Endocrine Flashcards
(357 cards)
1
Q
Define type 1 diabetes
A
Type 1 diabetes mellitus is a metabolic disorder characterised by hyperglycaemia due to absolute insulin deficiency.
2
Q
What is the epidemiology for type 1 diabetes?
A
- Accounts for 5-10% of all patients with diabetes.
- More common amongst Europeans.
- Causes more than 85% of diabetes in under 20s.
- Highest incidents amongst 10–14-year-olds.
- Incidence increasing by 3% yearly
3
Q
What is the genetic aetiology of type 1 diabetes?
A
Some human leukocyte polymorphisms can increase susceptibility to the disease.(HLA-DR gene)
In susceptible people environmental factors may lead to immune-mediated destruction of beta cells.
Coeliac disease may have link
4
Q
What is the environmental aetiology of type 1 diabetes?
A
Much higher rates in Europe may indicate environmental factors no known specific ones.
Vitamin D can be protective
5
Q
What virus is believed to have a link to type 1 diabetes?
A
Human enterovirus
6
Q
What are the risk factors for type 1 diabetes?
A
Family history
7
Q
What is the usual physiological cause of type 1 diabetes?
A
Destruction of pancreatic beta cells (that produce insulin)
Up to 90% of people have autoantibodies
8
Q
How long does beta cells destruction occur for before symptoms usually start to present for type 1 diabetes?
A
Months to years
9
Q
What % of beta cells need to be destroyed before symptoms usually appear for type 1 diabetes?
A
80-90%
10
Q
What happens as a result of low insulin levels?
A
Due to insulin deficiency glucose can’t be utilised from muscle and adipose.
Stimulates secretion of glucagon (adrenaline, cortisol, and growth hormone)
So increased Lipolysis, = weight loss
More glucose in urine - Polyuria and Polydipsia
11
Q
What does the secretion of glucagon (adrenaline, cortisol, and growth hormone) result in? (Type 1 diabetes)
A
Gluconeogenesis, Glycogenolysis and ketogenesis.
Patients as a result present with ketoacidosis and hyperglycaemia.
12
Q
What are the most common key presentations of type 1 diabetes?
A
- Hyperglycaemia (above 11.1).
- Polyuria (passing urine frequently).
- Polydipsia (drinking water frequently)
- Tiredness
13
Q
What are some other common key presentations of type 1 diabetes?
A
young age, weight loss, blurred vision, nausea, and vomiting, Abdo pain,
14
Q
What are the first line investigations for children in type 1 diabetes?
A
- Random plasma glucose (above 11)
- Fasting plasma glucose (above 7)
15
Q
What are the first line investigations for adults in type 1 diabetes?
A
- Hyperglycaemia (above 11.1) (random plasma glucose) - one of Ketosis, Rapid weight loss, Age <50 years, BMI <25 kg/m², personal and/or family history of autoimmune disease this is for adults
16
Q
What is the gold standard test for diagnosing type 1 diabetes in children?
A
Glycohemoglobin test (HbA1c)
Reflects the degree of hyperglycaemia over the preceding 3 months greater than 6.5% (48 mmol/mol) indicates diabetes
17
Q
What are other diagnostic tests you do to confirm a diagnosis of type 1 diabetes?
A
- Plasma or urine ketones,
- C-peptide,
- Autoimmune markers
18
Q
What are some differential diagnoses of type 1 diabetes?
A
Monogenic diabetes: maturity onset diabetes of the young
Neonatal diabetes
Type 2 diabetes
19
Q
What is the management of type 1 diabetes?
A
o Basal-bolus insulin (insulin glargine s/c)
o Pre-meal insulin correction dose
o Amylin analogue (pramlintide)
2nd line: fixed insulin dose
20
Q
What is the difference between Basal and Bolus insulin dosing for Diabetes?
A
The two main ways to take insulin are bolus and basal.
Bolus insulin is the quick-acting delivery that you often take before mealtimes.
Basal insulin is longer-acting and helps keep your glucose levels steady day and night
21
Q
What is the main medical drug given to treat T1DM?
A
Using a combination of long-acting insulin (insulin detemir, degludec, or glargine) for basal dosing,
and rapid-acting insulin (insulin lispro, aspart, or glulisine) for bolus dosing
22
Q
What are the side effects of insulin?
A
hypoglycaemia, weight gain, lipodystrophy
23
Q
What would you monitor for patients with diabetes?
A
Measure HbA1c levels every 3 months in children and every 3-6 months in adults
Make sure level is under 6.5% (48 mmol/mol)
Also monitor BP and kidney function
24
Q
What are the short-term complications associated with type 1 diabetes?
A
Death due to ketoacidosis
25
What are some microvascular complications of diabetes?
Peripheral neuropathy- nerves in the body's extremities, such as the hands, feet and arms, are damaged
Retinopathy- damage to vessels in the eye
Kidney disease, particularly glomerulosclerosis
26
What are some macrovascular complications of diabetes?
Coronary artery disease is a major cause of death in diabetics
Peripheral ischaemia causes poor healing, ulcers and “diabetic foot”
Stroke
Hypertension
27
What are the long-term complications associated with type 1 diabetes?
- Microvascular: retinopathy, peripheral or autonomic neuropathy
- Cardiovascular disease, diabetic kidney disease.
- Potential for depression and eating disorder#
- Foot amputations
- Blindness
28
Define type 2 diabetes
A progressive disorder defined by deficits in insulin secretion and insulin resistance that lead to abnormal metabolism and related metabolic derangements
29
What percentage of diabetes cases are type 2?
90%
30
What is the epidemiology of type 2?
OLDER! >30 years of age. Often overweight around the abdomen
- More prevalent in South Asian, African and Caribbean ancestry
Common is all populations enjoying an affluent lifestyle
More common in males
31
By how much cases of type 2 diabetes have increased since 1980
4%
32
What is the aetiology of type 2 diabetes?
