours
head injury
brain infection (meningitis, encephalitis, tuberculosis)
neurosurgery, radiotherapy
163
What are the causes of nephrogenic diabetes insipidus?
inherited- mutations (most common)
iatrogenic- lithium (used in bipolar disorder)
systemic disease (e.g. CKD)
electrolyte disturbance (hypokalaemia, hypercalcaemia)
164
What is the difference nephrogenic and cranial diabetes insipidus?
cranial- when the hypothalamus does not produce ADH for the pituitary gland to secrete
nephrogenic- when the collecting ducts of the kidneys do not respond to ADH
165
How does diabetes insipidus present?
polyuria
polydipsia
dehydration
postural hypotension
hypernatraemia
166
How is diabetes insipidus diagnosed?
Gold standard: water deprivation test
in DI- continue to produce large amounts of dilute urine
then desmopressin test to establish cranial or nephrogenic
167
What is the main clinical features that distinguishes diabetes insipidus and diabetes mellitus?
there should not be glycosuria in diabetes insipidus
168
What is the treatment for diabetes insipidus?
if possible, treat underlying cause
in mild cases- rehydration
cranial- desmopressin (synthetic ADH)
nephrogenic- thiazide diuretics
169
What is desmopressin?
synthetic ADH/ vasopressin
170
What is the potential complication of diabetes insipidus?
severe hypernatraemia
171
What is hyperparathyroidism?
the excessive secretion of parathyroid hormone (PTH)
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What are the categories of hyperparathyroidism?
primary, secondary and teriary
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What is primary hyperparathyroidism?
tumour/ hyperplasia of the parathyroid glands leading to addition secretive tissue
results in excess PTH production thus hypercalcaemia
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What causes primary hyperparathyroidism?
80% due to solitary adenoma
20% due to hyperplasia of glands
<0.5% due to parathyroid cancer
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What is the most common type of hyperparathyroidism?
primary hyperparathyroidism
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What is secondary hyperparathyroidism?
when insufficient vitamin D or chronic renal failure leads to low absorption of calcium from the intestines, kidneys and bones causing hypocalcaemia
this causes parathyroid gland to release more PTH and becomes hyperplastic to further increase excess PTH secretion
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What is tertiary hyperparathyroidism?
usually occurs after prologues secondary hyperparathyroidism
the glands become autonomous, producing excessive PTH even after the cause of hypocalcaemia has been corrected
no response to negative feedback
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What causes secondary hyperparathyroidism?
CKD
low vitamin D
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What causes tertiary hyperparathyroidism?
prolonged secondary hyperparathyroidism which has most likely been caused by long-standing kidney disease
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What are the risk factors for hyperparathyroidism?
elderly women who have gone through menopause
having prolonged calcium or vitamin D deficiency
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How does hyperparathyroidism present?
'stones, bones, groans and moans'
painful bones
renal stones
constipation, nausea, vomiting
fatigue, depression, psychosis
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How is hyperparathyroidism diagnosed?
primary- raised calcium
secondary- low serum calcium, high PTH
tertiary- raised calcium, raised PTH
SCANS:
bones- dexa scan for osteoporosis (salt and pepper scans)
stones- ultrasound for kidney to find stones
groans- abdominal x-ray showing renal calculi or nephrocalcinosis
detect adenomas via radioisotope scanning
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How is hyperparathyroidism treated?
primary- surgical removal of adenoma, prescribe bisphophates
secondary- treat vitamin D and calcium deficiency, or kidney transplant if CKD
tertiary- total/ subtotal parathyroidectomy, and cinacalcet (calcimimetic- increases sensitivity of parathyroid cells to calcium, thereby causing less PTH secretion)
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What is hypocalcaemia?
low serum calcium levels < 8.5mg/dL or <2.20 mmol/L
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What are the causes of hypocalcaemia?
hypoparathyroidism (post thyroid/ parathyroid surgery)
pseudohypoparathyroidism
vitamin D deficiency
hyperventilation
drugs
malignancy
toxic shock
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How does hypocalcaemia present?
muscle spasms
cramps
tetany
seizures
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How is hypocalcaemia diagnosed?
blood calcium < 8.5 mg/ dL
ECG- prolonged QT interval (arrhythmia)
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How is hypocalcaemia treated?
acute management of severe hypocalaemia- intravenous calcium gluconate or calcium chloride
vit D supplementation for persistant hypocalcaemia
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What are the complications of hypocalcaemia?
