Endorine Flashcards
1
Q
what is the difference between water/fat soluble hormones?
A
water - unbound, bind to cell surface receptor, short halfe-life, fast clearance eg protein
fat - protein bound to transport, diffuse into cell, long half-life, slow clearance eg steroid, thyroid
2
Q
what is endocrine vs paracrine vs auto crine hormones?
A
Endocrine – blood-borne, acting at distant sites
Paracrine – acting on adjacent cells
Autocrine – feedback on same cell that secreted hormone
3
Q
what are the classes of hormones?
A
peptides
amines
Iodothyronines
Cholesterol derivatives and steroids
4
Q
how is hormone secretion controlled?
A
basal secretion - continuous or pulsatile
superadded rhythms - eg day night ACTH
Release inhibiting factors – dopamine inhibiting prolactin
releasing factors
5
Q
what determines the action of hormones?
A
Hormone metabolism – increased metabolism to reduce function
Hormone receptor induction – induction of LH receptors by FSH in follicle
Hormone receptor down regulation – hormone secreted in large quantities cause down regulation of its target receptors
Synergism – combined effects of two hormones amplified (glucagon with epinephrine)
Antagonism - one hormone opposes other hormone (glucagon antagonizes insulin)
6
Q
how are peptide hormones stored?
A
granules
7
Q
what is the definition of anorexia?
A
lack of appetite
8
Q
what are the BMI ranges classified as?
A
<18.5 underweight
18.5 - 24.9 normal
25.0 - 29.9 overweight
30.0 - 39.9 obese
>40 morbidly obese
9
Q
what are some risks of obesity?
A
Type II diabetes
Hypertension
Coronary artery disease
Stroke
Osteoarthritis
Obstructive sleep apnoea
Carcinoma
10
Q
what part of the body regulates appetite?
A
hypothalamus
11
Q
what gut peptides affect appetite?
A
CCK
Ghrelin
PYY
12
Q
what is leptin responsible for?
A
switching off appetite
13
Q
what are the blood levels of leptin after eating?
A
increased
14
Q
what central controllers increase appetite?
A
NeuroPeptideY
MCH - Melanin-Concentrating Hormone
AgRP - Agouti-related peptide
Orexin
endocannabinoid
15
Q
what central controllers decrease appetite?
A
alpha-MSH
CART - cocaine and amphetamine regulated transcript
GLP-1
seretonin
16
Q
what does peptide YY do?
A
inhibits gastric motility - reducing appetite
17
Q
how does CCK affect appetite?
A
delays gastric emptying
gall bladder contraction
insulin release
- satiety via VAGUS nerve
18
Q
what does Ghrelin stimulate?
A
Growth hormone release
appetite - orexigenic
19
Q
how do leptin and insulin work in appetite?
A
- Stimulate- POMC/CART neurons increase CART and alpha-MSH levels
- Inhibit NPY/AgRP neurons, so decrease NPY and AgRPNet effect : increase Satiety and decrease Appetite
20
Q
how does ghrelin work?
A
stimulates NPY/AgRP, increase NPY and AgRP secretion
↑ Appetite
21
Q
what cells secrete peptide YY?
A
neuroendocrine cells in ileum, pancreas and colon
in response to food
22
Q
what are the effects of incretin?
A
- blunting glucagon
- beta-cell stimulation of insulin production
- improved satiety
- decreased gstric motility
23
Q
where does glucose come from in the fasting state?
A
glycogen breakdown and gluconeogenesis from liver
little bit from kidney
24
Q
in the fasting state what are the insulin levels?
A
low
25
where does glucose go after ingestion (and percentage)?
40% to liver
60% to periphery, mostly muscle
26
what secretes insulin and glucagon?
islets of langerhans
27
what cells secrete insulin and glucagon?
beta - insulin
glucagon - alpha
28
what are the steps of insulin release from a cell?
glucose entry into cell by GLUT2 glucose transporter
glucokinase causes phosphorilation
K+ channels close - depolarisation
calcium channels open and ca2+ enters cell
insulin is released
29
what is the action of insulin in muscle and fat cells?
GLUT4 integrates into membrane and glucose enters cell
30
what are counterregulatory hormones of insulin?
glucagon
and adrenaline
(cortisol and growth hormones but take long time)
31
what is diabetes mellitus?
disorder of carbohydrate metabolism characterised by hyperglycaemia
32
what complications are associated with diabetes?
diabetes retinopathy
diabetic nephropathy
stroke
cardiovascular disease
diabetic neuropathy
33
what are the types of diabetes?
type 1
type 2 - includes gestational and medication induced
**monogenic diabetes** - youth
pancreatic
endocrine
malnutrition related
34
what plasma glucose levels show diabetes?
>11mmol/l
or >7mmol/l when fasting
35
what does HbA1c measure and show?
haemoglobin attachment to glucose
>48mmol/mol is diabetic
36
what is the definition of type 1 diabetes?
An insulin deficiency disease characterised by loss of beta cells due to autoimmune destruction
37
what does failure of insulin secretion lead to?
Continued **breakdown of liver glycogen**
Unrestrained lipolysis and **skeletal muscle breakdown** providing gluconeogenic precursors
Inappropriate** increase in hepatic glucose output **and **suppression of peripheral glucose uptake**
38
what is the renal thershold of glucose?
10mM
39
what happens when type 1 diabetes isnt treated with insulin?
- Increase in circulating glucagon
- further increasing glucose
perceived ‘stress’
- **increased cortisol and adrenaline**
- progressive catabolic state
- **increasing levels of ketones**
40
what is type 2 diabetes?
