Endocrine Flashcards
1
Q
Sources of glucose in fasting state
A
all glucose comes from liver (and a bit from kidney)
Breakdown of glucose- Gluconeogenesis
Glucose is delivered to insulin independent tissues, brain and red blood cells
2
Q
Gluconeogenesis
A
synthesises glucose from lactate, alanine and glycerol- reverse of glycolysis, occur in liver and kidney
3
Q
Insulin levels in fasting states
A
Insulin levels are low
4
Q
Sources of fuel for muscles
A
Muscle uses free fatty acids for fuel
5
Q
Physiological changes after feeding
A
Rising glucose (5-10 min after eating) stimulates insulin secretion and suppresses glucagon
40% of ingested glucose goes to liver and 60% to periphery, mostly muscle
Ingested glucose helps to replenish glycogen stores both in liver and muscle
High insulin and glucose levels suppress lipolysis and levels of non-esterified fatty acids (NEFA or FFA) fall
6
Q
Site of insulin and glucagon secretion
A
Islet of Langerhans of the pancreas
7
Q
Cell that secrete insulin
A
Beta cells of islet of Langerhans
8
Q
Cell that secrete glucagon
A
Alpha cells of islet of Langerhans
9
Q
Paracrine crosstalk
A
between alpha and beta cells is physiological, ie local insulin release inhibits glucagon an effect lost in diabetes
10
Q
Action of Insulin
A
Supresses hepatic glucose output
-Glycogenolysis
-Gluconeogenesis
Increases glucose uptake into insulin sensitive tissues (muscle, fat)
Suppresses
-Lipolysis
-Breakdown of muscle
11
Q
Action of Glucagon
A
Increases hepatic glucose output
-Glycogenolysis
-Gluconeogenesis
Reduce peripheral glucose uptake
Stimulate peripheral release of gluconeogenic precursors (glycerol, AAs)
-Lipolysis
-Muscle glycogenolysis and breakdown
12
Q
Diabetes mellitus
A
A chronic disorder of carbohydrate metabolism characterised by hyperglycaemia
13
Q
Type 1 DM- presentations
A
Typically childhood
Commonly present DKA
Polydipsia, Polyuria, Sudden unexplained weight loss
14
Q
Acute hyperglycaemia morbidity
A
If untreated leads to acute metabolic emergencies diabetic ketoacidosis (DKA) and hyperosmolar coma (Hyperosmolar Hyperglycaemic State )
15
Q
Chronic hyperglycaemia morbidity
A
Leads to tissue complications (macrovascular and microvascular)
16
Q
Side effects of DM treatment
A
Hypoglycaemia- can be fatal
17
Q
Diseases associated with DM
A
Stroke
CV disease
Diabetic retinopathy (vision loss), nephropathy, neuropathy (leading to lower extremity loss)
18
Q
DM diagnosis and investigation- symptomatic
A
Raised plasma glucose detected once-
fasting>7mmol/L
random>11.1 mmol/L
19
Q
DM diagnosis and investigation- asymptomatic
A
Raised plasma glucose detected on two separate occasions-
fasting>7mmol/L
random>11.1 mmol/L
or oral glucose tolerance test- fasting>7mmol/L
2 hours after taking glucose >11.1 mmol/L
20
Q
Pathogenesis of Type 1 diabetes
A
Autoimmune disease causing destruction of beat cells. No insulin production, cells cannot take glucose from blood and use it for fuel.
Cell think body is in fasting state, so has no glucose supply. Levels of glucose keep rising leads in to hyperglycaemia
21
Q
Type 1 diabetes- failure of insulin secretion
A
-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
22
Q
Type 1 diabetes- Failure to treat with insulin
A
Severe insulin deficiency due to autoimmune destruction of the cell lead to hyperglycaemia
23
Q
DKA initial management
A
ABC if unconscious
Replace fluid loss with IV 0.9% saline slowly to avoid cerebral oedema
Replace deficient insulin with insulin (to inhibit ketone production)+ glucose (to prevent hypoglycaemia)
Treat hypokalaemia as a result of therapy if necessary
Treat underlying triggers
24
Q
Why can insulin treatment for DKA cause hypokalaemia?
A
Insulin decreases potassium levels in the blood by redistributing K+ into the cells via increased sodium-potassium pump activity causing low serum K+ levels— HYPOKALAEMIA
25
Dangers of hypokalaemia
Low levels of K+ can cause arrythmia, weakness (as the heart and muscles can struggle to contract)
26
Complications of DKA treatment
Cerebral Oedema- due to rapid dilution of high conc salt in blood with IV fluids. This leads to water moving into tissues causing swelling, swelling in the brain can be cause coma/ fatal due to skull being an enclosed space
27
DKA pathophysiology
1. Absence of insulin+
unrestrained production of glucose + decreased peripheral glucose uptake
2. Hyperglycaemia+ osmotic diuresis+ dehydration
3. Peripheral lipolysis, increase free fatty acids, oxidised to acetyl CoA, increased ketone= acidosis
28
DKA diagnosis
Hyperglycaemia (blood glucose >11 mmol/L)
Ketosis (blood ketones> 3 mmol/L)
Acidosis (pH<7.3)
29
Type 2 diabetes aetiology
Impaired Insulin Secretion and Insulin Resistance
30
Type 2 diabetes- impaired insulin action
Reduced muscle and fat uptake after eating
Failure to suppress lipolysis and high circulating FFAs
Abnormally high glucose output after a meal
31
Pathogenesis of Type 2 Diabetes- chronic hyperglycaemia
Excessive glucose production, more blood in blood, hyperglycaemia, glycosuria
32
Pathogenesis of Type 2 Diabetes- muscle/fat insulin resistance
Impaired glucose clearance, less glucose in peripheral tissues, hyperglycaemia, glycosuria
33
Glycosuria
the presence of reducing sugars in the urine
34
Principles of treatment of diabetes
Control of symptoms
Prevention of acute emergencies, ketoacidosis, hyperglycaemic hyperosmolar states
Identification and prevention of long-term microvascular complications
35
Sulphonylureas
work mainly by stimulating beta cells in the pancreas to make more insulin (e.g gliclazide, glibenclamide)
36
Thiazolidinediones
Activate genes concerned with glucose uptake and utilisation and lipid metabolism
Improve insulin sensitivity (e.g pioglitazone - ACTOS)
37
GLP-1 action
stimulating glucose-dependent insulin release from the pancreatic islets, slows gastric emptying, inhibit inappropriate post-meal glucagon release, and reduce food intake
38
Metformin (biguanide)
Best treatment for type 2 diabetes
Reduces rate of gluconeogenesis, so hepatic glucose output decreases, this increases insulin sensitivity
No impact on insulin secretion/ induce hypoglycaemia/ predispose weight gain
39
Type 1 Diabetes
Autoimmune condition (β-cell damage) with genetic component
Profound insulin deficiency
40
Type 2 Diabetes
Insulin resistance
Impaired insulin secretion and progressive β-cell damage but initially continued insulin secretion
Excessive hepatic glucose output
Increased counter-regulatory hormones including glucagon
41
Modern insulin therapy in T1D
Separation of basal from bolus insulin to mimic physiology
42
T1D treatment-Basal insulin
control blood glucose in between meals and particularly during the night
Given once or twice a day
43
T1D treatment-Bolus insulin
Pre-meal rapid acting boluses adjusted according to pre-meal glucose and carbohydrate content of food to cover meals
44
T1D treatment-Basal vs Bolus insulin
Basal- base level of insulin
Bolus- simulates insulin increase after eating
45
T2D- needing insulin duration of diabetes
Year 0- 0% needing insulin
Year 5- 20% needing insulin
Year 10- 50% needing insulins
46
Basal insulin in type 2 diabetes- Pros
Simple for the patient, adjusts insulin themselves, based on fasting glucose measurements
Carries on with oral therapy, combination therapy is common
Less risk of hypoglycaemia at night
47
Basal insulin in type 2 diabetes- Cons
Doesn’t cover meals
Best used with long-acting insulin analogues which are considered expensive
48
Limited role for pre-mixed insulin in diabetes- pros
Both basal and prandial components in a single insulin preparation
Can cover insulin requirements through most of the day
49
Limited role for pre-mixed insulin in diabetes- cons
Not physiological
Requires consistent meal and exercise pattern
Cannot separately titrate individual insulin compononents
50
Limited role for pre-mixed insulin in diabetes- risks
Increased risk for nocturnal hypoglycaemia2,3
Increased risk for fasting hyperglycaemia if basal component does not last long enough
51
Best treatment for T1D
Intensive basal-bolus insulin therapy
52
Hypoglycaemia
low blood glucose levels
53
Level 1 (alert level) hypoglycaemia
Plasma glucose <3.9 mmol/l (70 mg/dl) and no symptoms
54
Level 2 (serious biochemical) hypoglycaemia
