Endocrinology Flashcards
1
Q
What is acromegaly?
A
Condition of excessive GH secretion
2
Q
Aetiology of acromegaly?
A
Pituitary adenoma
Ectopic GHRH or GH production
3
Q
Features of acromegaly?
A
Growing taller (acromegaly is also referred to as gigantism, if it occurs prior to closure of the epiphyses in childhood)
Gloves/socks/shoes no longer fitting, as their hands/feet grow
Jaw/face growing
Tongue growing
Increased space between teeth
Organomegaly resulting symptoms depending on organ involved, such as a goitre, breast enlargement/gynecomastia/galactorrhea, or abdominal mass
Headache
Visual distrubance
Deeper voice
Erectile dysfunction
Mood disturbance and fatigue
Ancanthosis nigricans
Shortness of breath
Ankle swelling
Osteoarthritis
Carpal tunnel syndrome
4
Q
Investigations to diagnose acromegaly?
A
Fundoscopy; optic atrophy
Perimetry; assess visual fields
Urine dip
ECG
Bloods; IGF-1, prolactin, TFT, LH, FSH, oestrogen, testosterone, cortisol, HbA1c
Chest Xray, MRI, CTCAP
Sleep studies
Surveillance colonoscopy due to risk of colorectal cancer
5
Q
Management of acromegaly?
A
Surgical removal of adenoma
Somatostatin analogues; octreotide, lanreoride
Growth hormone antagonist; pegvisomant
Dopamine agonist; bromocriptine, cabergoline
6
Q
Monitoring requirements in acromegaly?
A
Colonoscopy; bowel malignancy
Echocardiography; heart failure
ECG
Serial IGF-1 measurement
7
Q
Complications of acromegaly?
A
Visual fields defect
Hypopituitarism (post-operatively/due to pressure on the remaining pituitary tissue by the adenoma)
Obstructive sleep apnoea
Type two diabetes mellitus
Arthritis
Carpal tunnel syndrome
Hyperhidrosis
Osteoporosis
Hypertension
Increased risk of colonic polyps which can become malignant
Ischaemic heart disease
Cerebrovascular disease
Congestive cardiac failure
Increased prevalence of regurgitant valvular heart disease
8
Q
What is adrenal insufficiency?
A
Clinical syndrome due to insufficient production of glucocorticoids and mineralocorticoids from the adrenal cortex
9
Q
Pathophysiology of adrenal insufficiency?
A
Disruption of hypothalamo- pituitary- adrenal axis. Lack of cortisol leads to disruption in negative feedback leading to elevated ACTH levels
10
Q
Aetiology of primary adrenal insufficiency?
A
Auto-immune destruction (most common)
Surgical removal of the adrenal glands
Trauma to the adrenal glands
Infectious diseases, such as tuberculosis (more common in developing countries)
Haemorrhage (e.g., Waterhouse-Friderichsen syndrome)
Infarction
Less commonly, neoplasms, sarcoidosis, or amyloidosis
11
Q
Aetiology of secondary adrenal insufficiency?
A
Congenital disorders
Fracture of the base of the skull
Pituitary or hypothalamic surgery or Neoplasms in the pituitary or hypothalamus
Infiltration or infection of the brain
Deficiency of corticotropin-releasing hormone (CRH)
12
Q
Classification of adrenal insufficiency?
A
Primary; problem arises from adrenal gland
Secondary; problem arises from pituitary gland
Tertiary; problem arises from hypothalamus
13
Q
Signs and symptoms of adrenal insufficiency?
A
Hypotension
Fatigue and weakness
Gastrointestinal symptoms
Syncope
Skin pigmentation due to increased ACTH which stimulates production of alpha melanocyte stimulating hormone (MSH)
If Addisons disease is the cause upto 60% may have other autoimmune endocrinopathies
14
Q
Differentials for adrenal insufficiency?
A
Chronic fatigue syndrome
Dehydration
Septic shock
Primary psychiatric syndrome
15
Q
Investigations to diagnose adrenal insufficiency?
A
U+E; hyponatraemia, hyperkalaemia
Serum cortisol; low
Glucose; low
ACTH; high in primary insufficiency
Renin; high in addison’s disease
Aldosterone; low
Short synacten test
CXR
CT of adrenals
MRI of brain
16
Q
What is seen on a blood gas in addison’s disease?
A
Hyperkalaemia, hypokalaemic, hypoglycaemic metabolic acidosis
16
Q
Management of addisons disease?
A
Sick day rules, steroid card, medical alert bracelet
Double steroid replacement during illness
Glucocorticoid replacement; hydrocortisone
Mineralocorticoid replacement; fludrocortisone
16
Q
Gold standard test to diagnose addisons disease?
A
Short synacthen test
17
Q
Management of addisonian crisis?
A
Aggressive fluid resuscitation
IV/IM steroids
Glucose
18
Q
Complications of adrenal insufficiency?
A
Addisonian crisis (life-threatening adrenal crisis)
Severe electrolyte imbalances
Cardiovascular collapse
Hypoglycemia
Side effects of long term corticosteroid use e.g. osteoporosis
19
Q
What is amiodarone induced thyrotoxicosis?
A
Adverse effect of amiodarone
Type 1; direct toxic effect of amiodarone causing thyroiditis
Type 2; amiodarone triggers underlying thyroid autoimmunity
20
Q
Signs and symptoms of amiodarone induced thyrotoxicosis?
A
Weight loss
Tremors
Palpitations
Nervousness
Fatigue
21
Q
Management of amiodarone induced thyrotoxicosis?
A
Type 1; antithyroid medication
Type 2; corticosteroids
Consult cardiology regarding continuing amiodarone
22
Q
What type of medication is metformin?
A
Biguanide
23
Mechanism of action of metformin?
Increasing peripheral insulin sensitivity and enhancing hepatic glucose uptake which lowers blood glucose levels
24
What is the starting dose of metformin?
500mg OD/ BD, upto 2000mg daily
25
Side effects of metformin?
Nausea
Vomiting
Abdominal discomfort
Diarrhoea
Lactic acidosis is a rare but serious adverse effect
26
Contraindications to metformin?
Severe renal/ hepatic impairment
Acute conditions which affect renal function; AKI
27
Examples of sulphonylurea?
Gliclazide, glibenclamide, Glipizide, tolbutamide
28
Mechanism of action of sulphonylurea?
Stimulate pancreatic beta cells to release insulin
29
Starting dose of gliclazide?
40-80mg daily
Maximum dose of 320mg
30
Side effects of gliclazide?
Hypoglycemia is a significant risk with sulfonylureas.
Weight gain
Nausea
Diarrhoea
Allergic reactions
31
Contraindications to sulphonylureas?
Type 1 diabetes
Diabetic ketoacidosis
Severe renal or hepatic impairment
32
Examples of thiazolidinediones?
Pioglitazone, rosiglitazone, netoglitazone
32
Mechanism of action of Thiazolidinediones?
Increase peripheral insulin sensitivity
33
Dosing of Thiazolidinediones?
15-30mg OD maximum dose of 45mg OD
34
Side effects of Thiazolidinediones?
Weight gain
Fluid retention leading to heart failure
Increased risk of fractures
Potentially an increased risk of bladder cancer.
35
Contraindications to thiazolidinediones?
Heart failure
Hepatic impairment
Bladder cancer
36
Examples of SGLT-2 inhibitors?
Dapagliflozin, empagliflozin
37
Mechanism of action of SGLT-2 inhibitors?
Inhibit SGLT-2 channels in renal tubule to increase urinary glucose excretion
37
Contraindications to SGLT-2 inhibitors?
Severe renal impairment
End stage renal disease
37
Dose of dapagliflozin?
10mg OD
37
Examples of DPP-4 inhibitors?
Sitagliptin
37
Side effects of SGLT-2 inhibitors?
Genital mycotic infections
UTI
Euglycaemic DKA
Increased risk of lower limb amputation
38
Side effects of DPP4 inhibitors?
Nasopharyngitis
Upper respiratory tract infection
Headache
Pancreatitis
38
Contra-indications to DPP4 inhibitors?
Caution in pancreatitis
Dose adjusted in renal impairment
38
Mechanism of action of DPP4- inhibitors?
Inhibits DPP4 enzyme which breaks down incretin, so rise in incretins leads to increased insulin secretion and reduced glucagon secretion
38
Dosage of sitagliptin?
100mg OD
39
Mechanism of action of GLP1 analogues?
Stimulate insulin secretion and and reduce glucagon secretion
40
Side effects of GLP1 analogues?
GI disturbance
Hypoglycaemia
Pancreatitis
41
Contra-indications to GLP 1 analogues?