- impaired insulin secretion or insulin resistance
- causing impaired glucose tolerance
- progressive hyperglycaemia and high free fatty acids
41
what happens to glucose disposal rate in type 2 diabetes?
becomes lower
42
what does impaired insulin action in type 2 diabtes lead to (metabolically?
high circulating free fatty acids
abnormally high glucose output after a meal
(no weight loss or ketones like in type 1)
43
what causes both glycosuria and ketonuria?
type 1 diabetes
44
what is treatment for type 2 diabetes?
- lifestyle - weight loss, exercise
- medication - metformin, Sulfonylureas, DPP4 etc..
- management of BP and lipids
45
what do sulphonylureas do?
stimulate insulin release by binding to beta receptors
- can cause weight gain and hypoglycaemia
eg - gliclazide, glibenclamide
46
what do thiazolidinediones do?
improve insulin sensitivity
- rarely used due to side effects like weight gain
(used in type 2)
47
what secretes GLP-1?
L cells in intestine
48
what do SGLT2 inhibitors do?
block glucose reabsorption - more glucose excreted in urine
49
what medication is used for type 2 diabetes?
**metformin** first line
DPP-IV inhibitors, GLP1 analogues, SGLT-2 inhibitors
50
give examples of GLP-1 analogues
(stimulate insulin secretion, inhibit glucagon production)
Exenatide(BYETTTA) twice daily
Once weekly exenatide (BYDUREON)
Liraglutide (VICTOZA) once daily
Lixisenatide (LYXUMIA) once daily
Dulaglutide (TRULICITY) once weekly
Semaglatide (OZEMPIC) once weekly
Oral semaglutide (RYBELSUS) daily
51
when does diabetes ketoacidosis occur in type 2 diabetes?
It is **rare** because the low insulin levels are sufficient to suppress catabolism and prevent ketogenesis.
It can occur if hormones such as **adrenaline rise** to high levels (eg during an MI)
52
what is the difference in insulin in type 1 and 2 diabetes?
1 - Profound insulin deficiency
2 - Insulin resistance, Impaired insulin secretion and progressive β-cell damage but initially continued insulin secretion
53
what are the Different insulin approaches in diabetes?
once-daily basal insulin - only in type 2 - mimics pancrease, longer acting
twice-daily mix-insulin - both
basal-bolus therapy - mostly type 1 - after eating
54
what are the 2 levels of hypoglycaemia?
1 - Alert value
Plasma glucose <3.9 mmol/l (70 mg/dl) and no symptoms
2 - Serious biochemical
Plasma glucose <3.0 mmol/l
(55 mg/dl)
55
what are some of the effects of hypoglycaemia on the body?
brain - cognitive dysfunction, seizures,comas
heart - increased risk of myocardial ischaemia
circulation - inflammation, blood coagulation abnormality
musculoskeletal - falls, fractures
56
what are some autonomic symptoms of hypoglycaemia?
trembling
palpitations
sweating
anxiety
hunger
57
what are some neuroglycopenic symptoms of hypoglycaemia?
confusion
weakness
drowsiness
vision changes
difficulty speaking
difficulty concentrating
58
at what blood glucose level do hypoglycaemia most commonly cause symptoms?
under 3.9mmol/l
- can be higher in patients with poor glycaemic control with elavated HbA1c
59
how is hypoglycaemia treated?
- 15g of fast acting carbohydrate to relieve symptoms
- glucagon injection/ IV dextrose if unable to swallow
- Eat a long-acting carbohydrate to prevent recurrence of symptoms
60
why is it important to retest glucose levels in hypoglycaemia?
to make sure blood glucose is over 4mmol/l and retreat if needed
61
what are some risk factors that screening for hypoglycaemia is based of?
Low HbA1c; high pre-treatment HbA1c in T2DM
Long duration of diabetes
A history of previous hypoglycaemia
Impaired awareness of hypoglycaemia (IAH)*
Recent episodes of severe hypoglycaemia
Daily insulin dosage >0.85 U/kg/day
**Physically active (e.g. athlete)
Impaired renal and/or liver function**
62
what are some causes of hypoglycaemia?
- taking higher levels of antidiabetic medications
- antimalarial drugs
- hormone deficiency eg cortisone
- skipping meals
over exercising
- excess alcohol
63
what are some of the effects of the parathyroid hormone?
- increased Ca2+ reabsorption, decreased phosphate reabsorption
- increased hydroxylation of 25-OH vit D - increases Ca2+ absorption
- increased bone resorption
64
how do you work out correct calcium levels in the blood?
total serum calcium + 0.02 * (40-serum albumin)
65
what signs does hypoglycaemia cause?
- parathesia
- muscle spasm
- seizures
- basal ganglia calcications
- cataracts
- ECG abnormalities - **long QT interval**
- chvosteks sign and trousseaus sign
66
what is the chvosteks sign and trousseaus sign?
chvosteks sign - spasm of facial muscle when tapping over facial nerve
trousseaus - inflation of BP cuff to 20mmHg above systolic for 5 min - flexion of wrist andadduction of thumb, extension of IP joints
- show low calcium
67
what are the causes of hypocalcaemia?
- low vit D intake
- hypoparathyroidism
eg due to
surgery, radiation
syndromes - Di George, HDR, Kenney-Caffey
genetic , autoimmune
infiltration - haemochromatosis, Wilsons disease
magnesium deficiency
- pseudohypoparathyroidism
68
what is pseudohypoparathyroidism?
resistance to parathyroid hormone
- type 1 albright hereditary ostodystophy
- mutation with deficient Galpha subunit 1a
69
what are the symptoms of hypercalcaemia?