Plasma glucose <3.0 mmol/l 55 mg/dl)
55
Non-severe symptomatic hypoglycaemia
Patient has symptoms but can self-treat and cognitive function is mildly impaired
56
Severe symptomatic hypoglycaemia (Level 3)
Patient has impaired cognitive function sufficient to require external help to recover
57
Hypoglycaemia- pathophysiology brain
Cognitive dysfunction
Blackouts, seizures, comas, Psychological effects
58
Hypoglycaemia- pathophysiology heart
Increased risk of myocardial ischaemia, Cardiac arrhythmias
59
Hypoglycaemia- pathophysiology musculoskeletal
Falls, accidents, driving accidents, Fractures, Dislocations
60
Hypoglycaemia- pathophysiology heart
Inflammation, Blood coagulation abnormalities, Haemodynamic changes, Endothelial dysfunction
61
Common hypoglycaemia symptoms- autonomic
Trembling, palpitations, sweating, anxiety, hunger
62
Common hypoglycaemia symptoms- neuroglycopenic
difficulty concentrating, confusion, weakness, drowsiness, dizziness, vision changes, difficulty speaking
63
Common hypoglycaemia symptoms- non specific
Nausea, headache
64
Treatment of non severe hypoglycaemia
Carbohydrate
65
Normal physiological responses preventing hypoglycaemia at 4.6 mmol/L
Inhibition of endogenous insulin secretion
66
Normal physiological responses preventing hypoglycaemia at 3.8 mmol/L
Glucagon
67
Normal physiological responses preventing hypoglycaemia at 3.6 mmol/L
Adrenaline
68
Impaired response to hypoglycaemia
No glycogen release, adrenaline is released at 2.5 mmol/L
Altered thresholds lead to impaired awareness and increased risk of severe hypoglycaemia
69
Causes of hypoglycaemia
Long duration of diabetes, Tight glycaemic control with repeated episodes of non severe hypoglycaemia, increased age, use of drugs, sleeping, increased physical activity
70
Screening for risk of severe hypoglycaemia
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
71
Strategies to prevent hypoglycaemia- patient education
Discuss hypoglycaemia risk factors and treatment with patients on insulin or sulphonylureas
Educate patients and caregivers on how to recognize and treat hypoglycaemia
Instruct patients to report hypo episodes to their doctor/educator
72
Treatment of hypoglycaemia
Recognize, confirm, treat, retest, eat
73
Treatment of hypoglycaemia- recognize
Recognize symptoms so they can be treated as soon as they occur
74
Treatment of hypoglycaemia- Confirm
Confirm the need for treatment if possible (blood glucose <3.9 mmol/l is the alert value)
75
Treatment of hypoglycaemia- Treat
Treat with 15g fast-acting carbohydrate to relieve symptoms
76
Treatment of hypoglycaemia- Retest
Retest in 15 minutes to ensure blood glucose >4.0 mmol/l and re-treat (see above) if needed
77
Treatment of hypoglycaemia- Eat
Eat a long-acting carbohydrate to prevent recurrence of symptoms
78
Complications of DM- microvascular
Peripheral Neuropathy, Retinopathy, Nephropathy
79
Complications of DM- macrovascular
Stroke, hypertension, peripheral artery disease, coronary artery disease
80
Parathyroid hormone action- bone
increased bone resorption
inhibits osteoblast activity and stimulates osteoclast activity leading to bone breakdown and calcium release
81
Parathyroid hormone action- kidney
Increased Ca2+ reabsorption and 1 α - hydroxylation of 25-OH vit D, decreased phosphate reabsorption
82
Parathyroid hormone action- small intestine
No direct effect on small intestine however increase Ca2+ absorption because of increased 1,25 (OH) 2 vit D
83
PTH response to decreased serum calcium
Decreased serum Ca2+ detected, increased in PTH causes increased Bone resorption and Ca2+ reabsorption in the kidney.
PTH causes decrease of phosphate in the kidneys causing increased urinary phosphate excretion and decrease serum phosphate, resulting in increased 1,25-(OH)2 vit D so increased Ca2+ absorption from the small intestine
84
Ca2+ homeostasis is an example of +ive or -ive feedback
negative feedback
85
Does PTH have big or small changes to small changes in serum Ca2+
small changes in serum calcium result in big changes in PTH
86
Importance of maintenance of serum Ca2+
Functioning of nerves and muscles
87
Hypocalcaemia
Low levels of low ionised calcium in the blood
88
Corrected calcium equation
corrected calcium =
total serum calcium + 0.02 * (40 – serum albumin)
89
Consequences of Hypocalcaemia
Paraesthesia
* Muscle spas (Hands and feet, Larynx, Premature labour)
* Seizures
* Basal ganglia calcification
* Cataracts
* ECG abnormalities- Long QT interval
90
Chvostek’s Sign
Tap over the facial nerve
Look for spasm of facial muscles
91
Trousseau’s Sign
Inflate the blood pressure cuff to 20 mm Hg above systolic for 5 minutes
92
Causes of Hypocalcaemia
Vitamin D inadequacy or vitamin D resistance.
Hypoparathyroidism following surgery.
Hypoparathyroidism owing to autoimmune disease or genetic causes.
Renal disease or end-stage liver disease causing vitamin D inadequacy
93
Hypoparathyroidism
diminished concentration of PTH in the blood, which causes deficiencies of calcium and phosphorus compounds in the blood
94
Hypoparathyroidism causes
* Syndromes
* Genetic
* Surgical
* Radiation
* Autoimmune
* Infiltration
* Magnesium deficiency
95
Hypoparathyroidism pathology
Decreased renal Ca2+ reabsorption (increased Ca2+ excretion), increased renal phosphate reabsorption (increased serum phosphate), decreased bone resorption, decreased formation of 1,25(OH)2D (decreased intestinal Ca2+ absorption)
OVERALL DECREASED SERUM Ca2+
96
Pseudohypoparathyroidism
Resistance to parathyroid hormone
97
Pseudohypoparathyroidism symptoms
* Short stature
* Obesity
* Round facies
* Mild learning difficulties
* Subcutaneous ossification
* Short fourth metacarpals
* Other hormone resistance
98
Pseudohypoparathyroidism cause
Type 1 Albright hereditary osteodystrophy
– mutation with deficient Gα subunit
99
Pseudohypoparathyroidism pathology
= PTH resistance
So if Ca2+ decreases, there is no increased bone resorption or no Ca2+ reabsorption/ absorption
100
Hypercalcaemia
High levels of low ionised calcium in the blood
101
Hypercalcaemia- reason for false readings
* Tourniquet on for too long
* Sample old and haemolysed
102
Hypercalcaemia: Symptoms
* Thirst, polyuria
* Nausea
* Constipation
* Confusion > coma
103
Hypercalcaemia: Consequences
* Renal stones
* ECG abnormalities- Short QT
104
Causes of hypercalcaemia
* Malignancy- bone mets, myeloma, PTHrP, lymphoma
* Primary hyperparathyroidism
* Thiazides
* Thyrotoxicosis
* Sarcoidosis
* Familial hypocalciuric / benign hypercalcaemia
* Immobilisation
* Milk-alkali
* Adrenal insufficiency
* Pheochromocytoma
105
Most common causes of hypercalcaemia
Malignancy
Primary hyperparathyroidism
106
Consequences of Primary Hyperparathyroidism
* Bones
-Osteitis fibrosa cystica
- Osteoporosis
* Kidney stones
* Psychic groans
- confusion
* Abdominal moans
- Constipation
* Acute pancreatitis
107
Consequences of Primary Hyperparathyroidism rhyme
Bones, Stones, Groans, Moans
108
Primary Hyperparathyroidism pathology
Increased PTH leads to increased bone resorption, renal Ca2+ reabsorption, Ca2+ absorption
HYPERCALCAEMIA
109
Blood supply of anterior pituitary
The anterior pituitary has no arterial blood supply but receives blood through a portal venous circulation from the hypothalamus
110
Regulation of the pituitary
Growth, thyroid, puberty + fertility, steroids
111
Location of pituitary gland
Sella turcica
112
Structures at risk of enlarged pituitary gland
Optic chiasm, contents of cavernous sinus (CN III, CN IV, V1, V2, CN VI + internal carotid artery)
113
Thyroid axis
Hypothalamus produces TRH, causes pituitary gland to release TSH, causes thyroid to produce T4 +T3. T4 + T3 causes negative feedback loop and decrease in TRH and TSH production
114
Pituitary problem impact on thyroid axis
TSH, T4 and T3 are low and TRH is high
115
Gonadal Axis
Hypothalamus produces GnRH, causes pituitary gland to release LH and FSH, causes testes/ ovaries to produce testosterone/ oestrogen. Testosterone/ oestrogen causes negative feedback loop and decrease in GnRH, LH and FSH production
116
HPA Axis
Hypothalamus produces CRH, causes pituitary gland to release ACTH, causes adrenal glands to produce cortisol. Cortisol causes negative feedback loop and decrease in CRH and ATCH.
