Endocrine Flashcards
1
Q
What is endocrinology?
A
The study of hormones (and their glands of origin), their receptors, their intracellular signalling pathways, and their associated diseases.
2
Q
What can the two chains of a peptide hormone be joined by?
A
Carbohydrates
3
Q
Are peptide hormones released continuously or at intervals?
A
They are released in pulses/bursts.
4
Q
How are peptide hormones cleared from the bloodstream?
A
By tissues or circulating enzymes.
5
Q
What are the three ‘forms’ of a peptide hormone?
A
- Preprohormone
- Prohormone
- Hormone
6
Q
What is the stage of hormone production called when a preprohormone is cleaved to form a prohormone?
A
Synthesis
7
Q
What is the stage of hormone production called when a prohormone is cleaved to form a hormone?
A
Packaging
8
Q
Which amino acid are amine hormones produced from?
A
Tyrosine
9
Q
Give the stages in adrenaline production from an amino acid.
A
- Phenylalanine
- Tyrosine
- L-DOPA
- Dopamine
- Noradrenaline
- Adrenaline
10
Q
How do thyroid hormones travel in the bloodstream?
A
99% protein bound
11
Q
Which amino acid are thyroid hormones produced from?
A
Tyrosine
12
Q
Is T3 or T4 more active?
A
T3 (T4 is cleaved to T3 in the peripheries)
13
Q
Give five factors that influence hormone action.
A
- Metabolism
- Receptor induction
- Receptor downregulation
- Synergism
- Antagonism
14
Q
Give an example of hormone receptor induction.
A
FSH induces LH receptors.
15
Q
When does hormone receptor downregulation occur?
A
When the hormone is in high concentrations.
16
Q
Give an example of hormone synergism.
A
Glucagon and epinephrine
17
Q
Which hormones bind to receptors on the cell membrane?
A
Peptide hormones
18
Q
Which hormones bind to receptors in the cytoplasm?
A
Adrenocorticosteroids
Androgens
Progesterone
19
Q
Which hormones bind to receptors in the nucleus?
A
Oestrogen
Thyroid hormones
Vitamin D
20
Q
How is a positive feedback loop stopped?
A
An outside factor is required to shut off the cycle.
21
Q
Give four patterns of hormone secretion.
A
- Basal secretion
- Superadded rhythm
- Releasing factors
- Release inhibiting factors
22
Q
Is basal hormone secretion continuous or pulsatile?
A
It can be either.
23
Q
Give an example of a superadded hormone secretion.
A
Diurnal rhythm
24
Q
Give three factors that can be releasing factors for hormones.
A
Humoural
Neural
Hormonal
25
What is appetite?
A psychological desire to eat food.
26
What is hunger?
A physiological need of eating.
27
What is satiety?
Feeling of fullness (disappearance of appetite after a meal)
28
What is the formula for BMI?
Weight (KG)/Height2 (M2)
29
What range of BMI is classed as underweight?
<18.5
30
What range of BMI is classed as normal?
18.5-24.9
31
What range of BMI is classed as overweight?
25.0-29.9
32
What range of BMI is classed as obese?
30.0-39.9
33
What range of BMI is classed as morbidly obese?
>40
34
Is subcutaneous fat or visceral fat more dangerous in obesity?
Visceral fat
35
What two factors influence weight regulation?
| Which factor has the bigger influence?
Genes and Environment
| Environment has the bigger influence.
36
What are the three structures/parts of the body which contribute hormones to weight regulation?
- Brain
- GI tract
- Adipose tissue
37
How is weight influenced by genes?
It is polygenic.
38
Where is the hunger centre located?
Lateral hypothalamus
39
Where is the satiety centre located?
Ventromedial hypothalamic nucleus
40
Where is leptin expressed?
White fat
41
Where are leptin receptors located and what family are they part of?
Cytokine receptor family in hypothalamus
42
What is the ultimate role of leptin?
Switches off appetite
43
How does leptin affect the immune system?
It is immunostimmulatory
44
What is the result of a leptin deficiency or an improperly functioning leptin receptor?
Obesity
45
Name another hormone which works in a similar way to leptin.
Insulin
46
What is the role of peptide YY?
Binds to NPY receptors to inhibit them.
47
Where is peptide YY secreted, and by what cells?
Ileum
Pancreas
Colon
By neuroendocrine cells
48
How does peptide YY affect gastric motility?
Inhibits it
49
How does peptide YY affect appetite?
Inhibits it
| NPY increases appetite
50
Where is cholecystokinin released?
Duodenum
51
Where are the receptors for cholecystokinin located?
Pyloric sphincter
52
Give four functions of cholecystokinin.
- Delays gastric emptying
- Gall bladder contraction
- Insulin release
- Stimulates vagus nerve to signal satiety
53
How does cholecystokinin affect appetite?
Reduces it
54
Where is ghrelin expressed?
Stomach
55
What hormone is released in response to ghrelin release?
Growth hormone
56
How does ghrelin affect appetite?
Increases it
57
What is proopiomelanocortin (POMC)?
A hormone precursor which is cleaved to form multiple hormones.
58
Which hormone is cleaved from POMC which affect appetite?
A-MSH (melanocyte stimulating hormone)
59
Which melanocortin receptors does a-MSH act on to affect appetite?
MCR3 and MCR4 in the brain
60
How does POMC/a-MSH affect appetite?
Signals satiety
61
What condition results from POMC deficiency?