Pancreatitis
Severe renal impairment
42
What is arginine vasopressin disorder?
Syndrome of either inadequate production or response to arginine vasopressin
43
Causes of arginine vasopressin disorder?
AVP- Deficiency;
Head trauma
Inflammatory conditions (e.g., sarcoidosis)
Cranial infections such as meningitis
Vascular conditions such as sickle cell disease
Rare genetic causes
AVP- Resistance;
Drugs (e.g., lithium)
Metabolic disturbances (e.g., hypercalcaemia, hypokalaemia, hyperglycaemia)
Chronic renal disease
Rare genetic causes (e.g., Wolfram's syndrome)
44
Signs and symptoms of AVP?
Large volumes of dilute urine; >3 litres and osmolality <300mOsm/ kg
Nocturia
Excessive thirst
In children; failure to thrive, enuresis
45
Differentials for AVP?
Diabetes mellitus
Primary polydipsia
CKD
46
Investigations to diagnose AVP?
U+E; raised sodium
Blood glucose
Urine dip
Serum and urine osmolality; raised serum osmolality >295, low urine osmolality <300
Water deprivation test
47
Management of AVP?
AVP-D
Desmopressin
Monitor sodium- risk of hyponatraemia
AVP-R
Thiazide diuretic
NSAID
High dose desmopressin
Correct underlying metabolic abnormalities
48
What is carcinoid tumour?
Neuroendocrine tumour which can become malignant and most commonly originates in appendix and small bowel which secretes serotonin
49
Epidemiology of carcinoid tumour?
1-2 cases per 100,000
50
Aetiology of carcinoid tumour?
Tumour in neuroendocrine tissue
51
Signs and symptoms of carcinoid tumour?
Abdominal pain
Diarrhoea
Flushing
Wheezing
Pulmonary stenosis
52
Differentials for carcinoid tumour?
IBS
IBD
Mastocytosis
53
Investigations for carcinoid tumour?
Hormone level; 5-hydroxyindoleacetic acid
CT/ MRI/ octreotide scan
Tissue biopsy
54
Management of carcinoid tumour?
Pharmacological; octreotide
Surgery; remove tumour
Embolisation, radiofrequency ablation, chemotherapy
55
What is cushings syndrome?
Excess glucocorticoids
56
What is cushings disease?
Excess glucocorticoids due to ACTH secreting pituitary adenoma
57
Epidemiology of cushings syndrome?
More common in women
Peak incidence 25-40 years
58
Causes of cushings syndrome?
ACTH-dependent disease: This is caused by excessive production of ACTH, most often due to a pituitary tumour (Cushing's disease) or ectopic ACTH-producing tumours (e.g. lung carcinoids, thymic carcinoids, and others).
ACTH-independent: This arises from primary adrenal diseases, such as adrenal adenomas or adrenal carcinomas, which produce excess cortisol independently of ACTH stimulation. Exogenous steroids can also cause ACTH-independent Cushing's.
59
Clinical features of cushings syndrome?
Proximal myopathy
Striae and easy bruising
Osteoporosis and fractures
Glucose intolerance or diabetes mellitus
Obesity, particularly truncal or "centripetal" obesity
Hypertension
Hypokalaemia
Facial changes, such as moon face and acne
Hirsutism in women
Fat redistribution leading to interscapular and supraclavicular fat pads
Thin extremities due to muscle wasting
Thin, fragile skin
Erectile dysfunction in men
Psychological issues, such as depression or cognitive dysfunction
Osteopenia or osteoporosis
60
Differentials for cushings syndrome?
Metabolic syndrome
PCOS
Adrenal insufficiency
Alcohol excess
Depression
61
Investigations to diagnose cushings syndrome?
24 hour urinary free cortisol
Low dose dexamethasone suppression test, followed by high dose
Plasma ACTH
CT/ MRI to find ectopic sources
62
Interpretation of dexamethasone suppression test?
Not suppressed by low dose - Cushing’s syndrome (e.g. exogenous steroid use)
Not suppressed by low dose but suppressed by high dose - Cushing’s disease (pituitary source)
Not suppressed by low dose or by high dose dexamethasone – ectopic ACTH (not under axis control, likely ACTH-producing tumour)
63
Management of cushings syndrome?
Medical management; metyrapone, ketoconazole, mifepristone, pasireotide
Surgical management; resection of pituitary tumour
Radiotherapy
64
What is delayed puberty?
Delayed puberty is a medical condition in which there is an absence of pubertal development by the age of 14 in boys and 13 in girls.
65
Epidemiology of delayed puberty?
2-5%
More common in boys
66
Aetiology of delayed puberty?
Low gonadotrophin secretion: This can be due to pituitary disorders (such as craniopharyngiomas, Kallmann syndrome, panhypopituitarism, or isolated gonadotrophin deficiency), hypothyroidism, or systemic diseases (e.g., cystic fibrosis or Crohn's disease).
High gonadotrophin secretion: This could be due to chromosomal disorders (like Turner's XO or Klinefelter's XXY), congenital adrenal hyperplasia, or acquired hypogonadism (for example, after chemotherapy).
67
Investigations to diagnose delayed puberty?
Hand- wrist X ray
FSH, LH, TFT, sex hormones
68
Differentials for delayed puberty?
Hypogonadotropic hypogonadism; kallmann syndrome
Hypergonadotropic hypogonadism; klinefelter syndrome, turner's syndrome
Cystic fibrosis
Crohn's disease
Hypothyroidism
69
What is type 1 diabetes mellitus?
Autoimmune destruction of insulin producing beta cells in pancreas
70
Epidemiology of T1DM?
More common in children and young adults
Northern European
FHx of autoimmune disease
71
Signs and symptoms of T1DM?
Polyuria
Polydipsia
Weight loss
72
Differentials for T1DM?
Diabetes insipidus
MODY3; mutation in HNF1A
MODY2; glucokinase mutation
MODY5; HNF1 beta
Hyperthyroidism
73
Glucose readings to diagnose diabetes?
Random blood glucose ≥ 11.1mmol/l or Fasting plasma glucose ≥ 7mmol/l
2-hour glucose tolerance ≥ 11.1mmol/l
HbA1C ≥ 48mmol/mol (6.5%)
74
What will C-peptide levels be in T1DM?
Low due to reduced insulin secretion
75
Management of T1DM?
Glucose targets;
Pre-meal blood glucose: 4-7 mmol/L (72-126 mg/dL)
Bedtime blood glucose: 6-10 mmol/L (108-180 mg/dL)
HbA1c: Less than 7% (53 mmol/mol)
Long acting insulin at night time
Short acting insulin after meal and snack
Strict BP control below 135/ 85
Annual eye screening
76
Sick day rules for T1DM?
Stop ACE-i
Adjust dose of insulin therapy
Glucose monitoring every 3-4 hours
Ketone monitoring every 3-4 hours
Maintain normal meal pattern
Fluid and carbohydrate replacement
77
Association of T1DM
Growth and pubertal delay
Thyroid disease
Coeliac disease
78
What is T2DM?
Chronic metabolic condition characterised by inadequate insulin production from pancreatic beta cells resulting in insulin resistance
79
Epidemiology of T2DM?
Family history
Most common type of diabetes
More common in south asian ethnicity
More common in obese people
80
Aetiology of T2DM?
Poor dietary habits
Lack of physical activity
Obesity
81
Signs and symptoms of T2DM?
Polyuria
Polydipsia
Unexplained weight loss
Blurry vision
Fatigue
82
Differentials for T2DM?
T1DM
MODY
Secondary diabetes mellitus; glucocorticoids, antipsychotics, cystic fibrosis,
83
Management of T2DM?
Lifestyle modification; diet, exercise, smoking cessation
Metformin
If risk of CKD or CVD add SGLT-2 inhibitor
DPP-4 inhibitor, pioglitazone, sulphonylurea
Consider insulin
84
HbA1c targets?
Lifestyle management; 48
Lifestyle + metformin; 48
Lifestyle + hypoglycaemic agent; 53
85
Complications of T2DM?
Macrovascular;
Cardiac disease
Peripheral arterial disease
Cerebrovascular disease
Microvascular;
Diabetic retinopathy
Diabetic nephropathy
Diabetic neuropathy
Sexual dysfunction
86
Sick day rules for T2DM?
Stop ACE-i if risk of dehydration and AKI
Metformin; stop if risk of lactic acidosis, dehydration
Monitor blood glucose and ketones every 3-4 hours
87
What is diabetic ketoacidosis?
Hyperglycemia (blood glucose >11 mmol/L)
Ketosis (blood ketones >3 mmol/L or urinary ketones ++ or higher)
Acidosis (pH <7.3 or bicarbonate <15 mmol/L)
Patients on SGLT-2-i may present with euglycaemic DKA
88
Epidemiology of DKA?