- thirst
- nausea
- constipation
- confusion - later coma
- renal stones
- ECG abnormalities - **Short QT**
70
what are the most common causes of hypercalcaemia?
malignancy
primary hyperparathyroidism
71
what is a way to rememeber consequences of primary hyperparathyroidism?
BONES - osteitis fibrosa cystica, osteoporosis
STONES - kindey stones
GROANS - confusion
MOANS - constipation - acute pancreatitis
72
what are the main causes of primary hyperparathyroidism?
80% due to single benign adenoma
12-20% due to four gland hyperplasia (may be MEN1/2)
rarely malignant
73
what is the normal range of PTH in blood?
14 to 65 pg/mL
74
what are normal calcium levels?
2.2 to 2.6 millimoles per litre (mmol/L)
75
what are the hormones released by the hypothalamus and piuitary gland?
*GHRH & SMS
* GnRH
* CRH
* TRH
* Dopamine
Pituitary
* GH
* LH & FSH
* ACTH
* TSH
* Prolactin
76
what causes some pituitary gland conditions?
* Benign pituitary adenoma
* Craniopharygioma - tumours
* Trauma
* Apoplexy / Sheehans - severe bleeding
* Sarcoid / TB - inflammation
77
what do pituitary tumours cause?
- pressure on local structures eg optic chiasm - bitemporal hemianopia
- pressure on pituitary - hypopituitarism
- functioning tumour - prolactinoma, acromegaly, cushings disease
78
what is precocious puberty?
onset of secondary sexual characteristics before 8 for girls and 9 for boys
79
what is delayed puberty?
absence of secondary sexual characteristics by 14 for girls and 16 for boys
80
what can delayed puberty lead to?
reduced peak bone mass and osteoporosis
delay in secondary sex characteristics
psychological problems
defects in reproduction
81
what reactivates GnRH pulse generator in puberty?
GPR54
82
what is the difference between precocious puberty and precocious pseudopuberty?
true - stimulated LH:FSH ratio >1
pseudo - LH:FSH <1
83
what is precocious puberty treated with?
GnRH super-agonist to suppress LH and FSH secretion
84
what causes precocious puberty?
CNS tumours
CNS disorders
85
what causes precocious pseudopuberty?
Increased androgen secretion
gonadotropin secreting tumours
McCune-albright syndrome
ovarian cyst
oestrogen secreting neoplasm
hypothyroidism
latrogenic or exogenous sex hormones
86
what signs in girls indicate need for investigation for delayed puberty?
* Lack of breast
development by 13 yrs
* More than five years
between breast
development and
menarche
* Lack of pubic hair by age
14 yrs
* Absent menarche by age
15-16 yrs
87
what signs in boys indicate need for investigation for delayed puberty?
* Lack of testicular
enlargement by age 14
yrs
* Lack of pubic hair by age
15 yrs
* More than 5 years to
complete genital
enlargement
88
what is an example of primary hypogonadism?
testes/overies failing = low test/prog/oest = LH/FSH increase
eg Klinefelter syndrome in males
89
what is an example of secondary hypogonadism?
hypothalamus/pituitary failing - LH/FSH are low
90
what does kallmanns syndrome and prader-willi syndrome cause?
hypogonadotrophic hypogonadism
91
what causes hypergonadotrophic hypogonadism in males/females?
males - klinefelters syndrome
females - turners syndrome
92
what is given to males/females for replacement therapy?
males - **testosterone enanthate** - IM injection 2-4 years
females - **ethinyl estradiol tablets or oestrogen** - starting with low does for gradual growth, once full replacement dose achieved, progesterone is added
93
what is constitutional delay of growth and puberty?
- diagnosis of exclusion
- delayed puberty, delayed bone age, short stature
94
what are the secondary sexual characteristics of puberty for boys/girls?
boys - external genitalia and pubic hair growth
enlargement of larynx and laryngeal muscles
girls - growth of breast and female genitalia (ovarian oestrogens) and pubic and axillary hair growth (ovarian/adrenal androgens)
95
where is vasopressin and oxytocin made in posterior pituitary?
paraventricular nucleus
supraoptic nucleus
96
what vasopressin receptors are found in a) vasculature, b) renal collecting tubules, c) pituitary gland
v1a
v2
v1b
97
what is vasopressin release controlled by?
osmoreceptors in hypothalamus
baroreceptors in brainstem and vessels - emergencies
98
what happens after water ingestion?
plasma osmolarity decreases
vasopressin secrertion decreases
urine water excretion increases
99
where does ADH bind to work on the kidneys?
v2 receptors in collecting duct principle cells
100
what is normal osmolarity?
282-295 mOsmol/Kg
101
what is cranial diabetes insipidus characterised by?
lack of vasopressin
102
what is nephrogenic diabetes insipidus characterised by?
resistance to vasopressin
103
what is SIAD?
syndrome of anti-diuretic hormone secretion
- too much vasopressin released
- common
104
what are features of diabetes insipidus?
polyuria - excessive urine production
polydypsia - extreme thirst
no glycosuria - glucose in urine
105
what are the causes of nephrogenic DI?
familial - rare
- x-linked - v2 receptor defect
- autosomal - aquaporin 2 defect
acquired - reduction in medullary conc gradient or antagonism of effects of AVP
- eg drugs, chronic renal impairment, metabolic
106
how is AVP deficiency (cranial DI) treated?
desmopressin
- treat any underlying conditions
107
what can be used to measure AVP concentartion?
copeptin
108
how is AVP resistance (nephrogenic DI) treated?