seizure
cardiac arrest
long QT syndrome
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What is hypercalcaemia?
serum calcium > 2.6 mmol/L
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What are the causes of hypercalcaemia?
hyperparathyroidism
malignancy
sarcoidosis
thyrotoxosis
drugs
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How does hypercalcaemia present?
bones, stone, moans and groans- basically exactly the same as hyperparathyroidism
painful bones
renal stones
abdominal pain (groans)
psychiatric moans (depression, anxiety)
and SHORT QT ON ECG
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How is hypercalcaemia diagnosed?
fasting serum calcium and phosphate samples both high
serum PTH- elevated
ultrasound if pointing towards hyperparathyroidism
24hr urinary calcium
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How is hypercalcaemia treated?
rehydration with saline
then rehydration with bisphosphonates
loop diuretics like furosemide sometimes used
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What is hypokalaemia?
serum potassium < 3.5 mmol/L
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What causes hypokalaemia without alkalosis/ acidosis?
decreased potassium intake
increased potassium entry into cells
increased potassium excretion
magnesium depletion
hyperaldosteronism
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What causes hypokalaemia with acidosis?
diarrhoea
renal tubular acidosis
acetazolamide
partially treated DKA
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What causes hypokalaemia with alkalosis?
vomiting
thiazide and loop diuretics
Cushing's syndrome
Conn's syndrome
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How does hypokalaemia present?
muscle weekness
hypotonia
hyporeflexia
cramps
tetany
palpitations
light headedness
arrhythmias
constipation
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What are the ECG changes in hypokalaemia?
small/ inverted T waves
prominent U waves
long PR interval
depressed ST segment
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How is hypokalaemia diagnosed?
metabolic panel
ECG
U+Es
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Why are U+Es useful in hypokalaemia?
differentiated between renal and non-renal causes
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How is hypokalaemia treated?
mild: oral replacement, consider IV
severe: IV replacement 40mmol KCL in 1L 0.9 NaCl
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What are the complications of hypokalaemia?
cardiovascular: chronic heart failure, acute MI, arrythmias
muscle: weakness, rhabdomyolysis, depression of deep tendon reflexes
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What is hyperkalaemia?
serum potassium > 5.5 mmol/L
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What are the causes of hyperkalaemia?
increased intake
increased production
reduced excretion
redistribution (intracellular to extracellular)
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How does hyperkalaemia present?
muscle weakness/ paralysis
fast irregular pulse
chest pain
light headedness
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How does the ECG look for hyperkalaemia?
tall, tented T waves
small P waves
wide QRS complex
ventricular fibrillations
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How is hyperkalaemia diagnosed?
metabolic panel
ECG
U+Es
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How is hyperkalaemia treated?
CAN CAUSE LIFE-THREATENING ARRYTHMIAS
If ECG changes- stabilise cardiac membrane with IV calcium gluconate
If no ECG changes, shift potassium into cells with combines insulin/ dextrose infusion + nebulised salbutamol
remove potassium from body with calcium resonium, loop diuretics, dialysis
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What is carcinoid syndrome?
occurs due to release of serotonin and other vasoactive peptides into systemic circulation from a carcinoid tumour
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What is the chemical name for serotonin?
5-hydroxytryptamine
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What is a carcinoid tumour?
type of neuroendocrine tumour that grows from neuroendocrine cells
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What are the causes of carcinoid syndrome?
most commonly arises from GI tract, following by lungs, liver, ovaries, thymus
- small intestine malignancy (most common)
- appendix most common GI tract site
- liver most common site for metastases
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How does carcinoid syndrome present?
flushing
diarrhoea
abdominal cramps
bronchospasm (wheezing, asthma)
fibrosis (heart valve dysfunction, palpitations)
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How is carcinoid syndrome diagnosed?
1st line: urinary 5-hydroxyindoleacetic acid test - elevated
CXR + chest/ pelvic MRI/ CT - locate primary tumours
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How is carcinoid syndrome treated?
SURGERY:
resection of tumour is only cure for carcinoid tumours so it is vital to find primary tumour
SOMATOSTATIN ANALOGUES:
octreotide
debulking, embolisation, or radio frequency ablation for hepatic metastases/ masses can decrease symptoms
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Why is ocreotide used to treat carcinoid syndrome?
blocks release of tumour mediators and counters peripheral effects