Affects those with T1DM
Highest incidence in 18-24 year olds
Can be presenting feature of T1DM
89
Aetiology of DKA?
Insulin deficiency
90
Pathophysiology of DKA?
Insulin deficiency leads to hyperglycaemia
Excess glucose is converted to ketones
Ketones result in acidosis and hyperglycaemia produces an osmotic diuresis contributing to dehydration and electrolyte imbalance
91
Triggers for DKA?
Infections
Dehydration and fasting
Missing doses of insulin
Medications e.g. steroid treatment or diuretics
Surgery
Stroke or myocardial infarction
Alcohol excess or illicit drug use
Pancreatitis
92
Criteria to diagnose severe DKA?
Blood ketones > 6mmol/L
Bicarbonate < 5mmol/L
Blood pH < 7
Anion gap above 16
Hypokalaemia on admission
GCS less than 12
Oxygen saturations < 92% in air
Systolic BP < 90mmHg
Brady or tachycardia (heart rate < 60 or > 100bpm)
93
Signs of DKA?
Dry mucous membranes
Hypotension
Tachycardia
Altered mental state (drowsiness, confusion, coma)
Kussmaul's breathing (deep, sighing breathing to compensate for metabolic acidosis by blowing off carbon dioxide)
Fruit-like smelling breath (due to ketosis)
94
Symptoms of DKA?
Nausea and vomiting
Abdominal pain
Polyuria
Polydipsia
Weakness
95
Investigations to diagnose DKA?
Bedside;
Capillary blood glucose
Blood or urinary ketones
Urine dip
ECG
Blood tests;
VBG, U+E, FBC, CRP, Blood cultures, HbA1c
Imaging;
CXR
96
Management of DKA?
A to E assessment
NG tube insertion
Fluid replacement with normal saline
K+ replacement
Fixed rate insulin infusion; 50 units of actrapid in 50mls of 0.9% saline at a rate of 0.1 units/ kg/ hour
Continue long acting insulin
VTE prophylaxis
Ongoing management;
Ketones should fall by >0.5mmol/ L/ hour
Blood glucose should fall by 3mmol/ L/ hour
Once blood glucose below 14, 10% glucose infusion alongside saline and insulin
97
What is diabetic peripheral neuropathy?
Spectrum of peripheral nerve disorders as a result of chronic hyperglycaemia
98
Pathophysiology of diabetic peripheral neuropathy?
Chronic hyperglycaemia leads to damage of peripheral nerves due to build up of advanced glycation end products, oxidative stress, inflammatory pathways
99
Clinical features of diabetic peripheral neuropathy?
Distal symmetrical sensory neuropathy;
Most common form of DPN.
Resulting from loss of large sensory fibres.
Presents with sensory loss in a 'glove and stocking' distribution, typically affecting touch, vibration and proprioception.
Small fibre predominant neuropathy;
Due to the loss of small sensory fibres.
Manifests as deficits in pain and temperature sensation in a 'glove and stocking' distribution, often accompanied by episodes of burning pain.
Diabetic Amyotrophy
Originates from inflammation of the lumbosacral plexus or cervical plexus.
Characterised by severe pain around the thighs and hips, along with proximal weakness.
Mononeuritis Multiplex
Typically painful.
Defined as neuropathies involving two or more distinct peripheral nerves.
Autonomic Neuropathy
Presents with postural hypotension, gastroparesis, constipation, urinary retention, arrhythmias, and erectile dysfunction.
100
Differentials for diabetic peripheral neuropathy?
Vitamin B12 deficiency
Alcohol induced peripheral neuropathy
Chronic inflammatory demyelinating polyneuropathy
Hypothyroidism
101
Investigations to diagnose diabetic peripheral neuropathy?
Neurological examination
Nerve conduction studies
Blood tests; HbA1c, B12 levels, TFT, LFT,
102
Complications of diabetic peripheral neuropathy?
Foot ulcers due to loss of sensation
Autonomic neuropathy leading to cardiac, gastrointestinal and genitourinary disturbance
103
Management of diabetic peripheral neuropathy?
Good blood glucose control
Pain control; gabapentin
Manage complications; foot ulcers, autonomic disturbance
104
What is charcot arthropathy?
Chronic progressive condition characterised by painful or painless bone and joint destruction in the limbs that have lost sensory innervation
105
Aetiology of charcot arthropathy?
Diametes mellitus
Syringomyelia
Chronic alcohol abuse
Syphilis
106
Signs and symptoms of charcots arthropathy
Destruction of bone and joint
Deformity
Degeneration
Dense bones
Debris of bone fragments
Dislocation
107
Differentials for charcots arthropathy?
Osteomyelitis
108
Investigations to diagnose charcots arthropathy?
X-ray
MRI
Bone scans
109
Management of charcots arthropathy?
Prolonged off- loading
Use of orthotics
Medications; bisphosphonates, gabapentin/ pregabalin
Surgical; resection of bony prominence, amputation
110
Grades of diabetic retinopathy?
Mild NPDR: Microaneurysms and dot haemorrhages on fundoscopy.
Moderate NPDR: Microaneurysms, dot and blot haemorrhages, cotton-wool spots, and hard exudates.
Severe NPDR: Beaded veins, intraretinal microvascular abnormalities (IRMA), and extensive retinal hemorrhages.
Proliferative diabetic retinopathy; neovasculariation and fibrous proliferation on the retina or vitreous posing a higher risk of vision loss
111
Pathophysiology of diabetic retinopathy?
Chronic hyperglycaemia leads to structural changes to the retinal capillaries, thickening of basement membrances and loss of pericytes
This results in capillary occlusion, leakage leading to retinal ischaemia and formation of new fragile vessels
112
Symptoms of diabetic retinopathy?
Floaters or dark spots in the vision
Blurred or distorted vision
Difficulty seeing at night
Sudden loss of vision
113
Differentials for diabetic retinopathy?
ARMD
Retinal vein occlusion
Hypertensive retinopathy
114
Investigations to diagnose diabetic retinopathy?
Fundoscopy
OCT
Fluorescien angiography
115
What is seen on fundoscopy in diabetic retinopathy?
Signs of milder disease include:
Microaneurysms
Hard exudates
Blot haemorrhages
Severe disease presents with:
Engorged tortuous veins
Large blot haemorrhages.
116
Management of diabetic retinopathy?
Blood glucose control
Laser photocoagulation
Intravitreal injections of anti- VEGF
Vitrectomy
117
Complications of diabetic retinopathy?
Vitreous haemorrhage
Tractional retinal detachment
Macular oedema
Neovascular glaucoma
Blindness
118
What is galactorrhoea?
Inappropriate and spontaneous milky secretion from the breasts
119
Aetiology of galactorrhoea?
Idiopathic
Prolactinoma
Drugs; antipsychotics, SSRI, cimetidine, beta blocker
Metabolic conditions; hypothyroidism, liver disease, chronic renal impairment
Physiological
120
Signs and symptoms of galactorrhoea?
Spontaneous, persistent milky discharge
121
Investigations to find cause of galactorrhoea?
Serum prolactin
TFT
Renal and liver function tests
MRI of brain and pituitary gland
122
Management of galactorrhoea?
Stop any medications that caused it
If antipsychotics are still needed co-prescribe dopamine agonist such as cabergoline
Management of underlying condition
Surgery or radiation
123
What is goitre?
Abnormal enlargement of the thyroid gland
124
Types of goitre?
Smooth Goitre: Enlargement of the thyroid gland without distinct nodules.
Nodular Goitre: Presence of one or more distinct nodules within the thyroid gland, which can be further classified into hot (functioning) or cold (non-functioning) nodules.
125
Epidemiology of goitre?
Worldwide iodine deficiency is the most common cause, in the UK Grave's disease is the most common cause
126
Aetiology of goitre?
Smooth goitre;
Graves disease
Hashimoto's thyroiditis
Drugs; lithium, amiodarone
Iodine deficiency/ excess
De Quervians thyroiditis
Infiltrative thyroiditis; sarcoiditis, haemochromatosis
Nodular goitre;
Toxic solitary adenoma
Non functional thyroid adenoma
Multinodular goitre
Thyroid cyst
Thyroid cancer
127
Signs and symptoms of goitre?
Visible/ palpable swelling which moves up and down on swallowing but not on tongue protrusion
Voice hoarseness
Difficulty swallowing or breathing
Symptoms of hypothyroidism or hyperthyroidism
128
Differentials for goitre?
Thyroid lymphoma
Thyroglossal duct cyst
Branchial cleft cyst
129
Investigations to diagnose goitre?