- avoiding precipitating drugs
- congenital - very hard
- free acces to water and very high dose desmopressin
109
what causes cranial DI?
tumour
head injury
complications during surgery
110
what is normal serum sodium?
135-144mmol
111
what are the classifications of hyponatraemia?
Mild 130-135mmol/l
Moderate 125-129mmol/l
Severe <125mmol/l
112
what are moderate symptoms of hyponatraemia?
Headache
Irritability
Nausea / vomiting
Mental slowing
Unstable gait / falls
Confusion / delirium
Disorientation
113
what are more servere symptoms of hyponatraemia
Stupor / coma
Convulsions
Respiratory arrest
114
what is the onset of hyponatraemia?
Acute < 48 hours
Chronic > 48 hours
115
how is hyponatraemia treated?
- fluid restriction
- saline replacement if due to dehydration
116
what are the causes of SIAD?
CNS disorders - eg meningitis, head injury, brain tumour
tumours - eg lymphoma, sarcoma
respiratory - eg TB, pneumonia
drugs - eg thiazides, oxytocin etc...
117
what treatment goals should be achieved in SIAD?
ensure correct diagnosis
allow increase in serum Na+
treat any underlying condition
identify and stop any causative drug
118
how is SIAD managed?
- fluid restriction <1L/24h
- sometimes demeclocycline/ vaptan
- if Na+ <115 mmol/l AND fitting hypertonic N/Saline on ITU
<8mmol/l increase in Na+ per 24 hour if chronic
119
what can happen to the brain if hyponatraemia is left untreated?
Osmotic demyelination syndrome
120
what is Osmotic demyelination syndrome?
Massive demyelination of descending axons
- shows as white areas in middle of pons
- may be upto 2 weeks to manifest
121
what are the risk factors for Osmotic Demyelination Syndrome (ODS)?
-caused by rapid sodium correction
Serum Na+ <105mmol/L
>18mmol/L Na+ increase in 48 hour
Hypokalaemia
Chronic excess alcohol
Malnutrition
Advanced Liver disease
122
what antagonist to AVP is used to manage SAID?
tolvaptan
- causes excretion of water without electrolytes
123
what is the Management of acute severe symptomatic hyponatraemia?
- iv 150ml of 3% Saline or equivalent
over 20 mins
- Check serum Na+
- Repeat twice until 5mmol/L increase Na+
- After 5mmol/L increase
Stop hypertonic saline
Establish diagnosis
Na+ 6 hourly for 1st 24 hours
Limit increase to 10mmol/l first 24 hour
124
what is graves disease an example of?
autoimmune hyperthyroidism
125
what are examples of autoimmune hypothyroidism?
Hashimotos thyroiditis
Atrophic thyroiditis
126
what antibodies are found in most autoimmune hypothyroidism patient?
thyroglobulin
thyroid peroxidase
- also in 75% of graves patients - so not specific
127
what cells are responsible for throid cell destruction in autoimmune hypothyroidism?
cytotoxic CD8+ T cells
128
what causes graves disease?
thyroid stimulating antibodies
129
what are the risk factors of thyroid autoimmunity?
- female, onset common postpartum
- genetic - eg HLA-DR3 gene
- environmental factors - stress, smoking, iodine intake
130
what autoimmune diseases are associated with thyroid autoimmunity?
type 1 diabetes mellitus
addisons disease
perniccious anaemia
vitiligo
alopecia areata
coeliac disease
myasthesia gravis
131
what happens in thyroid associated ophthalmopathy?
swelling in extraocular muscles
- present in most graves patients
132
what is a sporadic non-toxic goitre?
benign enlargement of throid gland
- most common endocrine disorder
133
what is the definition of hyperthyroidism?
excess of throid hormone in the blood
134
what are the 3 mechanisms for increased levels of thyroid hormone in the blood?
- overproduction of thyroid hormone
- leakage of preformed hormone from thyroid
- ingestion of excess thyroid hormone
135
what are the most common causes of hyperthyroidism?
- graves diease (75-80% of cases)
- toxic multinodular goitre
- toxic adenoma
136
what drugs induce hyperthyroidism?
iodine
amiodarone - contains iodine, controls HR
Interferon-alpha- for HCV
lithium - rare
radiocontrast agents - contain iodine
137
what are the clinical features of hyperthyroidism?
weight loss
tachycardia
hyperphagia - excess hunger
anxiety
tremor
heat intolerance
sweating
diarrhoea
lid lag + stare
menstraul disturbance
138
what are graves disease specific clinical signs?
diffuse goitre
thyroid eye disease
pretibial myxoedema
acropachy - swelling hands, clubbing of fingers
139
what are the results of a throid function test in hyperthyroidism?
increased free T4 and T3
primary - suppressed TSH
secondary - high TSH
140
what supporting investigations are done to test for hyperthyroidism?
thyroid antibodies - TSI, TRAb, TPO, TgAb
isotope uptake scan - shows nodules, subacute thyroiditis=low uptake
141
what is are the treatments for hyperthyroidism?
antithyroid drugs
radioiodine 131I
surgery - partial, subtotal thyroidectomy
142
what are some antithyroid drugs and what do they do?