Obesity
62
Give seven risks that come with obesity.
- Type II diabetes
- Hypertension
- Coronary artery disease
- Stroke
- Osteoarthritis
- Obstructive sleep apnoea
- Carcinoma (breast, endometrium, prostate, colon)
63
Why do people who do shift work have a higher risk of becoming obese?
Their metabolic circadian rhythms are altered.
64
Give three reasons why people eat?
- Internal physiological drive to eat
- Feeling that prompts thought of food and motivates food consumption
- External psychological drive to eat
65
How does highly refined sugar affect satiety?
Quick and short satiety
66
How do foods high in protein affect satiety?
They result in a prolonged satiety
67
How are water-soluble hormones stored?
In vesicles
68
How are water-soluble hormones transported?
Unbound
69
How do water-soluble hormones interact with cells?
Bind to surface receptor
70
Describe the half-life of water-soluble hormones.
Short
71
Describe the rate of clearance of water-soluble hormones.
Fast
72
Give two examples of hormone classes that are water-soluble.
Peptides
| Monoamines
73
Describe the storage of fat-soluble hormones.
They are not stored - they are synthesised on demand
74
How are fat-soluble hormones transported?
Protein-bound
75
How do fat-soluble hormones interact with cells?
Diffuse into cell
76
Describe the half-life of fat-soluble hormones.
Long
77
Describe the rate of clearance of fat-soluble hormones.
Slow
78
Give two classes of hormones which are fat-soluble.
Thyroid hormones
| Steroids
79
What is the effect of leptin/insulin on anabolic processes (food intake)?
Inhibition
80
What is the effect of leptin/insulin on catabolic processes (energy expenditure)?
Activation
81
Name two central controllers which increase appetite.
NPY (neuropeptide Y)
| AgRP (agouti-related peptide)
82
Name four central controllers which decrease appetite.
A-MSH
CART
GLP-1
Serotonin
83
What does CART stand for?
Cocaine and amphetamine regulated transcript
84
How do leptin/insulin affect POMC and CART neurons?
Stimulate them
85
How does leptin/insulin affect NPY and AgRP neurons?
Inhibit them
86
What affect do GABA and NPY have on POMC and CART neurons?
Inhibition
87
What affect does ghrelin have on NPY and AgRP neurons?
Stimulation
88
Where are POMC/CART/NPY/AgRP neurons found?
Arcuate nucleus
89
How does AgRP increase appetite?
Blocks MCR receptors to stop aMSH from working.
90
Where do a-MSH and NPY have their effects?
Paraventricular nucleus
91
What happens to AMPK in cells in the fasted state?
It is activated
92
What is the role of AMPK?
Inhibits acetyl CoA carboxylase so reduces Malonyl CoA production
93
How does malonyl CoA affect appetite?
Increased malonyl CoA decreases appetite.
94
What happens to AMPK in cells in the fed state?
It is deactivated
95
What is an orexigenic drug?
An appetite stimulant
96
What is obesity?
Abnormal or excessive fat accumulation that may impair health.
97
Give four consequences of poor nutrition in childhood.
- Emotional and behavioural effects (stigma, bullying, self-esteem)
- School absence
- Poor physical health
- Long-term effects into adulthood
98
What are the four As which determine someone’s chances of becoming obese?
- Accessibility
- Availability
- Acceptability/awareness
- Affordability
99
What does tier 1 of the obesity care pathway involve?
Universal prevention
100
What does tier 2 of the obesity care pathway involve?
Lifestyle intervention
101
What does tier 3 of the obesity care pathway involve?
Specialist services
102
What does tier 4 of the obesity care pathway involve?
Surgery
103
What are the four stages of the satiety cascade?
Sensory
Cognitive
Postingestive
Postabsorptive
104
Name two hormones which are released from the posterior pituitary gland.
Oxytocin
| Vasopressin
105
What type of hormone is oxytocin?
Peptide
106
What type of hormone is vasopressin?
Peptide
107
Where is oxytocin synthesised?
Paraventricular nucleus in hypothalamus
108
Where is vasopressin synthesised?
Supraoptic nucleus in hypothalamus
109
Give six factors that stimulate vasopressin release.
| Which factor is vasopressin most responsive to?
- Increased osmolality (most responsive)
- Low blood volume
- Exercise
- Stress
- Nausea
- Vomiting
110
Which receptors does vasopressin act on in smooth muscle and what is the effect.
Acts on V1a receptors to cause vasoconstriction.
111
What receptors does vasopressin act on in the kidney and what is the effect?
Acts on V2 receptors to increase aquaporins and water retention.
112
What two sites does oxytocin act on?
- Myoepithelial cells of mammary glands
| - Uterus/cervix
113
What is the effect of oxytocin acting on myoepithelial cells?
Milk ejection
114
What is the effect of oxytocin acting on the uterus?
Labour
115
Give two factors which stimulate oxytocin release.
- Suckling
| - Uterine contractions
116
What are three features that pituitary dysfunction can cause?
- Tumour mass effects (pressure on local structures)
- Hormone excess (functioning tumour)
- Hormone deficiency (tumour pressing on normal pituitary)
117
What investigations should be carried out if a pituitary dysfunction is suspected?
- Hormonal tests
| - If hormonal tests abnormal or tumour mass effects perform MRI pituitary
118
What types of hormones are released by the hypothalamus?