Genetic
33
What are some risk factors for type 2 diabetes?
Ageing
high BMI
gestational diabetes
non-white ancestry
polycystic ovary syndrome
hypertension
34
What BMI is overweight?
25-29.9
35
What BMI is considered obese?
>30
36
What is the pathophysiology for type 2 diabetes?
Insulin resistance affects primarily the liver, muscle, and adipocytes,
It is characterized by complex derangements in cellular receptors, intracellular glucose kinase function, and other intracellular metabolic processes
Over time, the pancreas (specifically the beta cells) becomes fatigued and damaged by producing so much insulin and they start to produce less.
37
How does type 2 diabetes cause damage to blood vessels and nerves?
Glycated end products accumulating in tissues damages them.
38
What are the key presentations for type 2 diabetes?
Hyperglycaemia with presence of risk factors
E.g., Overweight, certain ethnic groups, age
39
What are some signs of type 2 diabetes?
High blood glucose levels
40
What are symptoms of type 2 diabetes?
Polydipsia
Polyuria
candidal infections,
skin infection,
UTIs,
fatigue,
blurred vison
uncommon symptoms
41
What are first line investigations for type 2 diabetes?
Fasting glucose, 2-hour post load glucose (75g orally) random plasma glucose
42
What is the gold standard test for type 2 diabetes?
HbA1c
43
What are some differential diagnosis for type 2 diabetes?
Type 1 diabetes, other types e.g. gestational, adolescent
44
What is the initial management for type 2 diabetes?
1st lifestyle changes plus agree glycaemic (HbA1c) target
Adjunct of BP and lipid management
45
What is the management for acute type 2 diabetes?
HbA1c is above target 1st metformin plus lifestyle measures, cardiovascular risk reduction, and specific considerations
46
How would you manage type 2 diabetes?
Every 3 to 6 months (tailored to individual needs), until the patient’s HbA1c is stable on unchanging therapy *
Every 6 months once the patient’s HbA1c level and blood glucose-lowering therapy are stable.
First-line is metoformin
47
When should a second anti-diabetic drug be added to the use of metformin?
When HBA1c rises above 58mmol/mol despite maximum dose of metformin
48
How does metformin work?
- Metformin which increases the rate of gluconeogenesis in the liver??????? tom i think this is the exact opposite of what it does
- Increases cell sensitivity to insulin
- Helps with weight issues
- reduces CVS risk in diabetes
49
What are some other anti-diabetic drugs?
- **Sulfonylureas (gliclazide)** they promote insulin secretion but only work in people with functional B-cells. Risk of hypoglycaemia and weight gain. Increased risk of CVD when used as a monotherapy
- **Dipeptidyl peptidase-4 inhibitor (DPP-4i) (incretins)**: they are hormones produced in the GI tract which increase Increase insulin secretions, Inhibit glucagon production, Slow absorption by the GI tract
- **SGLT-2 inhibitors “-gliflozin”, such as empagliflozin, canagliflozin and dapagliflozin**- it inhibits glucose reabsorption from the the urine into the blood
50
What is a basal bolus that is given in type 1 DM and sometimes in bad T2DM
Givng a dose before each meal in order to miminc the effect of insulin released
So three times a day
*eg. Insulin Inspiro, or Insulin Aspart*
51
What insulin medication pattern do you see in T2DM
Just once a day, (Basal) sometimes twice (BD)
52
What else would you monitor in a patient with type 2 diabetes?
Measure blood pressure at least once a year in an adult with type 2 diabetes without previously diagnosed hypertension or renal disease.
53
What are some low likelihood complications associated with type 2 diabetes?
Diabetic kidney disease, impaired vision, lower extremity amputation
54
What are the most likely complications associated with type 2 diabetes?
Cardiovascular disease, congestive heart failure, stroke.
Diabetic ketoacidosis if very poorly managed
55
Why are you more at risk of infections if you have type 2 diabetes?
Hyperglycaemia impairs immune function
56
How years on average is someone's life shortened by type 2 diabetes?
Men lose 5.8 years women lose 6.8 years
57
What is ketoacidosis?
Diabetic ketoacidosis (DKA) is characterized by a biochemical triad of hyperglycaemia (or a history of diabetes), ketonemia, and metabolic acidosis, with rapid symptom onset.
58
What is the main cause of ketoacidosis?
Uncontrolled/undiagnosed diabetes
59
What is the pathophysiology of ketoacidosis?
Reduced insulin concentration and insulin counter regulatory hormones leads to hyperglycaemia and electrolyte imbalance.
Insulin deficiency leads to release of fatty acids (lipolysis), hepatic fatty acid oxidation and increased formation of ketone bodies (hydroxybutyrate and acetoacetate (most common)).
This results in ketonemia and acidosis
60
What are the key presentations of ketoacidosis?
Patients with known diabetes who are experiencing nausea, vomiting, abdominal pain, hyperventilation, dehydration and reduced consciousness
Or patients with suspected diabetes and these symptoms
61
What are the common symptoms of ketoacidosis?
Nausea, vomiting, abdominal pain, hyperventilation, dehydration and reduced consciousness
62
What are some biochemical signs of ketoacidosis?
Hyporkalaemia, high plasma osmolarity, blood ketones.
63
What are some other symptoms of ketoacidosis?
Acetone smell on breath
Hypothermia
64
What is the first line investigation for ketoacidosis?
Venous blood gas greater
65
What blood PH indicates mild to moderate ketoacidosis?
Below normal but above 7
66
What blood PH indicates severe ketoacidosis?
Below 7
67
What is the gold standard test for ketoacidosis?
Urinary analysis
68
What other tests would you order for a patient with ketoacidosis?
ECG, pregnancy test
69
What are some differential diagnoses for diabetic ketoacidosis?
- Hyperosmolar hyperglycaemic state,
- Latic acidosis (order serum lactate).
- Starvation/alcoholic ketoacidosis
70
How would you treat ketoacidosis?
