Endocrinology Flashcards
1
Q
What is a hormone?
A
endogenous, signalling molecule released from endocrine gland travelling in the blood and binding to target cells causing a change/response
2
Q
What is the other term for the neurohypophysis?
A
Posterior pituitary
3
Q
What is the other term for the adenohypophysis?
A
Anterior pituitary
4
Q
What neurones originate in the SON and PVN of the hypothalamus and project into the posterior pituitary?
A
Magnocellular neurones
5
Q
What hormones are stored in the posterior pituitary gland?
A
OT and AVP
6
Q
Outline the blood supply to the anterior and posterior pituitary gland.
A
Superior hypophyseal artery supplies entering primary capillary plexus then hypophyseal portal veins of infundibulum and then to the secondary plexus of hypophyseal portal system Inferior hypophyseal artery supplies posterior pituitary gland by entering capillary plexus of infundibular process and leaves by posterior hypophyseal veins
7
Q
What is the venous drainage of the pituitary gland?
A
Posterior hypophyseal vein drains posterior pituitary
Anterior hypophyseal vein drains anterior pituitary
8
Q
Where is the pituitary gland located?
A
3/4cm directly between middle of the eyebrows in sphenoid bone fossa called sella turcica
9
Q
Outline the MOA of ADH in dehydration.
A
Dehydration —> plasma osmolarity increases —> osmoreceptors in hypothalamus (circumventricular organs) fire —> ADH released —> retain water by absorption at the collecting duct of the nephron in kidney —> homeostatic
10
Q
What hormones are released from the anterior pituitary gland?
A
Mnemonic: FLAT PeG
FSH
LH
ACTH
TSH
PL
GH
11
Q
What is a tropic hormone?
Give an example of a pituitary hormone that is a tropic hormone.
A
stimulates another gland to produce its hormone
FSH
LH
ACTH
TSH
12
Q
What two anterior pituitary cell types exist?
How may these be detected?
A
Eosin staining in histology
Acidophilic (pink cytoplasm):
- Sommatotrophs
- Lactotrophs
Basophilic (purple cytoplasm):
- Corticotrophs
- Thyrotrophs
- Gonadotrophs
Mnemonic: PeG is Pink
Prolactin
GH
13
Q
What is unique about somatomammotrophs?
A
degree of plasticity and under differing physiological conditions can be converted to allow production of more than one type of hormone
14
Q
What is the MOA of Tolvaptan?
A
V2 receptor non-selective antagonist binding at V2r in kidney
15
Q
What tubular protein allows retrograde movement of AQP2 vesicles towards the apical membrane along actin filaments?
A
Dynein
16
Q
Which type of cells produced GH?
A
Somatotrophs in the anterior pituitary gland
17
Q
What gene polymorphism can increase your risk of T1DM?
A
DR4-DQ8
18
Q
Where is Insulin produced?
A
ß-cells of Islets of Langerhans in Pancreas
19
Q
Outline the process of Ketogenesis.
A
Prolonged starvation with insufficient intracellular glucose, leading to exhaustion of glycogen stores which then results in ketogenesis involving lipolysis and conversion to ketones.
Three ketones:
- Acetoacetate
- ß-HB
- Acetone
20
Q
What is the clinical presentation of T1DM?
A
- Polyuria (b/c osmotic diuresis > tubular reabsorption)
- Polydipsia (fluid and electrolyte losses 2º to polyuria)
- Weight loss (fluid depletion and muscle atrophy 2º insulin deficiency)
- Fatigue
- Candida infection
- Young individual
- Blurred vision
- Nausea/ vomiting (DKA)
- Abdominal pain (DKA)
- Tachypnoea (DKA)
- Coma/ Unresponsive (DKA)
21
Q
What investigations would you order in a suspected case of T1DM and what would you expect to see?
A
- Random Plasma Glucose (RPG): ≥ 11mmol/L
- Oral Glucose Tolerance Test (OGTT): ≥11mol/L
- Fasting Plasma Glucose (FPG): ≥7mmol/L
- Serum/urine ketones: Present
- HbA1c: ≥48mmol/L (≥6.5%)
- Autoimmune markers: Positive
- C peptide (low)
22
Q
To be positive in T1DM, what value threshold should be exceeded in a RPG?
A
> 11mmol/L
23
Q
To be positive in T1DM, what value threshold should be exceeded in a FPG?
A
> 7mmol/L
24
Q
To be positive in T1DM, what value threshold should be exceeded in a OGTT?
A
> 11mmol/L
25
What is the long-term management of T1DM?
- Conservative: Physical activity/ Diet (low sugar, high in low GI carbs, sweeteners, protein)/ 3 meals/ Notify DVLA
+
- Insulin (Basal-bolus or CSII): insulin glargine (SC OD)/ insulin isophane (SC BD)/ insulin detemir (SC BD)/ insulin degludec (SC OD) + insulin lispro/ insulin aspart
26
When calculating insulin doses, how much energy is related to units of insulin?
1U insulin = 10g carbs
27
What drug may be given should postprandial hyperglycaemia persist?
Pramlintide
28
Outline how Pramlintide works?
Amylin is co-secreted with insulin to reduce postpradial glucose by: increases gastric emptying time, reduces appetite (anorexia) and reduces postprandial glucagon secretion
29
Give an example of a rapid-acting insulin.
Insulin Lispro
Insulin Aspart
30
What type of insulin is Isophane insulin?
Intermediate
31
Give an example of a long-acting insulin.
Insulin Glargine
Insulin degludex
Insulin Detemir
32
How is Insulin Glargine made?
Glycine substituted for Asparagine (N-terminal) and 2 arginine AAs added to end of beta chain thus ∆ isoelectric point = less soluble thus dissolve slowly
33
How is insulin degludec made?
Conjugation to FA (hexadecanedioic acid) -> hexamer formation
34
How is Insulin Detemir made?
FA (myristic acid) conjugated to lysine -> albumin binding = slowly dissociates
35
Give some side effects of insulin.
Oedema;
Lipodystrophy
Hypoglycaemia
36
Give 5 RFs of T2DM.