Mostly peptide.
| Dopamine is an amine hormone
119
Give the six hormones that are released from the hypothalamus.
- Growth hormone releasing hormone
- Somatostatin
- Corticotropin releasing hormone
- Thyrotropin releasing hormone
- Gonadotropin releasing hormone
- Dopamine
120
Give the six hormones released from the anterior pituitary.
- Growth hormone
- Adrenocorticotropic hormone
- Thyroid stimulating hormone
- FSH
- LH
- Prolactin
121
Describe the indirect actions of growth hormone.
Stimulates the liver to release insulin-like growth factors which stimulate growth.
122
Describe the direct actions of growth hormone.
Metabolic and anti-insulin, so increased fat breakdown and increased blood glucose.
123
Give three main consequences of cortisol release.
- Gluconeogenesis
- Fat breakdown
- Immune suppression
124
Give eight functions of thyroid hormones.
- Increased food metabolism
- Increased protein synthesis
- Increased carbohydrate metabolism
- Increased fat metabolism
- Increased ventilation rate
- Increased heart rate and cardiac output
- Brain development in foetal life
- Increased growth rate
125
What is the function of prolactin?
Milk production
| Inhibition of FSH/LH
126
Which cells does FSH act on?
Sertoli cells
| Granulosa cells
127
Which cells does LH act on?
- Granulosa cells
- Theca cells
- Leydig cells
128
How many people are living with diabetes in England?
3.8 million
129
What is meant by primary prevention of diabetes?
Preventing diabetes
130
What is meant by secondary prevention of diabetes?
Diagnosing diabetes earlier
131
What is meant by tertiary prevention of diabetes?
Effective management and supporting self-management of diabetes
132
Give three environmental factors that increase risk of diabetes.
- Sedentary job / leisure activities
- Diet high in calorie-dense foods / low in fruit and vegetables, pulses, and wholegrain
- Obesogenic environment
133
Give three aspects of the obesogenic environment, with examples.
- Physical Environment (TV remote, lifts, cars)
- Economic environment (cheap TV, expensive fruit)
- Sociocultural environment (family eating patterns)
134
Give three types of mechanisms that maintain obesity.
- Physical/physiological
- Psychological
- Socioeconomic
135
How do physical/physiological mechanisms maintain obesity?
More weight results in difficulty exercising and dieting.
| There is also a metabolic response.
136
How do psychological mechanisms maintain obesity?
Low self-esteem
Guilt
Comfort eating
137
How do socioeconomic mechanisms maintain obesity?
- Reduced employment opportunities
- Relationships
- Social mobility
138
Give some risk factors for diabetes that may be recorded in a patient record.
- Age
- Sex
- Ethnicity
- Family history
- Weight
- BMI
- Waist circumference
- History of gestational diabetes
- Hypertension / vascular disease
- Impaired glucose tolerance (IGT)
- Impaired fasting glucose (IFG)
139
Give five screening tests available for impaired glucose tolerance and impaired fasting glucose.
- HbA1c
- Random capillary blood glucose
- Random venous blood glucose
- Fasting venous blood glucose
- Oral glucose tolerance test (venous blood glucose 2 hours after oral glucose load)
140
What is the diagnostic threshold for diabetes for a fasting blood glucose?
7.0mmol/L or higher
141
What is the diagnostic threshold for diabetes in a 2 hour glucose tolerance test?
11.1mmol/L or higher
142
Give four approaches used to diagnose diabetes earlier.
- Raising awareness of diabetes and symptoms in community
- Raising awareness of diabetes and symptoms in health professionals
- Using clinical records to identify those at risk
- Blood tests to screen
143
Give four steps for preventing a wide spread public health issue like diabetes.
1. Identify people at risk
2. Early prevention in those at risk
3. Diagnose earlier
4. Effective management and support self management
144
Name the sinuses which are located close to the pituitary gland.
Sphenoid sinus
| Cavernous sinus
145
What is the bony structure in which the pituitary gland sits?
Sella turcica
146
Why is the optic chiasm important when looking at pituitary disorders?
It is located just above the pituitary gland so can be compressed by pituitary tumours.
147
Describe the blood supply of the anterior pituitary gland.
Receives blood through a portal venous circulation from the hypothalamus.
148
Give four things that the pituitary gland is responsible for.
- Growth
- Thyroid function
- Puberty
- Steroids
149
What is the difference between primary and secondary thyroid dysfunction?
```
Primary = problem with thyroid gland
Secondary = problem with pituitary gland
```
150
Do can anabolic steroids affect LH and FSH levels?
They will decrease due to negative feedback.
151
What will be the effect on prolactin if a patient is on dopamine antagonists?
More prolactin
152
Give five diseases of the pituitary.
- Benign pituitary adenoma
- Craniopharyngioma
- Trauma
- Apoplexy/Sheehans
- Sarcoid/TB
153
Which is the most common disease of the pituitary?
Benign pituitary adenoma
154
What is a craniopharyngioma?
A benign cystic lesion
155
What can be a consequence of pituitary trauma?
Severed pituitary stalk
156
What is Sheehans?
Bleeding after childbirth results in no perfusion and pituitary necrosis.
157
What is an 'incidentaloma'?
A tumour which is identified on a scan which was originally carried out for a different reason.
158
What are the symptoms of a pituitary tumour which is pressing upwards?
- Headaches
| - Bitemporal hemianopia
159
Give two reasons why pituitary tumours can cause headaches.