TFT
Ultrasound scan
Fine needle aspiration biopsy
130
131
What is gynaecomastia?
Enlargement of male breast tissue as a result of benign increase in glandular breast tissue rather than adipose tissue
132
Aetiology of gynaecomastia?
Obesity
Chronic liver disease
Anabolic steroid use
Tumour; sertoli cell, leydig cell and germ cell tumours
Exogenous oestrogen
Hyperthyroidism
Hypogonadotrophic hypogonadism
Hyperprolactinaemia
Testicular failure
Medications; spironolactone, GnRH agonist, chemotherapy agents, ketoconazole
Illicit drugs
133
Signs and symptoms of gynaecomastia?
Enlargement of one or both breasts
Can be tender
134
Investigations to diagnose gynaecomastia?
LFT, U+E, TFT, LH, FSH, testosterone, oestrogen, prolactin
Imaging; breast ultrasound, mammogram
Testicular ultrasound
135
Management of gynaecomastia?
Observe
Treat underlying cause
Medciations; tamoxifen, danazol
Surgery; breast reduction
Psychological management
136
What is hirsutism?
Females have excess hair growth in a male pattern distribution, including areas such as the face, back, chest, and abdomen.
137
Epidemiology of hirsutism?
5-10% of premenopausal women
PCOS is the most common cause affecting 6-10% of women at reproductive age
138
Aetiology of hirsutism?
Polycystic Ovary Syndrome (PCOS): The most common cause in women of reproductive age.
Androgen-secreting tumours.
Congenital adrenal hyperplasia.
Cushing's syndrome.
Acromegaly.
Severe insulin resistance.
Idiopathic hirsutism.
Medications: Such as steroids, phenytoin, and ciclosporin.
Anorexia nervosa.
Hypothyroidism.
Familial trait: In some cases, hirsutism is an inherited trait.
139
Signs and symptoms of hirsutism?
Deep voice
Acne
Frontal balding
Large muscles
Mood changes
140
Differentials for hirsutism?
Hypertrichosis
Medication induced hirsutism
141
Investigations to diagnose hirsutism?
Serum testosterone
DHEAS, 17- hydroxyprogesterone, prolactin, TSH
Pelvic USS
142
Management of hirsutism?
Address cause
Cosmetic strategies
Pharmacological treatment; spironolactone, flutamide, COCP
143
What is hyperaldosteronism?
Over production of aldosterone produced by the adrenal glands resulting in fluid retention, high blood pressure, low serum potassium
144
Aetiology of hyperaldosteronism?
Adrenal adenoma (Conns syndrome)
Bilateral adrenal hyperplasia
Familial hyperaldosteronism
Adrenal carcinoma
145
Signs and symptoms of hyperaldosteronism?
Polyuria: Increased frequency of urination.
Polydipsia: Increased thirst.
Lethargy: Persistent tiredness and fatigue.
Headaches: Often severe and frequent.
Association with osteoporosis
146
Differentials for hyperaldosteronism?
Essential hypertension
Cushing's syndrome
Phaeochromocytoma
147
Investigations to diagnose hyperaldosteronism?
Aldosterone to renin ratio
High resolution CT
MRI
Selective adrenal venous sampling
148
Management of hyperaldosteronism?
Surgical removal of tumour
Medication; K+ sparring diuretics (amiloride, spironolactone, eplerenone)
149
What is HHS?
Marked hyperglycaemia (30 mmol/L or more) without significant ketosis (<3 mmol/L) or acidosis (pH>7.3, bicarbonate >15 mmol/L) [though this condition may occur concomitantly with DKA] and,
Osmolality 320 mosmol/kg or more: 2Na+ + glucose + urea
150
Risk factors for HHS?
Type 2 diabetes, often with a prior history of poor glycemic control
Advanced age
Infections or other illnesses
Medications that affect glucose metabolism
151
Pathophysiology of HHS?
Severe hyperglycaemia as a result of profound insulin deficiency, increased hepatic glucose production, osmotic diuresis leading to severe dehydration, hyperosmolality resulting in neurological symptoms
152
Signs and symptoms of HHS?
Profound dehydration with dry mucous membranes
Excessive thirst (polydipsia) and urination (polyuria)
Altered mental status, ranging from confusion to coma
Neurological symptoms, such as seizures or focal deficits
Hypotension and tachycardia
153
Investigations to diagnose HHS?
Measurement of blood glucose levels
Serum osmolality assessment
Electrolyte panel (especially sodium and potassium levels)
Urinalysis for ketones (typically absent in HHS)
Evaluation of underlying causes (e.g infections)
154
Management of HHS?
0.9% saline fluid resuscitation
Insulin
155
Complications of HHS?
Hypovolemic shock
Cerebral oedema
Thromboembolic events
Acute kidney injury
Cardiac arrhythmias
Respiratory failure
Long-term neurological sequelae
156
What is hyperparathyroidism?
Excessive secretion of PTH
157
Causes of hyperparathyroidism?
Primary Hyperparathyroidism (PHPT): Commonly caused by a parathyroid gland adenoma, hyperplasia of all four glands, or parathyroid carcinoma.
Secondary Hyperparathyroidism (SHPT): Typically due to vitamin D deficiency, loss of extracellular calcium, calcium malabsorption, abnormal parathyroid hormone activity, or inadequate calcium intake.
Tertiary Hyperparathyroidism (THPT): Occurs after prolonged secondary hyperparathyroidism due to conditions like chronic kidney disease.
158
Signs and symptoms of hyperparathyroidism?
Moans: Painful bones
Stones: Renal stones
Groans: Gastrointestinal symptoms (nausea, vomiting, constipation, indigestion)
Psychiatric Moans: Neurological effects (lethargy, fatigue, memory loss, psychosis, depression)
159
Differentials for hyperthyroidism?
Hypoparathyroidism
Vitamin D deficiency
Chronic kidney disease
Multiple endocrine neoplasia
160
Management of hyperparathyroidism?
Primary Hyperparathyroidism (PHPT): Definitive management is parathyroidectomy.
Secondary Hyperparathyroidism (SHPT): Address underlying causes; vitamin D supplementation and phosphate binders may be needed.
Tertiary Hyperparathyroidism (THPT): Managed with medication like Cinacalcet, a calcimimetic that mimics the action of calcium on tissues, or via total or subtotal parathyroidectomy.
161
What is hyperthyroidism?
Overactive thyroid gland producing an excess of thyroid hormone
162
What is thyrotoxicosis?
Syndrome resulting from the presence of excessive thyroid hormones in the body and not necessarily related to an overactive thyroid gland
163
Epidemiology of hyperthyroidism?
Affects women more than men
Graves disease is the most common cause
1-2% prevalence in the general population
164
Aetiology of hyperthyroidism?
Primary causes;
Grave's disease: Resulting from autoimmune stimulation of the thyroid gland by TSH receptor auto-antibodies.
Toxic adenoma: Adenoma that produces thyroid hormones.
Toxic multinodular goitre: Multiple thyroid nodules that produce thyroid hormones, leading to goitre.
Medications: Such as amiodarone.
Thyroiditis: Inflammation of the thyroid gland, e.g., de Quervain's thyroiditis.
Radiation exposure
Secondary causes;
Amiodarone
Lithium
TSH producing pituitary adenoma
Choriocarcinoma (beta-hCG can activate TSH receptors)
Gestational hyperthyroidism
Pituitary resistance to thyroxine (i.e., failure of negative feedback)
Struma ovarii (ectopic thyroid tissue in ovarian tumours)
165
Signs and symptoms of hyperthyroidism?
↑ Basal metabolic rate
Heat intolerance
Tachycardia and arrhythmias
Weight loss
Diarrhoea
Sweaty skin
Insomnia and sleep disturbances
Restlessness and tremors
Goitre (depending on cause)
Anxiety
Specific for graves disease;
Exophthalmos/ proptosis
Thyroid acropachy
Pretibial myxoedema
166
Differentials for hyperthyroidism?
Anxiety
Phaeochromocytoma
Hypothyroidism
167
Pathophysiology of graves disease?
Anti- TSH IgG antibodies which activate TSH receptors on thyroid gland and increase T3/ T4 production
168
Investigations for hyperthyroidism?
Elevated T3/T4
Elevated thyroid stimulating immunoglobulins, thyrotropin receptor antibodies in graves disease
USS of thyroid
Radio-iodine uptake test
169
Management of hyperthyroidism?
Carbimazole/ propylthiouracil
Betablockers; symptom control
Radio-iodine
Thyroidectomy
Treat malignancy
170
Main adverse effect of carbimazole?
Agranulocytosis
171
What is thyroid storm?