- thionamides: - decreases synthesis of new thyroid hormone
- **carbimazole** - first line treatment
- propylthiouracil (PTU) - also inhibit T4 to T3 conversion
- methimazole
143
what are the treatment courses for hyperthyroidism with antithyroid drugs?
titration regimen - 12-18 months - based on thyroid function tests
block and replace regimen with T4 6-12 months - fixed, high-dose
144
what factors can indicate poor prognosis of antithyroid drugs?
- large goitre
- serve boichemical hyperthyroidism
- TRAb +ve at end of course of drugs
- male
- disease onset at young age
145
what are some side effects of thionamides?
- common - rash
- less common - arthralgia, hepatitis, neuritis
- most serious - **agranulocytosis** - sore throat, fever, mouth ulcers - Must warn patients before starting ATD
146
what are the 3 types of hypothyroidism?
primary - absence or dysfunction of thyroid gland
secondary - pituitary dysfunction
tertiary - hypothalamic dysfunction
147
what are the causes of primary hypothyroidism in adults?
hashimotos thyroiditis
131I therapy
thyroidectomy
drugs
thyroid hormone resistance
148
what are the causes of secondary/tertiary hyperthyroidism?
pituitary disease
hypothalamic disease
149
what drugs cause hypothyroidism?
iodine- deficiency/excess
amiodarones - given for heart problems
lithium - eg for BPD
thionamides - for hyperthyroidism
interferon-alpha
150
what causes neonatal hypothyroidism?
thyroid agenesis - no thyroid gland
thyroid ectopia - undecended thyroid
thyroid dyshormonogeneis - congenital thyroid deficiency
resistance to TH
TSH deficiency
151
what are the clinical feature of hypothyroidism?
fatigue
weight gain
cold intolerance
constipation
menstrual disturbance
muscle cramps
slow cerebration
dry, rough skin
periorbital oedema
delayed muscle reflexes
carotenaemia
oedema
152
what are the hormone test levels in primary hypothyroidism?
high TSH
usually low T4 and T3
153
what are the hormone test levels in secondary/tertiary hypothyroidism?
- TSH inappropriately low for reduced T4/T3
154
what antibodies are positive in hashimotos disease?
TPO (thyroid peroxidase)
155
how is hypothyroidism treated?
synthetic L-thyroxine - T4 - LEVOTHYROXINE
- titrate according to TSH
- requirements vary according to cause - high dose in thyroid ablation
156
what kind of patients need a lower staring dose of T4 when treating hypothyroidism?
patients with ischemic heart disease
157
what is the difference in monitoring treatment for primary and secondary/tertiary hypothyroidism?
primary - dose titrated until TSH normalises. T4 levels checked after 6-8 weeks
secondary/tertiary - TSH levels always low. T4 is monitored
158
what are Craniopharyngioma?
Arise from squamous epithelial remnants of Rathke’s pouch
- benign tumour - infiltrates surroundings
Adamantinous: cyst formation and calcification
Squamous papillary: well circumscribed
159
what is Rathke’s Cyst?
derived from rathkes pouch
- near or within the pituitary gland
- mostly asymptomatic and small
- iflarge causes hormone imbalance, visual problems and headaches
- Mostly intrasellar component, may extend into parasellar area
160
what is a meningioma?
in meninges - Commonest tumour of region after pituitary adenoma
Associated with visual disturbance and endocrine dysfunction
161
what is Lymphocytic Hypophysitis
Inflammation of the pituitary gland due to an autoimmune reaction
162
what are non-functioning/silent pituitary adenomas signs of aggressivness?
Large size
Cavernous sinus invasion
Lobulated suprasellar margins
(diagnosed 20-60)
163
what are examples of pituitary mass lesions?
Non-Functioning Pituitary Adenomas (silent)
Pituitary cysts: Rathke's cleft cyst
Perisellar meningioma
164
what are features of non functioning tumours?
absence of hormone secretion
165
what test results show hypopituitary?
Low pituitary hormones - low TSH etc.
(low IGL-1 for GH)
166
what does High Ft4 with normal or high TSH show?
(high ft4+high tsh = not normal)
- TSH-secreting Pituitary Adenoma
- hormone resistance
167
what does Low T, raised LH/FSH show?
primary hypogonadism
168
how is hypopituitary diagnosed in women?
Oligo or amenorrhoea with low oestradiol and low LH and FSH
169
how do GH levels change throught day?
pulses - highest at night
low/undetectable inbetween pulses
170
what raises prolactin levels?
Stress
Drugs: antipsychotics
Stalk pressure
Prolactinoma
171
what is acromegaly pathogenesis?
pituitary gland produces excess growth hormone
so liver produces excess IGF-1
172
what are acromegaly co-morbitites?
hypertension and heart disease
sleep apneaa
Cerebrovascular events and headache
Arthritis
Insulin-resistant diabetes
173
what are clinical feature of acromegaly?
Acral enlargement - large hands/feet
Arthralgias -joint pain
Maxillofacial changes
Excessive sweating
Headache
Hypogonadal symptoms
174
how is acromegaly diagnosed?
- increased IGF-1
- 75 gm oral glucose tolerance test - GH increases rather than decreases after glucose intake
175
what are the treatment options for acromegaly?
Pituitary surgery - primary treatment, harder on larger tumours >1cm
Medical therapy - Dopamine agonists – cabergoline
Somatostatin analogues
GH receptor antagonist
- rapid onset, can be ineffective & side effects
Radiotherapy - depends on GH levels and tumour extension
- possible hypopituitarism and damage to local structures.