1. Give a fluid bolus of 500 mL of normal saline (0.9% sodium chloride) over 10 to 15 minutes if the initial systolic blood pressure (SBP) is <90 mmHg.
2. Give IV insulin to lower blood glucose
3. Add potassium to the second litre of intravenous fluid if serum potassium is ≤5.5 mmol/L. As giving insulin lowers potassium
71
How would you monitor ketoacidosis?
- order hourly blood glucose and hourly blood ketones.
- Perform a venous blood gas for pH, bicarbonate, and potassium at 60 minutes, 2 hours and then every 2 hours after
- Assess GCS
72
What are some complications associated with ketoacidosis?
- Hypokalaemia (due to high dose insulin therapy)
- Arterial/venous thrombotic events
- Cerebral oedema (main cause of death)
- ARDS (occurs when too much fluid is given)
73
What is the prognosis for a patient with ketoacidosis?
0.67% mortality
74
What is Hyperosmolar hyperglycaemic state?
A profound state of hyperglycaemia and hyperosmolarity and volume depletion in the **absence of ketoacidosis** more commonly a side effect of T2DM
75
What is the epidemiology of HHS?
- Usually occurs in the elderly but is more recognised in younger patients
- Average age is 60
- Often the first presentation of T2DM (20-30% of cases)
76
What causes HHS?
- Usually triggered by an infection. Due to the relative lack of insulin, coupled with a rise in cortisol, growth hormone, glucagon there is a profound rise in glucose
- The excessive glucose leads to massive osmotic diuresis within the kidneys with loss of Na and K.
- There is profound dehydration which leads to the viscosity of the blood increasing the risk of DVT and stroke and MI
77
What are the signs of HHS?
- Reduced GCS - reduced consciousness/ coma
- Dehydration - tachycardia and hypotension, dry mucous membranes, reduced skin turgor
- Could be confused for a stroke - e.g. hemiparesis
- Seizures
78
What are the investigations for HHS?
Laboratory glucose, urea & electrolytes blood test (electrolyte derangement and AKI due to dehydration), ABG/VBG (hyperglycaemia without a metabolic acidosis) and a blood or urinary ketone level.
79
What is the diagnostic criteria for HHS?
- Hyperglycaemia > 30 without hyperketonaemia and acidosis
- Hyperosmolarity >320
80
What is the treatment for HHS?
- IV fluid (0.9% saline)- results in reduction in osmolality and glucose. Insulin not always required
- Potassium replacement
- Anti-coagulant
81
What is Graves' disease?
An autoimmune disease associated with hyperthyroidism
82
What are some other causes of Hyperthyroidism?
Toxic adenoma
Toxic multinodular goitre
83
What is the cause of Graves' disease?
TSH (thyroid-stimulating hormone) receptor antibodies cause the hyperthyroid syndrome and underlie the extrathyroidal manifestations.
84
Describe the epidemiology of Graves' disease
- 2.5% prevalence.
- More common in older age groups.
- 6 times more common in women.
- 20-50 cases per 100,000 per year
85
Is graves' disease more common in men or women?
Women (6x more likely)
86
What is the aetiology of Graves'?
TSH receptor antibodies
Combination of genetic and environmental risk factors.
No specific genes but HLA linked.
87
What 2 autoantibodies are found in 75% of patients with Graves' disease
Thyroglobulin and thyroid peroxidase.
88
What are some risk factors for Graves'?
- Family history of autoimmune disease (HLA-DR3)
- Tobacco use
- Female sex
- Radiation
- High iodine intake (increases TRH)
- Lithium therapy
89
What is the pathophysiology of Graves?
1. TSH receptor antibodies bind to thyroid
2. This causes increased thyroid hormone production
3. The increased production leads to thyroid hypertrophy
4. Symptoms occur as result of increase in thyroid hormone
90
What are the key presentations for Graves'/hyperthyroidism?
- Presence of risk factors
- Heat intolerance + increased sweating
- Weight loss
- Palpitations
- Goitre
- Orbitopathy
91
What are some signs of Graves?
- Elevated TSH receptor antibodies
- Suppressed TSH levels
- Elevated T3 and T4
92
What are some other symptoms associated with Graves/hyperthyroidism?
- Irritability
- Cardiac flow murmur
- Moist velvety skin
- Scalp hair loss
93
What is the first line investigation for Graves?
- Serum TSH (levels will be surppressed)
94
What is the gold standard test for Graves disease?
- Presence of TSH receptor antibodies
95
What are some other tests you can do to make a diagnosis of Graves?
- Serum T3 and T4
- Thyroid isotope scan
- Ultrasound of thyroid
- Pregnancy test
96
What are some differential diagnosis for Graves?
- Toxic nodular goitre,
- Pregnancy related,
- TSH producing pituitary adenoma
97
What are some side effects of Antithyroid drugs (thionamides)
Rash (most common)
hepatitis
vasculitis
Agranulocytosis (most serious side effect)- sore throat fever, mouth ulcers
98
What is the main goal when treating Graves?
- To normalise thyroid function parameters
There is nothing done to counteract autoimmune aspect
99
How would you treat Graves?
- Antithyroid medications- decreases synthesis of of new thyroid hormone (carbimazole)
- Radioactive Iodine
- Thyroid ablation
100
How would you monitor Graves?
Measure TSH levels at 6 week intervals until levels are stable
101
What are some complications associated with Graves?
- AF
- Congestive heart failure
- Bone mineral loss
102
What risk associated with Graves?
Cardiovascular problems
103
What are the four main types of thyroid cancer?
- Follicular
- Anaplastic
- Medullary
- Papillary
FAMP
104
What percentage of thyroid cancers do the 4 main types make up?
98%
105
Is thyroid cancer more common in men or women?
Women
106
What is the most common age to be diagnosed with thyroid?
45-54
107
What is the prevalence of thyroid cancer?
15.8 per 100,000
108
What are risk factors for developing thyroid cancer?
