Endocrinology Flashcards
1
Q
Describe endocrine action
A
Blood-borne, acts on distant sites
2
Q
Describe paracrine action
A
Acts on adjacent cells
3
Q
Describe autocrine action
A
Feedback on same cell that secreted the hormone
4
Q
Give examples of fat-soluble hormones
A
-Steroids
-Thyroid hormones
5
Q
Give examples of water-soluble hormones
A
-Peptides
-Monoamines
6
Q
Describe 4 properties of water-soluble hormones
A
-Unbound
-Bind to surface receptor
-Short half-life
-Fast clearance
7
Q
Describe 4 properties of fat-soluble hormones
A
-Protein bound
-Diffuse into cell
-Long half-life
-Slow clearance
8
Q
What are the 4 hormone classes?
A
-Peptides
-Amines
-Iodothyronines
-Cholesterol derivatives + steroids
9
Q
How are peptide hormones stored?
A
-Stored in secretory granules
10
Q
How are peptide hormones released?
A
-Released in pulses/bursts
11
Q
How are peptide hormones cleared?
A
-Cleared by tissue/circulating enzymes
12
Q
What is the formation pathway for epinephrine?
A
Phenylalanine->Tyrosine->L-DOPA->Dopamine->Norepinephrine->Epinephrine
13
Q
Describe thyroid hormone properties
A
-Not water soluble
-99% water bound
14
Q
How are iodothyronines formed?
A
Iodine incorporated on tyrosine molecule
15
Q
What is the base for thyroid hormone synthesis?
A
Colloid
16
Q
How are T3 + T4 formed + where are they stored?
A
Formed by conjugation of iodothyronines
Stored in colloid
17
Q
What are the 3 hormone receptor locations + what type of hormone acts there?
A
-Cell membrane-peptide
-Cytoplasm-steroid
-Nucleus-thyroid
18
Q
What class of hormone is vit D?
A
Cholesterol derivative
19
Q
What do adrenocortical + gonadal steroids do after entering cells
A
Pass into nucleus
-Become active metabolite
-Bind to cytoplasmic receptor
20
Q
How do adrenocortical + gonadal steroids become inactivated?
A
Reduced + oxidised, or conjugated to glucoronide and sulphate groups in the liver
21
Q
How do steroid hormones work?
A
-Diffuses through plasma membrane + binds to receptor
-Receptor-hormone complex enters nucleus
-Complex binds to GRE
-Binding initiates transcription of gene to mRNA
-mRNA directs protein synthesis
22
Q
How can hormones be released?
A
Continuously or pulsatile
23
Q
In what 3 ways can hormone release be stimulated?
A
-Humoral stimulus (change in levels of ions/nutrients)
-Neural stimulus-neural input
-Hormone stimulus-another hormone causes release
24
Q
Name 3 hormones with diurnal rhythms
A
-Cortisol
-Prolactin
-GH
25
Name 5 ways in which hormone action can be controlled
-Hormone metabolism
-Hormone receptor induction/down regulation
-Synergism
-Antagonism
26
How does hormone metabolism control hormone action?
Increased metabolism to reduce function
27
How does hormone synergism control hormone action?
Combined effects of 2 hormones causes amplification
28
How does hormone antagonism control hormone action?
One hormone can oppose another
29
Where are oxytocin + ADH synthesised?
Hypothalamic neurons
30
Where are oxytocin + ADH stored?
Posterior pituitary
31
What hormones are produced in the anterior pituitary + where in the body do they act?
-TSH-thyroid
-ACTH-adrenal cortex
-FSH + LH-testes + ovaries
-GH-entire body
-Prolactin-mammary glands
32
What can pituitary dysfunction cause?
-Tumour mass effects
-Hormone XS
-Hormone deficiency
33
How does GH work + what does it act on?
-Acts on liver to produce IGFs
34
What effect does GH have?
-Increased cartilage formation + skeletal growth
-Increased protein synthesis, cell growth + proliferation
35
What are the direct metabolic effects of GH?
-Fat metabolism-increases fat breakdown + release
-Carb metabolism-increases blood glucose
36
Describe the hypothalamic-pituitary-thyroid axis
-Hypothalamus releases TRH which acts on anterior pituitary
-This releases TSH which causes thyroid to release hormones + positive feedback on hypothalamus
37
Where is T4 converted to T3?
Liver + muscle
38
What does TH do?
-Accelerates food, carb + fat metabolism
-Increases protein synthesis
-Increases ventilation rate
-Increases CO + HR
-Increases growth rate
-Helps foetal + postnatal brain devlopment
39
Where are the adrenal glands?
On top of kidneys
40
What are the parts of the adrenal glands?
Medulla + cortex
41
What are the layers of the adrenal cortex (out to in)?
-Zona glomerulosa
-Zona fasciculata
-Zona reticularis
42
How is BMI calculated?
weight (kg)/height (m2)
43
What is an underweight BMI?
<18.5
44
What is a normal BMI?
18.5-24.9
45
What is an overweight BMI?
25-29.9
46
What is an obese BMI?
30-39.9
47
What is a morbidly obese BMI?
>40
48
What does weight regulation depend on?
-Environment
-Genes
-Normal fat mass
-Homeostasis system
49
Where is the hunger centre of the body?
Lateral hypothalamus
50
Where is the satiety centre of the body?
Ventromedial hypothalamic nucleus
51
How does leptin work?