- Stretching of dura
| - Ventricle obstruction
160
Give two consequences of a pituitary tumour pressing sideways.
- Cranial nerve palsies
| - Temporal lobe epilepsy
161
What does a pituitary tumour cause if it presses downwards?
CSF rhinorrhoea
162
Give three symptoms of a tumour pressing on the normal pituitary.
- Pale
- Lack of body hair
- Central obesity
163
What mechanism controls circadian rhythms in humans?
The body clock
164
How long is the body clock cycle in humans?
24.2 hours
165
How do central body clocks and peripheral body clocks in individual organs communicate?
Glucocorticoids act as a secondary messenger
166
Which area of the brain controls the circadian rhythm in humans?
Suprachiasmatic nucleus in the hypothalamus
167
What is a zeitgeber?
Any external or environmental cue that synchronises the circadian rhythm to the Earth's 24 hour/12 month cycle.
168
What is the primary zeitgeber?
Light
169
Name another factor, apart from light, which affects circadian rhythms.
Food
170
What is meant by nadir in a circadian rhythm?
The lowest level of a hormone
171
What is meant by acrophase in a circadian rhythm?
The peak of a hormone level
172
What is meant by MESOR in a circadian rhythm?
The overall average level of a hormone.
173
Give eight functions of cortisol.
- Permissive effects on glucagon
- Carbohydrate metabolism (increased glucose)
- Lipolysis and ketogenesis
- Gluconeogenesis
- Increased myocardial contraction
- Increased vascular tone
- Conserves glucose for brain
- Suppresses immune system
174
What time of day is the peak in cortisol levels?
Morning, between 08:00 and 09:00.
175
What is the threshold for a diabetes diagnosis in a random blood glucose sample?
11.1 mmol/L or higher
176
Give the four effects of parathyroid hormone.
- Increased bone resorption
- Increased intestinal calcium absorption (via Vitamin D activation)
- Increased renal calcium reabsorption
- Increased renal phosphate excretion
177
Give the three effects that parathyroid hormone has on the kidneys.
- Increased calcium reabsorption
- Decreased phosphate reabsorption
- 1a-hydroxylation of vitamin D
178
Give the effect of parathyroid hormone on bone.
- Increased bone remodelling (bone resorption outweighs bone formation)
179
Give the effect of parathyroid hormone on the intestines.
No direct effect (but increased calcium absorption due to increased vitamin D activation)
180
Why is calcium important?
For the functioning of nerves and muscles
181
What is the prevalence of hyperthyroidism?
2.5%
182
What is the prevalence of hypothyroidism?
5%
183
What is the prevalence of goitres?
5-15%
184
Define hyperthyroidism.
An excess of thyroid hormone in the blood.
185
Which gender is more likely to get thyroid autoimmunity?
Females
186
When does thyroid autoimmunity commonly present in females?
Post partum
187
What causes neonatal thyrotoxicosis?
Maternal antibodies for thyroid stimulating hormone receptor cross the placenta.
188
Which genes play a part in a person's predisposition to thyroid autoimmunity?
HLA genes
189
Give three environmental factors which increase risk of predisposition to thyroid autoimmunity.
- Stress
- High iodine intake
- Smoking
190
What is a goitre?
A palpable and visible thyroid enlargement.
191
Where in the world do goitres commonly occur?
Iodine deficient areas
192
What are the three mechanisms for increased thyroid hormone in the blood?
- Overproduction of thyroid hormone
- Leakage of preformed hormone from thyroid
- Ingestion of excess thyroid hormone
193
Name four drugs or types of drugs which commonly cause thyroid dysfunction.
- Amiodarone
- Lithium
- Interferon
- Immune therapies
194
Give two drugs used in immune therapies which affect the thyroid.
Ipilimumab
| Nivolumab
195
What is amiodarone used for?
Anti-arrhythmic drug used in atrial fibrillation.
196
Why does amiodarone commonly affect the thyroid?
37% iodine by weight
197
Give two thyroid conditions that amiodarone can cause.
- Amiodarone induced hypothyroidism (AIH)
| - Amiodarone induced thyrotoxicosis (AIT)
198
What is the Wolf-Chaikoff effect?
Presumed reduction in thyroid hormone in response to excess iodine ingestion.
199
What is the Jode-Basedow effect?
Increased thyroid hormone in response to increased iodine intake.
200
Give an alternative drug to amiodarone which does not contain iodine.
Dronedarone
201
Give three predominantly intracellular ions.
- Potassium
- Magnesium
- Phosphate
202
Give three predominantly extracellular ions.
- Sodium
- Chloride
- Bicrobonate
203
Define osmolality.
Concentration of solute per kilo.
204
Define osmolarity.
Concentration of solute per litre.
205
Give six solutes which affect osmolality.
- Sodium
- Potassium
- Chloride
- Bicarbonate
- Urea
- Glucose
206
Give four exogenous solutes which may affect osmolality.
- Alcohol
- Methanol
- Polyethylene glycol
- Manitol
207
Give an equation used to estimate osmolality at the bedside.
2Na + urea + glucose
208
What is the day to day release of ADH controlled by?
Osmoreceptors in the hypothalamus
209
What stimulates ADH release in an emergency?
Baroreceptors in brainstem and great vessels.
210
Where is the V1a receptor found?
Vasculature
211
Where is the V1b receptor found?
Pituitary
212
Where is the V2 receptor found?