- Head and neck irradiation
- Female sex
- Genetic factors
109
What is the most common pathophysiology of
a papillary carcinoma?
- Papillary carcinoma tends to spread to local lymph nodes
110
What is the common pathophysiology of a follicular tumour?
- Follicular and Hurthle cells often spread haematogenous.
111
How does anaplastic thyroid cancer spread?
- Anaplastic thyroid cancer is a rare, aggressive, undifferentiated carcinoma with a high propensity for local invasion and metastatic spread.
112
What are the key presentations for thyroid cancer?
- Presence of risk factors
- Palpable thyroid nodule
113
What are some symptoms of thyroid cancer?
- Hoarseness
- Tracheal deviation
- Dyspnoea
- Dysphagia
114
What is a first-line investigation for thyroid cancer
Normal TSH with reduced thyroid function
115
What is the gold standard test for thyroid cancer?
Fine-needle biopsy
116
What is a differential diagnosis for thyroid cancer?
A benign thyroid nodule
117
How would you manage a follicular tumour?
The standard approach is surgery followed by radioactive iodine ablation and suppression of TSH for most patients
118
How would you manage a medullary tumour?
Total thyroidectomy
119
How would you treat an anaplastic tumour?
Total thyroidectomy and if that is not possible then with chemo/radio therapy
120
How would you treat a thyroid lymphoma?
With radio and chemotherapy
121
What are some disease related complications of thyroid cancer?
- Airway obstruction
- Secondary tumours
122
What are some complications of a thyroidectomy?
- Hypoparathyroidism due to damage to parathyroid glands
- Recurrent laryngeal nerve damage
123
What is the prognosis for a papillary/follicular carcinoma?
>90% 10 year survival rate
- medullary is slightly worse due to more metastasis
124
What is the prognosis for a anaplastic thyroid tumour?
Average survival of a few months after diagnosis
125
What is the prognosis for a medullary tumour?
80% 5 year survival rate
126
What is the prognosis for a primary thyroid lymphoma?
<50% 5 year survival rate
127
What is Cushing's syndrome?
Cushing syndrome is the clinical manifestation of pathological hypercortisolism from any cause.
128
What's the most common cause of Cushing's syndrome?
Exogenous corticosteroid exposure
For example taking steroids e.g., prednisone
129
What is the difference between Cushing's syndrome and Cushing's disease
- Cushing's syndrome disease is pathological hypercortisolism from any cause.
- Cushing's disease is hypercortisolism caused by a endogenous source e.g., pituitary adenoma
130
What is the incidence of Cushing's syndrome per year
0.7-2.4 per million population
131
Is Cushing's syndrome more common in men or women?
Women, Cushing's disease is also more common in women
132
What is the most likely age range to be diagnosed with Cushing's?
20-50
133
What is the most common cause of Cushing's disease?
Pituitary adenomas- make up 70-80% of all cases
134
What % of Cushing's disease is caused by pituitary adenomas?
70-80%
135
What % of pituitary adenomas result in excessive ACTH production?
10%
136
What % of Cushing's disease is caused by adrenal adenomas?
10%
137
Name 2 other causes of Cushing's disease?
- Ectopic neuroendocrine tumours (usually masses in the lungs)
- Adrenal carcinoma
138
What is ACTH-dependant Cushing's disease?
overproduction of ACTH which stimulates adrenal gland to secrete more cortisol.
139
What two types of tumour are ACTH-dependant causes of Cushing's disease?
Pituitary adenoma, ectopic neuroendocrine ACTH secreting tumours
140
What is ACTH-independant Cushing's disease
When there is excessive cortisol production without high levels of ACTH
141
What are the 6 hormones secreted by the anterior pituitary?
Adrenocorticotrophic hormone (ACTH)
Thyroid-stimulating hormone (TSH)
Luteinising hormone (LH)
Follicle-stimulating hormone (FSH)
Prolactin (PRL)
Growth hormone (GH)
142
What are the two hormones secreted by the posterior pituitary?
Oxytocin
Anti-diuretic hormone (ADH)
143
What two types of tumour are ACTH-independent causes of Cushing's disease?
Adrenal adenomas and adrenal carcinomas
144
How does Cushing's cause disease?
- The clinical manifestations is due to excess tissue exposure to cortisol.
- The degree to which symptoms present is due to the amount of excess.
145
What cause of Cushing's is most likely to be severe and abrupt in its presentation?
Ectopic ACTH secretion from neuroendocrine tumours
146
What are some key presentations associated with Cushing's?
- Presence of risk factors
- Facial plethora (redness)
- Weight gain
- Supraclavicular fulness, torso weight gain but weak arms
- Absence of pregnancy, alcoholism, malnutrition
147
What are some key signs of Cushing's?
Increased serum glucose, elevated cortisol in saliva, high urinary cortisol
148
What are some symptoms associated with Cushing's?
- Hypertension
- Weight gain
- Glucose intolerance
- Premature osteoporosis
- Decreased libido
- Muscle weakness
- Facial rounding
- Acne
think of a bloke with massive fat stomach and face, really skinny limbs and really stressed
149
How many key investigations are there you can do to confirm a diagnosis of Cushing's?
4
150
What are the 4 main diagnostic tests for Cushing's?
1. Late night salivary cortisol (4nmol)
2. 1mg overnight dexamethasone suppression test (50 nmol/litre),
3. 24 hour urinary free cortisol.
4. 48- hour 2 mg dexamethasone suppression testing
151
How do you perform a late night salivary cortisol test?
- Samples are collected by saturating a collection swab with saliva or by passively drooling into a collection tube between 11 p.m. and midnight.
Sampling should be done on 2 separate nights
152
Why is the salivary test performed at night?
This is when cortisol levels are at their lowest. Will give the most accurate baseline figure
153
What is the 1mg overnight dexamethasone test
Patient is given 1 mg of dexamethasone at 11 p.m., and a plasma cortisol level is obtained the following morning at 8 a.m
154
What value would indicate Cushing's?
morning cortisol >50 nanomol/L
155
What is a positive result for the 24 hour urinary free cortisol?