- Ageing
- Physical inactivity
- Overweight/Adiposity
- Hypertension
- Dyslipidaemia
- FHx
37
Outline the pathophysiology involved in T2DM.
- Reduced insulin sensitivity: pre-receptor (Abs/secretion defects)/receptor (volume/ affinity)/ post-receptor (IRS-1/PI3K/AKT/GLUT4) -> reduced uptake of glucose = hyperglycaemia -> increased conversion to lipid (WAT) = adiposity -> reduced HDL/ increased TGs/ increased LDL; accumulation of AGEPs/free radicals -> chronic inflammation -> macroscopic + microscopic complications of diabetes
38
What are the clinical features of T2DM?
- Fatigue
- Blurred vision
- Recurrent candida infection: vaginal/ penile/ skin folds
- Skin infection: cellulitis/abscesses
- UTI: Cystitis/ Pyelonephritis
39
What are the glucose thresholds for the following investigations:
- FPG
- RPG
- OGTT
- HbA1c
- HbA1c: ≥ 48mmol/L (6.5%)
- FPG: ≥ 7mmol/L
- RPG: ≥ 11mmol/L
- OGTT: ≥ 11mmol/L
40
What is the long-term management of a patient with T2DM?
- Conservative: diet/ physical activity/ sweeteners/ weight loss/ smoking cessation
+
- Biguanide: Metformin
±
- Antihypertensives: Lisinopril/Enalapril/ Amlodipine/ Diltiazem
+
- Lipid control: Atorvastatin/ Rosuvastatin/ Simvastatin/ Pravastatin
+
- Antiplatelets: Aspirin/ Clopidogrel
HbA1c above goal on metformin
- Metformin
+
- Hypoglycaemic drug: SGLT2i/ GLPi/ DPP4i/ Sulfonylurea/ Basal insulin
41
What is the MOA of Metformin?
Enters via OCT-1 and acts on Mt to increase AMP:ATP ratio. Activation of AMPK increases glucose transport, FA oxidation, reduces lipogenesis and reduces glycogenolysis
42
What are the side effects of Metformin?
Appetite suppression
Weight gain
Diarrhoea
43
Give an example of a Sulfonylurea.
Gliclazide
Tolbutamide
Glibenclamide
44
What is the MOA of the sulfonylureas?
Block ATP-sensitive K+ channels in ß-cells which causes ß-cell depolarisation and increased insulin secretion
45
What are the side effects of Gliclazide?
Nausea
Diarrhoea
Hypoglycaemia
Abdominal pain
46
Give an example of a GLP-1 analogue.
Exenatide
Liraglutide
47
What is the MOA of Exenatide?
Give the class of Exenatide.
Mimic GLP-1 binding at A-cells and ß-cells to cause insulin release and reduce glucagon
48
What side effects would you warn a patient about regarding commencing Exenatide?
Reduced appetite
Nausea/Vomiting
Diarrhoea
GI disorder/discomfort
Dizziness
Skin reactions
Pancreatitis
49
Which anti-diabetic medication may cause Pancreatitis?
GLP-1 Analogues such as Exenatide/Liraglutide
DPP4-i such as Sitagliptin
50
Give an example of a drug that is a DPP4-inhibitor?
Sitagliptin
Linagliptin
51
What class of drug is Sitagliptin?
DPP4-i
52
What class of drug is Sitagliptin?
DPP4-i
53
What is the MOA of Sitagliptin?
Inhibit DPP4 thus enhance endogenous incretin effects to increase insulin and decrease glucagon
54
A patient is about to commence drug trial on Sitagliptin. What side effects should you warn them about?
Headache
Pancreatitis
Hypersensitivity
55
What class of drug is Empagliflozin?
SGLT2 inhibitor
56
What is the MOA of Cangliflozin?
Inhibit Na+-Glucose transporters in PT and LoH thus giving glycosuria
57
A patient is about to commence drug treatment on Empagliflozin. What side effects would you warn them about?
Hypoglycaemia
Hypovolaemia
Skin reaction
UTI
Urosepsis
Balanoposthitis
Constipation
58
What class of drug is Pioglitazone?
Thiazolidnediones (TZD)
59
What is the MOA of Glitzone?
What class is it?
Thiazolidinedione (TZD)
PPARy agonist thus increases transcription of insulin signalling
60
What side effects would you warn a patient commencing Glitazone?
They ask you what class this drug is, what do you say?
Risk of infection
Visual impairment
Weight gain
Bone fracture
61
What anti-diabetic medication may increase the risk of bone fracture?
Thiazolidinediones (TZDs) such as Pioglitazone which suppress bone formation
62
What class of drug is acarbose?
Alpha-glucosidase inhibitor
63
Give an example of an alpha-glucosidase inhibitor.
Acarbose
64
What is the MOA of acarbose?
Alpha-glucosidase inhibitor which results in reduced carbohydrate absorption.
65
What are the common side effects of alpha-glucosidase inhibitors such as Acarbose?
Flatulence
Diarrhoea
66
Outline the pathophysiology of a DKA.
Reduced insulin production causing hyperglycaemia which results in osmotic diuresis causing polyuria and polydipsia whilst starvation state leads to lipolysis and ketogenesis with ketoacidosis resulting in metabolic acidosis and abdominal pain due to gastroparesis
67
What are the clinical features of DKA?
- Nausea/ vomiting
- Pear smelling breath
- Reduced consciousness: Reduced mental status
- Abdominal pain: peritonitis (guarding)/ early bowel obstruction (tinkling bowel sounds)/ late bowel obstruction (absent bowel sounds)
- Hyperventilation: Kussmaul breathing
68
What breathing pattern may be noted in DKA?
Why does it happen?
Deep, rapid breathing pattern as respiratory compensation to blow of CO2 to counteract metabolic acidosis
69
What investigations may be suggestive of a DKA?
- Blood glucose: ≥ 11.0mmol/L
- VBG: Metabolic acidosis (raised anion gap, reduced bicarbonate); pH ≤ 7.40
- Blood ketones: Ketonaemia (≥ 3.0mmol/L)
- U+E: Raised SCr and hyperkalaemia
70
How would you manage a patient with DKA?