Renal collecting tubules
213
How does the cell absorb more water when ADH binds to the receptor?
ADH binding increases levels of cAMP.
| Vesicles with aquaporin 2 are inserted into membrane.
214
What is hyponatraemia defined as?
Serum sodium <135mmol/L
215
What level does sodium have to drop to to be classed as severe hyponatraemia?
<125mmol/L
216
What are 10 signs/symptoms of hyponatraemia?
- Asymptomatic
- Headache
- Lethargy
- Anorexia/abdominal pain
- Weakness
- Confusion/hallucinations
- Agitation
- Decreased consciousness
- Fitting
- Coma
217
What nine investigations should be done if hyponatraemia is suspected?
- Plasma osmolality
- Urine osmolality
- Plasma glucose
- Urine sodium
- Urine diptest for protein
- TSH
- Cortisol
- Short synacthen if low cortisol
- Consider alcohol
218
Describe how the CNS adapts to hyponatraemia.
Water gain causes loss of sodium/potassium/chloride and in the long term, organic osmolytes.
Water follows out of brain and the brain adapts.
219
How should hyponatraemia be corrected in an acute situation?
Rapid correction is safer and may be necessary.
220
How should hyponatraemia be corrected in a chronic case?
Correction must be slow because brain has adapted.
| <8mmol/24hr
221
Does onset of puberty correspond better with bone age or chronological age?
Bone age
222
What is puberty?
Puberty describes the physiological, morphological, and behavioural changes as the gonads switch from infantile to adult forms.
223
What are the definitive signs of puberty for boys and girls?
Boys - First ejaculation
| Girls - Menarche
224
What are the true signs of the start of puberty for girls and boys?
Boys - Testes >3ml
| Girls - breast bud noted/palpable
225
What is thelarche?
Breast development
226
What is thelarche induced by?
Oestrogen
227
What changes does oestrogen induce in the breast at puberty?
- Ductal proliferation
- Adipose deposition
- Nipple/areola enlargement
228
Other than oestrogen, give three other hormones involved in thelarche.
- Prolactin
- Glucocorticoids
- Insulin
229
What is adrenarche?
Maturation of the adrenal gland.
230
Which zone of the adrenal cortex develops during adrenarche?
Zona reticularis
231
Which steroid is produced in adrenarche?
DHEA
232
What physical changes occur at adrenarche?
- Growth of pubic/axillary hair
- Oily skin
- Mild acne
- Body odour
233
What is pubarche?
First appearance of pubic hair at puberty.
234
What may occur as a consequence of menarche before 9 years?
Short stature
235
Define precocious puberty.
Onset of secondary sexual characteristics before 8 years (girl), 9 years (boy).
236
What causes true precocious puberty?
Increased GnRH secretion.
237
What other condition has to be ruled out in precocious puberty?
Brain tumour
238
Is precocious puberty more common in boys or girls?
Girls
239
Describe the relative stimulated LH/FSH levels in true precocious puberty.
LH:FSH ratio >1, levels are high.
240
What causes precocious pseudopuberty?
Secreting tumours or production of adrenal sex hormones.
241
Describe the relative stimulated levels of LH/FSH in precocious pseudopuberty.
LH/FSH ratio <1. Levels in normal range.
242
What treatment is given for precocious puberty?
GnRH superagonist (suppresses pulsatile secretion)
243
Will congenital adrenal hyperplasia cause true precocious puberty or precocious pseudopuberty?
Precocious pseudopuberty
244
Give two consequences of delayed puberty.
- Osteoporosis
| - Reduced peak bone mass
245
Is delayed puberty more common in boys or girls?
Boys
246
Define delayed puberty.
Absence of secondary sexual characteristics by 14 years (girl), 16 years (boy)
247
Give three types of delayed puberty.
- Constitutional delay of growth and puberty (CDGP)
- Hypogonadotrophic hypogonadism
- Hypergonadotrophic hypogonadism
248
What causes constitutional delay of growth and puberty?
Delayed activation of hypothalamic pulse generator.
249
What will the family history often reveal in constitutional delay of growth and puberty?
Frequent family history of late menarche (mother/sister) or delayed growth spurt (father).
250
What can hypogonadotrophic hypogonadism also be known as?
Secondary hypogonadism
251
Name a syndrome which can cause hypogonadotrophic hypogonadism.
Kallmann’s syndrome
252
What is a common feature of Kallmann’s syndrome?
Anosmia (no smell)
253
Why is GnRH not released properly in Kallmann’s syndrome?
Failure of migration of GnRH neurones.
254
What are four mechanisms which can cause hypogonadotrophic hypogonadism?
- Failure of GnRH neurone migration
- Failure of GnRH synthesis/release
- Failure of GnRH action
- Failure of gonadotropin synthesis
255
What is the most common cause of delayed puberty in both sexes?
Constitutional delay in growth and puberty
256
What is another name for hypergonadotrophic hypogonadism?
Primary hypogonadism
257
Give two syndromes which can cause hypergonadotrophic hypogonadism.
- Klinefelter’s Syndrome (47XXY)
| - Turner’s Syndrome (45XO)
258
Give six features of Klinefelter’s syndrome.
- Azoospermia
- Gynaecomastia
- Reduced secondary sexual hair
- Osteoporosis
- Tall stature
- Reduced IQ in 40%
259
Give six features of Turner’s syndrome.