-Binds to leptin receptor in hypothalamus
-Switches off appetite by:
-Inhibiting NPY/AgRP neurons + activating POMC neurons
52
What does peptide YY do?
Binds to inhibitory NPY receptors + inhibits gastric motility-reduces appetite
53
What secretes peptide YY?
Neuroendocrine cell sin ileum, pancreas + colon
54
What does CCK do?
Delays gastric emptying, contracts gallbladder + insulin release + via vagus-satiety
55
Which hormone causes satiety via the vagus?
CCK
56
What does ghrelin do?
-Stimulates release of GH + causes appetite
57
Where is ghrelin expressed?
Stomach
58
Name 4 hunger hormones that integrate with the hypothalamus
-NPY - Neuro peptide Y
-AgRP - Agouti-related peptide
-POMC - Pro-opiomelanocortin
-CART - cocaine and amphetamine regulated
transcript
59
How do leptin + insulin increase satiety + reduce appetite?
-Stimulate POMC/CART neurons
-Increases CART + alpha-MSH levels
-Inhibit NPY/AgRP neurons
-Decreases NPY + AgRP levels
60
How does ghrelin increase appetite?
-Stimulates NPY/AgRP neurons
Increases NPY + AgRP secretion
61
What are hunger hormone levels like in the fasted state? (NPY, glucose, insulin, ghrelin, leptin, alpha MSH, AgRP)
-High NPY
-Low glucose
-Low insulin
-High ghrelin
-Low leptin
-Low alpha MSH
-High AgRP
62
What 4 effects do incretins have?
-Blunting of glucagon
-Stimulation of beta cells to produce insulin
-Improve satiety
-Decrease gastric motility
63
What 4 things happen 5-10 mins after eating in a normal, healthy human?
-Glucose levels rise
-Stimulates insulin secretion
-Glucagon suppressed
-Lipolysis suppressed + non-esterified fatty acid levels fall
64
Where does ingested glucose go in a healthy human?
-40% to liver
-60% to periphery, mostly muscle
to replenish glycogen stores
65
What cells secrete insulin?
Beta cells in Islets of Langerhans in pancreas
66
What cells secrete glucagon?
Alpha cells in Islets of Langerhans in pancreas
67
What does insulin do?
Helps convert glucose into glycogen stores-reduces blood glucose
68
What does glucagon do?
Helps break down glycogen stores when blood glucose levels are low
69
What is the benefit of paracrine 'crosstalk' between alpha + beta cells?
Physiological response to the release of one e.g. local insulin release inhibits glucagon, this is lost in diabetes
70
How does glucose cause the release of insulin from beat cells?
-Glucose enters cell through GLUT2 transporter + is metabolised to ATP
-ATP binds to K+ channels + causes build up of K+
-This activates Ca+ channels and Ca+ rushes into the cell
-Ca+ activates vesicles which release insulin
71
Name 3 other hormones with similar effects to glucagon
-Adrenaline
-Cortisol
-GH
72
Define diabetes mellitus
A disorder of carbohydrate metabolism characterised by hyperglycaemia
73
What can untreated diabetes mellitus lead to?
DKA - diabetic ketoacidosis
-HHS - hyperosmolar hyperglycaemic state
74
Name 5 key complications of untreated diabetes
-Diabetic retinopathy-vision loss + cataracts
-Diabetic nephropathy-CKD
-Stroke
-CVD
-Diabetic neuropathy-foot ulcers
75
Which type of diabetes includes gestational + medication induced?
Type 2
76
Name the 6 types of diabetes
-Type 1
-Type 2
-MODY (maturity onset diabetes of youth) aka monogenic
-Pancreatic diabetes
-Endocrine diabetes (acromegaly/Cushings)
-Malnutrition related
77
What causes type 1 diabetes?
-Autoimmune destruction of Beta cells
78
What antigen on Beta cells causes them to be targeted + destroyed in type 1 diabetes?
HLA antigens
79
What is chronic insulitis?
A chronic cell mediated immune process that leads to the destruction of beta cells + therefore reduced/stopped production of insulin
80
What is the first line Tx for type 2?
Metformin
81
Name 5 alternative Txs for type 2 (not metformin)
-Sulphonylureas
-DPP-IV inhibitors
-GLP 1 analogues
-SGLT-2 inhibitors
-Glitazones
82
Why doesn't diabetic ketoacidosis happen in type 2?
-Rare as normally still have low levels of insulin suppressing catabolism + preventing ketogenesis
83
Name 3 causes of impaired insulin secretion in type 2?
-Lipid deposition in pancreatic islets stop normal secretion of insulin
-Also genetic predisposition to abnormalities in secretion
-Hyperglycaemia could also cause glucotoxicity + inhibit secretion
84
What are the types of insulin given called?
-Basal
-Bolus
85
What does basal insulin do?
Long-acting, should control blood glucose between meals + at night
86
What does bolus insulin do?
Given pre-meal, rapid acting to mimic normal physiology
87
Name the 3 most common approaches to insulin delivery schedules for diabetes
-Once-daily basal insulin (type 2)
-Twice-daily mix-insulin (type 1 + 2)
-Basal-bolus therapy (mostly type 1, some type 2)
88
What are the disadvantages of basal insulin with type 2?
-Doesn't cover meals
-Best with long-acting insulin analogues-expensive
89
What are the advantages of basal insulin with type 2?
-Simple
-Less chance of hypos at night
90
What are the disadvantages for pre-mixed insulin?