176
what do Somatostatin Analogs do?
reduce production of various hormones
eg GH and IGF-1
177
what is Pegvisomant?
treats acromegaly
- genetically modified analogue of GH - highly selective growth hormone receptor antagonist
178
what are clinical feautres of high prolactin levels?
menstrual irregularity/amenorrhoea
infertility
galactorrhoea
low libido
low testosterone in men
179
what are causes of Hyperprolactinaemia?
Prolactinomastumours
Hypothalamic Disease
stress,
hypothyroidism,
PCOS,
drugs,
renal failure,
chest wall injury
180
patients with hyperprolcatinoma and on antidopaminergic drugs what is done different?
prolactin not measured
- careful drug history
181
what is Management of prolactinoma?
Dopamine agonists – cabergoline, bromocriptine, quinagolide
- only small dose required for microprolactinoma
182
what does prolactinoma lead to in woman?
infertility
- high prolactin stops ovulation
183
how does hcg effect tsh?
highhcg = tsh is suppressed
184
how is hypothyroidism managed in pregnancy?
thyroid function test before pregnancy
- increase thyroxine dose by 30%
185
what happens if hypothyroidism is left untreated in pregnancy?
gestational hypertension
placental abruption
low birth weight
186
what patients with thyroid disease getting pregnant should be screened?
over 30
over 40 BMI
previous miscarrige
autoimmune disorders - Type1 diabetes
family history
187
for pregnant women what choice of drug is used for hyperthyroidism?
Propylthiouracil (PTU)
(rather than carbimazole)
188
what is a rare, serious side effect of Propylthiouracil (PTU)?
Agranulocytosis
189
what causes neonatal thyrotoxicosis?
transplacental passage of thyroid-stimulating immunoglobulin (TSI)
from a mother eg with Graves disease
- thyrotropin receptor antibody (TRAb) level/ TSH-R antibodies measured at 22-26 weeks and 3rd trimester - at risk if 2-3 fold higher
190
what is gestational transient thyrotoxicosis?
excessive stimulation of thyroid gland by hCG
- usually limited to the first 12-16 weeks of pregnancy
- can cause hyperemesis gravidarum - extreme vomiting - needs treatment
- more common in twins etc
191
what is diabetes insupidus new name?
AVP deficiency
192
what is cushings disease?
- hypercortisolism caused by an (ACTH)-secreting pituitary adenoma
- causes cushings syndrome (not the same as cushings disease)
- cushings syndrome most commonly caused by Exogenous corticosteroid
- weight gain, fatigue, glucose intolerance, moon face
193
what are the 2 types of amiodarone induced thyrotoxicosis?
type 1 underlying disease eg graves
type 2 - no underlying disease
194
ipilimumab and nivolumab are cancer drugs, how do they effect the endocrine system?
- effects thyroid and pituitary
- eg. hypophisitis, hyper/hypothyroidism
- need to check visual fields and MRI scan
195
in pregnancy, what are the ranges for TFT?
vary according to hospital policy/lab
- ranges increase per trimester
- overal lower
196
what is the blood glucose and HbA1c in diabetics?
random plasma glucose > 11.1 mmol/l
Fasting plasma glucose > 7.0 mmol/l
HbA1c > 48 mmol/mol
197
what are the signs/symptoms of diabetes?
- thirst
- polyuria - increased urination
- weight loss - more common in type 1
- fatigue
- hunger
- Pruritis vulvae and balanitis (Vaginal candidiasis and Chest / skin infections)
- blurred vision
198
what are suggestive features of type 1 diabetes (opposed to type 2)?
- Onset in childhood / adolescence (commonly 5-15yrs diagnosis, can be any age)
- Lean body habitus
- Acute onset of osmotic symptoms
- Prone to ketoacidosis
- High levels of islet autoantibodies
199
what are suggestive features of type 2 diabetes?
- Usually presents in over-30s
- Onset is gradual
- Family history is often positive
- Almost 100% concordance in identical twins
- Diet, exercise and oral medication can often control hyperglycaemia; insulin may be required later in the disease
200
what antibodies are associated with diabetes?
- Anti GAD(65)
- islet cell Ab
- insulin Ab
- ZnT8
- 90% of patients will have 1 or more Abs
201
what other autoimmune diseases are associated with diabetes?
Hypothyroidism
Addisons
Coeliac disease
202
what happens if diabetes is not treated?
reduced insulin - fat breakdown - glycerol and free fatty acid formation - form ketone bodies
203
what is diabetic ketoacidosis?
- Hyperglycaemia (plasma glucose usually <50 mmol/l)
- Raised plasma ketones (urine ketones > 2+)
- Metabolic acidosis – plasma bicarbonate < 15 mmol/l
204
what causes diabetic ketoacidosis?
- Intercurrent illness
infection
myocardial infarct
- Treatment errors – stop/reduce insulin dose
- Previously undiagnosed diabetes
- Unknown
205
what happens during ketoacidosis?
- increasing dehydration, hyperglycaemia and increasing acidosis
- Glucose and ketones escape in the urine but lead to an osmotic diuresis and falling circulating blood volume
- Ketones (weak organic acids) cause anorexia and vomiting
206
what are symptoms of DKA?
- develop over days
- polyuria and polydipsia
- nausea and vomiting
- weight loss
- weakness
- abdominal pain (confused with surgical abdomen)
- Drowsiness / confusion
207
what are signs of DKA?
- hyperventilation (Kussmaul breathing)
- dehydration (average fluid loss 5-6 litres)
- hypotension
- Tachycardia
- coma
208
what are the biochemical diagnostics of DKA?