117
GH / IGF-I AXIS
Hypothalamus produces GHRH to simulate release of GH from the pituitary gland or SMS to inhibit GH release. GH acts on liver and produces IGF-I. IGF-I causes negative feedback loop.
118
Diseases of the pituitary
* Benign pituitary adenoma
* Craniopharyngioma
* Trauma
* Apoplexy / Sheehans
* Sarcoid / TB
119
Craniopharyngioma
Epithelial tumours located near pituitary gland, extending to involve the hypothalamus, optic chiasm, cranial nerves, third ventricle, and major blood vessels
120
What's the difference between a craniopharyngioma and a pituitary adenoma?
Craniopharyngiomas and pituitary adenomas can both affect hormone function.
-Pituitary adenomas come from your pituitary gland
-craniopharyngiomas are located near that gland
121
Causes of Presentation of pituitary gland tumour
Pressure on local structure, pressure on normal pituitary and functioning tumours
122
Symptoms causes by pituitary tumour pressing on local structures
- Bitemporal hemianopia
- Headaches (stretching dura or hydrocephalus)
- Carinal nerve palsy and temporal lobe epilepsy
123
Prolactinomas symptoms
* More common in women
* Present with galactorrhoea/ amenorrhoea/ infertility
* Loss of libido
* Visual field defect
124
Amenorrhoea
absence of menstrual periods
125
Galactorrhoea
a milky nipple discharge unrelated to the usual milk production of breastfeeding
126
Prolactinomas treatment
Treatment dopamine agonist eg Cabergoline or bromocriptine
127
Prolactinomas- 1st line investigations
Elevated serum prolactin
Pituitary MRI
128
Prolactinomas
Noncancerous tumour of the pituitary gland. This tumour causes the pituitary gland to make too much prolactin
129
Acromegaly
Hormonal disorder that develops when your pituitary gland produces too much growth hormone during adulthood
130
At which stage does pitiuarty tumours cause Acromegaly, not Gigantism
Fusion of the long bone epiphysis
131
Cushing syndrome
disorder that occurs when your body makes too much of the hormone cortisol over a long period of time
132
Cushing syndrome symptoms
Weight gain in the trunk+ face, with thin arms and legs.
A fatty lump between the shoulders
Pink or purple stretch marks
Thin, frail skin that bruises easily
Slow wound healing
Acne
133
Most common causes of Cushing syndrome
long-term, high-dose use of the cortisol-like glucocorticoids
134
Do benign pituitary tumours affect anterior or posterior pituitary
Anterior pituitary
135
Definitive signs of female puberty
Menarche – first menstrual bleeding
136
Definitive signs of male puberty
First ejaculation, often nocturnal
137
Secondary sexual characteristics that occur at puberty- female
Ovarian oestrogens regulate the growth of breast and female genitalia
Ovarian and adrenal androgens control pubic and axillary hair
138
Secondary sexual characteristics that occur at puberty- male
Testicular androgens
–External genitalia and pubic hair growth
–enlargement of larynx and laryngeal muscles voice deepening
139
Tanner stages
Scale of physical development based on external primary and secondary sex characteristics
140
Adrenarche
developmentally programmed peri-pubertal activation of adrenal androgen production
141
Pubarche
Most pronounced clinical result of adrenarche
* Result of androgen action on the pilosebaceous unit transforming vellus hair into terminal hair in hair-growth prone parts of the skin
142
PRECOCIOUS PUBERTY
when children's bodies begin to change into adult bodies too soon
143
True PRECOCIOUS PUBERTY
Early activation of all of the HPG axis, 90% female
144
True PRECOCIOUS PUBERTY differential diagnosis
Brain tumour, especially in boys
145
PRECOCIOUS PSEUDOPUBERTY
GnRH-independent and occurs due to excess production of sex hormones either from the gonads, the adrenal glands or secreting tumours, HPG axis is not active
146
PRECOCIOUS PUBERTY – TREATMENT
Treatment with GnRH super agonist to suppress pulsatility of GnRH secretion
147
Causes of True Precocious Puberty
Idiopathic, CNS tumour/disorder, secondary central precocious puberty, psychosocial
148
Causes of Precocious Pseudo-Puberty
Increases androgen secretion, gonadotropin secreting tumour, ovarian cyst
149
Indication of delayed puberty
Girls- lack of breast development by 13
Boys- lack of testicular enlargement by age 14
150
CONSTITUTIONAL DELAY OF GROWTH AND PUPERTY (CDGP)
Children experience delayed puberty compared to their peers of similar age associated with a delay in the pubertal growth spurt
151
CONSTITUTIONAL DELAY OF GROWTH AND PUPERTY RFs
Family history of delayed puberty, congenital pituitary abnormalities, gene mutations, malnutrition, congenital and acquired gonadal abnormalities
152
Primary Hypogonadism
Testis/ovaries fail
-Hypergonadotropic and Hypogonadism
-Testosterone/ oestrogen go down, lack of feedback, FSH and LH go up
153
Secondary/Tertiary Hypogonadism
Hypothalamus/ Pituitary fail
-Hypogonadotropic and Hypogonadism
- FSH and LH go down, no response to feedback feedback, Testosterone/ oestrogen go down
154
Klinefelter’s syndrome
Affects males, 47,XXY Primary hypogonadism
155
Turner’s syndrome
Affects girls, 45,X0, Hypergonadotropic hypogonadism
156
Turner's syndrome- characteristics
Short stature, Short neck with a webbed appearance, low hairline at the back of the neck, low-set ears, hands and feet that are swollen or puffy at birth, and soft nails that turn upward
157
Klinefelter’s syndrome- characteristics
* Azoospermia, Gynaecomastia
* Reduced secondary sexual hair
* Osteoporosis
* Tall stature
* Reduced IQ in 40%
* 20-fold increased risk of breast cancer
158
Hormone replacement therapy- female puberty
Low doses of (Ethinyl estradiol (tablet) or Oestrogen (tablets, transdermal)) and gradual increasing doses to provide time for pubertal growth until full adult dose is achieved, then progesterone is added
159
Where is vasopressin and oxytocin made and where is it released from?