-Not physiological
-Need constant meal + exercise pattern
-Higher risk nocturnal hypos
91
What are the 3 classes of hypoglycaemia?
-Lvl 1 - plasma glucose <3.9mmol, no symptoms
-Lvl 2 - PG <3
-Lvl 3-impaired cognitive function, assistance required
92
What are the pathophysiological effects of hypos on the brain?
-Blackouts
-Seizures
-Comas
-Psychological effects
93
What are the pathophysiological musculoskeletal effects of hypos?
-Falls
-Driving accidents
-Fractures
-Dislocations
94
What are the pathophysiological effects of hypos on the heart?
-Increased risk of MI
-Cardiac arrhythmias
95
What are the pathophysiological effects of hypos on the circulation?
-Inflammation
-Blood coagulation abnormalities
-Endothelial dysfunction
96
What are the autonomic symptoms of a hypo?
-Trembling
-Palpitations
-Sweating
-Anxiety
-Hunger
97
What are the neuroglycopenic symptoms of a hypo?
-Difficulty concentrating
-Confusion
-Weakness
-Drowsiness
-Vision changes
-Difficulty speaking
98
What are the non-specific symptoms of a hypo?
-Nausea
-Headache
99
Name 6 causes of hypoglycaemia
-Use of drugs/alcohol
-Sleeping
-Increased physical activity
-Increasing age
-Long duration diabetes
-Tight glycaemic control with repeated episodes of non-severe hypos
100
What are the 5 steps for treating hypos?
-Recognize symptoms
-Confirm need for Tx
-Treat with 15g fast-acting carbs
-Retest in 15 mins, check BG >4mmol/l + retreat if needed
-Eat a long-acting carb to prevent recurrence
101
How do you calculate corrected calcium?
Total serum calcium + 0.02 * (40-serum albumin)
102
What are the consequences of hyposcalcaemia?
-Paraesthesia
-Muscle spasm
-Seizures
-Basal ganglia calcification
-Cataracts
-ECG abnormalities
103
Name 2 signs associated with hypocalcaemia
-Chvostek's
-Trousseau's
104
What are the causes of hypocalcaemia?
-Vit D deficiency
-Hypoparathyroidism following surgery/radiation/genetic causes/immunodeficiency/magnesium deficiency
105
Name 5 symptoms of hypercalcaemia
-Thirst
-Polyuria
-Nausea
-Constipation
-Confusion->coma
106
Name 3 consequences of hypercalcaemia
-Renal stones
-ECG abnormalities e.g. short QT
107
What are the causes of hypercalcaemia?
-Malignancy (bone metastasis, myeloma, lymphoma)
-Primary hyperparathyroidism (with malignancy makes up 90%)
-Adrenal insufficiency
-Immobilisation etc
108
What is pseudoparathyroidism?
Resistance to PTH-end organs not responding but PTH produced + released normally
109
What is the effect of PTH on calcium?
Increases reabsorption
110
What is the effect of PTH on phosphate?
Decreases phosphate
111
What is the effect of PTH on bones?
Increases bone resorption, remodelling + formation
112
What are the consequences of primary hyperparathyroidism?
-Bone conditions e.g. osteoporosis
-Kidney stones
-Confusion
-Constipation
-Acute pancreatitis
113
What is the rhyme for symptoms of hyperparathyroidism?
-Bones-osteoporosis + osteitis fibrosa cystica
-Kidney stones
-Psychic groans-confusion
-Abdominal moans-constipation + pancreatitis
114
How does the anterior pituitary receive blood?
Through a portal venous circulation from the hypothalamus
115
What is the HPA axis?
Interaction between hypothalamus, pituitary + adrenal glands
116
What hormones are released by the anterior pituitary?
-TSH
-ACTH
-FSH
-LH
-GH
-Prolactin
117
What hormones does the posterior pituitary release?
-Oxytocin
-ADH
118
Describe the 3 steps of the thyroid axis
-Hypothalamus releases TRH
-TRH stimulates an. pituitary to release TSH
-TSH stimulates thyroid to release T3 + T4
119
How do the hypothalamus + anterior pituitary react to high levels of T3 + T4?
They suppress release of TRH + TSH-less T3 + T4 released
120
In what manner is cortisol released?
-In pulses throughout day + in response to stress
-Diurnal variation-peaks in early morning, lowest in evening prompting sleep
121
What is TRH?
Thyrotropin-releasing hormone
122
What is TSH?
Thyroid-stimulating hormone
123
What is T3?
Triiodothyronine
124
What is T4?
Thyroxine
125
What is CRH + what releases it?
-Corticotropin-releasing hormone
-Released by hypothalamus
126
What are the 3 steps of the adrenal axis?
-Hypothalamus releases CRH
-CRH stimulates ant pituitary to release ACTH
-ACTH stimulates adrenal glands to release cortisol
127
Name 5 actions of cortisol on the body
-Increased alertness
-Immune inhibition
-Bone formation inhibition
-Raised blood glucose
-Increased metabolism
128
What are the 3 steps of the GH axis?
-Hypothalamus produces GHRH
-GHRH stimulates pituitary to release GH
-GH stimulates liver to release IGF-1
129
Where is PTH released from?
4 parathyroid glands situated at 4 corners of thyroid gland
130
What is PTH released in response to?
-Low calcium
-Low magnesium
-Low phosphate
131
What does PTH do?