- Short stature
- Oedema of hands/feet at birth
- CV malformations
- Renal malformations
- Recurrent otitis media
- Distinct physical features
260
Give four indications for investigation in girls with delayed puberty.
- Lack of breast development (13yrs)
- >5yrs between breast development and menarche
- Lack of pubic hair (14yrs)
- Absent menarche (15-16yrs)
261
Give three indications for investigation in delayed puberty in boys.
- Lack of testicular enlargement (14yrs)
- Lack of pubic hair (15yrs)
- >5yrs to complete genital enlargement
262
What four laboratory tests should be carried out to test for delayed puberty?
- Complete RBC count, U&E, renal, LFT, Coeliac Ab
- LF, FSH, Testosterone, Oestradiol
- Thyroid, prolactin, DHEA-S, ACTH, cortisol
- Karyotyping & GnRH stimulation test
263
What replacement therapy are females with delayed puberty usually given?
Gradual oestrogen, with the eventual addition of progesterone.
264
What replacement therapy are males with delayed puberty usually given?
Gradual testosterone
265
Which cells do craniopharyngiomas arise from?
Squamous epithelial remnants of Rathke’s pouch
266
Is a craniophryngioma benign or malignant?
Benign, although it can infiltrate surrounding tissues.
267
Give five consequences of a craniopharyngioma.
- Raised ICP
- Visual disturbances
- Growth failure
- Pituitary hormone deficiency
- Weight increase
268
What is Rathke’s cyst derived from?
Remnants of Rathke’s pouch
269
Describe the histology of a Rathke’s cyst.
Single layer of epithelial cells with mucoid, cellular, or serous fluid.
270
What are the typical presentations of a Rathke’s cyst?
- Headache/hydrocephalus
| - Amenorrhoea/hypopituitarism
271
What is the most common tumour of the pituitary region after a pituitary adenoma?
Meningioma
272
How do patients typically present with a meningioma?
- Loss of visual acuity
- Endocrine dysfunction
- Visual field defects
273
Briefly describe lymphocytic hypophysitis.
Inflammation of the pituitary gland due to an autoimmune reaction.
274
Give three types of lymphocytic hypophysitis.
- Lymphocytic adenohypophysitis
- Lymphocytic infundibuloneurohypophysitis
- Lymphocytic panhypophysitis
275
What is the preferred imaging method for the pituitary gland?
MRI
276
What is measured when testing thyroid function?
Free T4 and TSH
277
How is the gonadal axis tested in men?
Measure 0900h fasted testosterone and LH/FSH
278
How is the HPA axis tested?
Measure 0900h cortisol and ACTH, and do a synacthen test
279
How is the GH/IGF-1 axis tested?
Stimulation tests (insulin stress test / glucagon test)
280
How is prolactin tested?
Via a cannula (prolactin is released in stress (potentially of venipuncture))
281
How is ADH release tested?
Water deprivation test
282
Give four consequences of growth hormone deficiency.
- Short stature
- Abnormal body composition
- Decreased muscle mass
- Poor quality of life
283
What is the treatment for growth hormone deficiency?
Growth hormone
284
Give four consequences of LH/FSH deficiency.
- Hypogonadism
- Decreased sperm count
- Infertility
- Menstruation problems
285
How is LH/FSH deficiency treated in males and females?
```
Males = testosterone
Females = oestradiol with or without progesterone
```
286
How is hypothyroidism treated?
Levothyroxine
287
Give two consequences of ACTH deficiency.
- Adrenal failure
| - Decreased pigmentation
288
What will the blood results be for a patient with primary hypothyroidism?
Low T4
| Raised TSH
289
What will the blood results be for a patient with hypopituitary thyroid dysfunction?
Low T4
| Normal/Low TSH
290
What will the blood results be for a patient with Graves’ disease?
High T4
| Suppressed TSH
291
What will the blood results be for a patient with a TSHoma?
High T4
| Normal/high TSH
292
What will the blood results be for a patient with thyroid hormone resistance?
High T4
| Normal/high TSH
293
What will the blood results be for a patient with primary hypogonadism (male)?
Low testosterone
| High LH/FSH
294
What will the blood results be for a patient with hypopituitary gonadal dysfunction (male)?
Low testosterone
| Normal/low LH/FSH
295
What will the blood results be for a patient with anabolic use (male)?
Low testosterone
| Suppressed LH
296
What will the blood results be for a patient before puberty (female)?
Low/undetectable oestradiol
| Low LH/FSH (FSH>LH)
297
What will the blood results be for a patient during puberty (female)?
Oestradiol increased
| Pulsatile LH increased
298
What will the blood results be for a patient post menarche (female)?
Oestradiol increase throughout cycle.
| Mid-cycle surge of LH/FSH.
299
What will the blood results be for a patient with primary ovarian failure / menopause (female)?
Low oestradiol
| High LH/FSH (FSH>LH)
300
What will the blood results be for a patient with hypopituitary gonadal dysfunction (female)?
Low oestradiol
| Normal/low LH/FSH
301
What will the blood results be for a patient with primary adrenal insufficiency?
Low cortisol
High ACTH
Poor response to synacthen
302
What will the blood results be for a patient with hypopituitary adrenal insufficiency?
Low cortisol
Low/normal ACTH
Poor response to synacthen
303
What will the water deprivation test results be for a patient with cranial diabetes insipidus?
Plasma osmolality increases and then decreases after administration of desmopressin.