Made in PVN (paraventricular nucleus) and SON (supraoptic nucleus) transported to the posterior pituitary in the axoplasm of the neurons
160
Osmoreceptors
maintain the osmolality of the blood through a coordinated set of neuroendocrine, autonomic, and behavioral feedbacks
161
Arginine Vasopressin (AVP or ADH) release controlled by
osmoreceptors in hypothalamus - day to day
baroreceptors in brainstem and great vessels - emergency
162
ECF ions
large amounts of sodium, chloride, and bicarbonate ions
163
ICF ions
potassium, magnesium and phosphate ions
164
Sodium concentration ([Na+]) and ECF osmolarity
considered together because sodium ions comprise the majority of the solute in the extracellular compartment
165
Water balance is regulated by a feedback loop: water excess
Ingestion of water, decrease Plasma osmolality, increase in cellular hydration, decrease in thirst, vasopressin secretion + water intake, increase in urine excretion, decrease in total body water
166
Water balance is regulated by a feedback loop: water deficit
Water loss, increase Plasma osmolality, decrease in cellular hydration, increase in thirst, vasopressin secretion + water intake, decrease in urine excretion, increase in total body water
167
Under normal conditions what mediates variable water excretion by the kidneys
Vasopressin
168
Osmolality
Concentration in plasma (mOsmol/kg), number of (not size of) particle
169
Serum osmolality equation
serum osmolality = 2(Na) + glucose/18 + Urea/2.8
170
AVP deficiency (cranial diabetes insipidus)
Lack of vasopressin, uncommon not life threating
171
AVP resistance (nephrogenic diabetes insipidus)
Resistance to action of vasopressin, uncommon not life threating
172
Syndrome of anti-diuretic hormone secretion – SIAD
Too much vasopressin release when it should not be released, common, and can be life threatening
173
AVP deficiency and resistance symptoms
polyuria (wee), polydipsia (excess thirst), no glycosuria (decreased glucose in urine)
174
AVP deficiency and resistance investigations
Measure urine volume - unlikely if urine volume <3L/day
Check renal function and serum calcium
175
AVP deficiency and resistance- diagnostic investigation
Water deprivation test
176
AVP resistance (nephrogenic DI) causes
Genetic disorders,
-acquired: either reduction in medullary concentrating gradient or antagonism of effects of AVP
177
AVP deficiency (Cranial DI) causes
Damage to the hypothalamus or pituitary gland – ie after an infection, operation, brain tumour or head injury
Or genetic/ idiopathic (often autoimmune)
178
Management of AVP deficiency (Cranial DI)
Treat underlying condition, desmopressin, high activity at V2 receptor
179
Management of AVP resistance (Nephrogenic DI)
-try and avoid precipitating drugs
-congenital DI - very difficult
free access to water
very high dose desmopressin
180
Hyponatraemia
serum sodium < 135 mmol/l
181
Biochemically serve hyponatremia
serum sodium < 125 mmol/l
182
Normal serum sodium
135-144mmol
183
Moderate symptoms of Hyponatraemia
Headache
Irritability
Nausea / vomiting
Mental slowing
Unstable gait / falls
Confusion / delirium
Disorientation
184
Severe symptoms of Hyponatraemia
Stupor / coma
Convulsions
Respiratory arrest
185
Hyponatremia and the brain
The brain undergoes volume adaptation in response to gradual-onset hyponatraemia
186
Acute or chronic hyponatremia
Acute < 48 hours
Chronic > 48 hours
187
Aetiology of hyponatremia
Hypovolaemic
Euvolemic (blood)
Hypervolaemic
188
General Hyponatraemia treatments
Stop hypotonic fluids- fluid restriction
Review drug card – long list - PPI etc.
189
Hyponatraemia causes- dehydration + low urine Na+< 20mmol/l
Vomiting and diarrhoea
Burns
Pancreatitis
Sodium depletion after diuretics
*Saline replacement*
190
Hyponatraemia causes- dehydration + high urine Na+>40 mmol/l
Diuretics
Addison’s (or occasionally pituitary failure)
Cerebral salt wasting
Salt wasting nephropathy
*Saline replacement*
191
Hyponatraemia causes- fluid overload
Cirrhosis of liver/liver failure
CCF
Inappropriate IV fluids
*Fluid restrict*
192
SIAD - syndrome of antidiuresis
Too much AVP, when it should not be being secreted
193
SIAD- causes
Malignancy, primary brain injury (meningitis, bleed), drugs, infections
194
Biochemistry of SIAD - syndrome of antidiuresis
Low osmolality
Plasma sodium is low
Urine is inappropriately concentrated
Water retention - ECF volume increased mildly
Increase GRF - less Na reabsorption in PCT
thus - urine Na+ usually >30mmol/l
normal thyroid and adrenal function
195
Treatment goals of SIAD
allow/facilitate increase in serum Na+
treat any underlying condition
in acute setting - daily U+E - hospital
in chronic setting - weekly to monthly U+E - hospital/GP
196
Most common causes of hyperthyroidism
Graves diseases
Toxic multinodular goitre
Toxic adenoma
197
Goitre
Palpable & visible thyroid enlargement
Commonly sporadic or autoimmune
198
Name a disease that is Endemic in iodine deficient areas
Goitre
199
SPORADIC NON-TOXIC GOITRE
Commonest endocrine disorder
An enlargement of the thyroid gland in a euthyroid subject living in an iodine-sufficient area
200
3 mechanisms for Hyperthyroidism
a. overproduction thyroid hormone
b. leakage of preformed hormone from thyroid
c. ingestion of excess thyroid hormone
201
Hyperthyroidism
excess of thyroid hormones in blood
202
DRUG INDUCED HYPERTHYROIDISM
Iodine
Amiodarone (antiarrhythmic drug)
Lithium
Radiocontrast agents
203
CLINICAL FEATURES of hyperthyroidism
Weight loss
Tachycardia +/ AF
Hyperphagia (very hungry)
Anxiety
Tremor
Heat intolerance
Sweating
Diarrhoea
Lid lag + stare
Menstrual disturbance
204
GRAVES’ SPECIFIC clinical features
Diffuse goitre
Thyroid eye disease (infiltrative)
Pretibial myxoedema
Acropachy
205
Investigations of hyperthyroidism
Thyroid function tests to confirm biochemical hyperthyroidism
Diagnosis of underlying cause important because treatment varies
Clinical history, physical signs usually sufficient for diagnosis
206
Investigations of primary hyperthyroidism- thyroid functions test
Increase free T4 + T3
Suppressed TSH
207
Investigations of secondary hyperthyroidism- thyroid functions test
Increase free T4 +T3
But inappropriately high TSH
208
If thyroid function test shows high T4+T3, but low TSH, what is the likely diagnosis
Graves disease- thyroid function test
209
Graves disease
Immune system disorder that results in the overproduction of thyroid hormones (hyperthyroidism)
210
Thyroiditis
Inflammation of the thyroid gland
211
Treatment for destructive thyroiditis
Antithyroid drugs (course or long-term)
Radioiodine 131I
Surgery (partial, subtotal thyroidectomy)
212
Thionamides
Drug class that decreases synthesis of new thyroid hormone
213
SIDE EFFECTS OF THIONAMIDES
Generally well tolerated
Common side effect:
rash
Less common:
arthralgia
hepatitis
neuritis
thrombocytopenia
vasculitis
214
Dangerous side effect of thionamides
AGRANULOCYTOSIS (destruction of WBCs)
215
Radioiodine mechanism
Emission of beta particles results in ionization of thyroid cells
Direct damage to DNA and enzymes
Indirect damage via free radicals
216
Surgical treatment for graves disease and multinodular goitre
Near total thyroidectomy for Graves’ disease and multinodular goitre
217
Surgical treatment for toxic adenoma
Near total thyroidectomy / lobectomy for toxic adenoma
218
HYPOTHYROIDISM
Thyroid hormones levels abnormally low
219
3 types of hypothyroidism
PRIMARY (>99%)
- absence / dysfunction thyroid gland
- most cases due to Hashimoto’s thyroiditis
SECONDARY / TERTIARY
- pituitary / hypothalamic dysfunction
220
Causes of primary HYPOTHYROIDISM - ADULT
Hashimoto’s thyroiditis
131I therapy
Thyroidectomy
Postpartum thyroiditis
Drugs
Thyroiditides
Iodine deficiency
Thyroid hormone resistance
221
Postpartum thyroiditis
Transient phenomenon observed following pregnancy
May cause hyper/hypothyroidism
Often misdiagnosed as postpartum depression
222
Hashimoto’s thyroiditis
Autoimmune thyroiditis that produces atrophic changes with regeneration, leading to goitre formation
More common in late middle aged women
Common cause of hypothyrodism
223
Causes secondary/tertiary HYPOTHYROIDISM - ADULT
Pituitary disease
Hypothalamic disease
224
Clinical features of hypothyroidism
Fatigue
Wt gain
Cold intolerance
Constipation
Menstrual disturbance
Muscle cramps
Slow cerebration
Dry, rough skin
Periorbital oedema
Delayed muscle reflexes
Carotenaemia
Oedema
225
Investigation for primary hypothyroidism
high TSH (most sensitive marker)
usually low free T4 + T3
226
Investigations for SECONDARY/TERTIARY HYPOTHYROIDISM
TSH inappropriately low for reduced T4 / T3 levels
227
Investigation for Hasimoto's
T4/ T3 may be low/normal in mild hypothyroidism positive titre of TPO antibodies in Hashimoto’s
228
Treatment for hypothyroidism
Replacement therapy- synthetic L-thyroxine (T4)
229
Human chorionic gonadotrophin hormone (hCG)
hormone produced by the placenta during pregnancy.