>50 micrograms/24 hour
156
What is the difference between the low and high dose dexamethasone tests?
This higher dose is enough to suppress the cortisol in Cushing’s syndrome caused by a pituitary adenoma (Cushing’s disease), but not when it is caused by an adrenal adenoma or ectopic ACTH.
157
What other test would be performed on a patient with suspected Cushing's?
Pregnancy test
158
What are some differntial diagnosis of Cushing's
- Obesity
- Metabolic syndrome
- Pregnancy
Lack of facial plethora, bruising weakness and osteoporosis
159
How would you treat Cushing's disease?
First line : If an adenoma remove adenoma as that is the cause.
Adjunct: If only mild use or very severe (before surgery) use a steroidogenesis (pasireotide) inhibitor or a glucocorticoid receptor antagonist (mifepristone).
Monitor cortisol levels after removal of pituitary adenoma. May require hormone replacement due to dysfunction of HPA
160
How would you monitor Cushing's?
Recurrence of adrenocorticotrophic hormone-dependent Cushing syndrome is common, with at least a 5% to 26% risk of recurrence at 5 years.
Patients who have achieved remission should be screened periodically (every 6-12 months) for recurrence of disease.
161
What are some complications associated with Cushing's?
CVD, Hypertension, Diabetes, Osteoporosis
162
What is the prognosis for untreated Cushing's?
5 year survival of 50%
163
What is Hypothyroidism?
The deficiency of thyroid hormones, which leads to a generalised slowing of metabolic processes.
164
What is primary hypothyroidism?
The failure of the thyroid gland to produce thyroid hormones.
165
What is secondary/central hypothyroidism?
Arises from an anatomical or functional disorder of the pituitary gland and/or the hypothalamus.
166
What % of hypothyroidism cases are caused by primary hypothyrodism?
99%
167
What is the epidemiology of hypothyroidism?
- More common in women
- More common in white people
- Incidence increases with age
168
What is the most common cause of primary hypothyroidism?
Hashimoto's thyroiditis (8-9 times more likely in women)
169
Name some other causes of hypothyroidism (non-drug related)
- Damage or destruction of the thyroid gland from thyroidectomy,
- Radioactive iodine therapy for Graves' disease
- Nodular goitre,
- Radiotherapy for head and neck cancer.
- Sarcoidosis and haemochromoatosis
170
Name some drugs that can cause hypothyroidism
lithium, amiodarone, interferon alpha
171
What can cause transient primary hypothyroidism?
- Sub-acute granulomatous (De Quervain's
- Post partum
172
Name some risk factors for hypothyroidism
Iodine deficiency, female, middle age, family history, hyper treatment, turners and down syndrome.
173
Describe the pathophysiology of Hashimoto's thyroiditis
- T3 and T4 create negative feedback loop with TSH so low levels of T3 and T4 equal elevated TSH
- In autoimmune lymphocytes, Thyroglobulin and thyroid peroxidase antibodies invade the thyroid causing damage (High iodine makes thyroid more antigenic).
This means less T4 and T3 are produced resulting in the clinical symptoms
174
How do some drugs cause hypothyroidism?
Amiodarone contains iodine, which interferes with thyroid hormone synthesis.
Lithium interferes with thyroid hormone synthesis and release.
Both are reversible
175
What are the key presentations for hypothyroidism?
Risk factors.
Lots of non-specific features e.g., tiredness but don't know why, weakness
176
What are some signs of primary hypothyroidism?
High levels of TSH but low T3 and T4.
177
What are the signs of secondary hypothyroidism?
Low TSH and low T3 and T4.
178
Name some symptoms of hypothyroidism?
- Fatigue
- Weight gain
- Cold intolerance
- Constipation
- Menstrual disturbance
- Dry rough skin
- Bradycardia
- Oedema
- Delayed muscle reflexes
179
What would be the first line investigations for hypothyroidism?
Serum TSH
Free T4
180
Name 3 differential diagnosis for hypothyroidism?
Depression
Alzheimer's
Anaemia
All have normal TSH levels
181
What is the main treatment for hypothyroidism?
L-thyroxine (levothyroxine)
182
How should you monitor patients with hypothyroidism?
Levothyroxine has a long half-life, TSH levels should be measured 4-12 weeks after dose change.
183
What changes should be made during pregnancy?
Pregnancy requires increased dose of levothyroxine
184
What are some side effects of L-thyroxine
Angina, resistant hypothyroidism, AF, osteoporosis.
185
What are some complications of untreated hypothyroidism?
myxoedema coma (older patients) , complications in pregnancy
186
What is acromegaly?
Acromegaly is a rare, chronic disease caused by excessive secretion of growth hormone (GH), usually due to a pituitary somatotroph adenoma.
187
What is crucial when treating acromegaly?
Early recognition but the disease has an insidious onset
188
When is acromegaly most likely to be diagnosed?
Middle age
189
What is the most common cause of acromegaly?
Pituitary somatotroph adenoma (95-99%)
Prolactin is co-secreted in 25% of cases
190
What is another potential cause of acromegaly?
Neuroendocrine tumours
191
What gene mutation is shown in 30-40% of pituitary somatotroph adenomas?
GNAS1
192
Describe the pathophysiology of acromegaly
- Dysregulation of hormones and transcription factors lead to growth of tumours
- Pituitary somatotroph adenomas secrete excess GH
- GH binds to liver which causes the release of insulin growth factor 1 (IGF-1)
- IGF-1 causes symptoms
193
What are the key presentations of acromegaly?
- Coarsening of facial features (enlarged nose, jaw - Enlargement, separation of teeth)
- Thickening skin
- Carpal tunnel
- Joint pain,
- Alterations of sexual function
- Headaches
194
What are some signs of acromegaly?