-Increases activity + number osteoclasts
-Stimulates Ca reabsorption in kidneys
-Stimulates kidneys to convert vit D to calcitriol
-All of these increase serum calcium
132
What 3 things can pituitary tumours cause?
-Pressure on local structures e.g. optic nerve
-Pressure on normal pituitary e.g. hypopituitarism
-Functioning tumour
133
Give 3 examples of functioning pituitary tumours
-Prolactinoma
-Acromegaly
-Cushing's Disease
134
What are 4 local symptoms of a pituitary tumour?
-Headaches
-Visual field defects
-Cranial nerve palsies + temporal lobe epilepsy
-CSF rhinorrhoea
135
How do prolactinomas present?
-More common in women
-Loss of libido
-Visual field defect
Present with galactorrhoea/amenorrhoea/infertility
136
How are prolactinomas treated?
Dopamine agonist
137
What is Cushing's syndrome?
Prolonged high levels of glucocorticoids in the body
138
What is Cushing's disease?
A pituitary adenoma secreting XS ACTH which stimulates XS cortisol release
139
What kinds of medication can cause Cushing's?
Exogenous corticosteroids e.g. prednisolone or dexamethasone
140
How does Cushing's present on inspection?
-Round face
-Central obesity
-Abdominal striae (stretch marks)
-Enlarged fat pad on upper back
-Proximal limb muscle wasting
-Hyperpigmentation of the skin due to high ACTH
141
What is the pneumonic for causes of Cushing's?
CAPE
142
What are the causes of Cushing's Syndrome?
C-Cushing's disease
A-adrenal adenoma
P-paraneoplastic syndrome
E-exogenous steroids
143
What is acromegaly?
The result of XS GH
144
What is the most common cause of unregulated GH secretion?
Pituitary adenomas
145
How would acromegaly present on inspection?
-Frontal bossing (prominent forehead + brows)
-Coarse, sweaty skin
-Large nose, tongue, hands, feet
-Large protruding jaw
146
What testicular volume indicates puberty?
>3ml
147
What is thelarche?
Breast development
148
What ovarian volume suggests start of puberty?
>2.8ml
149
How does the vagina change in a pubertal/adult?
-Thickening epithelium
-pH change from neutral to acidic 3.8-4.2
-Secretion of whitish discharge in mths pre-menarche
150
What effects does adrenarche have?
-Mild advanced bone age
-Axillary hair
-Oily skin
Mild acne
-Body odour
151
Who most commonly has delayed puberty?
Boys
152
When should you investigate delayed puberty in girls?
-No BD by 13
-More then 5yrs between BD + menarche
-No PH by 14
-No menarche by 15/16
153
When should you investigate delayed puberty in boys?
-No testicular development by 14
-No pH by 15
154
What is CDGP?
Constitutional delay of growth + puberty-extremes of normal physiologic variation, most common with family history of short stature + delayed puberty
155
Give an example of a hypogonadotropic hypogonadism syndrome
Kallman syndrome
156
Give 2 examples of hypergonadotropic hypogonadism syndromes
-Klinefelter's syndrome
-Turner's syndrome
157
What is the karyotype for Turner's?
45,X0
158
What are the symptoms of Turner's?
-Oedema of dorsa of hands, feet, neck at birth
-Webbing of neck
-Renal malformations e.g. horseshoe kidney
-Short stature
-recurrent otitis media
159
What is the karyotype for Klinefelter's?
47,XXY
160
What are the symptoms of Klinefelter's?
-Azoospermia
-Gynaecomastia
-Reduced PH
-Osteoporosis
-Tall stature
-Reduced IQ (in 40%)
161
Why does diabetes insipidus occur?
-Lack of ADH
-Lack of response to ADH
162
What is another name for ADH?
Vasopressin
163
What are the presenting features of diabetes insipidus?
-Polyuria
-Polydipsia
-Dehydration
-Postural hypotension
164
What is primary polydipsia?
When a patient has a normally functioning ADH system but drinks XS water. leading to XS urine production-not diabetes insipidus
165
What are the 2 types of diabetes insipidus?
-Nephrogenic
-Cranial
166
What is nephrogenic diabetes insipidus?
When collecting ducts of kidneys don't respond to ADH
167
What is cranial diabetes insipidus?
When the hypothalamus doesn't produce ADH for pituitary to secrete
168
Name 5 non-idiopathic causes of nephrogenic diabetes insipidus
-Meds e.g. lithium
-Genetic mutations
-Hypercalcaemia
-Hypokalaemia
-Kidney diseases e.g. PKD
169
Name 6 non-idiopathic causes of cranial diabetes insipidus
-Brain tumours
-Brain injury
-Brain surgery
-Brain infections e.g. meningitis
-Genetic mutations
-Wolfram syndrome
170
Where are vasopressin + oxytocin made?
In the paraventricular nucleus + supraoptic nucleus + transported to posterior pituitary
171
Name 2 exogenous solutes that can affect osmolality
-Alcohol
-Methanol
172
What is a normal osmolality?
282-295
173
What is the most common cause of hyponatraemia?
Too much water, rather than salt loss
174
What serum sodium indicates severe hyponatraemia?
<125mmol/l
174
What serum sodium indicates hyponatraemia?
<135mmol/l
175
What should a normal serum sodium be?
135-144mmol/l
176
What are the symptoms of hyponatraemia?
-Headache
-Irritability
-N + V
-Mental slowing
-Unstable gait/falls
-Confusion/delirium
177
What are the acute/chronic symptoms of hyponatraemia?