- Insulin: 0.1units/kg/hr
- IV Fluids: NaCl (0.9%) at 1L in 30 minutes, 1L over 1hr, 1L over 2hr, 1L over 4hr
± (Hypokalaemia)
- IV Fluids: KCl added (1L for 2hr, 1L for 2hr, 1L for 4hr, 1L for 4hr, 1L for 6 hr)
- -> 10mmol/L KCl if [K+] = 3-5mmol/L; 20mmol/L KCl if [K+] = ≤3.5mmol/L
± (Glucose ≤ 14mmol/L)
- IV Glucose: Glucose (10%)
71
Describe a Hyperosmolar Hyperglyaecimic State?
Profound hyperglycaemia (≥ 30mmol/L) and hyperosmolality (≥ 320mOsm/kg) and volume depletion in the absence of ketoacidosis – a complication of diabetes.
72
What are the osmolality and blood glucose thresholds for HHS?
- Blood glucose: ≥30mmol/L
| - Serum osmolality: ≥ 320mOsm/kg
73
How do you manage a Hyperosmolar Hyperglycaemic State?
```
- Insulin: 0.05units/kg/hr
+
- IV Fluids: NaCl (0.9%) at 1L in 30 minutes, 1L over 1hr, 1L over 2hr, 1L over 4hr
+
- IV Fluids: KCl added (1L for 2hr, 1L for 2hr, 1L for 4hr, 1L for 4hr, 1L for 6 hr)
+
± (Glucose ≤ 14mmol/L)
- IV Glucose: Glucose (10%)
```
74
A patient asks you what the complications of Diabetes Mellitus are. Outline what you may tell them.
Infection: Hyperglycaemia reduces function of leucocytes which increases risk of infection: cellulitis, boils, abscesses, candidiasis.
Skin disease: Diabetes produces a myriad of common dermatological manifestations
Iatrogenic hypoglycaemia: Increased usage of insulin results in hypoglycaemia.
Lactic Acidosis: Rare complication when taking Metformin presenting with severe metabolic acidosis without hyperglycaemia or ketosis. Treat by rehydrating and infusing bicarbonate (1.26%)
Retinopathy (background/proliferative): Damage to the vessels supplying the retina (central retinal artery) seen as haemorrhage, oedema, microaneurysms and exudate (HOME).
Nephropathy: Damage to vessels (ischaemic lesion) or urinary tract (infective lesion, UTI) or glomerular basement membrane (glomerulopathy) leading to compromised filtration (renal insufficiency) demonstrated by proteinuria, Hypercreatinemia and hypoalbuminemia.
Erectile Dysfunction (ED): Damage to vasculature of penis (pudendal artery)/ cavernosal artery leading to inability for corpus cavernosum to remain filled in erect state. Manage with PDEi (sildenafil) and counselling.
Diabetic Foot: Potential damage due to neuropathy which results in tissue necrosis, similar to PAD: pale, pulseless, painless, absence of hair, shiny skin. Diabetic foot ulcers may be seen
Macrovascular complications: Diabetes is a risk factor for atherosclerosis which is summative with other risk factors (hypertension/hyperlipidaemia/obesity/ low physical inactivity) resulting in damage to large vessels which is territory-dependent – PAD (peripheral), CVA (brain) and MI (heart).
75
What types of Diabetic Neuropathy exist?
Symmetrical sensory neuropathy: reduced sense of vibration, pain sensation and temperature
Diabetic amyotrophy: painful wasting which is asymmetrical in the quadriceps causing loss of bulk and diminished reflexes
Acute Painful neuropathy: Neuropathic pain with paraesthesia dn dysesthesia
Mononeuritis (/Multiplex): Inflammation of nerves with sudden onset and pain common at sites of external pressure (e.g. Carpal Tunnel Syndrome)
Autonomic neuropathy: affects ANS causing CVS and GI and urinary and sexual Sx and S
76
What is the most common form of pituitary disease?
Pituitary adenoma
77
How may a pituitary adenoma present?
Headache
Visual changes: Reduced visual acuity; Bitemporal hemianopia; Diplopia
Hypogonadism Sx: infertility; reduced libido; hot flushes
Prolactinoma: gynaecomastia; galactorrhoea; reduced libido; amenorrhoea/oligomenorrhoea
Acromegaly: coarsened facial features; joint pain; soft tissue hypertrophy; galactorrhea; erectile dysfunction
Cushing's Disease: Mood change; Striae; Facial plethora; Amenorrhoea; Weight gain; OP; Acne; Reduced libido
78
What is the first-line, gold standard investigation used to diagnose a Pituitary Ademona?
MRI-Pituitary to delineate characteristics of tumour including invasion and compression of surrounding structures
79
How do you manage a Pituitary Adenoma?
Microadenoma:
- Observation
Macroadenoma: Abutting or Not Abutting Optic Chiasm
- Trans-sphenoidal surgery
+
- Hormone replacement (FLAT PeG): Testosterone; Estradiol; Progesterone; Hydrocortisone; Levothyroxine; Somatropin
± Mass Effect
- Radiotherapy: Stereotactic gamma knife
± (Residual tumour if surgery + radiotherapy fails)
- Octreotide
80
How may pituitary adenomas be classified?
Non-Functional: No hyper secretion of hormone
'Clinically Non-Functioning Pituitary Adenoma' (CNFPA)
Functional: Hyper-secretion of hormone
Microadenoma <1cm
Macroadenoma >1cm
Functional (hormone type):
- Prolactinoma
- Somatrotroph adenoma
- Gonadotroph adenoma
Pituitary apoplexy: associated with neurological deficit or symptomatic (haemorrhage/infarction) with few/no symptoms
81
The rapid enlargement of a pituitary tumour due to infarction or haemorrhage causing severe headache and sudden, severe vision loss is termed?
Pituitary Apoplexy
82
In hypopituitarism, radiographic imaging of via MRI-Pituitary showing an empty space is termed?