Urine osmolality stays the same but rises after administration of desmopressin.
304
What will the water deprivation test results be for a patient with nephrogenic diabetes insipidus?
Plasma osmolality continues to increase even after desmopressin administration.
Urine osmolality does not rise even after administration of desmopressin.
305
Why doesn't ketoacidosis occur in people with type 2 diabetes?
Even low levels of insulin can suppress unrestrained lipolysis.
306
Describe the paracrine signalling in the islets of the pancreas.
Local insulin suppresses glucagon and local glucagon suppresses insulin.
307
How do blood glucose levels rise in the fasting state?
Glucose is released from the liver via glycogenolysis and gluconeogenesis.
308
Which tissues receive glucose in the fasting state?
- Insulin-independent tissues
- Brain
- Red blood cells
309
What do muscles use as fuel in the fasting state?
Free fatty acids
310
Name four hormones that act in opposite ways to insulin.
- Glucagon
- Adrenaline
- Cortisol
- Growth hormone
311
Give three roles of glucagon.
- Increase hepatic glucose output
- Reduce peripheral glucose uptake
- Stimulate release of gluconeogenic precursors
312
What is the overall name for monogenic causes of diabetes?
Maturity onset diabetes of the young (MODY)
313
Give five mutations or types of MODY.
- HNF1A
- HNF4A
- Glucokinase mutation
- Permanent neonatal diabetes
- Maternally inherited diabetes and deafness
314
What treatment usually works best for HNF1A diabetes?
Sulfonylurea treatment
315
What treatment is usually given in glucokinase mutation diabetes?
No treatment is usually required.
316
Which mutations occur in permanent neonatal diabetes?
Mutations occur to the Kir6.2 and SUR1 subunits of the beta cell metabolic potassium channel.
317
Give three signs associated with permanent neonatal diabetes.
- Small baby
- Epilepsy
- Muscle weakness
318
Describe the pathogenesis of maternally inherited diabetes and deafness.
Mutation in mitochondrial DNA results in loss of beta cell mass.
319
Give four clinical features of MODY.
- Parent affected
- Absence of autoantibodies
- Sensitive to sulfonylurea
- Evidence of non-insulin dependence
320
Describe lipodystrophy diabetes.
Selective loss of adipose tissue associated with insulin resistance, dyslipidaemia, hepatic steatosis, hyperandrogenism, and PCOS.
321
Describe diabetes causes by an acute disease of the exocrine pancreas.
Usually transient hyperglycaemia due to increased glucagon secretion.
322
What is chronic pancreatitis commonly caused by?
Alcohol
323
How does chronic pancreatitis cause diabetes?
- Altered secretions
| - Formation of proteinaceous plugs that block ducts and act as foci for calculi formation
324
What are three disorders of depositions that can cause diabetes?
- Hereditary haemochromatosis
- Amyloidosis
- Cystinosis
325
How does pancreatic neoplasia cause diabetes?
Pancreatic resection removes insulin and glucagon function.
326
How does cystic fibrosis lead to diabetes?
Viscous secretions lead to duct obstruction and fibrosis.
327
Give three ways that insulin can improve cystic fibrosis.
- Improves body weight
- Reduces infection
- Improves lung function
328
Give three endocrine causes of diabetes.
- Acromegaly
- Cushing's syndrome
- Pheochromocytoma
329
Give four drugs that can induce diabetes.
- Glucocorticoids
- Thiazides
- Protease inhibitors (HIV)
- Antipsychotics
330
Define diabetes.
A disorder of carbohydrate metabolism characterised by hyperglycaemia.
331
What are the two general categories of diabetes complications?
Microvascular and macrovascular
332
Give three macrovascular complications of diabetes.
- Stroke
- Cardiovascular disease
- Peripheral vascular disease
333
Give three microvascular complications of diabetes.
- Diabetic retinopathy
- Diabetic nephropathy
- Diabetic peripheral neuropathy
334
What is the commonest form of diabetic neuropathy?
Distal symmetrical polyneuropathy
335
What percentage of patients with diabetes are affected by diabetic neuropathy?
30-50%
336
What is the typical pattern of sensory loss in diabetic neuropathy?
Glove and stocking
337
What are the two common symptoms of diabetic neuropathy?
Pain
| Insensitivity
338
Give six consequences of autonomic diabetic neuropathy.
- Orthostatic hypotension
- Gastroparesis
- Diarrhoea
- Constipation
- Incontinence
- Erectile dysfunction
339
Give the six steps leading to diabetic amputation.
1. Neuropathy/vascular
2. Trauma
3. Ulceration
4. Failure to heal
5. Infection
6. Amputation
340
Why do people with diabetes often get dry skin on their feet?
Autonomic neuropathy results in decreased sweating, leading to dry skin.
341
What are the two symptoms of peripheral vascular disease?
- Intermittent claudication
| - Rest pain
342
Give four signs of peripheral vascular disease in a diabetic patient.
- Diminished/absent pedal pulses
- Coolness of feet and toes
- Poor skin and nails
- Absence of hair on feet and legs
343
What three treatments are used for peripheral vascular disease in diabetes?
- Quit smoking
- Walk through the pain
- Surgical intervention
344
Give five factors that increase a patients’ risk of diabetic retinopathy.
- Long duration diabetes
- Poor glycaemic control
- Hypertensive
- On insulin treatment
- Pregnancy
345
What three mechanisms cause damage in diabetic retinopathy?