-Stupor/coma
-Convulsions
-Resp arrest
178
What are the 4 ways hyponatraemia can be classified?
-Biochemical-mild, moderate, severe
-Symptoms-mild, moderate, severe
-Aetiology-Hypovolaemic, euvolaemic, hypervolaemic
-Acuity of onset-acute (<48hrs), chronic (>48hrs)
179
What is SIAD?
Syndrome of Inappropriate Antidiuretic Hormone Secretion-too much ADH secreted
180
What are the signs of SIAD?
-Low osmolality
-Low plasma sodium
-Wrong conc of urine
-Normal circulating vol, no oedema
181
What are the causes of SIAD?
-CNS disorders e.g. meningitis, head injuries
-Tumours
-Drugs
-Res causes e.g. pneumonia, TB
182
How do you manage SIAD?
-Diagnose + treat underlying
-Fluid restriction <1L/24hr
-Sometime demeclocycline/vaptan
-hypertonic slaien on ITU if fitting + N+ <115mmol/l
183
What is ODS?
Osmotic demyelination syndrome-quick change in Na+ levels can cause demyelination of neurons
184
What is hypothyroidism?
Insufficient T3 + T4 (thyroid hormones)
185
What is primary hypothyroidism?
When the thyroid doesn't produce enough T3 + T4, so negative feedback is absent + more TSH is produced. Raised TSH, low T3 + T4
186
What is secondary hypothyroidism?
When the pituitary doesn't produce enough TSH, so the thyroid isn't stimulated to make T3 + T4. TSH, T3 + T4 are all low
187
What is the most common cause of hypothyroidism in the developed world?
Hashimoto's thyroiditis
188
What is Hashimoto's thyroiditis?
Autoimmune condition causing inflammation of the thyroid
189
What antibodies are associated with Hashimoto's thyroiditis?
-Anti-thyroid peroxidase (anti-TPO)
-Anti-thyroglobulin (anti-TG)
190
What is the most common cause of hypothyroidism in the developing world?
Iodine deficiency
191
Name 4 Tx's for hyperthyroidism that can cause hypothyroidism
-Carbimazole
-Proplythiouracil
-Radioactive iodine
-Thyroid surgery
192
Name an element that inhibits the production of thyroid hormones + can cause a goitre + hypothyroidism
Lithium
193
What is hypopituitarism?
Lack of pituitary hormones e.g. ACTH
194
Name 5 causes of secondary hypothyroidism
-Tumours
-Pituitary surgery
-Radiotherapy
-Sheehan's syndrome
-Trauma
195
What are the symptoms of hypothyroidism?
-Weight gain
-Fatigue
-Dry skin
-Coarse hair + hair loss
-Fluid retention
-Heavy/irregular periods
-Constipation
196
What causes Graves' disease?
TSH-R antibodies (thyroid stimulating antibodies)
197
What factors make you predisposed to thyroid conditions?
-Female
-Postpartum
-Stress
-High iodine intake
-Smoking
198
What is goitre?
Palpable + visible thyroid enlargement
199
Name 4 drugs that can cause hypothyroidism
-Iodine
-Lithium
-Thionamides
-Interferon alpha
200
What is the main Tx for hypothyroidism?
Oral levothyroxine (synthetic T4, metabolised to T3 in the body)
201
What is hyperthyroidism?
Over-production of T3 + T4 by the thyroid
202
What is thyrotoxicosis?
Effects of the abnormal + XS T3/T4 in the body
203
What causes primary hyperthyroidism?
Thyroid pathology-producing XS hormones
204
What causes secondary hyperthyroidism?
Hypothalamic/pituitary pathology causing over-production of TSH, which then stimulates the thyroid to produce too much T3/T4
205
What is subclinical hyperthyroidism?
Normal T3 + T4 levels but low TSH, symptoms are absent/mild
206
What is Graves' disease?
Autoimmune condition where TSH receptor antibodies stimulate TSH receptors on the thyroid + cause primary hyperthyroidism
207
What is another name for Plummer's disease?
Toxic multinodular goitre
208
What is Plummer's disease?
Condition where nodules develop on the thyroid gland + continuously produce XS thyroid hormones
209
In what group of patients is Plummer's disease most common?
Over 50s
210
What is exophthalmos?
Bulging of the eyes caused by Graves' disease. Inflammation, swelling + hypertrophy make eyes bulge out of sockets
211
What is pretibial myxoedema?
Discolouration + waxy appearance of skin associated with Graves' disease
212
What causes pretibial myxoedema?
Deposits of glycosaminoglycans under the skin on the front of the leg that form as a reaction to TSH receptor antibodies
213
What pneumonic can be used to remember causes of hyperthyroidism?
GIST
214
What are the causes of hyperthyroidism (using GIST)?
G-Graves' disease
I-Inflammation
S-Solitary toxic thyroid nodule
T-Toxic multinodular goitre
215
Name the 4 types of thyroiditis
-De Quervain’s thyroiditis
-Hashimoto’s thyroiditis
-Postpartum thyroiditis
-Drug-induced thyroiditis
216
What are the symptoms of hyperthyroidism?
-Anxiety + irritability
-Sweating + heat intolerance
-Tachycardia
-Weight loss
-Fatigue
-Insomnia
-Brisk reflexes on exam
217
What are the 4 specific feature of Graves' disease?
-Diffuse goitre (no nodules)
-Graves' eye disease
-Pretibial myxoedema
-Thyroid acropachy (hand swelling + finger clubbing)
218
What are the 4 types of goitre?