Empty sella syndrome
83
A deficiency of GnRH in a patient with anosmia is termed?
Kallmann's Syndrome
84
Pituitary infarction following severe postpartum haemorrhage is termed?
Sheehan's Syndrome
85
What is the aetiology of Hypopituitarism?
VITAMIN-C
Vascular: Pituitary apoplexy; Sheehan's Syndrome; Carotid artery aneurysms
Infective: Basal meningitis; Encephalitis; Syphilis
Infiltrations: Haemochromatosis; Sarcoidosis
Trauma: Skull Fx; Surgery
Acquired: Drugs
M
Immunological: Pituitary antibodies
Neoplasia: Primary tumour; Secondary tumour; Lymphoma
86
What investigations would you conduct in a suspected Hypopituitarism?
FBC
Hormones
MRI-Pituitary
87
How do you manage hypopituitarism?
HRT: Hydrocortisone; Levothyroxine; Testosterone; Estriol; Somatropin
88
What is the most common cause of Hyperprolactinaemia?
Give other causes.
Prolactinoma (functional pituitary adenoma)
Pituitary adenoma which compresses pituitary stalk to disinhibit DA which suppresses PL (disconnection)
Primary hypothyroidism
Drugs (D2 antagonists)
Acromegaly/PCOS (co-secretion)
89
What effect does thyroid have on prolactin?
High TSH levels in hypothyroidism can stimulate prolactin
90
What is the criteria for a macroadenoma?
>10mm
91
How do you manage Hyperprolactinaemia?
```
Conservative: Withdraw offending drugs
+
Medical: Cabergoline; Bromocriptine
+
Surgery: Transphenoidal approach
```
± Macroadenoma pressing optic chaise
- Radiotherapy
92
What is the difference between acromegaly and gigantism?
Excessive GH production in children prior to growth plate closure results in gigantism
Excessive GH production in adults once epiphyseal plates are closed results in acromegaly
93
What is the main cause of acromegaly?
Somatotroph adenoma (functional GH-secreting pituitary adenoma)
94
What are the clinical features of acromegaly?
Changes n facial appearance
Headaches
Visual deterioration
Deep voice
Galactorrhoea; Impotence; Poor libido
Tiredness; Weight gain; Diaphoresis; Musculoskeletal pain
Prognathism
Interdental separation
Large tongue
Hirsutism
Spade-like hands and feet
Tight rings
CTS
```
Arthropathy
Glycosuria
Hypertension
Heart failure
Oedema
```
95
What is the management of Acromegaly?
Medial: Octreotide; Cabergoline
+
Surgical: Trans-sphenoidal surgical resection
± Incomplete surgical excision
External radiotherapy
96
Explain the difference between Cushing's Disease and Cushing Syndrome.
Cushing disease is a condition caused by ectopic cortisol production in pituitary adenoma or ectopic ACTH production from adrenal adenoma
Cushing Syndrome is the myriad of symptoms associated with elevated cortisol
97
Outline the clinical features of Cushing's Syndrome.
```
Mood change
Facial plethora; Facial rounding
Dorsocervical rounding (buffalo hump)
Supraclavicular fullness
Violaceous striae
Weight gain and central adiposity
Easy bruising
Reduced libido; Impotence
```
98
How would you manage a patient with Cushing's Disease?
Surgery: Transphenoidal pituitary adenomectomy
±
Medical: Pasireotide; Octreotide
+
Medical (HRT): Hydrocortisone; Levothyroxine; Testosterone; Estradiol; Somatotropin; Desmopressin
99
Outline how you would treat Cushing's Syndrome.
Tx cause: Adrenalectomy (adrenaloma); Trans-sphenoidal pituitary adenomectomy
+
Medical (HRT)
--> If no output e.g. in trans-sphenoidal pituitary adenomectomy; or bilateral adrenalectomy
100
What role does mifepristone have in Cushing's syndrome?
Anti-progesterone thus blocks cortisol at receptor level, attenuating effect of cortisol elevation
101
Which thyroid hormone is produced in greater amounts?
T4
102
What binding protein is the majority of thyroid hormone bound to?
Thyroid Binding Globulin (TBG)
103
How can you assess thyroid function?
TFTs: TSH; T4
Thyroid antibodies
104
Outline the differences between Primary, Secondary and Subclinical hypothyroidism.
The following are classifications of Hypothyroidism based on the balance of TSH and T4.
Primary: elevated TSH; low T4
Secondary: low TSH; low T4
Subclinical: slightly elevated TSH; normal T4
105
What conditions are Hashimoto's Thyroiditis associated with?
Type 1 Diabetes
Addison's Disease
Pernicious anaemia
Lupus
106
How may hypothyroidism present?
```
Lethargy
Constipation
Weight gain
Coarse skin and hair
Bradycardia
Bradyreflexia
Cold sensitivity
Eyelid oedema
Tibial myxoedema
```
107
What is Myxoedema?
Accumulation of mucopolysaccharide in subcutaneous tissues
108
What is the most common cause of primary hypothyroidism?
What investigations would show this?
Autoimmune Thyroiditis
anti-TPO Abs; high TSH; low T4
109
How do you manage Hypothyroidism?
Supportive: Monitoring 4-6 weeks post-initiation; Annual review
+
Medical: Levothyroxine 1.6mcg/kg/day PO
110
What are some of the common side effects of Levothyroxine?
```
Anxiety
Insomnia
Thyrotoxic crisis
Angina pectoris
Arrhythmias
SOB
Muscle weakness
Reduced weight
Tremor
Arthralgia
```
111
What is Myxoedema coma?
What derangements occur in it?
Severe hypothyroidism in a vulnerable elderly patient resulting in reduced consciousness.
Features:
- Cardiac failure
- Hypoventilation
- Hypoglycaemia
- Hyponatraemia
- Hypothermia
112
What is Myxoedema madness?
When may this occur?
Severe hypothyroidism in elderly patients resulting in psychoses - delusions, demented, depression etc.
May occur after starting thyroxine.