It helps thicken uterine lining to support a growing embryo and stops menstruation
230
Metabolic Changes in pregnancy
Increased erythropoetin, cortisol, noradrenaline
High cardiac output
Plasma volume expansion
High cholesterol and triglycerides
Pro thrombotic and inflammatory state
Insulin resistance
231
Gestational Syndrome
specific to being pregnant
232
Gestational Syndrome examples
Pre-Eclampsia
Gestational Diabetes
Obstetric cholestasis
Gestational Thyrotoxicosis
Transient Diabetes Insipidus
Lipid disorders
Postnatal depression
Postpartum thyroiditis
Postnatal autoimmune disease
Paternal Disease
233
Thyroid gland development
Foetal thyroid follicles and thyroxine synthesis occurs at 10 weeks
Axis matures at 15-20 weeks
Maternal T4 0-12 weeks regulates neurogenesis, migration and differentiation then foetal T4
234
What week does Fetal thyroid follicles and thyroxine synthesis occur
Week 10
235
What weeks does the fetal thyroid axis mature
Weeks 15-20
236
Hypothyroidism in pregnancy signs and symptoms
Weight gain, cold intolerance, poor concentration, poor sleep pattern, dry skin, constipation, tiredness
Symptoms can predate pregnancy
237
Prevalence of hypothyroidism during pregnancy
2-3%
238
hCG and Thyroxine
hCG can bind to the TSH receptors present in thyroid tissue and act like a weak form of TSH to cause the thyroid to produce and release more T3 and T4
239
Do expecting mother with hypothyroidism need an increase or decrease in thyroxine dosage
Increase as hCG acts of a weak form of TSH causing competition at the receptors
240
Target screening for hypothyroidism
Age >30
BMI >40
Miscarriage preterm labour
Personal or family history
Goitre
Anti TPO
Type 1 DM
Head and neck irradiation
Amiodarone, Lithium or contrast use
241
Craniopharyngioma
Arise from squamous epithelial remnants of Rathke’s pouch
Benign tumour although infiltrates surrounding structures (pituitary gland and the hypothalamus)
242
LIMITS (not targets) for NA+ rise for hyponatremia treatment
High risk- <8mmol/l in any 24 hour period
Normal- <10-12mmol/l in any 24 hour period
243
SIAD - management
-Diagnose and treat underlying condition
-fluid restriction <1L/24 hour
-sometimes demeclocycline/ vaptan (vasopressin receptor antagonist)
244
Risk factor for Osmotic Demyelination Syndrome
Serum Na+ <105mmol/L
Hypokalaemia
Chronic excess alcohol
Malnutrition
Advanced Liver disease
>18mmol/L Na+ increase in 48 hour
245
Risk of improper therapy for hyponatraemia
Rapid correction of the hypotonic state leads to central pontine myelinolysis (osmotic demyelination syndrome)
246
Central pontine myelinolysis (Osmotic demyelination syndrome)
Massive demyelination of descending axons
May take up to 2 weeks to manifest
247
Management of acute severe symptomatic hyponatraemia
1. iv 150ml of 3% Saline or equivalent over 20 mins
2. Check serum Na+
3. Repeat twice twice until 5mmol/L increase Na+
4. After 5mmol/L increase
Stop hypertonic saline
Establish diagnosis
Na+ 6 hourly for 1st 24 hours
Limit increase to 10mmol/l first 24 hour
248
Craniopharyngioma peak ages
5 to 14 years; 50 to 74 years
249
Craniopharyngioma symptoms
Raised ICP, visual disturbances, growth failure, pituitary hormone deficiency, weight increase
250
Rathke’s pouch
gives rise to the anterior pituitary during week 4
251
Rathke’s Cyst
Derived from remnants of Rathke’s pouch
Single layer of epithelial cells with mucoid, cellular, or serous components in cyst fluid
252
Rathke’s Cyst symptoms
Mostly asymptomatic and small
Present with headache and amenorrhoea, hypopituitarism and hydrocephalus
253
Meningioma symptoms
Associated with visual disturbance and endocrine dysfunction
Usually present with loss of visual acuity, endocrine dysfunction and visual field defects
254
Lymphocytic Hypophysitis
Inflammation of the pituitary gland due to an autoimmune reaction
255
Non-Functioning Pituitary Adenoma (NFPA) or Silent Pituitary Adenoma (SPA)
benign anterior pituitary tumour not associated with clinical evidence of hormonal hypersecretion
256
Non-Functioning Pituitary Adenoma
begin tumour can cause visual disturbances, headaches
257
Non-Functioning Tumours
No specific test but absence of hormone secretion
* Test normal pituitary function
258
Non-Functioning Tumours treatment
Trans-sphenoidal surgery if threatening eyesight or progressively increasing in size
259
Testing Pituitary Function- guiding principle
If the peripheral target organ is working normally the pituitary is working
260
Thyroid function test- Primary Hypothyroid
Raised TSH low Ft4
261
Thyroid function test-Hypopituitary
Hypopituitary - Low Ft4 with normal or low TSH
262
Thyroid function test- Graves disease (toxic)
Suppressed TSH high Ft4
263
Thyroid function test- TSHoma- functioning tumour of pituitary (very rare)
High Ft4 with normal or high TSH
264
Thyroid function test- Hormone resistance
High Ft4 with normal or high TSH
265
Gonadal function test- male- Primary Hypogonadism
Low T raised LH/FSH
266
Gonadal function test-male- Hypopituitary
Low T normal or low LH/FSH
267
Gonadal function test-male- Anabolic use
Low T and suppressed LH
268
Gonadal function test-female- Before puberty
Oestradiol very low/undectable with low LH and FSH although FSH slightly higher than LH
269
Gonadal function test-female- Puberty
Pulsatile LH increases and oestradiol increases
270
Gonadal function test-female- Post menarche
Monthly menstrual cycle with LH/FSH, mid-cycle surge in LH and FSH and levels of oestradiol increase through cycle
271
Gonadal function test-female- Primary ovarian failure (includes menopause)
High LH and FSH with FSH greater than LH and low oestradiol
272
Gonadal function test-female- Hypopituitary
Oligo or amenorrhoea with low oestradiol and normal or low LH and FSH
273
How to test HPA axis
Measure cortisol and synacthen at 0900h
274
HPA function test- Primary AI
Low cortisol, high ACTH, poor response to Synacthen
275
HPA function test- Hypopituitarism
Low cortisol, low or normal ACTH, poor response to synacthen
276
When is GH levels highest and lowest?
GH is secreted in pulses with greatest pulse at night and low or undetectable levels between pulses
277
Affects of obesity on GH
Low in obesity
278
Affects of Age on GH
falls with age
279
Testing GH/IGF1 axis
Measure: IGF-I and GH stimulation test
-Insulin stress test
-Glucagon test
280
How to measure prolactin testing
Measure prolactin or cannulated prolactin (3 samples over an hour to exclude stress of venepuncture)
281
Prolactin may be raised as a result of
Stress
Drugs: antipsychotics
Stalk pressure
Prolactinoma
282
Measure for pituitary disease
Measure Ft4
Measure 0900h fasted T and LH/FSH in pituitary disease
283
Investigation of Vasopressin Deficiency/ Resistance
water deprivation test
Hypertonic Saline Stimulation Test
284
Water deprivation test
assess the ability of the patient to concentrate urine when fluids are withheld. Water deprivation should normally cause increased secretion of ADH, resulting in smaller volumes of concentrated urine.