-Diffuse
-Multinodular
-Solitary nodule
-Dominant nodule
219
What are the 3 mechanisms for hyperthyroidism?
-XS production of hormones
-Leakage of preformed hormone from thyroid
-Ingestion of XS hormone
220
Name 4 drugs that can cause drug-induced hyperthyroidism
-Iodine
-Amiodarone
-Lithium?
-Radiocontrast agents
221
What are 3 Tx's for hyperthyroidism?
-Antithyroid drugs e.g. Carbimazole
-Radioiodine
-Surgery to remove thyroid (life-long Levothyroxien required)
222
What is the most serious side effect of thionamides such as Carbimazole used to treat hyperthyroidism?
Agranulocytosis which manifests as sore throat, fever, mouth ulcers
223
What happens to levels of thyroid hormones in the first trimester of pregnancy?
Rise in T3 + T4 production, causing inhibition of TSH
224
How can hypothyroidism affect pregnancy?
-Gestational hypertension
-Placental abruption
-Post partum haemorrhage
-Low birth weight
-Preterm delivery
-Neonatal goitre
225
How can hyperthyroidism affect pregnancy?
-Low birth weight
-Pre eclampsia
-Preterm delivery
-Risk of stillbirth/miscarriage
226
What women are most at risk of post partum thyroiditis?
Those with:
-Type 1 diabetics
-Graves' in remission
-Chronic viral hepatitis
227
How do thyroid function test ranges change during pregnancy?
Ranges are lower
228
What is a Rathke's cyst?
Single layer of epithelial cells with cyst fluid-derives from remnants of Rathke's pouch
229
What are the symptoms of a Rathke's cyst?
-Headache
-Amenorrhoea
-Hypopituitarism
-Hydrocephalus
230
What is a craniopharyngioma?
Benign tumour derived from the squamous epithelial remnants of Rathke's pouch
231
What are the symptoms of a craniopharyngioma?
-Raised ICP
-Visual disturbances
-Growth failure
-Pituitary hormone deficiency
-Weight increase
232
What can cause meningiomas?
Complications of radiotherapy
233
What are the symptoms of meningiomas?
-Visual disturbance
-Endocrine dysfunction
-Visual field defects
234
What is lymphocytic hypophysitis?
Inflammation of the pituitary gland due to an autoimmune reaction
235
What are 3 signs that a pituitary tumour is aggressive?
-Large size
-Cavernous sinus invasion
-Lobulated suprasellar margins
236
What controls the release of prolactin?
Negative control of dopamine
237
Name 4 factors that could cause a raised prolactin level
-Stress
-Drugs e.g. antipsychotics
-Stalk pressure
-Prolactinoma
238
Name 5 co-morbidities of acromegaly
-Hypertension/heart disease
-Sleep apnea
-Arthritis
-Insulin-resistant diabetes
-Cerebrovascular events + headaches
239
What 3 things would be used to diagnose acromegaly?
-Clinical features
-GH levels
-IGF-I levels
240
How is acromegaly treated?
-Trans sphenoidal pituitary surgery
-Radiotherapy
-Medical therapy e.g. dopamine agonists, somatostatin analogues, GH receptor antagonists
241
How are prolactinomas managed?
Medical Tx e.g.
-Dopamine agonists
242
What random plasma glucose indicates diabetes?
> 11.1 mmol/l
243
What fasting plasma glucose indicates diabetes?
> 7.0 mmol/l
244
What HbA1c indicates diabetes?
> 48 mmol/mol
245
Name 6 presenting features of diabetes
-Thirst
-Polyuria
-Weight loss
-Fatigue
-Hunger
-Recurrent thrush/skin/chest infections
-Blurred vision
246
Name 5 suggestive features of type 1 diabetes
-Onset in childhood/adolescence
-Lean body
-Acute onset osmotic symptoms
-Prone to ketoacidosis
-High levels of islet antibodies
247
What 3 features indicate type 1 + immediate start of insulin Tx?
-Weight loss
-Short history of severe symptoms
-Moderate/large urinary ketones
248
What is the most common ages for diagnosis of type 1?
5-15yrs
249
Name 2 viruses that may be associated with type 1 diabetes
-Coxsackie B
-Enterovirus
250
What is the normal range for blood glucose concentrations?
4.4-6.1 mmol/l
251
What is ketogenesis + when does it occur?
-Production of ketones
-Occurs when glycogen stores are exhausted so liver converts f.a. to ketones to use as fuel
252
How does type 1 diabetes cause ketoacidosis?
-Insulin not produced so glucose levels rise
-Ketones produced as fuel source instead
-Rise in ketones is so significant, kidneys can't control it anymore by buffering blood
-Ketones are acidic-causes DKA
253
What are the 3 key features of DKA?
-Ketoacidosis
-Dehydration
-Potassium imbalance
254
In what 3 scenarios can DKA occur?
-Initial presentation of type 1
-Infection/illness of existing type 1 diabetic
-Non-adherence of insulin regime in existing type 1 diabetic
255
How does type 1 cause dehydration?
-Hyperglycaemia overwhelms kidneys
-Causes glucose to leak into urine
-Glucose in urine draws water with it by osmotic diuresis
-Causes polyuria
-Causes severe dehydration + polydipsia
256
How does DKA cause potassium imbalance?