113
How do you manage a myxoedema coma?
Correct the derangements
Supportive: A-E; Oxygen; IV fluids; Gradual rewarming;
+
Medical: Glucose infusion; IV Thyroid hormone (T3)
114
Outline the causes of Hypothyroidism?
Autoimmune
Drug-induced
Iatrogenic
Congenital
Post-partum
Iodine deficiency
115
What drugs may commonly cause drug-induced hypothyroidism?
Amiodarone
Lithium
Carbimazole
Interferon
116
What are the causes of Hyperthyroidism?
Give the key aspects of each.
Grave's Disease: TSH-R Abs (TRAbs)
Toxic Multinodular Goitre: multiple nodules
Solitary toxic adenoma: sole nodule
Amiodarone-induced: I (Jod-Basedow phenomenon); II (release of pre-made hormones)
De Quervain's Thyroiditis: post-viral, painful and progressive (hyperthyroid, hypothyroid, normal)
Follicular thyroid cancer
Struma ovarii: ectopic thyroid tissue from dermoid tumour and ovarian teratoma
ß-hCG related: Pregnancy; hydatidiform mole; choriocarcinoma; testicular germ cell tumour
117
What are the clinical features of Hyperthyroidism?
```
Weight loss
Irritability; Restlessness; Diaphoresis
Exopthalmos; Lid lag; Stare; Periorbital oedema
Goitre; Bruit
SOB
Palpitations; Arrhythmia (AF)
Thirst; Vomiting; Diarrhoea;
Tremor; Arthralgia; Choreoathetosis
Oligomenorrhoea; Loss of libido; Gynaecomastia
```
118
How do you manage Hyperthyroidism?
```
Supportive: ß-blockers
+
Medical: Propylthiouracil; Carbamizole
+
Surgical: Thyroidectomy; Hemithyroidectomy
```
119
What are the complications of Thyroidectomy?
Recurrent laryngeal nerve damage
Hypocalcaemia
120
What are the common side effects of Carbimazole?
Agranulocytosis thus infections
Thrombocytopaenia
Haemolytic anaemia
121
How is Grave's ophthalmopathy classified?
ATA - 6 grades
Mnemonic: NO SPECS
```
N = 0 = no Sx + S
O = I = only signs
```
```
S = II = Soft tissue involvement
P = III = Proptosis
E = IV = Extra-ocular involvement
C = V = Corneal involvement
S = VI = Sight loss
```
122
How do you manage a Thyroid storm?
Supportive: A-E assessment; admission; IV fluids;
```
Medical: Propylthiouracil
+
Hydrocortisone
+
Propanalol
+
Potassium iodide
```
123
What antithyroid drug is given as first line to pregnant women?
Propylthiouracil
124
What is the management of Grave's Orbitopathy?
Supportive: Smoking cessation; monitoring; annual review; Selenium; eye drops
+
Medical: Propylthiouracil (maintain euthyroidism); oral prednisolone (0.3-0.5mg/kg/day);
+
Surgery: Surgical decompression
125
Why may administration of corticosteroids be useful in Thyroid storm?
Glucocorticoids reduce conversion of T4 to T3 thus reduce active form of thyroid
126
What are the potential causes of a goitre?
Hypothyroidism:
Iodine deficiency
Autoimmune thyroiditis
Congenital hypothyroidism
Hyperthyroidism:
Grave's
Solitary adenoma
Toxic Multinodular Goitre
Pituitary disease (pituitary adenoma)
Thyroid cancer
127
What investigations may you conduct for a patient presenting with a goitre?
Bloods: FBC; U+Es; TFTs; CRP
Abs: TPO; TSH-R
US-Thyroid
Fine-Needle Aspiration (FNA)
128
How is thyroid cancer diagnosed?
Fine-needle aspiration
129
What are the clinical features of Thyroid Cancer?
Thyroid nodule/mass
Hoarseness of voice
Cervical lymphadenopathy
Stridor
130
When should you admit someone urgently with a neck lump?
Stridor (signs of upper airway obstruction)
131
What are the suspected thyroid cancer criteria for the urgent cancer referral (2-week)?
Unexplained thyroid lump
Lymphadenopathy and lump
Voice change
Rapidly increasing size
132
What investigations would you conduct for a patient presenting initially with a thyroid lump?
Bloods: FBC; U+E; TFTs; LFTs; Hormones;
Abs: TPO; TSHR
US-Thyroid
Fine-Needle Aspiration and Cytology
Diagnostic hemithyroidectomy (if Thy3f cytology and cannot differentiate between follicular cancer and benign lesions)
133
What classification system is given in US-Thyroid?
Which ones get referred for FNAC?
British Thyroid Association U1-5
U1 = Normal
U2 = benign
U3 = indeterminate
U4 = suspicious
U5 = malignant
134
What cytological classification system is there for FNAC in suspected Thyroid cancer?
Thy1 = non-diagnostic
Thy2 = non-neoplastic
Thy3a = atypical features
Thy3f = follicular neoplasm suspected - cannot determine
Thy4 = likely malignancy (<70%)
Thy5 = malignancy (98%
135
What does triple assessment in suspected Thyroid cancer consist of?
TFTs
USS
FNAC
136
When would a diagnostic hemithyroidectomy be indicated?
Following FNAC with classification as Thy3f whereby cannot differentiate.
137
What is the most common form of Thyroid cancer?
Papillary
138
What Thyroid cancer has the worst prognosis?
Anaplastic
139
Which thyroid cancer most commonly appears in the elderly?
Anaplastic
140
What type of thyroid cancer is associated with MEN type 2?
Medullary
Remember Medullary is associated with MEN 2
141
Which form of Thyroid cancer occurs at a higher frequency in females?
Follicular
Remember: Follicular is for Females
142
Elevated calcitonin and hypocalcaemia are associated with what type of Thyroid Cancer?
Medullary Carcinoma
143
Elevated Thyroglobulin is associated with what type of Thyroid cancer?
Follicular or Papillary Thyroid Cancer
144
What is Riedel's Thyroiditis?