Elevated IGF-1, elevated GH
195
What are some symptoms of acromegaly?
Fatigue, hypertension, organmegaly, increased appetite, headaches
196
What are first line investigations of acromegaly?
Serum IGF-1 test
Serum GH test
197
What is the gold standard test for diagnosing acromegaly?
Oral glucose tolerance test (lack of supressed GH)
198
What is a differential diagnosis of acromegaly?
Pseudo-acromegaly clinical features but all tests will be normal
199
How would you manage acromegaly?
For enclosed pituitary tumour surgery will be the first option.
SSA somatostatin analogue (octreotide).
Dopamine agonist in some groups
200
How would you monitor acromegaly?
lifelong monitoring of growth hormone and insulin-like growth factor 1 (IGF-1) levels
201
What are complications associated with untreated acromegaly?
Cardiac complications, hypertension, sleep apnoea, diabetes, pre-cancerous colon polyps, carpal tunnel syndrome
202
What is the prognosis for a patient diagnosed with acromegaly?
2-3 time higher chance of mortality then general population
203
What is Conn's syndrome?
Primary aldosteronism (PA) is the most common specifically treatable and potentially curable form of hypertension.
204
What is aldosterone?
Aldosterone is a mineralocorticoid, a steroid hormone released from the zona glomerulosa of the adrenal cortex
Causes sodium to be reabsorbed through ENaC to be pumped into the blood by the sodium/potassium pump.
In exchange, potassium is moved from the blood into the principal cell of the nephron. This potassium then exits the cell into the renal tubule to be excreted into the urine.
205
What % of hypertension cases are caused by Conn's?
It accounts for at least 5% of hypertensive patients
206
What causes unilateral Conn's and what % of cases does it make up?
Benign cortical adenomas correctable by unilateral laparoscopic adrenalectomy
Accounts for 30% of cases
207
What causes bilateral Conn's and what % of cases does it make up?
Bilateral adrenal hyperplasia in which hypertension responds well to aldosterone antagonist medicines.
Accounts for 70% of cases
208
Name a form of genetically inherited PA
familial hyperaldosteronism type I (FH-I)
209
What are some risk factors for PA
Familial history of PA, family history of early onset hypertension/stroke
210
Explain the pathophysiology of Conn's
Aldosterone production is excessive to the body's requirements, and autonomous to the RAAS.
This results in excessive Na+ absorption which leads to hypertension and suppression of RAAS and in severe cases low K+ (hypokalaemia) and metabolic acidosis (22%) of cases
211
What are some microvascular complications of diabetes?
Peripheral neuropathy- nerves in the body's extremities, such as the hands, feet and arms, are damaged
Retinopathy- damage to vessels in the eye
Kidney disease, particularly glomerulosclerosis
212
What are some microvascular complications of diabetes?
Peripheral neuropathy- nerves in the body's extremities, such as the hands, feet and arms, are damaged
Retinopathy- damage to vessels in the eye
Kidney disease, particularly glomerulosclerosis
213
What are key presentations for Conn's?
Hypertension, presence of risk factors, 20-70 years of age.
214
What are signs of PA?
Low potassium, high aldosterone to renin ratio
215
What are some symptoms of PA
Polyuria, lethargy, mood disturbance, difficulty concentrating
216
What are some investigations for getting a diagnosis of PA?
Plasma potassium- won't be low only present in 20% of cases
Aldosterone /renin ratio
217
What further tests could be done for a patient with suspected PA?
Genetic testing, adrenal CT, fludrocortisone suppression test
218
What are some differential diagnosis for PA?
- Idiopathic Hypertension- aldosterone/renin ratio will be normal.
- Renal artery stenosis
- Liddle syndrome- hypokalaemia and low renin but also low aldosterone levels
219
How can you manage a patient with PA?
1st line: Unilateral adrenalectomy/bilateral adrenalectomy
adjunct preoperative aldosterone antagonists
adjunct postoperative aldosterone antagonists
220
How would you monitor a patient who has undergone an adrenalectomy?
Plasma electrolytes, and aldosterone and renin levels should be monitored every 6 to 12
221
How would you monitor a patient who is treating their PA through the use of aldosterone antagonists?
Electrolytes and renal function should be monitored regularly (e.g., every 3 to 6 months), watching for development of hyperkalaemia (for patients on medication)
222
What are the complications associated with Conn's?
Untreated: Stroke, MI, heart failure, AF, impaired renal function
Treatment: aldosterone antagonist induced hyperkalaemia
223
What is the prognosis for PA?
Surgery leads to cure of hypertension in 50% to 60% of carefully selected patients
Medication leads to improved control of hypertension in most cases
224
What is Addison's/primary adrenal insufficiency?
A disorder that results from intrinsic diseases that affect the cortex of the adrenal gland.
This results in impairment in the synthesis of all steroids.
225
What are the 3 layers of the adrenal gland and what do they secrete?
Zona glomerulosa- mineralocorticoids (aldosterone)
Zona fasciculata- glucocorticoids ( Cortisol)
Zona reticularis- dehydroepiandrosterone (DHEA)
226
What is secondary/central adrenal insufficiency
When the hormones are not secreted due to lack of ACTH release from pituitary/CRH from the hypothalamus.
Mineralocorticoids (aldosterone) are maintained
227
What is the epidemiology of Addison's in the UK?
300-350 new cases a year
Women are at greater risk of developing an autoimmune disease
Therefore in the UK the predominant cohort is women
228
What is the predominant cause of Addison's in developed countries?
- In developed countries 75-95% of cases are autoimmune
- In 90% of these cases 21-hydroxylase autoantibodies are present
- Is often associated with other autoimmune endocrine disorders
229
What is the main cause of Addison's worldwide?
TB
230
What are some risk factors for developing Addison's ?
Female sex, adrenocortical autoantibodies, adrenal haemorrhage, autoimmune diseases, coeliac disease
231
Describe the process in which Addison's causes symptoms?