Life threatening emergency caused by untreated/ inadequetly managed hyperthyroidism
172
Triggers for thyroid storm?
Surgery
Trauma
Infection
173
Features of thyroid storm?
Restlessness and agitation
High-output heart failure
Profound tachycardia
Fever
Delirium and altered mental status
174
Management of thyroid storm?
Counteract peripheral thyroid action; propanolol digoxin
Inhibit thyroid synthesis; propylthiouracil through NG tube
Corticosteroids; prednisolone, hydrocortisone
175
Complications of hyperthyroidism?
Thyroid eye disease
Exposure keratopathy
Compressive optic neuropathy
Atrial fibrillation
High output heart failure
Osteopenia/ osteoporosis
Upper airway obstruction
Thyroid cancer
Thyroid storm
176
What is hypocalcaemia?
Adjusted serum calcium below 2.2 mmol/ L
177
Aetiology of hypocalcaemia?
Hypoparathyroidism; iatrogenic, autoimmune, infiltration (malignancy, thalassaemia, amyloidosis, Wilson's disease, haemochromatosis), congenital
Hypomagnesaemia
Vitamin D deficiency; lack of sun exposure, malnutrition, malabsorption, abnormal metabolism due to CKD, liver disease
Medications; calcimimetics, bisphosphonates, loop diuretics, cisplatin, foscarnet, phenytoin, ketoconazole
Genetics; AD hypocalcaemia
Psuedohypoparathyroidism
Alkalosis
Massive blood transfusion
Renal replacement therapy
Acute pancreatitis
Hyperphosphataemia; CKD, tumour lysis syndrome, rhabdomyolysis
Sepsis
178
What is the cause of genetic hypocalcaemia?
Autosomal dominant gain of function mutation in the calcium sensing receptor gene
179
Signs and symptoms of hypoparathyroidism?
Paraesthesias (typically periorally and affecting the digits)
Muscle cramps
Muscle spasms
Anxiety and depression
Confusion
Weakness and fatigue
Myalgia
Dry skin
Coarse hair
Brittle nails
Signs;
Hyperreflexia
Muscle fasiculations
Chvostek's sign; tapping the facial nerve where it passes in front of the ear provokes muscle spasm of the face
Neuromuscular hyperexcitability
Trousseau's sign; inflating a blood pressure cuff above patients systolic level and keeping the cuff above systolic level causes spasms in muscles of the forearm
Hypotension (rarely)
Bradycardia
Decreased consciousness
Delirium
Papilloedema
Skin changes e.g. eczema, dermatitis, hyperpigmentation
Patchy alopecia
Transverse grooving of nails
180
Differentials for hypocalcaemia?
Pseudohypocalcaemia
Contamination of blood bottles
181
Investigations to diagnose hypocalcaemia?
ECG; prolonged QTc, AF
Blood gas; rapidly confirm hypocalcaemia
Urine dip
Bone profile
PTH levels
FBC
U+E
CRP
LFT
Vitamin D
Amylase
Creatinine kinase
182
Management of hypocalcaemia?
Increase oral intake
IV calcium replacement; calcium gluconate with glucose over 10 minutes if under 1.9mmol/ L
Vitamin D supplementation
Replace magnesium
183
What other electrolyte needs to be corrected when treating hypocalcaemia?
Magnesium
184
Complications of hypocalcaemia?
Acute;
Seizures - may be generalised motor or absence seizures, or focal
Arrhythmias - e.g. torsades de pointes due to QTc prolongation
Laryngospasm - common in infancy but rarer in adults
Bronchospasm - also uncommon in adults, may mimic an asthma exacerbation
Chronic;
Cataracts
Dental disease
Basal ganglia calcification
185
What is hypoglycaemia?
Abnormally low blood glucose level, typically defined as less than 3.5 mmol/L.
186
Epidemiology of hypoglycaemia?
Common in patients with diabetes, especially those taking insulin or sulphonylurea therapies
187
Aetiology of hypoglycaemia?
Drugs: Insulin, Sulphonylureas, GLP-1 analogues, DPP-4 inhibitors, Beta-blockers
Alcohol
Acute liver failure
Sepsis
Adrenal insufficiency
Insulinoma
Glycogen storage disease
188
Symptoms of hypogycaemia?
Adrenergic symptoms; blood glucose <3.3 mmol/ L
Trembling
Sweating
Palpitations
Hunger
Headache
Neuroglycopenic symptoms; blood glucose below 2.8mmol/ L
Double vision
Difficulty concentrating
Slurred speech
Confusion
Coma
189
Differentials for hypoglycaemia?
Diabetic ketoacidosis
Adrenal insufficiency
Insulinoma
Alcohol intoxication
190
What is whipples triad?
Plasma hypoglycaemia
Symptoms attributable to a low blood sugar level
Resolution of symptoms with correction of the hypoglycaemia
191
Investigations to diagnose hypoglycaemia?
Capillary glucose
Insulin levels, C-peptide, pro-insulin levels
Synacten test
Abdominal imaging
192
Management of hypoglycaemia?
Conscious;
ABCDE
15-20g of fast acting carbohydrates
Follow with slow acting carbohydrates
Severe hypoglycaemia; seizures/ unconscious;
ABCDE
200mls of 10% dextrose
1mg IM glucagon
193
What is hypogonadism?
Testes produce insufficient sex hormones leading to physical, cognitive and sexual symptoms
194
Epidemiology of hypogonadism?
Increases with age
20% over 60 and 50% over 80
195
Risk factors for hypogonadism?
Obesity
T2DM
Genetic disorders
Treatments for prostate cancer
196
Aetiology of hypogonadism?
Primary hypogonadism: Klinefelter syndrome, orchitis, testicular trauma or torsion, chemotherapy, radiation therapy.
Secondary hypogonadism: Kallmann syndrome, pituitary adenomas, hyperprolactinemia, anorexia nervosa, opioid use, glucocorticoid use, HIV/AIDS, hemochromatosis.
197
Signs and symptoms of hypogonadism?
Lethargy
Weakness
Weight gain
Loss of libido
Erectile dysfunction
Gynaecomastia
Depression
198
Differentials for hypogonadism?
Depression
Thyroid disorders
Chronic fatigue syndrome
199
Investigations to diagnose hypogonadism?
Full Blood Count (FBC)
Urea and Electrolytes (U&E)
Liver Function Tests (LFTs)
Bone profile
Fasting glucose and lipids
Prostate-Specific Antigen (PSA)
Oestrogen, testosterone, Sex Hormone Binding Globulin (SHBG)
Luteinizing Hormone (LH)/ Follicle Stimulating Hormone (FSH)
Prolactin
Thyroid-stimulating Hormone (TSH), Thyroxine (T4), Triiodothyronine (T3)
Cortisol
Magnetic Resonance Imaging (MRI) of the pituitary
Chest radiograph
Karyotyping
Dual-energy X-ray absorptiometry (DEXA) scan
200
Management of hypogonadism?
Hormone replacement therapy; topical/ buccal/ IM injection
Monitor FBC, Bone mineral density
201
What is hypoparathyroidism?
Abnormally low PTH levels leading to disturbance in calcium and phosphorous metabolism
202
Epidemiology of hypoparathyroidism?
Rare disease, affecting all ages
Primary hypoparathyroidism is often due to surgical causes or autoimmune
203
Risk factors for hypoparathyroidism?
Neck surgery/ radiation therapy
Autoimmune conditions
Genetic/ familial forms of the disease
204
Pathophysiology of hypoparathyroidism?
Decreased PTH production or function disrupts calcium and phosphorous homeostasis leading to decreased calcium absorption from the intestines, reduced bone resorption and impaired renal reabsorption of calcium
205
Signs and symptoms of hypoparathyroidism?
Hypocalcemia-related manifestations: muscle cramps, paresthesias, tetany, and seizures
Neuropsychiatric symptoms: anxiety, depression, and cognitive impairment
Ocular symptoms: cataracts and impaired night vision
Dental abnormalities: dental enamel hypoplasia and tooth discoloration
206
Differentials of hypoparathyroidism?
Hypocalcemia due to other causes (e.g. renal failure)
Vitamin D deficiency
Neuromuscular disorders
Psychiatric conditions
207
Investigations to diagnose hypoparathyroidism?
Low serum calcium, high phosphate
PTH levels; low/ normal
Vit D
Urinary calcium
ECG; prolonged QTc
208
Management of hypoparathyroidism?
Calcium and vitamin D supplementation
Regular monitoring
Address symptoms
Surgical replacement
IV calcium gluconate may be required
209
Complications of hypoparathyroidism?
Severe hypocalcaemia
Kidney stones
Impaired renal function
Cataracts
Neurological/ neuropsychiatric sequelae
210
What is pseudohypoparathyroidism?