-Insulin normally drives potassium into cells
-So lack of it = high serum potassium, but low body potassium
-When insulin Tx starts, patients can develop hypokalaemia which can lead to fatal arrhythmias
257
What are the ranges for hyperglycaemia, ketosis + acidosis that indicate DKA?
-BG >11mmol/l
-Blood ketones >3 mmol/l
-pH <7.3
258
What are first-line Txs for DKA?
-Fluid resuscitation
-Insulin infusion
259
What pneumonic can be used for management of DKA?
FIG-PICK
260
What are the principles of management for DKA, using FIG-PICK?
F-fluids (IV)
I-insulin
G-glucose, monitor BG + add glucose infusion when less than 14 mmol/l
P-potassium-add K to IV + monitor
I-infection, treat underlying triggers e.g. infection
C-chart fluid balance
K-ketones, monitor blood ketones, pH + bicarbonate
261
What 3 factors must be present before Tx for DKA is stopped?
-Ketosis + acidosis resolved
-Eating + drinking
-Re-started regular subcutaneous insulin
262
What are the main complications during Tx for DKA?
-Hypoglycaemia
-Hypokalaemia
-Cerebral oedema, particularly in children
-Pulmonary oedema
263
Name 3 types of antibodies present in type 1 diabetes
-Anti-islet cell antibodies
-Anti-GAD antibodies
-Anti-insulin antibodies
264
What serum levels can be used as a measure of insulin?
Serum C-peptide
265
What is lipodystrophy + what can cause it?
-Hardening of the subcutaneous fat
-Can be caused by injecting in the same spot
266
What are the advantages of insulin pumps?
-Better BG control
-More flexibility with eating
-Less injections
267
What are the disadvantages of insulin pumps?
-Difficulties learning to use it
-Having it attached at all times
-Blockages in infusion set
-Small risk of injection
268
What does HbA1c measure?
Glycated haemoglobin-reflects average glucose levels over previous 2-3mths (RBC lifespan of 4mths)
269
Name 3 types of glucose monitor
-Capillary BG monitor (finger-prick test)
-Flash glucose monitor (sensor on skin, pass phone over to read)- 5 min lag time!
-Continuous glucose monitor (similar to flash monitors but connected to phone by bluetooth)
270
Name 3 short-term complications of insulin + BG management
-Hypoglycaemia
-Hyperglycaemia
-DKA
271
What effect can chronic hyperglycaemia have?
-Damages endothelial cells of blood vessels + makes them leaky
-Immune system dysfunction-prone to infection
272
What is a closed loop system of Tx for type 1?
AKA artificial pancreas, combination of continuous glucose monitor + insulin pump, automatic communication + adjustment of insulin
273
Name 4 macrovascular complications of poorly controlled diabetes
-Coronary artery disease
-Peripheral ischaemia-can cause foot ulcers
-Stroke
-Hypertension
274
Name 3 microvascular complications of poorly controlled diabetes
-Peripheral neuropathy
-Retinopathy
-Kidney disease, particularly glomerulosclerosis
275
Name 4 infection-related complications of poorly controlled diabetes
-UTIs
-Pneumonia
-Skin infections
-Fungal infections, particularly oral + vaginal candidiasis
276
What is MODY?
Maturity-onset diabetes of the young, monogenic diabetes
277
What is the inheritance pattern for MODY?
Autosomal dominant
278
At what age is MODY diagnosed?
<25
279
What mutations cause MODY + how do they work?
Hepatic nuclear factor (HNF) mutations alter insulin secretion, reduce beta cell proliferation
280
What is the typical presentation for MODY?
-FH
-Young age
-Non-obese
-Neonatal hypoglycaemia
281
Name 5 diseases of the exocrine pancreas that can cause diabetes
-Chronic pancreatitis
-Transient hyperglycaemia
-Hereditary haemochromatosis
-Pancreatic neoplasia
-Cystic fibrosis
282
Name 3 endocrine causes of diabetes
-Acromegaly
-Cushings
-Pheochromocytoma
283
Name 4 drugs that can cause drug-induced diabetes
-Glucocorticoids
-Thiazides
-Protease inhibitors
-Antipsychotics
284
Name 3 causes of adrenal insufficiency
-Primary-Addison's disease
-Secondary-Hypopituitarism
-Tertiary-suppression of HPA e.g. by steroids
285
What are the signs + symptoms of adrenal insufficiency?
-Fatigue
-Weight loss
-Poor recovery from illness
-Adrenal crisis
-Headache
-Pigmentation + pallor
-Hypotension
286
What family history might be indicative of adrenal insufficiency?
Autoimmunity, congenital disease
287
What past history might be indicative of adrenal insufficiency?
-TB
-Post partum bleed
-Cancer
288
How would you manage an adrenal crisis?
-Immediate hydrocortisone
-Fluid resuscitation
289
What are sick-day rules for adrenal insufficiency?
-Always carry 10 x 10mg tablets hydrocortisone
-If unwell-double dose steroids
-If vomiting take emergency injection 100mg hydrocortisone
-Go to A&E/ring ambulance
290
What levels should be checked if suspicion of adrenal insufficiency?
-Cortisol
-ACTH
291
What are the aims of type 2 diabetes treatment?
-Manage blood glucose
-Reduce risk of comorbidities
-Weight loss
292
What conditions/complications does type 2 diabetes Tx aim to manage?
-CVD
-CKD
-Microvascular complications
293
What are the 4 pillars of diabetes mellitus management?