Rare autoimmune condition resulting in fibrosis of the thyroid and surrounding soft tissues resulting in enlargement and subsequent compression of adjacent tissues
145
LH binds to ___ cells to increase ___ production?
Leydig
Testosterone
146
FSH stimulates ____ cells to produce ____?
Sertoli cells
Inhibins and Activins
147
47, XXY is the genotype for what condition?
Klinefelter's Syndrome
148
What are the causes of male hypogonadism?
```
HP axis:
Hypopituitarism
Kallann's Syndrome
Malnutrition
Hyperprolactinaemia
```
```
Primary Gonadal Disease:
Anorchia/Leydig Cell Agenesis
Cryptorchidism
Chromosomal abnormality (Klinefelter's)
Enzyme defects (e.g. 5a-reductase deficiency)
```
```
Testicular torsion
Orchidectomy
Chemotherapy
Orchitis
CKD
Cirrhosis
```
149
Why may CKD cause hypogonadism?
CKD is related to a reduction in LH thus low T occurs
150
What investigations may you conduct in a patient with suspected hypogonadism?
Bloods: FBC; U+Es; TFTs; LFTs
Sex hormones: FSH; LH; Testosterone
Chromosomal analysis
MRI-Pituitary
US-Abdomen
151
Define erectile dysfunction.
Inability to attain or sustain an erection until ejaculation
152
What drug is commonly used to treat Erectile Dysfunction?
Sildenafil
153
Define Gynaecomastia.
Enlargement of breast tissue in males
154
Outline some causes of gynaecomastia.
HP axis:
- Any cause of hypogonadism
- Hyperthyroidism
Neoplasm:
- Oestrogen-producing tumours
- hCG-producing tumours
- Carcinoma of the breast
Drugs:
- Oestrogen
- Digoxin
- Cannabis
- Diamorphine
- Spironolactone
- Cimetidine
- Gonadotrophins
155
Define the menopause.
Cessation of periods for 12 months with oestrogen decline resulting in symptoms of hot flushes, vaginal dryness and breast atrophy. There may also be symptoms of mood change.
156
How is the menopause managed?
HRT is the mainstay and Tx concomitant symptoms
HRT is either continuous (menopause) or sequential (perimenopause)
HRT should be oestrogen and progesterone (if uterus)
Vaginal Atrophy:
- Vaginal oestrogen
Mood changes:
- SSRIs
Urinary incontinence:
- Pelvic floor exercises
157
What are the indications for Transdermal Oestrogen in the menopause?
Mnemonic: ABCDE
```
Allergy - lactose intolerance
BMI - BMI >30kg/m2
CVD - CV RFs
Disabling symptoms - from oral medication and GI conditions
Embolism risk - VTE risk is high
```
158
When should bleeding on HRT be investigated?
Breakthrough bleeding bleeding after 6 months on Tx
159
What are the adverse effects of HRT?
Oestrogen-related:
- Bloating
- Mastalgia
- Breast enlargement
- Leg cramps
- Dyspepsia
Progesterone-related:
- Headaches
- Mood swings
- Acne vulgaris
- Lower abdomen pain/back pain
160
Define Primary Amenorrhoea.
Absence of menses by 16 years old
161
How may amenorrhoea be classified.
Primary: No menses by 16
Secondary: No menses for 3 months
162
What are the causes of amenorrhoea.
Hypothalamic:
- GnRH deficiency
- Post-OCP therapy
Pituitary:
- Hypopituitarism
- Hyperprolactinaemia
Gonadal:
- PCOS
- Premature ovarian failure
- Ovarian dysgenesis
- Androgen-secreting ovarian tumours
- Radiotherapy
Other:
- Thyroid dysfunction
- Cushing's syndrome
- Adrenal tumours
O+G:
- Imperforate hymen
- Absent uterus
163
What is the difference between hirsutism and hypertrichosis?
Hirsutism is excess hair growth in a woman in the male pattern (androgen-dependent) such as: beard, abdominal wall, thigh, axilla and around nipples.
Hypertrichosis is androgen-independent with increase in general body hair
164
Give 3 signs of virilisation.
Hirsutism
Clitoromegaly
Deepening of voice
Loss of female body shape
165
What are the clinical features of Polycystic Ovarian Syndrome?
```
Amenorrhoea/Oligomenorrhoea
Hirsutism
Acne
Obesity
Virilisation
```
166
What criteria is used to diagnose PCOS?
Rotterdam Criteria (2/3):
- Menstrual irregularity
- Clinical features of hyperandrogenism
- Polycystic ovaries (multiple cysts) on TVUS
167
What investigations would be diagnostic in a suspected case of PCOS?
Hormones: LH:FSH ratio >3; elevated Testosterone; elevated DHEAS
TFTs: Negative
PL: Negative
TVUS: multiple fluid-filled lesions in the ovaries
168
How is PCOS managed?
Supportive: Weight loss
± Fertility desired
- Clomiphene
± Fertility not desired
- COCP
± Excess hair
- Minoxidil
or
- Mechanical removal
169
What is the MOA of Clomiphene?
GnRH agonist thus release FSH and LH leading to development and release of ovum.
170
Outline the structural anatomy of the adrenal glands.
Adrenal gland consists of a cortex and a medulla.
Cortex is derived from the intermediate mesoderm
Medulla is derived from ectoderm (neuroendocrine cells)
Adrenal cortex comprises of 3 layers (GFR; 'Salt, sugar' sex')
Zona glomerulosa = salt
Zona fasciculata = sugar
Zona reticularis = sex
171
Which hormones are secreted from the anterior pituitary gland?
FSH
LH
ACTH
TSH
PL
GH
Mnemonic: FLAT PG
172
How may Addison's disease be classified?
Addison's disease is classified with respect to where the dysfunction is within the HPA Axis.
Primary: Addison’s (adrenal)
Secondary: ACTH (pituitary)
Tertiary: CRH (hypothalamic)
173
What are the clinical features of Addison's Disease?
```
N/V
Fatigue
Anorexia
Weight loss
Hyperpigmentation
```
Salt craving (secondary to hyponatraemia)
174
What is the gold-standard investigation for Addison's disease?