- Symptoms are a result of decreased production of main adrenal steroids
- This is a result of destruction of the 3 layers of the cortex or disruption of the synthesis of these hormones
Approximately 90% of the cortex needs to be destroyed for symptoms to appear
232
What can cause the destruction of the adrenal cortex?
- Autoimmune process (adrenalitis)
- Infection (TB)
- Infiltrating diseases (amyloidosis hemochromatosis)
- Tumours
Haemorrhage within the adrenals can also result in acute destruction
233
What are the key presentations of Addison's?
- Hyperpigmentation
- Anorexia/weight loss
- Fatigue
- Salt craving
234
What are the signs of Addison's?
- Postural hypotension
- Lowered serum cortisol
- Increased ACTH (only in primary)
- Elevated urea and creatine
235
What are some other symptoms of Addison's?
- Vomiting
- Axillary and pubic hair loss
236
What are some first line investigations for Addison's?
- Na+ low and K+ high (result of reduced aldosterone)
- Morning serum cortisol (>140 low)
- Plasma ACTH (>12 high)
237
What is the gold standard test for diagnosing Addison's?
ACTH stimulation test of cortisol ( exclude Addison's if serum cortisol is greater than 550 after stimulation)
238
What would some other tests be for Addison's?
Antibodies (presence of 21-hydroxylase) , CT or MRI of adrenals
239
What would some other test be for addisons?
Antibodies (presence of 21-hydroxylase) , CT or MRI of adrenals
240
What are some differential diagnosis of Addison's?
Hemochromatosis
Hyperthyroidism
Anorexia nervosa
241
How should Addison's be managed?
- Oral glucocorticoid and mineralocorticoid replacement on diagnosis (hydrocortisone is the preferred steroid)
- Give prasterone if reduced libido
Note dose may need to be increased during pregnancy
242
What is an Addisonian crisis?
- Patients present in shock
- increased HR, vasoconstriction, postural hypotension, weak and confused
- Occurs in undiagnosed Addison's or someone who has forgotten meds
- Hypoglycemia
Can occur in acute bilateral adrenal haemorrhage
Can look like hypoglycaemia
243
How would you treat an Addisonian crisis?
- 100mg IV hydrocortisone
- IV fluids to support BP
- Correct glucose
244
What should be monitored in a patient with Addison's
- Fatigue and increasing pigmentation suggests insufficient dosage
- Weight gain and facial plethora suggest excess ( Cushing's disease)
245
What are some complications of Addison's?
Secondary Cushing syndrome, adrenal crisis, osteoporosis due to glucocorticoid replacement , treatment related hypertension and hypokalaemia
246
What is SIADH?
- Syndrome of inappropriate antidiuretic hormone is when too much ADH is secreted
- Characterised by hypotonic hyponatremia, concentrated urine and euvolemic state
247
What can cause SIADH?
- Drugs: SSRI, amiodarone, NSAIDs
- Pulmonary processes: Pulmonary infections and lung cancers
- Malignancy: GI, GU, Lymphomas, sarcomas
- CNS disorders: infections, brain trauma
248
What stimulates ADH release?
- Osmotic pressure is the most sensitive stimulus
- Arterial pressure reduction also stimulates ADH release
249
How does SIADH cause problems?
- ADH binds to AVP v2 receptors and this results in aquaporin 2 channels on the collecting duct membrane
- Too much ADH results in too many channels resulting in hyponatremia and suppression of RAAS
250
What are the key presentations of SIADH?
- Low Na+ and low osmolarity with the absence of: hypo/hypervolemia, Addison's, hypothyroidism
251
What are the symptoms of SIADH?
- Headache
- Seizure
- Mental state change
- Concentrated urine
252
How would you diagnose SIADH?
- Concentrated urine (>20 Na+) with hyponatremia and low plasma osmolarity
253
What are the 4 different types of SIADH?
Type A: unregulated release of arginine vasopressin (AVP). Approximately 30% of patients. Marked increase in plasma AVP levels that fluctuate in a manner unrelated to changes in plasma osmolarity/sodium during infusion of hypertonic saline.
Type B: slow leak of AVP. Approximately 30% of patients. Milder increase in plasma AVP in comparison to type A. Plasma AVP remains stable during hypertonic saline infusion and only rises when serum sodium levels reach normal range.
Type C: Approximately 30% of patients. Low AVP levels during hyponatremic state; however, AVP levels rise inappropriately during hypertonic saline infusion before hyponatremia is corrected.
Type D: pseudo-SIADH. Approximately 10% of patients. Low or undetectable AVP. Low levels of AVP during hyponatremic state with apparent normal osmoregulation of AVP release. Antidiuresis occurs through an alternative mechanism, one of which is nephrogenic syndrome of inappropriate diuresis (SIADH), a genetic disorder characterized by gain-of-function mutation of vasopressin 2 (V2) receptor.
254
How would you treat SIADH?
- Treat the underlying cause and restrict fluid
- Consider salt loop diuretic if severe
- Vasopressin receptor antagonists (tolvaptans)
255
What is a complication of SIADH?
Central pontine myelinolysis- too much sodium due to treatment and brain compensation
256
What are some differential diagnosis of SIADH?
Hypo/hypervolemia
Cerebral salt-wasting
Renal failure
Addison's
Hypothyroidism
257
What is diabetes insipidus?
Diabetes insipidus is a metabolic disorder characterised by an absolute or relative inability to concentrate urine, resulting in the production of large quantities of dilute urine
258
What % of cases of DI are genetic?
<10%
259
What are the 4 different types of DI?
Central acquired- pituitary affected
Central genetic- pit affected
Nephrogenic acquired- collecting duct affected
Nephrogenic inherited- collecting duct affected
260
What can cause central acquired DI?
pituitary surgery, craniopharyngioma, post-traumatic brain injury, pituitary stalk lesion autoimmune disorder, CNS infections, meds
261
What can cause central genetic DI?
malformations in hypo/pituitary, wolfram syndrome
262
What can cause nephrogenic genetic DI?