285
Hypertonic Saline Stimulation Test
technique for distinguishing partial diabetes insipidus from psychogenic polydipsia, and for the diagnosis of complex disorders of osmoreceptor and posterior pituitary function
286
Dynamic Testing
assess the dynamic responses of hormonal and metabolic axes. These tests may involve: Stimulation of a hormonal axis by releasing hormones or other agents e.g. Synacthen to stimulate release of cortisol from adrenal glands
287
Preferred imaging study for the pituitary
MRI
288
Why is MRI the Preferred imaging study for the pituitary
Better visualization of soft tissues and vascular structures than CT
No exposure to ionizing radiation
289
Microparticulate
any particle in a micrometer scale are used as drug delivery systems. They offer higher therapeutic and diagnostic performance
290
Thyroxine replacement
Aim to achieve levels to mid to upper half of reference range
Higher doses usually required in patients on oestrogens or in pregnancy
291
Growth hormone replacement
Aiming for mid-range IGF1 levels, lower doses in older people
Improves lipid profiles, body composition and bone mineral density
292
Testosterone replacement
Improve bone mineral density, libido, sexual function, energy levels and sense of well being, muscle mass and reduce fat
293
Oestrogen Replacement
Alleviate flushes and night sweats; improve vaginal atrophy
Reduce risk of cardiovascular disease, osteoporosis and mortality
294
Desmopressin replacement therapy
Adjust according to symptoms
Monitor sodium levels
295
-Low Ft4 with normal or low TSH
-Low T normal or low LH/FSH
-Low cortisol, low or normal ACTH, poor response to synacthen
Hypothyroidism measurement
296
Hypothyroidism measurement
-Low Ft4 with normal or low TSH
-Low T normal or low LH/FSH
-Low cortisol, low or normal ACTH, poor response to synacthen
297
Acromegaly mean duration of symptoms
8 years
298
Acromegaly mean age at diagnosis
44 years
299
Acromegaly Co-morbidities
Cerebrovascular events, headaches, arthritis, insulin-resistant diabetes, sleep apnoea, CVD, hypertension
300
Acromegaly presenting clinical symptoms
Acral enlargement
Arthralgias
Maxillofacial changes
Excessive sweating
Headache
Hypogonadal symptoms
301
Criteria for diagnosis of acromegaly
Acromegaly excluded if:
random GH <0.4 ng/ml and normal IGF-I
If either abnormal proceed to:
75 gm Glucose tolerance test (GTT)
Acromegaly excluded if:
IGF-I normal
and
GTT nadir GH <1 ng/ml
302
Options for treatment of acromegaly
Pituitary surgery
Medical therapy
Radiotherapy
303
Two important determinants of success of surgery for acromegaly
size of tumour (hence importance of finding early)
surgeon
304
Medical therapy for acromegaly
Dopamine agonists – cabergoline
Somatostatin analogues
Growth Hormomne receptor antagonist
305
Mainstay of acromegaly therapy
Pituitary surgery mainstay of therapy
306
Prolactinoma
Noncancerous tumour of the pituitary gland
Produces prolactin
307
High prolactin levels
Reduces the production of the hormones oestrogen and testosterone
Anovulation (prevent release of eggs) in females
Decreased sperm production
Bone loss (osteoporosis)
308
Clinical features of Prolactinoma- local effects of tumour
Headache
Visual field defect (bi-temporal hemianopia)
CSF leak (rare)
309
Any pituitary tumour local effect clinical features
Headache
Visual field defect (bi-temporal hemianopia)
CSF leak (rare)
310
Clinical features of Prolactinoma- effect of prolactin
menstrual irregularity/ amenorrhoea
infertility galactorrhoea
low libido
low testosterone in men
311
Hyperprolactinaemia
high prolactin levels
312
Hyperprolactinaemia causes
Macroprolactinoma
Microprolactinoma
Non functioning pituitary tumour – compression of pituitary stalk – prolactin <4000 mIU/L
Antidopaminergic drugs
Other causes: stress, hypothyroidism, PCOS, drugs, renal failure, chest wall injury
313
Management of prolactinoma vs other pituitary tumour
Unlike other pituitary tumours management is medical rather than surgery
314
Clinical presentation of newly diagnosed
Type 1 diabetes- common
2-6 weeks of Polyuria, polydipsia, weight loss, ketonuria (high levels of ketone in urine)
315
Differences between Type 1 and Type 2 diabetes
Type 1-immune-mediated, idiopathic, insulin insufficient, younger people
Type 2- insulin resistance with inadequate insulin secretion, result of lifestyle, older people
316
Epidemiology of Type 1 diabetes
5-10% of all cases of diabetes, typically present in childhood, however can present later in life
317
Diabetic ketoacidosis (DKA)
metabolic emergency in which hyperglycaemia us associated with a metabolic acidosis due to greatly raised ketone levels
318
Diabetic ketoacidosis- ketone levels vs normal
>3mmol/L vs <0.6mmol/L
319
Diabetic ketoacidosis- clinical features
Prostration (state of extreme physical exhaustion, weakness or collapse), dehydration, nausea, vomiting
Occasionally- abdominal pain +/ confusion
320
Diabetic ketoacidosis investigation results
Ketonemia (>3mmol/L), high blood glucose (>11mmol/L), bicarbonate <15mmol/L +/ venous pH<7.3
321
Diabetic ketoacidosis- treatment
Replacement of fluid/ electrolytes lost, restoration of the acid-base balance, insulin replacement, treat underlying cause
322
Diabetic ketoacidosis- pathophysiology- increased glucose
Increase glucose due to insulin deficiency >
hyperglycaemia + glycosuria >
osmotic diuresis >
fluid and electrolyte depletion>
renal hypoperfusion >
impaired excretion of ketones + H+
323
Diabetic ketoacidosis- pathophysiology- increased ketones
Increase ketones as a result of uncontrolled ketogenesis in the liver due to insulin deficiency > acidosis > vomiting > fluid and electrolyte depletion > renal hypoperfusion > impaired excretion of ketones + H+
324
Aims of treatment of Type 1 diabetes
Prevention of diabetes emergencies (ie hypoglycaemia, DKA), Treatment of hyperglycaemic symptoms
Minimise risk of long term complications by screening and control of hyperglycaemia
325
Treatment options in Type 1 diabetes
Insulin replacement- pump or injection
Islet cell transplant
326
Monogenic diabetes mellitus (MODY- maturity-onset diabetes of the young)
caused by single gene mutation, dominantly inherited, which predominantly affects beta cell function, non-insulin dependence
327
Monogenic vs type 1 diabetes
Type 1- doesn't present before 6 months, immune cell mediated
Monogenic- can affect infants from birth, single genetic cause
328
When to consider monogenic diabetes
<6 months, patient presenting with early onset diabetes an affected parent, evidence of non-insulin dependence
329
Secondary diabetes subdivisions
secondary to genetic defects beta cell function or insulin action, exocrine pancreatic disease, endocrine disease, drugs/chemicals, infection
330
C peptide
Not present in synthetic insulin, longer half life than insulin, type 1 diabetes c-peptide is negative as result of complete destruction of beta cells
331
Will C-peptide persist or disappear with type 1 diabetes?