What would you expect to see if Addison's Disease is present?
Short Synacthen test
Cortisol will remain <487nm/L as adrenal glands are failing
175
How do you manage a patient with Addison's Disease?
Replace what is lost
Medical: Hydrocortisone (15-30mg/day) + Fludrocortisone (0.1-0.2mg/day)
176
What is the dosage of steroid replacement in Addison's disease and how is this administered?
Hydrocortisone PO BD 15-30mg/day
2/3 am; 1/3 nocte
177
What are the clinical features of an Addisonian crisis?
```
= acute episode of severe Addisons
Altered consciousness
Hypotension
Hypoglycaemia
Hyponatraemia
Hyperkalaemia
```
178
What are the types of Conn's Syndrome?
Determined by level of HP axis has excess Aldosterone
Primary: Adrenal adenoma
Secondary: High renin due to RAS, renal artery obstruction, HF
179
What are the clinical features of Conn's Syndrome?
```
Nocturia
Polyuria
Mood ∆ -> irritable, depressed
Hypertension
Muscle weakness
Palpitations
```
180
What is the gold-standard investigation for suspected Conn's Syndrome?
Aldosterone: Renin Ratio
Aldosterone
Renin
High aldosterone, low renin = primary Conn's
High aldosterone, high renin = secondary Conn's
181
What investigations should be conducted following elevated aldosterone in suspected Conn's Syndrome?
CT/MRI-Adrenals
US-Kidneys
182
How may RAS be treated?
Percutaneous Renal Artery Angioplasty
183
What would you expect the Us+Es to come back as in a patient with Conn's Syndrome?
Hypokalaemia; Hypernatraemia
184
What would you expect the Us+Es to come back as in a patient with Addison's Disease?
Hyponatraemia
Hyperkalaemia
185
How do you manage a patient with Conn's Syndrome?
Medical: Spironolactone (12.5-50mg PO OD) or Eplerenone (25-100mg PO OD)±
Surgery: Lap adrenalectomy >2.5cm
186
A patient is to be started on Hydrocortisone 30mg PO BD as part of their treatment for Addison's disease.
They are worried about the potential side effects, what are they?
Hypertension
Weight gain
Glycosuria
Hyperglycaemia
Peptic ulcers
Acute pancreatitis
Osteoporosis
Myopathy
Aseptic necrosis of hip/Jaw
Polyuria
Nocturia
Depression
Euphoria
Psychosis
Insomnia
Cataracts
Skin thinning; Bruising
Increased risk of infection (immunosuppression)
187
What are the potential causes of Cushing's Syndrome?
Pituitary adenoma
Ectopic ACTH tumour - carcinoid tumour; SCLC
Adrenal adenomas
Adrenal carcinomas
Drugs
Alcohol-induced pseudo-Cushing's Syndrome
188
What is the gold-standard investigation of Cushing's Syndrome?
How is this conducted?
Dexamethasone-suppression test
Dexamethasone 0.5mg QDS for 48 hours which if positive, cortisol >50nmol/L 2 hours after last dose of dexamethasone
189
Where is Angiotensinogen produced?
Liver
190
Where is renin produced?
Juxtaglomerular cells of Kidney
191
Where is ACE produced?
Pulmonary endothelium
192
What enzyme converts Angiotensin I to Angiotensin II?
ACE
193
What are the functions of Angiotensin II?
Powerful vasoconstriction
Stimulates adrenal zona glomerulosa to increase aldosterone production
194
What type of cells are undergoing proliferation in Phaeochromocytoma?
Chromaffin Cells of the adrenal medulla
195
What are the clinical features of Phaeochromocytoma?
Headache
Palpitations
Diaphoresis
Hypertension
196
What is the gold-standard investigation in a patient with suspected Phaeochromocytoma?
Urinary metanephrines
Appropriate if clinical suspicion is high
197
How is Phaeochromocytoma managed?
Supportive: IV Fluids; High salt diet (>5g/day)
+
Medical: Prazosin; Atenolol
± Surgical candidate
- Lap total/partial adrenalectomy
± Non-surgical candidate
- Continue medical treatment
+
Iobenguane
198
Why are alpha-blockers given before beta-blockers in Phaeochromocytoma?
Chronically vasoconstrictor due to high circulating levels of catecholamines thus secondary decrease in blood volume.
Full alpha blockage allows restoration of blood volume with ß-blockers following after.
199
What gene is responsible for MEN I?
Menin gene on chromosome 11
200
What gene is responsible for MEN II?
Ret gene on chromosome 10
201
What are the functioning adenomas in MEN I?
3Ps
Pituitary adenoma
Parathyroid
Pancreatic tumours (gastrinoma; insulinoma; glucagonoma; VIPoma)
202
What are the functioning adenomas in MEN 2A?
2Ps and 1M
Parathyroid
Phaeochromocytoma
MTC
203
What are the functioning adenomas in MEN 2B?
2Ms, 1P
MTC
Mucosal neuroma
Phaeochromocytoma
204
What is the management for Multiple Endocrine Neoplasia?
Treat abnormalities; Family screening
Surgical excision of tumours
205
Where is ADH released from?
Posterior pituitary
206
What are the functions of ADH?
Reabsorption of water in the collecting duct via AQP4 transporters
Vasoconstriction
207
What are the two types of Diabetes Insipidus?
Cranial DI
Nephrogenic DI
208
What are the causes of Diabetes Insipidus?
```
Iatrogenic: Neurosurgery
Trauma
Idiopathic
Infiltrative: Sarcoidosis; Histiocytosis
Congenital: Wolfram Syndrome (DIDMOAD)
```
```
Vascular: RAS
Idiopathic
Trauma
Metabolic: hypercalcaemia; hypokalaemia
Iatrogenic: Surgery; Lithium
Neoplasm: Pituitary stalk lesions; Craniopharyngioma
```
Congenital: Wolfram syndrome
209
What is histiocytosis?