Genetic disorder where bone, kidney and gut fails to respond to PTH due to defects in the PTH receptors with no deficiency in PTH
211
Aetiology of pseudohypoparathyroidism?
Mutations in the GNAS1 gene, which codes for the alpha subunit of the Gs protein. This protein is vital for PTH to exert its action on its target cells
212
Signs and symptoms of pseudohypoparathyroidism?
Short stature and shortened 4th and 5th metacarpals in fingers
Hypocalcemia leading to:
Numbness or tingling of the fingers and toes
Muscle cramps
Carpopedal spasm
Seizures
Chvostek's sign: Twitching of the face after tapping the facial nerve
Trousseau's sign: Carpopedal spasm after inflating a blood pressure cuff
Symptoms related to vitamin D deficiency such as bone pain and fractures
213
Differentials for pseudohypoparathyroidism?
Hypoparathyroidism
Vitamin D deficiency
Malnutrition
214
Management of pseudohypoparathyroidism?
Calcium and vitamin D supplementation
215
What is hypothyroidism?
Insufficient production of thyroid hormones
216
Epidemiology of hypothyroidism?
High prevalence in women
Iodine deficiency is most common cause worldwide and hashimotos thyroiditis is most common in UK
217
Aetiology of hypothyroidism?
Autoimmune thyroiditis; hashimotos, atrophic thyroiditis, autoimmune polyendocrine syndromes
Iatrogenic causes; surgical removal, radioablation, radiation therapy
Congenital; thyroid aplasia, pendred syndrome
Iodine deficiency
Infiltrative disorder
Sarcoidosis
Haemochromatosis
218
Signs and symptoms of hypothyroidism?
Peripheral Features: Dry, thick skin, Brittle hair, Scanty secondary sexual hair.
Queen Anne's sign - loss of outer 1/3 of eyebrows
Cold intolerance, may result in wearing additional layers of clothing
Head and Neck Features: Macroglossia, puffy face, goitre (depending on cause).
Cardiac Features: bradycardia, cardiomegaly.
Neurological Features: Carpal tunnel syndrome, slow relaxing reflexes, cerebellar ataxia, peripheral neuropathy, difficulty concentrating
Joint pain
Menorrhagia
219
Differentials for hypothyroidism?
Iron deficiency anaemia
Chronic fatigue syndrome
Depression
220
Investigations to diagnose hypothyroidism?
Thyroid examination
TFT, antibody testing, iodine levels
USS of the neck
Thyroid gland biopsy
221
Management of hypothyroidism?
Levothyroxine
Review TSH every 3 months then annually when stable
222
Hypothyroidism during pregnancy?
Usually increase levothyroxine by 25-50 mcg
TFT should be checked once pregnancy is confirmed
223
Pregnancy related complications of hypothyroidism?
Miscarriage
Preterm birth
Gestational hypertension
Pre-eclampsia
Placental abruption
Low birth weight
Neurodevelopmental delay
Congenital hypothyroidism
224
What is MEN?
Genetic conditions characterised by development of multiple neoplasms in multiple endocrine organs
225
Epidemiology of MEN?
Rare with each subtypes with different incident rates
Inherited in Autosomal dominant manner
226
Aetiology of MEN?
MEN-1 is caused by mutations in the MEN1 gene.
MEN-2a and MEN-2b are caused by mutations in the RET gene.
227
Features of MEN-1?
Parathyroid: hyperplasia/adenomas causing hypercalcemia
Pancreas: gastrinomas causing peptic ulcers, insulinomas causing hypoglycaemia
Pituitary: prolactinomas causing galactorrhoea and amenorrhoea in women, reduced libido in men
228
Features of MEN-2a?
Thyroid: medullary thyroid cancer causing dysphagia, hoarseness
Adrenal: pheochromocytomas causing episodic hypertension, palpitations, headache
Parathyroid: hyperplasia/adenomas causing hypercalcemia
229
Features of MEN-2b?
Thyroid: medullary thyroid cancer causing dysphagia, hoarseness
Adrenal: pheochromocytomas causing episodic hypertension, palpitations, headache
Parathyroid: hyperplasia/adenomas causing hypercalcemia
Mucosal neuromas: presenting as bumps on the lips, tongue, and inner cheeks
230
Differentials for MEN?
Non MEN endocrine neoplasia
Carney complex
Von Hippel Lindau
231
Investigations to diagnose MEN syndromes?
MEN1 and RET gene testing
Hormonal assay
CT/ MRI
232
Management of MEN?
Surgical removal of tumours
Hormonal therapy to control hormone overproduction
Lifelong surveillance
233
Factors that influence development of obesity?
Genetics
Environmental
Socio-economic status
Psychological factors
Medical conditions
234
Signs and symptoms of obesity?
Increased Body Weight: As a primary indicator, obesity is defined by an elevated BMI.
Central Obesity: Accumulation of excess fat around the abdomen, leading to an "apple-shaped" body.
Joint Pain: Obesity can cause joint strain and musculoskeletal pain.
Fatigue: Individuals with obesity may experience reduced energy levels.
Breathlessness: Obesity can result in shortness of breath, especially during physical activity.
Sleep Apnea: Obesity is a common cause of obstructive sleep apnea.
Psychological Impact: Obesity may lead to depression, low self-esteem, and poor body image.
235
BMI reference ranges?
Underweight < 18.5
Normal weight 18.5-24.9
Overweight 25-29.9
Obesity (Class I) 30-34.9
Obesity (Class II) 35-39.9
Obesity (Class III/Severe) ≥ 40
236
Management of obesity?
Dietary changes
Physical activity
Lifestyle modifications
GLP-1 analogues
Bariatric surgery
237
What is osteomalacia?
Metabolic bone disease that occurs in adults characterised by insufficient osteoid mineralisation
238
Risk factors for vitamin D deficiency?
Older age (aged over 65)
Darker skin pigmentation (e.g. South Asian or African-Caribbean patients)
Obesity
Patients who cover their skin for cultural, religious or health reasons
Housebound patients or those living in care homes
Malabsorption due to a gastrointestinal disorder or previous weight-loss surgery
End-stage chronic kidney disease
Severe liver cirrhosis
Vegetarian or vegan diets
Medications increasing risk of vitamin D deficiency (e.g. orlistat, carbamazepine, antacids)
239
Aetiology of osteomalacia?
Vitamin D deficiency
Inadequet dietaey intake
Lack of sunlight exposure
Malabsorption syndrome
Medications; anti-epileptics, corticosteroids, rifampicin, thiazide diuretics
CKD, liver cirrhosis
Fanconi syndrome
240
Sings and symptoms of osteomalacia?
Bony pain (e.g. lower back, pelvis, shoulders, legs or ribs)
Muscular weakness and pain
Difficulty walking
Malaise and lethargy
Persistent fatigue
Paraesthesias (late sign)
A waddling gait
Proximal muscle weakness
Generalised bone and joint tenderness
Signs of hypocalcaemia (e.g. tetany, carpopedal spasm)
Spinal deformities e.g. kyphoscoliosis
241
Differentials for osteomalacia?
Rickets
Primary hypoparathyroidism
Bone metastases
Renal osteodystrophy
Osteoporosis
Pagets disease
Hypothyroidism
Polymyalgia rheumatica
242
Investigations to diagnose osteomalacia?
Urinalysis; proteinuria, reduced urinary calcium, 24 hour urinary phosphate
Vit D, bone profile, PTH, U+E, LFT, FBC, ferritin, B12, folate, TFT, coeliac serology
DEXA
Bone X-ray
243
Management of osteomalacia?
Loading dose of Vit D; 300,000 IU over 6-10 weeks
Maintenance vit D; 800-2000 IU
Calcium supplementation
244
What is osteoporosis?
State of low bone mineral density with structural deterioration of bones causing bones to weaken increasing risk of fragility fracture
245
What is the definition of osteoporosis?
Bone mineral density atleast 2.5 standard deviations below the mean peak mass of a healthy adult
246
Epidemiology of osteoporosis?
Post menopausal women are at most risk
Increases with age
More common in white ethnicity
247
Risk factors for osteoporosis?
Reduced bone density;
Low body weight
Menopause
immobility
Chronic disease; CKD, COPD, liver disease
Malabsorption; coeliac, IBD, pancreatic insufficiency
Hyperparathyroidism, hyperthyroidism
Medications; PPI, SSRI, carbamazepine
Do not impact bone density;
Older age
Inflammatory arthritis
Prolonged use of corticosteroids
Smoking
Alcohol excess
Hx of fragility fractures
Paternal hip fracture
248
Signs and symptoms of osteoporosis?