C-peptide will not be present with type 1 diabetes as beta cell are destroyed but will persist for type 1, monogenetic or secondary
332
Secondary diabetes to genetic defects of beta cell function
monogenic diabetes, glucokinase/hepatic nuclear factor mutations, neonatal diabetes, mitochondrial diabetes
333
Secondary diabetes to exocrine pancreatic disease causes
Chronic pancreatic (alcohol abuse, alters secretions leads to blocked ducts), haemochromatosis (genetic, excess iron deposited), pancreatic trauma, CF, neoplasia,
334
Secondary diabetes to endocrine causes
Acromegaly, Cushing's syndrome, pheochromocytoma
Due to insulin resistance
335
Secondary diabetes to acromegaly
insulin resistance due to excess GH simulating gluconeogenesis and lipolysis, causing hyperglycemia and elevated free fatty acid levels
336
Secondary diabetes to Cushing's syndrome
Excess glucocorticoid leads to reduced glucose uptake and increased gluconeogenesis so increase increased insulin resistance
337
Secondary diabetes to Pheochromocytoma
Catecholamines excess leads to increase gluconeogenesis and decrease glucose uptake leading to insulin resistance
338
Secondary to drug induced diabetes
Glucocorticoids- increase insulin resistance
thiazides/ protease inhibitors/ antipsychotic- not fully understood
339
Pharmacological name for cortisol
hydrocortisone
340
Cortisol rising to peak times
Starts rising at 3 am to peak shortly before waking up
341
Cortisol decline period
From wake up to 7pm
342
Cortisol quiescent period
7pm-3am
343
Adrenal insufficiency (AI) causes
Primary- Addison's disease
Secondary- hypopituitarism
Tertiary- suppression of HPA (steroids)
344
Addison's disease
Primary adrenal insufficiency- intrinsic diseases that affect the cortex of the adrenal glands, causing impairment in the synthesis and secretion of all steroids
345
Addison's disease- Causes
Adrenal destruction
Autoimmune- most common
Infections, mets, haemorrhagic infection, surgical removal
346
Secondary adrenal insufficiency
Occurs when the pituitary gland doesn't make enough of the hormone ACTH
347
0900 Cortisol and AI- investigations
− Cortisol > 450-500 nmol/l AI unlikely
− Cortisol < 100 nmol/l AI likely
348
ACTH and AI- investigations
− ACTH > 22 pmol/l primary
− ACTH < 5 pmol/l secondary
349
Renin / Aldo and AI- investigations
− Elevated renin in primary
350
Synacthen Test
uses synacthen to test how well the adrenal glands make cortisol
− 250ug IV, measure after 0’ & 30’
− > 450-550 nmol/l AI unlikely
351
Management- Adrenal Crisis
Bloods- cortisol +ATCH
Hydrocortisone 100mg IV/IM/SC
352
Treatment of Adrenal insufficiency (AI)
Glucocorticoid/ Mineralocorticoid/ Androgen Replacement
353
Sick Day Rules- Adrenal insufficiency (AI)
Always carry 10 x 10mg tablets hydrocortisone
* If unwell with fever or flu like illness double dose of steroids
* If in doubt double dose of steroids
* If vomiting or increasingly unwell take emergency injection
of hydrocortisone 100mg IM (SC)
* If unable to have injection take hydrocortisone 20mg 6
hourly and repeat if vomit
* Go to emergency room / ring ambulance
354
Most common complication of type 2 diabetes
Cardiorenal- CVD and CKD
355
Aims of type 2 DM treatment
Manage blood glucose
Reduce risk of CVD, CKD, microvascular complications
Weight reduction- (increased PA, decreases dietary fat)
356
HbA1c
average blood glucose levels for the last 2-3 months
357
Diabetic complications that risk increases with mean HbA1c
Diabetic retinopathy, nephropathy, Serve non-proliferative/ proliferative DR, neuropathy, microalbuminuria
358
Treatment options for controlling excess blood glucose in type 2 diabetes
Sensitise body to insulin- metformin and pioglitazone
Replace insulin- insulin injections/pumps
Secrete more insulin- sulphonylureas, DPP-4 inhibitors, GLP-1 receptor agonist
359
Initial pharmaceutical therapy for Type 2 DM
Metformin
360
Incretins
They stimulate pancreatic β-cells after meals, to secrete insulin i.e. glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1)
361
Sodium glucose co-transporter 2 inhibitor (SGLT-2i)
Current treatments are act as insulin secretagogues or sensitisers
Kidney key role in glucose homeostasis-glucose reabsorption
362
SGLT-2i limitations
Higher risk of infection, more common in women and more often mycotic than bacterial
363
Diabetic Complications
Diabetic retinopathy, stroke, CVD, Diabetic nephropathy, peripheral vascular disease, DPN (Diabetic peripheral neuropathy)
364
Diabetic Neuropathy
uncontrolled high blood sugar damages nerves and interferes with their ability to send signals, leading to diabetic neuropathy
365
Clinical consequences of Diabetic Neuropathy
painful neuropathic symptoms, autonomic neuropathy and insensitivity that results in foot ulceration and amputation
366
Diabetic Peripheral Neuropathy (DPN) and CVD
alarming association between DPN and cardiovascular disease
367
Does DPN commonly cause pain
Painful symptoms are present in about a third, however pain can disabling
368
Does DPN commonly cause significant motor deficits
No, Significant motor deficit is not common
369
Treatment of Diabetic Painful neuropathy
Good glycaemic control
Medications to manage Neuralgia - ie
Tricyclic antidepressants / SSRIs
Anticonvulsants
Opioids
IV lignocaine
Capsaicin
Transcutaneous nerve stimulation / acupuncture / spinal cord stimulators
Psychological interventions / hypnosis
370
Diabetic Foot Ulceration (DFU)
Foot ulceration occurs in 15% of people with DM during their lifetime, Lower limb amputations X 15 in people with DM2
371
Cause of diabetic amputation- common pathway
Neuropathy (damage to the nerves that serve the lower limbs and hands)/ vascular disease (affects the larger vessels of the lower limbs) > trauma >ulcer > failure to heal > infection> amputation
372
Will most people with neuropathy be aware if they are having any problems with their feet
most people with neuropathy are insensate (due to sensory nerve damage) and will not be aware of a problem
IMPORTANT TO GET PATIENT TO REMOVE SHOE
373
Euvolemia
the state or condition of having the normal volume of blood or fluids in the body
374
Satiety
The physiological feeling of no hunger
375
Location where most of the appetite regulation in the brain
Hypothalamus
376
Graves disease- thyroid function test
If thyroid function test shows high T4+T3, but low TSH, what is the likely diagnosis
377
T4/ T3 may be low/normal in mild hypothyroidism positive titre of TPO antibodies in Hashimoto’s
Investigation for Hasimoto's
378
Hyperosmolar hyperglycaemic state
Most common in T2DM
Characterised by profound hyperglycaemia, hyperosmolality and volume depletion in the absence of significant ketoacidosis
379
Hyperosmolar hyperglycaemic state cause
Often triggered after infection or acute illness (commonly MI, sepsis + stroke)
380
Hyperosmolar hyperglycaemic state- symptoms
Dehydration
Acute cognitive impairment
Polyuria, polydipsia, and weight loss
Weakness
Signs of the underlying cause (commonly MI, sepsis + stroke)
381
Hyperosmolar hyperglycaemic state- 1st order investigations
bloods- glucose (high), ketones (-ive or low), U+E, venous blood gas, serum osmolality (high)
ECG- for cardiac precipitants
382
Hyperosmolar hyperglycaemic state- treatment
Urgent IV fluids (with K+ replacement if needed)
Insulin
Identify/ treat underlying cause
Monitor biochemical markers
Monitor and treat complications
383
Hyperosmolar hyperglycaemic state- complications
cerebral oedema and central pontine myelinolysis
fluid overload
384
Subacute thyroiditis (De Quervain’s thyroiditis)
inflammation of the thyroid characterised by a triphasic course of transient hyperthyroidism (up to 6 weeks), hypothyroidism (upto 6 months), followed by a return to euthyroidism
385
Subacute thyroiditis (De Quervain’s thyroiditis)- aetiology
Presumed to be viral or autoimmune
386
Subacute thyroiditis (De Quervain’s thyroiditis)-
Hyperthyroid- supportive (NSAIDs, if unresponsive corticosteroids)
Hypothyroid- generally don't require thyroid replacement therapy
Most return to normal thyroid function (90%) but some need long term levothyroxine therapy