Group of syndromes resulting in increased numbers of histiocytes: macrophages; monocytes and dendritic cells
210
What are the clinical features of Diabetes Insipidus?
Polyuria
Polydipsia
Dilute urine
211
What are the clinical features of Wolfram Syndrome?
Mnemonic: DIDMOAD
Diabetes Insipidus
Diabetes Mellitus
Optic atrophy
Deafness
212
What is the gold-standard investigation in suspected Diabetes Insipidus?
Water deprivation test: urine osmolality <300mOsm/kg
Urine osmolality < 300mOsm/kg
213
How is Diabetes Insipidus managed?
```
Supportive: Oral/IV Fluids
+
Medical: Desmopressin
+
Tx underlying cause
```
214
What are the causes of SIADH?
Vascular
Iatrogenic: Opiates; Carbamazepine; Vincristine
Trauma: Head injury
Metabolic: Porphyria; Alcohol withdrawal
Infection: Meningitis; Cerebral abscess; Pneumonia
Neoplasm: SCLC; Brain tumour
215
What are the clinical features of SIADH?
Nausea
Irritability
Headache
If severe hyponatraemia (<115mmol/L)
Fits and comas
216
What is the gold-standard investigation to diagnose SIADH?
Urine sodium and osmolality: Elevated
Absence of:
- Diuretic use
- No D/V/burns/fistula/diaphoresis
- Negative Synacthen test
- No excessive polydipsia
217
Why is it important to correct sodium slowly in SIADH?
Avoid central pontine myelinolysis - no greater change than 10mmol/L per 24 hours
218
Outline what may happen if you correct hyponatraemia too quickly in SIADH?
Outline the pathophysiology behind this.
What are the clinical features of the potential condition?
Chronic hyponatraemia leads to the brain adapting to reduce the solutes of brain cells to ensure water balance across BBB to counteract potential cerebral oedema.
Rapid rise in blood sodium causes water to shift out of brain cells at BBB causing demyelination of neurones at the Pons presenting with spastic quadriparesis, pseudo bulbar palsy and cognitive behavioural changes.
219
What is the management of SIADH?
```
Tx cause
+
Supportive: Fluid restriction; Furosemide
+
Medical: Tolvaptan
```
220
Explain how PTH increases calcium concentration.
Calcium reabsorption
Activation of Vitamin D
221
How does corrected Calcium differ from total plasma calcium? Explain.
40% of Calcium is free, the remainder is bound to albumin.
Normal range is 2.2-2.6mmol/L however corrected Calcium accounts for albumin concentration.
You add or subtract 0.02mmol/L for every 1g/L by which the albumin differs from 40g/L
222
What are the causes of hypercalcaemia?
Infection: TB; Sarcoid
Metabolic: Primary hyperparathyroidism; Tertiary hyperparathyroidism; Addison's Disease
Iatrogenic: Vitamin D toxicity; Vitamin A; Lithium; Thiazides
Neoplasia: Multiple myeloma; Metastasis; PTH-related protein secretion
223
What are the clinical features of hypercalcaemia?
Bones, groans, stones and moans
224
Outline some key causes of Hypocalcaemia.
Vascular:
Inflammation/Infection: Acute Pancreatitis;
Metabolic: CKD; Phosphate therapy; Malabsorption; Reduced exposure to UV light; Severe hypomagnesaemia
Iatrogenic: Thyroidectomy; Parathyroidectomy; Antiepileptic drugs; Calcitonin; Bisphosphonates
Congenital: DiGeorge Syndrome;
225
What are the causes of hypophosphataemia?
DKA Tx
Refeeding syndrome
Poor oral intake
Diarrhoea
Hyperparathyroidism
Vitamin D Deficiency
Primary renal abnormality
226
What are the 3 pathophysiological mechanisms by which hypophosphataemia may occur?
- Reduced intake
- Reduced absorption of phosphate
- Increased excretion
227
What are the clinical features of hypophosphataemia?
Muscle weakness
Encephalopathy
Haemolysis
Mnemonic: MEH
228
How is hypophosphataemia managed?
Oral phosphate supplements
or
IV phosphate
229
What is the threshold for hypothermia?
<35C
230
What are the clinical features of hypothermia?
Depends on severity
Shivering
Altered consciousness
Coma
Reduced HR
Reduced BP
Muscle stiffness
Bradyreflexia
Ventricular arrhythmias
231
How is Hypothermia managed?
Supportive: Admission; A-E assessment; Oxygen; ECG monitoring; passive external warming (core T >32) or active external rewarming (core T 28-32) or active internal rewarming (core T <28)
Active rewarming involves humidification and warmed oxygen and warmed fluids
232
What is the threshold for hyperthermia?
>41C
233
What is the management for Hyperthermia?
Tx cause
+
Medical: Dantrolene sodium
234
What two signs may be pathognomonic for Hypocalcaemia?
Chvostek Sign (Cheek)
Trousseau Sign (Tense)
235
Other than pituitary adenoma, what other conditions may yield a bitemporal hemianopia?
Suprasellar meningioma
Craniopharyngioma
236
Should a patient on Carbimazole for Grave's disease develop a chest infection, what must you do?
Immediately stop
Request urgent same day bloods - could be neutropenic due to agranulocytosis from medication
237
What are the biochemical criteria for DKA?
raised blood glucose(>11.1 mmol/L), or known diabetes
ketonuria ++ or more
serum bicarbonate <15 mmol/L
pH<7.3 (if measured)
238
What is the difference between MEN 4 and MEN 1?
Clinically indistinguishable. With MEN IV, patients can have reproductive organ tumours and/or adrenal/renal tumours
239
What are the features of Wermer's Syndrome?
Pituitary tumour
Parathyroid hyperplasia
Pancreatic islet tumour (ZES/Insulinoma)
240
What are the clinical features of Sipple's Syndrome?
MEN 2A
Parathyroid hyperplasia
Phaeochromocytoma
Medullar thyroid carcinoma
241
Which antibody in type 1 diabetes mellitus is strongly correlated with age?
Insulin autoantibody (IAA) - 90% of young people with T1DM