Asymptomatic- presents with fragility fracture
Loss of height
Kyphosis
Shortened and externally rotated leg
Dinner fork deformity in wrist fracture
249
Common places to see fragility fractures?
Vertebral body
Neck of femur (hip)
Distal radius
Proximal humerus
Pelvis
250
Differentials for osteoporosis?
Bone metastases
Osteomalacia
Multiple myeloma
Pagets disease
Osteogenesis imperfecta
Avascular necrosis
251
When should a DEXA scan be offered?
Aged over 50 presenting with a fragility fracture
Aged under 40 with a major risk factor for fragility fracture (e.g. long-term steroids)
Those about to start treatment that will rapidly decrease bone density (e.g. hormone deprivation in breast cancer) - consider
All other patients with risk factors should have their fracture risk assessed as the initial step
252
Tools to assess risk of osteoporotic fractures?
QFracture, FRAX
253
Gold standard investigation to diagnose osteoporosis?
DEXA scan which gives T score
<-2.5; osteoporosis
-1 - -2.5; osteopenia
254
Management of osteoporosis?
Optimise risk factors; smoking cessation, alcohol reduction
Regular weight bearing exercise
Assess falls risk
Vitamin D, calcium replacement
First line; bisphosphonates
Denozumab
Teriparatide
HRT
Raloxifene hydrochloride
Surgical fixation of neck of femur
255
Complications of osteoporosis?
Hip fractures
Vertebral fractures
Wrist fractures
Complications from bisphosphonate treatment
256
Epidemiology of pagets disease?
In the UK, it is estimated that Paget's disease affects approximately 6.9% of men and 5.8% of women aged 85 years and older
257
Risk factors for pagets disease?
Age over 40 years
Family history of Paget's Disease
Anglo-Saxon descent
258
Pathophysiology of pagets disease?
Increased osteoclast activity followed by increased osteoblast activity leading to disorganised bone breakdown and formation leaving abnormal bone structure with a mix of woven and lamellar bone
259
Signs and symptoms of pagets disease?
Kidney stone symptoms
Joint pain
Bounding pulse and tachycardia due to high output
Positive Tinel and Phalen's due to carpal tunnel
Collapsing pulse
Bossed skull
Visual loss, cranial nerve abnormalities
Hearing aids
Features of heart failure
Bowing of the legs/bony deformity
Hot skin overlying the bone involved
Evidence of previous pathological fractures
Fundoscopy reveals optic atrophy and angioid streaks
260
Differentials for pagets disease?
Metabolic bone disease
Osteoporosis
Osteomalacia
Bone tumors
261
Investigations to diagnose pagets disease?
X-ray;
Early findings; osteolysis
Later findings; increased bone size, sclerosis, osteolytic lesions, pathological fractures
ALP- raised
262
Management of pagets disease?
Pain management with analgesics
Bisphosphonates; alendronic acid for 6 months
Monitoring every 6-12 months to check for recurrence
263
Complications of pagets disease
Pathological fracture
High output heart failure
Nerve entrapment - deafness, optic nerve atrophy, carpal tunnel, cord compression, spinal canal stenosis
Osteoarthritis
Osteosarcoma
Kidney stones
Bone deformity
264
What is phaeochromocytoma?
Catecholamine secreting tumour which originates from adrenal medulla
265
Epidemiology of phaeochromoytoma?
More common between 3rd and 5th decade of life
0.5-2 in 1000 patients with hypertension
266
Aetiology of phaeochromocytoma?
Genetic; genes such as RET, VHL, NF1, SDH
267
Signs and symptoms of phaeochromocytoma?
Episodic hypertension
Anxiety
Weight loss
Fatigue
Palpitations
Excessive sweating
Headaches
Flushing
Fever
Difficulty breathing (dyspnea)
Abdominal pain
Signs
Hypertension
Postural hypotension
Tremor
Hypertensive retinopathy
268
Differentials for phaeochromocytoma?
Anxiety disorder
Hyperthyroidism
Essential hypertension
269
Investigations to diagnose phaeochromocytoma?
Plasma metanephrines
CT chest abdomen pelvis
Extra adrenal phaeochromocytomas can be identified on MIBG or PET scans
270
Management of phaeochromocytoma?
Alpha blockade; phenoxybenzamine
Beta blockade to manage tachycardia/ arrhythmia
271
What is a pituitary adenoma?
Most common type of pituitary tumour which is typically benign and non secretory in nature
272
Epidemiology of pituitary adenoma?
More frequently occur in adults
Most common pituitary pathology
273
Pathophysiology of pituitary adenoma?
They may be non-functioning (non-secretory) or cause overproduction of specific hormones, leading to hormonal imbalances.
274
Signs and symptoms of pituitary adenoma?
Headache
Visual field defect
275
Investigations to diagnose pituitary adenoma?
MRI
Visual field assessment
Hormone testing
276
Management of pituitary adenoma?
Neurosurgery; transspenoidal
Radiotherapy
Medications that can block specific hormone overproduction
277
Complications of pituitary adenoma?
Hormonal imbalance
Recurrence
Surgical risks; damage to surrounding structures, potential hormonal deficiencies
278
What is a prolactinoma?
Pituitary tumours characterised by excessive production of proloactin
279
Pathophysiology of prolactinoma?
Arise within pituitary gland and lead to increased prolactin secretion
280
Signs and symptoms of prolactinoma?
Women: Oligomenorrhea or amenorrhea, galactorrhea (breast milk production outside of pregnancy or breastfeeding), infertility, and vaginal dryness.
Men: Erectile dysfunction, reduced facial hair growth.
In Both Sexes: tumor-related symptoms, such as headaches and visual field defects, may also occur.
281
Investigations to diagnose prolactinoma?
MRI brain
Serum prolactin
282
Management of prolactinoma?
Dopamine agonist; cabergoline
Hormone replacement therapy
Trans-sphenoidal surgery
Radiotherapy
283
Complications of prolactinoma?
Hyperprolactinaemia
Risks of surgery
Risks of radiation
284
What is hypopituitarism?
Partial or complete deficiency of hormones produced by pituitary gland affecting functions such as growth, reproduction, thyroid regulation, adrenal function and water balance
285
Causes of hypopituitarism?
Surgery
Radiotherapy
Infections
Infarction/ haemorrhage
Tumours
Congenital
286
Signs and symptoms of hypopituitarism?
Growth Hormone Deficiency: Manifests as central obesity, dry skin, reduced muscle strength, and decreased exercise tolerance.
FSH & LH Deficiency:
In Females: Oligomenorrhea or amenorrhea, infertility, sexual dysfunction, and breast atrophy.
In Males: Infertility, sexual dysfunction, and hypogonadism.
TSH Deficiency: Results in hypothyroidism.
ACTH Deficiency: Leads to adrenal deficiency, with symptoms including fatigue, reduced muscle mass, anorexia, myalgia, and gastrointestinal upset.
ADH Deficiency (Diabetes Insipidus): Causes excessive thirst and urination due to water imbalance
287
Management of hypopituitarism?
Replacement of hormones
288
What is prediabetes?
Prediabetes is a metabolic condition characterized by blood glucose levels higher than normal but not yet meeting the criteria for a diagnosis of type 2 diabetes. Prediabetes includes two subcategories: impaired fasting glucose (IFG) and impaired glucose tolerance (IGT).
289
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290
Epidemiology of prediabetes?
A significant global health concern with increasing prevalence
Prediabetes affects a substantial proportion of the adult population
It represents a critical stage in the progression to type 2 diabetes
291
Risk factors for pre-diabetes?
Overweight or obesity
Sedentary lifestyle
Family history of diabetes
Age, with increasing risk as individuals get older
Ethnicity, as some groups are at higher risk
292
Pathophysiology of pre-diabetes?
Prediabetes results from insulin resistance in target tissues (muscles, liver, adipose tissue) combined with impaired beta-cell function, leading to elevated blood glucose levels.
293
Investigations to diagnose pre-diabetes?
Impaired Fasting Glucose (IFG): Fasting blood glucose levels between 6.1-6.9 mmol/L
Impaired Glucose Tolerance (IGT): Two-hour oral glucose tolerance test (OGTT) values between 7.8-11.1 mmol/L
294
Management of pre-diabetes?
Lifestyle Modification: Emphasising healthy diet and increased physical activity
Weight Management: Achieving and maintaining a healthy weight
Pharmacotherapy: Considered in some cases with high risk factors
Regular Monitoring: Ongoing surveillance of blood glucose levels and cardiovascular risk factors
295
Complications of pre-dibetes?
Progression to type 2 diabetes
CVD
CKD
Neuropathy
296
What is pseudohypoparathyroidism?