- hyperglycaemia (<50 mmol/l)
- HCO3- <15 mmol/l
- urea and creatinine - raised due to pre-renal failure
- urinary ketones dipstix >2+ ketones
- blood ketones >3.0
- anticipate fall in K+
209
how is DKA treated/managed?
- rehydration - 3l first 3h
- insulin
- electrolyte replacement K+
- treat underlying cause
- follow DKA protocols in hospital
210
what are complications of DKA?
- cerebral oedema (deterioration in conscious level)
children more at risk
- adult respiratory distress syndrome
- thrombosis - DVT, PE
- aspiration pneumonia (in drowsy/comatose patients)
- death
211
what are microvascular complications of diabetes?
- neuropathy
- retinopathy
- nephropathy
212
what are Physiological defences to hypoglycaemia ?
release of glucagon and adrenaline
213
what symptoms are associated with hypoglycaemia with different glucose ranges?
4.6 mM inhibition of insulin secretion
3.8 mM counter-regulatory hormone release (glucagon and adrenaline)
3.8-2.8 mM autonomic symptoms - sweating, tremor, palpitations
<2.8 mM neuroglycopenic symptoms - confusion, drowsiness, altered behaviour, speech difficulty, incoordination
<1.5 mM severe neuroglycopenic - convulsions, coma, focal neurological deficit ie hemiparesis
214
what are inulin therapy options for diabetes?
MDI - multiple daily injections
pump
closed loop
215
what is Maturity-onset diabetes of the young- MODY?
non-insulin dependent diabetes
- autosomal dominant, Single gene defect altering beta cell function
- tend to be non-obese
216
what is MODY 2?
**glucokinase mutation** - rate determing step of glucose metabolism and insulin control
- **mild diabetes** - no treatment required
217
what is MODY 1?
HNF4A mutation - transcription factor for beta cells
FH, young age of onset, non-obese, Sus, AND
Macrosomia (>4.4kg at birth)
Neonatal hypoglycaemia
218
how is C-peptide used in diabetes diagnosis?
- In Type 1 diabetes C-peptide is negative within 5 years
- Type 2 and MODY C-peptide persists
219
what is Maternally inherited diabetes and deafness (MIDD)?
Mutation in mitochondrial DNA
Loss of beta cell mass
Similar presentation to Type 2
220
what is Lipodystrophy?
Selective loss of adipose tissue
Associated with insulin resistance, dyslipidaemia, hepatatic steatosis, hyperandrogenism, PCOS
221
what inflammatory endocrine condition can cause hyperglycaemia?
acute/chronic pancreatitis
(due to alcohol)
- treated with insulin
222
what conditions apart from diabetes may require insulin?
pancreatic neoplasia
cystic fibrosis - insulin helps gain weight and reduces infections and improves lung function
223
what conditions can cause isulin resistance?
acromegaly
Cushings syndrome
Pheochromocytoma tumors secreting (nor)adrenaline
PCOS
fatty liver disease
224
what drugs can cause drug-induced diabetes?
Glucocorticoids - increase insulin resistance
Thiazides
protease inhibitors (HIV) antipsychotics
225
what are the 4 pillars of diabetes management
glycomic management
BP managent
lipid management
CVD and kidney disease risks management
226
apart from glucose, what else is focused on when managing diabtes?
Reducing the risk of:
cardiovascular morbidity and mortality
chronic kidney disease
microvascular complications
Weight reduction
increasing physical activity
decreasing dietary fat
227
what are treatment options for controlling excess blood glucose in type 2 diabetes?
- metformin/pioglitazone - makes body responds better using own insulin
- insulin
- SGLT2 inhibitors - remove excess glucose
- sulphonylureas, DPP-4 inhibitors/GLP-1 receptor agonists - stimulate pancreas to release insulin
228
how is medication decided on when treating type 2 diabetes?
what the goals are
eg, weight loss, CVD risk reduction - different medications are better
eg. GLP-1 and SGLT2 has CVD benefits (also weight loss/neutral),
semaglutide and tirzepatide beneficial for weight loss
229
what medication for type 2 diabetes can cause weight gain?
Pioglitazone
Insulin
DPP4i
sulphonylureas
230
what are the consequences of diabetic neuropathy?
- pain
- autonomic - orthostatic hypertension, cardiac AN
- insensitivity - foot ulceration
231
what is the Treatment of Diabetic Painful neuropathy?
- Good glycaemic control
- Tricyclic antidepressants / SSRIs
- Anticonvulsants (carbamazepine, Gabapentin)
232
what are some features of diabetic foot disease?
- painless
- sensory nerve damage
- motor nerve damage
- localized callus
- autonomic nerve damage - dry feet, less sweating
233
what are Diabetic peripheral neuropathy screening tests?
- Test sensation
10 gm monofilament
neurotips
- Vibration perception
Tuning fork
biothesiometer
- ankle reflexes
234
what is Peripheral vascular disease in diabetes?
- Decreased perfusion due to narrowing or blockage of vessels to limbs esp. legs
- glucose/highBC can damage and cause atherosclerosis
(more likely to have lower limb amputation)
235
what is the difference in peripheral vascular in people w/without diabtes?
In people with diabetes, the **tibial and peroneal arteries** are often more involved than the **femoral/aortic-iliac vessels** - more in knee to ankle
236
what are Signs of vascular disease?
- Diminished/absent pedal pulses
- Cold feet/legs
- Poor skin and nails
- hair loss on feet/legs
- sores
- Leg numbness or weakness
- ED
237
what are Peripheral vascular disease non-invasive evaluations?