- Microaneurysms
- Leakage
- Ischaemia
346
How do microaneurysms occur in diabetic retinopathy?
Pericyte and smooth muscle loss result in aneurysms adjacent to or upstream of capillary non-perfusion.
347
Give three ways that leakage occurs in diabetic retinopathy.
- Basement membrane thickening
- Pericyte loss
- Reduced junctional complexes with endothelial cells
348
Why are microvessels formed in diabetic retinopathy?
Ischaemia or occlusion results in proliferation.
349
How does ischaemia occur in diabetic retinopathy?
Loss of pericytes, and endothelial cells respond by increasing turnover, resulting in thickening.
350
How does occlusion occur in diabetic retinopathy?
Glial cells grow down the capillaries.
351
What is the hallmark of diabetic nephropathy?
Development of proteinuria
352
Give two risk factors for developing diabetic nephropathy?
- Poor blood pressure control
| - Poor blood glucose control
353
Give the four steps leading to diabetic nephropathy.
1. Glomerulus changes (thicker basement membrane)
2. Increase of glomerular injury
3. Filtration of proteins
4. Diabetic nephropathy
354
How long after diagnosis of type 1 diabetes does microalbuminaemia typically occur?
5-10 years
355
How long after the diagnosis of type 2 diabetes does microalbuminaemia typically occur?
It can be present at the time of diagnosis.
356
Give five strategies for the treatment of diabetic nephropathy.
- Blood pressure control
- Glycaemic control
- ACEi
- Proteinuria control
- Cholesterol control
357
Give two decisions that must be made when choosing insulin treatment for someone with diabetes.
- Basal or rapid-acting
| - Human or analogues
358
Describe how injected insulin differs from physiological insulin secretion.
Levels rise slower and remain below normal physiological levels, and levels do not drop as low as normal baseline.
359
What is the best insulin treatment regime for type 1 diabetes?
Intensive basal-bolus
360
When is the insulin bolus given in type 1 diabetes and how much is injected?
Bolus is given just before a meal and amount is adjusted according to meal content.
361
What is the purpose of giving basal insulin in diabetes?
Controls blood glucose between meals and during the night.
362
How long does it usually take for basal insulin analogues to reach steady state?
1-2 days
363
What percentage of people with type 2 diabetes require insulin after 10 years?
50%
364
What is the usual schedule for insulin injections for type 2 diabetes?
Basal insulin at bedtime and occasionally prandial insulin for biggest meal of the day.
365
Give three possible insulin regimes for type 2 diabetes.
- Once daily basal insulin
- Twice daily mix insulin
- Basal-bolus therapy
366
What are the side effects of insulin?
Hypoglycaemia and weight gain
367
Give six possible mechanisms for non-insulin treatments for type 2 diabetes.
- Lifestyle intervention
- Sensitise
- Replace
- Secrete
- Excrete
- Bariatric surgery
368
What is the purpose of sensitisation treatment in type 2 diabetes?
Help the body to respond better to its own insulin.
369
Give two examples of sensitisation treatment in type 2 diabetes.
- Metformin
| - Pioglitazone
370
What is the purpose of replacement treatment in type 2 diabetes?
Inject insulin to promote uptake/storage of glucose in liver and muscle.
371
What is the purpose of lifestyle interventions to treat type 2 diabetes?
- Prevent or stall development of T2DM
| - Prevent or reduce associated complications
372
What is the purpose of secretion treatment for type 2 diabetes?
Stimulate the pancreas to secrete more insulin.
373
Give three examples of stimulatory treatments for type 2 diabetes.
- Sulfonylureas
- DPP-4 inhibitors
- GLP-1 receptor agonists
374
What is the purpose of excretion treatments for type 2 diabetes?
Remove excess glucose load
375
Give an example of an excretion treatment for type 2 diabetes.
SGLT2 inhibitors
376
Give three roles of metformin.
- Decreases gluconeogenesis
- Decreases intestinal absorption of glucose
- Increases peripheral glucose uptake and utilisation
377
What are incretins?
Hormones secreted by intestinal endocrine cells in response to nutrient intake.
378
Give three roles of incretins.
- Stimulate glucose-dependent insulin secretion
- Post-prandial glucagon suppression
- Slowing of gastric emptying
379
What is dipeptidyl peptidase 4?
Enzyme present in vascular endothelial lining which inactivates the incretin hormones GIP and GLP-1.
380
What is the role of DPP-4 inhibitors?
Enhance the effects of GIP and GLP-1.
381
What group of drugs does pioglitazone belong to?
Thiazolidinediones (TZD)
382
What are the benefits of TZDs in treating diabetes?
Low risk of hypoglycaemia and positive effects on biomarkers.
383
What are the disadvantages of using TZDs to treat diabetes?
Increased CV risk, lipid abnormalities, weight gain.
384
What is the role of TZDs?
Enhance tissue sensitivity to insulin and reduce gluconeogenesis.
385
What is the role of SGLT2 inhibitors?
Prevents glucose reabsorption in proximal convoluted tubule.
386
Explain one side effect of SGLT2 inhibitors.
Cause glycosuria, leading to thrush.
387
Name a dopamine agonist which is used as a medical treatment.
Cabergoline
388
How should normal urine osmolality relate to serum osmolality.
Urine osmolality should be double serum osmolality.
389
Which diabetes medication can cause weight loss?
Metformin