-Glycaemic management
-Blood pressure management
-Lipid management
-Agents with cardiovascular + kidney benefit
294
Name 7 Tx options for type 2 diabetes
-Metformin
-Pioglitazone
-Insulin
-SGLT2 inhibitors
-Sulphonylureas
-DPP-4 inhibitors
-GLP-1 receptor agonists
295
How does insulin help control type 2 diabetes?
Injected insulin promotes uptake storage in the liver + muscle
296
How do SGLT2 inhibitors help control type 2 diabetes?
They remove XS glucose load
297
How do metformin + pioglitazone help control type 2 diabetes?
Help body respond better to its own insulin
298
How do sulphonylureas, DPP-4 inhibitors + GLP-1 receptors help control type 2 diabetes?
They stimulate the pancreas to secrete more insulin
299
What HbA1c level indicates pre diabetes?
42-47 mmol/l
300
What HbA1c level indicates diabetes?
48+ mmol/l
301
What are the NICE targets for HbA1c levels for new type 2 diabetics?
-48 mmol/l for new diabetics
-53 mmol/l for patients on more then one antidiabetic medication
302
What is first line Tx for type 2 DM?
Metformin
303
When does NICE recommend adding an SGLT-2 inhibitor for type 2 DM?
-If patient has existing CVD/heart failure
304
When does NICE recommend CONSIDERING adding an SGLT-2 inhibitor for type 2 DM?
QRISK score above 10%
305
Name the 4 second lien Tx's for type 2 DM
-Sulfonylurea
-Pioglitazone
-DPP-4 inhibitor
-SGLT-2 inhibitor
306
What are 3rd line Ts options for type 2 DM?
-Triple therapy - metformin + 2 second line drugs
-Insulin therapy
307
What might you do if triple therapy for DM type 2 fails and the patient's BMI is over 35 kg/m2?
Could switch one drug to a GLP-1 mimetic
308
What is a potential sig. side effect for SGLT-2 Tx?
Diabetic ketoacidosis
309
How does metformin work?
It increases insulin sensitivity + decreases glucose production
310
What kind of medication is metformin?
Biguanide
311
Name the 2 main side effects of metformin
-GI symptoms e.g. pain, nausea + diarrhoea
-Lactic acidosis
312
Give 3 examples of SGLT-2 inhibitors
-Empagliflozin
-Canagliflozin
-Dapagliflozin
313
What do SGLT-2 inhibitors do?
The SGLT-2 protein reabsorbs glucose from urine back into blood so inhibitors block this action-increases glucose excreted in urine
314
What can the use of SGLT-2 inhibitors in combination with insulin or sulfonylureas do?
It can cause hypoglycaemia
315
What are SGLT-2 inhibitors?
Sodium-glucose co-transporter 2 protein inhibitors
316
Name 6 side effects of SGLT-2 inhibitors
-Glycosuria
-Increased urine output + frequency
-Genital + urinary tract infections e.g. thrush
-Weight loss
-Diabetic ketoacidosis
-Fournier's gangrene
317
What are the main 2 side effects of SGLT-2 inhibitors?
-Lots of sugar passing through urinary tract = increased infections + genital thrush
-Diabetic ketoacidosis
318
What does pioglitazone do?
Increases insulin sensitivity + decreases liver production of glucose
319
Name 4 side effects of pioglitazone
-Weight gain
-Heart failure
-Increased risk of bone fractures
-Small increase in risk of bladder cancer
320
What do sulfonylureas do?
Stimulate insulin release from pancreas
321
Name the most common sulfonylurea
Gliclazide
322
Name 2 side effects of sulfonylureas
-Weight gain
-Hypoglycaemia
323
What are incretins?
Hormones produced by the GI tract + secreted in response to large meals, they act to reduce blood sugar
324
Name 3 ways in which incretins reduce blood sugar
-Increase insulin secretion
-Inhibit glucagon production
-Slow absorption by GI tract
325
What is the main incretin?
GLP-1 (glucagon-like peptide-1)
326
Name the enzyme that inhibits GLP-1
DPP-4
327
How do DPP-4 inhibitors help reduce blood sugar?
-DPP-4 inhibitors block action of DPP-4
-This increases incretin activity
-Incretins reduce blood sugar
328
What are the main side effects of DPP-4 inhibitors?
-Headaches
-Low risk of acute pancreatitis
329
What are GLP-1 mimetics?
Imitate action of GLP-1 (incretin that reduces blood sugar)
330
What is first line Tx for type 2 diabetics to manage hypertension?
ACE inhibitors
331
What is HHS?
Hyperosmolar hyperglycaemic state-rare, potentially fatal complication of type 2
332
What 7 symptoms does HHS present with?
-Polyuria
-Polydipsia
-Weight loss
-Dehydration
-Tachycardia
-Hypotension
-Confusion
333
Describe TSH, T3 + T4 levels for primary hyperthyroidism
TSH-Low
T3/T4-High
334
Describe TSH, T3 + T4 levels for secondary hyperthyroidism
TSH-High
T3/T4-High
335
Describe TSH, T3 + T4 levels for primary hypothyroidism
TSH-High
T3/T4-Low
336
What is carcinoid syndrome?
Release of serotonin and other vasoactive peptides from carcinoid tumour (neuroendocrine tumour)
337
How does carcinoid syndrome present?
Diarrhoea, flushing, palpitations, abdo pain, wheezing
338
How do you treat carcinoid syndrome?
-Surgical resection
-Octreotide infusion
-Somatostatin analogue