387
Thyroid storm
happens when your thyroid gland releases a large amount of thyroid hormone in a short amount of time
Medical emergency
388
Thyroid storm causes
typically develops in untreated or partially treated hyperthyroidism conditions (ie graves' disease)
After radioactive iodine therapy because of release of stores of thyroid hormone
389
Thyroid storm presentation
volume depletion, congestive heart failure, confusion, nausea and vomiting, and extreme agitation
390
Thyroid storm- treatment
high-dose antithyroid drugs, corticosteroids, beta-blockers, iodine solution with supportive care
391
Thyroid- storm investigations
Elevated T3, T4
Supressed TSH
Shouldn't wait before treatment
392
Thyroid cancer types
Papillary (60%)- younger pts
Follicular (<25%)- middle age
Medullary (5%)- may produce calcitonin
Lymphoma (5%)
393
Thyroid cancer- common treatment
Total thyroidectomy
Iodine ablation
Node clearance
394
Thyroid cancer symptoms
Growing lump on thyroid
Hoarse voice
Sore throat
Difficult swallowing or breathing
Pain in front of neck (pressing)
395
Carcinoid tumour
a rare cancer of the neuroendocrine system
Typically found on bowels or appendix
396
Carcinoid syndrome
collection of symptoms of carcinoid tumour – usually one that has spread to the liver – releases hormones such as serotonin into the bloodstream
397
Carcinoid syndrome- signs and symptoms
Bronchoconstriction, paroxysmal flushing (esp in upper body), diarrhoea, congestive cardiac failure
398
Carcinoid syndrome- diagnosis
elevated levels of urinary 5-hydroxyindoleacetic acid (waste product that comes from the breakdown of serotonin by the liver)
399
Carcinoid syndrome- treatment
Surgery resection (radio+/radiotherapy if surgery not effective)
Management of symptoms
400
Serotonin syndrome
excess serotonin in the CNS, resulting from the therapeutic use or overdose of serotonergic drugs
401
Serotonin syndrome- triad of clinical features
neuromuscular excitation, autonomic effects, and altered mental status
402
Serotonin syndrome- treatment
cessation of offending medication(s) or dose reduction- if mild/ moderate
emergency supportive care if severe
403
Primary aldosteronism (Conn's syndrome)
Aldosterone production exceeds the body's requirements and is relatively autonomous with regard to RAAS
Most common specifically treatable/ curable form of HTN
404
Primary aldosteronism (Conn's syndrome)- key diagnostic factors
HTN
RFs- family history of primary aldosteronism, of early onset of hypertension and/or stroke
405
Primary aldosteronism (Conn's syndrome)- 1st order investigation
Aldosterone/renin ratio- most reliable screening tool- elevated aldosterone: renin
406
Primary aldosteronism (Conn's syndrome)- diagnostic test
Fludrocortisone suppression test- most reliable
Saline infusion testing + Oral salt loading are alternatives
407
Primary aldosteronism (Conn's syndrome)- treatment
Surgery- (unilateral) laparoscopic adrenalectomy
Aldosterone antagonists
408
409
Hyperkalaemia
too much K+ in blood
Serum potassium value >6.0 mmol/L
410
Hypokalaemia
too little K+ in blood
serum potassium level <3.5 mmol/L
411
Hyperkalaemia- common causes
-High intake of potassium in the setting of decreased renal excretion
-Extracellular redistribution of potassium from intracellular locations
412
Hyperkalaemia- acute manifestations
muscle weakness
ECG changes (life treating arrhythmia)
413
Hyperkalaemia- ECG changes
Peaked T waves and bradycardia
P wave flattening
PR prolongation
Wide QRS complex
414
Hyperkalaemia- ECG changes- pathophysiology
Increased extracellular potassium reduces myocardial excitability, with depression of both pace making and conducting tissues.
415
Hyperkalaemia- common differentials
Chronic kidney disease
Diabetic ketoacidosis/hyperosmolar hyperglycaemic state
Potassium supplementation with underlying renal dysfunction
Drug induced
416
Hypokalaemia- common causes
urinary or GI losses
417
Hypokalaemia- acute manifestations
muscle weakness and ECG changes
418
Hypokalaemia- prolonged manifestations
rhabdomyolysis (destruction of striated muscle cells), renal abnormalities, and cardiac arrhythmias
419
Hypokalaemia- ECG changes
T wave inversion
St depression
Prominent U waves
420
Hypokalaemia- ECG- Push-pull effect
Hypokalaemia creates the illusion that the T wave is “pushed down”, with resultant T-wave flattening/inversion, ST depression, and prominent U waves
421
Hyperkalaemia- ECG- Push-pull effect
In hyperkalaemia, the T wave is “pulled upwards”, creating tall “tented” T waves, and stretching the remainder of the ECG to cause P wave flattening, PR prolongation, and QRS widening
422
Hypokalaemia- common differentials
Vomiting, severe diarrhoea, eating disorders, alcoholism, drug induced, primary aldosteronism, DKA, Hyperosmolar hyperglycaemic state, Exercising in a hot climate
Stress response in critical illness
423
Parathyroid hormone
Normally secreted in response to low Ca2+ from parathyroid glands, controlled by a -ve feedback loop via Ca2+ levels
424
Parathyroid hormone- action
-Increase osteoclast activity producing PO(4)3- and Ca2+
-Increase Ca2+ and decrease PO(4)3- reabsorption in the kidneys
-Increased active 1,25 dihydroxy-vitamin D3
425
Parathyroid hormone- overall action
Increased Ca2+
Decrease PO(4)3-
426
Hyperparathyroidism
Too much parathyroid hormone
3 types- primary, secondary, tertiary
427
Primary hyperparathyroidism
Parathyroid gland produces too much Parathyroid hormone
428
Primary hyperparathyroidism- causes
-80% solitary adenoma
-20% hyperplasia
- <0.5% parathyroid cancer
429
Primary hyperparathyroidism- presentation
Often asymptomatic
Signs relate to- hypercalcaemia, increased bone resorption or HTN
430
Hypercalcaemia- signs
Weak, tired, depressed, thirsty, dehydrated-but-polyuric
Also renal stones, abo pain, pancreatitis, ulcers
431
Increased bone resorption- signs
Bone pain, fractures, osteopenia, osteoporosis
432
Primary hyperparathyroidism- diagnostic test
Increased serum Ca2+ and inappropriate elevation of PTH
433
Primary hyperparathyroidism- Indications for surgery
Symptomatic
Or asymptomatic with <50 yrs, vry serum Ca2+, low eGFR, osteoporosis, lumbar spine, total hip, femoral neck, or distal third of radius, and/or vertebral fracture
433
Primary hyperparathyroidism- definitive treatment
Parathyroidectomy
434
Primary hyperparathyroidism- treatment for asymptomatic with no surgical indications
Monitoring- serum Ca2+, BMD T-score, lumbar spine, fracture scan
Vitamin D supplementation for those deficient
435
Secondary hyperparathyroidism
elevation of PTH secondary to hypocalcaemia
436
Secondary hyperparathyroidism- causes
Vit D deficiency, chronic renal failure
437
Secondary hyperparathyroidism and chronic renal failure
Defect in the activation of vitamin D in the kidneys due to chronic kidney disease leads to hypocalcaemia, resulting in compensatory PTH production causing secondary hyperparathyroidism
438
Secondary hyperparathyroidism- diagnostic test
Low serum Ca+, Elevated (appropriately) PTH
439
Secondary hyperparathyroidism- treatment
Correct underlying cause
Phosphate binders, Vit D, cinacalcet if needed
440
Chvostek's sign
Tapping on the face just anterior to the ear and seeing a twitching of muscles around the mouth. Seen in most hypocalcaemic states. Demonstrates neuromuscular excitability.
441
Trousseau's sign
Inflating blood-pressure cuff above diastolic for about 3 minutes causes muscular flexion of the wrist, hyperextension of the fingers, and flexion of the thumb. Seen in most hypocalcaemic states. Demonstrates neuromuscular excitability.
442
What do Chvostek's and Trousseau's sign represent
Hypocalcaemia Demonstrates neuromuscular excitability.
443
Tertiary hyperparathyroidism
High Ca2+ and very high PTH (inappropriately)
Occurs in chronic renal failure
444
Tertiary hyperparathyroidism- pathophysiology
Occurs after prolong secondary hyperparathyroidism, causing gland to act autonomously having under gone hyperplasic or adenomatous change
This causes increased Ca2+ from very increased PTH secretion by feedback control
445