Pseudohypoparathyroidism is a genetic disorder where the target organs (bone, kidney, and gut) fail to respond to normal levels of parathyroid hormone.
297
Epidemiology of pseudohypoparathyroidism?
Rare inherited condition
Female predominance
298
Aetiology of pseudohypoparathyroidism?
Pseudohypoparathyroidism is most commonly due to mutations in the GNAS1 gene, which codes for the alpha subunit of the Gs protein. This protein is vital for PTH to exert its action on its target cells.
299
Signs and symptoms of hypoparathyroidism?
Short stature
Hypocalcaemia; numbness/ tingling of fingers and toes, muscle cramps, carpopedal spasm, seizure, chvostek's sign, trousseau's sign
Signs of vitamin D deficiency
300
Differentials for pseudohypoparathyroidism?
Hypoparathyroidism
Vitamin D deficiency
Secondary causes of hypoparathyroidism
301
Investigations to diagnose pseudohypoparathyroidism?
Hypocalcemia on serum calcium levels
Normal or elevated levels of parathyroid hormone
302
Management of pseudohypoparathyroidism?
Calcium and vitamin D supplementation
303
Secondary causes of T2DM?
Pancreatic causes;
Cystic fibrosis
Chronic pancreatitis
Haemochromatosis
Cancer
Endocrine causes;
Cushing's syndrome
Acromegaly
Phaeochromocytoma
Thyrotoxicosis
Drugs;
Steroids
Atypical neuroleptics
Thiazides
Beta blockers
Glycogen storage disorders;
Type 1; von Gierke's disease
Type 2; Pompe disease
304
Side effects of metformin?
Lactic acidosis
GI disturbance
305
Side effects of sulfonylurea?
Hypoglycaemia
Weight gain
306
Side effects of Thiazolidinediones?
Fluid retention
Weight gain
Worsening heart failure
307
Side effects of SGLT-2 inhibitors?
Diabetic ketoacidosis
Increased risk of UTI
308
Side effects of DPP4- inhibitors?
Hypoglycaemia
GI upset
309
Side effects of GLP-1 analogues?
Hypoglycaemia
GI upset
Increased risk of pancreatitis
310
Side effects of Intestinal alpha-glucosidase inhibitors?
Flatulence
GI disturbance `
311
What is subclinical hyperthyroidism?
Sub-clinical hyperthyroidism is defined as a condition where serum TSH levels are below the reference range, but free T3 and T4 levels are within the normal range
312
Epidemiology of subclinical hyperthyroidism?
1-10% of the population
More common in women and those with a history of thyroid disease
313
Causes of subclinical hyperthyroidism?
Early Graves' disease
Autonomous nodular disease (toxic adenoma or multinodular goiter)
Exogenous intake of thyroid hormones or iodine
Transient thyroiditis
314
Differentials for subclinical hyperthyroidism?
Anxiety disorders
Paroxysmal atrial tachycardia
Menopause
315
Management of subclinical hyperthyroidism?
Watchful waiting with regular monitoring for elderly patients or those with TSH levels slightly below normal.
Antithyroid medications, radioactive iodine treatment, or surgery for patients with persistent sub-clinical hyperthyroidism, significant TSH suppression, symptoms of hyperthyroidism, or associated heart disease.
316
What is subclinical hypothyroidism?
Sub-clinical hypothyroidism is a condition characterized by a mildly raised TSH level (<10 mU/L) with normal circulating free T3 and T4 levels.
317
Epidemiology of subclinical hypothyroidism?
4-20% prevalence
More common in elderly and women
318
Aetiology of subclinical hypothyroidism?
Thyroid gland failure
Autoimmune thyroiditis
Medications; lithium, amiodarone, radioiodine therapy
319
Differentials for subclinical hypothyroidism?
Chronic fatigue syndrome
Depression
Iron deficiency anaemia
320
Management of subclinical hypothyroidism?
Most patients, particularly if asymptomatic and TSH <10 mU/L, may require no treatment, but monitoring with periodic thyroid function tests.
Thyroxine replacement is an option for symptomatic patients, or those with TSH consistently >10 mU/L, although evidence showing benefit is limited.
321
What is SIADH?
Excessive production of ADH
322
Aetiology of SIADH?
Pituitary tumour
Tumours: small cell lung cancer, thymoma, lymphoma
Pulmonary disease: infections, pneumothorax, asthma, cystic fibrosis
CNS disease: infection, head injury
Drugs: chemotherapy, psychiatric drugs
Idiopathic
323
Signs and symptoms of SIADH?
Symptoms of hyponatraemia; muscle cramps, nausea+ vomiting, confusion, coma, seizures
324
Investigations to diagnose SIADH?
Urea and electrolytes: shows a hyponatraemia
Plasma osmolality: will be low (<270mOsm/kg)
Urine sodium: will be high (>20mmol/L)
Urine osmolality: will be inappropriately concentrated (>100mOsmol/kg)
Imaging: MRI brain for pituitary tumour
325
Management of SIADH?
Fluid restriction
Surgery if pituitary cause
Medical management: demeclocycline is a drug which works by reducing collecting tubule cell sensitivity to ADH
326
Monitoring requirements for SIADH?
Regular U+E to monitor Na+ as rapid overcorrection can result in central pontine myelinolysis
327
Types of thyroid cancer?
Papillary Thyroid Cancer: Constitutes around 70% of all cases (think Papillary = Popular). Generally presents between 30-40 years of age and can metastasise to bone and lung. Small tumours carry an excellent prognosis.
Follicular Thyroid Cancer: This type is more common in areas with low iodine and among women, and typically presents between 30-60 years of age. It tends to metastasise to lung and bones rather than locally invade.
Medullary Thyroid Cancer: Comprising around 5% of thyroid cancer cases, it originates from calcitonin-producing C-cells. It can present with hypocalcaemia and diarrhoea due to increased calcitonin. While 75% of cases are sporadic, it is associated with Multiple Endocrine Neoplasia (MEN) syndrome type 2A and 2B. Metastasis often occurs to lymph nodes, and the prognosis is worse than papillary and follicular carcinoma.
Anaplastic Thyroid Cancer: The rarest form, it generally presents between 60-70 years old. Characterised by its aggressive nature, patients present with rapidly growing masses. The prognosis is extremely poor with a median survival rate of 8 months.
Thyroid Lymphoma: Accounts for 10% of thyroid cancers and is typically Non-Hodgkins lymphoma. It is mainly seen between 50-80 years old and is strongly associated with Hashimoto's thyroiditis.
328
Signs and symptoms of thyroid cancer?
Lump/ swelling in neck
Difficulty swallowing
Pain in neck and throat
Persistent cough
329
Differentials for thyroid cancer?
Benign thyroid nodules
Thyroiditis
Thyroid cyst
Goitre
330
Investigations to diagnose thyroid cancer?
Thyroid USS
Fine needle aspiration
Serum TSH and calcitonin
331
Management of thyroid cancer?
Surgery: Thyroidectomy or lobectomy, often followed by radioactive iodine treatment.
Radioactive Iodine (RAI) Treatment: Used post-surgery to destroy remaining thyroid tissue and treat thyroid cancer cells throughout the body.
External Beam Radiation Therapy (EBRT): Employed in inoperable cases or to relieve symptoms in advanced disease.
Targeted Therapy: Used for advanced or metastatic disease, including tyrosine kinase inhibitors.
Chemotherapy: Used sparingly, often in combination with radiation for anaplastic thyroid cancer.
332
Complications of thyroid surgery?
Hypocalcaemia
Hypothyroidism
Damage to recurrent or superior laryngeal nerve
Neck haematoma
Thyrotoxic storm
333
What is Waterhouse-Friderichsen syndrome (WFS)?
Waterhouse-Friderichsen syndrome is a severe, potentially fatal condition caused by a significant bacterial infection, leading to disseminated intravascular coagulation (DIC) and subsequent bilateral (or occasionally unilateral) adrenal hemorrhage and failure. This results in the rapid onset of adrenal insufficiency, often with catastrophic consequences.
334
Aetiology of WFS?
Bacterial infection; commonly neisseria meningitidis
streptococcus pneumoniae
335
Signs and symptoms of WFS?
Non specific signs; fevers, malaise, body ache
Macular petechial eventual purpuric rash
Septic shock, adrenal insufficiency
Hypotension
DIC
Altered mental status
Multi-organ dysfunction
336
Differentials for WFS?
Meningococcal septiciaemia
Septic shock
TTP
Purpura fulminans
337
Investigations to diagnose WFS?
Clotting
CT/MRI- but not likely due to rapid progression
338
Management?
Rapid fluid replacement
Vasopressor support
Broad spectrum abx
Corticosteroid replacement
339