-ABI using Doppler ultrasound to get BP
- duplex arterial imaging/MRA
238
what is the treatment of Peripheral vascular disease?
- lifestyle - quit smoking, exercise
- medication - anti-platelet (aspirin/clopidogrel), BP control, cholesterol lowering (statins)
- Surgical intervention - bypass, plaque removal
239
what is the cause of most foot amputations in diabetics?
neuropathy - ulcer caused by trauma leading to infection
240
what is the pathogenesis of diabetic retinropathy?
- AGEs in retina causes damage and capillary BM thickening
- ischaemia/occlusion - due to thickening and reduced blood flow
241
what is the grading for diabetic retinopathy?
R0: None
R1: Background
R2: Pre-proliferative
R3: Proliferative
242
how is diabetic retinopathy risk reduced?
- glycemic control
- BP <130
- decrease lipids - statins
- stop smoking
243
when might diabetics be at increased risk of retinopathy?
pregnancy
244
what are characteristics of diabetic nephropathy?
- progressive kidney fibrosis resulting in loss of function <60 eGFR
- proteinuria - albumin >30mh/g
- risk factors are high BP and poor BG control
- risk factor for CVD
245
what are the treatments for diabetic kidney disease?
RAS blockers - decrease hyperfiltration in kidneys etc.
SGLT2 inhibitors
Finerenone - reduces inflammation
GLP-1RAs - metabolic regulation (decrease weight)
- Cholesterol control and Proteinuria control
- BP and glycemic control
246
what is the HPA axis?
hypothalamus produces CRH
pituitary produces ACTH
adrenal gland produces cortisol
247
what is the cortisol circadian rhythm?
- lowest as you fall asleep , start to increase around 2am
- peak around hour after you wake up
- levels decrease slowly
- peaks as you eat food
248
how does light effect the circadian rhythm?
- light received through retina
- info goes to 'clock' in Suprachiasmatic nucleus, then to paraventricular nucleus of hypothalamus - CRH secreted
249
what are melatonin levels at day/night?
day - low
night - high
250
what does cortisol (glucocorticoid) act as a secondary messenger between?
central to peripheral clock
251
what are adrenal insufficiencies divided into?
primary - Addison's disease (autoimmune) or congenital adrenal hyperplasia
secondary - hypopituitarism
tertiary - suppression of HPA - eg from stopping steroids or from morphine
252
what general points indicate a adrenal insufficiencies diagnosis?
- symptoms - fatigue, weight loss, aches, fainting, adrenal crisis, headache
- past history of TB, post partum bleed, cancer
- family history - autoimmunity, congenital disease
- patient taking steroids
- signs - pigmentation, hypotension
- biochemistry - low Na, high K, borderline elevated TSH
253
what time is cortisol and ACTH tested for?
between 0830 and 900
254
what are positive test results for adrenal insufficiencies?
- cortisol <100nmol/l
(ACTH >22 pmol/l is primary, <5 is secondary
high renin in primary)
- short Synacthen test - mimics ACTH - blood cortisol increase expected - gold standard
255
what are the investigations for testing the cause of adrenal insufficiencies?
primary
- adrenal antibodies (21-OH Ab) - Addison's disease
- 17-OHP - congenital adrenal hypoplasia
- very long chain fatty acids - adrenal leukodystrophy
- imaging
- genetic tests if negative
secondary
- steroids?
- MRI of pituitary
- genetic tests if all negative
256
how is an adrenal crisis managed?
- immediate hydrocortisone 100mg - part of crisis pack carried by patient
- test ACTH levels and cortisol
- give hydrocortisone if not given
- fluids
- fludrocortisone - for replacement of aldosterone
257
what is a steroid emergency card?
for patients at risk of adrenal insufficiency due to long term and/or high dose steroid use
258
how much hydrocortisone is given for an adrenal crisis?
15-25mg dependant on weight
divided 2-3 times per day - highest dose given on waking, then given midday and 1700hr
259
what is used as an alternate to hydrocortisone?
prednisolone
260
when may hydrocortisone dose be increased?
- mental health issues - eg depression
- high intensity exercise
261
how is fludrocortisone monitored in patients with AI?
- U&E
- BP
- Salt craving - craving salt if aldosterone is low
262
when is fludrocortisone dose increased/decreased?
increased if sweating due to exercise/hot climate
decreased in hypertension
263
when treating adrenal insufficiencies, what is the aim of renin levels?
upper half of normal range
264
what androgen can you be deficient when you have adrenal insufficiencies?
DHEA - replacement given to help libido and energy levels etc.
265
what new tablets of hydrocortisone can be given to children?
Alkindi - have lower doses
266
what can adrenal insufficiencies lead to in adults?
- worse metabolic profile (increased GC dose) - obesity, diabetes, hypotension
- impaired quality of life
- increased mortality rate
267
what new treatment is given for adrenal insufficiencies to mimic the circadian rhythm?
Efmody twice daily
(slow release)
268
what is an alternate test for cortisol?
waking salivary cortisone test - quicker and cheap
- <7nmol/l - AI
- 7<17 nmol/l - repeated with SST
269
what patients are most at risk of adrenal crisis?
those taking steroids and stopping/changing the dose
270
how can adrenal crisis be prevented in people who take steroids?
sick days rules
- information on how to manage steroid dose when sick. For example to increase steroid dose when unwell with fever
- carry extra supply of steroids for when needed
- supply of hydrocortisone
271
what causes an adrenal crisis in steroid users?
steroids supress the HPA axis causing adrenal atrophy
- when steroids are stopped not enough cortisol is produced causing adrenal crisis