Mutations in the AVPR2
263
What can cause nephrogenic acquired DI?
Medications (lithium + can be irreversible), systemic disease
264
What is the difference between central and nephrogenic DI?
- Central DI results from any condition that impairs the production, transportation, or release of AVP.
- Nephrogenic DI results from conditions that impair the renal collecting ducts' ability to respond to AVP.
265
What are the key presentations of DI?
History of pit/family, history of lithium therapy, polyuria, increased thirst
266
What are some signs of DI?
Hypernatremia
267
What are some first line investigations for DI?
Low urine osmolality, high serum osmolality, serum Na+
268
What are the gold standard tests for diagnosing DI?
- Water deprivation test- urine will fail to concentrate
- ADH stimulation test (used to distinguish between central and nephrogenic)
269
What are some differential diagnosis of DI?
Psychogenic polydipsia
Diabetes mellitus
Diuretic use
270
How would you treat central DI?
Use long acting synthetic ADH (DDAVP) also useful for pregnancy related
271
How would you treat nephrogenic DI?
Nephrogenic is harder to treat
high dose DDAVP can be partially effective,
fix underlying issue if possible, Low sodium diet can be effective
272
What are some complications of DI?
Hypernatremia, thrombosis, bladder and renal dysfunction, iatrogenic hyponatremia
273
What is primary hyperparathyroidism (pHPT)?
PHPT is an endocrine disorder in which autonomous overproduction of parathyroid hormone (PTH) results in derangement of calcium metabolism.
274
Describe the epidemiology of pHPT
Affects 1 in 500 women
Affects 1 in 2000 men
50 and 60 year olds are the most affected group
Incidence has gone up because of more testing and incidental findings
275
What is the main cause of pHPT?
80% of cases are caused by a single benign adenoma
276
Name some other causes of pHPT?
Carcinoma, lithium, irradiation. Also multiple adenomas and PT hyperplasia.
277
What % of cases are inherited?
5-10%
278
Describe the pathophysiology of pHPT
In normal physiology high calcium levels suppress PTH secretion.
However in pHPT high levels of calcium do not suppress release. This leads to more bone resorption, Vit D activation and GI absorption this leads to hypercalcaemia.
279
What are the key presentations of pHPT?
Symptoms often not related to hypercalcemia itself but related to effect on key target organ.
For example osteoporosis/osteopenia. Or renal stones.
280
What are the signs of pHPT?
High serum calcium (albumin adjusted)
Elevated/inappropriately normal PTH
281
What are some symptoms of pHPT?
Fatigue
Poor sleep
Myalgias
Anxiety
Depression
Memory loss
Pancreatitis
Ulcers
Constipation
polyuria
polydipsia `
282
What the first line investigations for pHPT?
Measure serum calcium and PTH
Also measure phosphate levels which will be low.
283
Name some differential diagnosis for pHPT?
Familial hypocalciuric hypercalcaemia
Humoral hypercalcaemia
Multiple myeloma
284
Name the management of pHPT?
Parathyroid surgery for most patients especially asymptomatic . (Parathyroidectomy). Consider Vit D sup.
285
What are some complications of pHPT/treatment of it?
Neck haematoma, recurrent laryngeal nerve injury, hypocalcaemia following surgery .
Osteoporosis/osteopenia , bone fractures, nephrolithiasis
286
What is the prognosis for pHPT?
75% have stable disease for up to 10 years asymptomatic
Parathyroidectomy has a cure rate of over 95%
287
What is secondary hyperparathyroidism (sHPT)
Secondary hyperparathyroidism (SHPT) is elevation of parathyroid hormone (PTH) secondary to hypocalcaemia.
288
What are the main causes of sHPT?
CKD results in low levels of activated Vit D. This is detected by receptors causes increase in PTH.
Crohn's, coeliac diseases with fat malabsorption will result in decreased absorption of Vit D and Calcium.
Lack of exposure to sunlight.
Also diminished dietary intake of calcium increased calcium loss or increased metabolic requirement
289
What % of patients with CKD are at risk of sHPT?
80%
290
What % of the population have severe Vit D deficiency?
7%
291
Describe the pathophysiology of sHPT?
Vit d2 and d3 found in food and by exposure to sunlight. Undergoes two hydroxylations one in liver to 25 hydroxyvitamin D. Then in kidney to 1-25-dihydroxyvitamin D. (does not occur in CKD)
In gut this increases absorption of calcium and also helps with bone resorption.
Any reason stated above can cause low calcium levels and thus an increase in PTH
292
What are the key presentations of sHPT?
Neuromuscular irritability. Numbness and paraesthesia in the fingers and toes. Muscle cramps or seizures .
293
What are some signs of sHPT?
Chvostek's sign (tapping on the face just anterior to the ear produces twitching of muscles around the mouth)
Trousseau's sign (inflating a blood-pressure cuff above diastolic for about 3 minutes causes muscular flexion of the wrist, hyperextension of the fingers, and flexion of the thumb)
294
What are some first line investigations for diagnosing sHPT?
Serum calcium (low) and serum PTH (high) and High phosphate
295
What other tests might you perform on a patient with expected sHPT?
Serum creatinine and urea to assess kidney function
296
How would you treat sHPT?
If malabsorption related manage the disease and consider UV exposure and Vit D sup
If sunlight exposure use UV and consider Vit D sup
297
Name some complications of sHPT?
Osteodystrophy, osteoporosis , calciphylaxis
298
What is tertiary hyperparathyroidism?
Prolonged secondary. Everything will be high phosphate calcium and PTH
299
What is Hypoparathyroidism (HPPT)?
A disorder caused by relative or absolute deficiency of plasma parathyroid hormone (PTH) synthesis and secretion.
This leads to low albumin-corrected serum total calcium and elevated serum phosphate
300
What is the main cause of HPPT?
Post surgery (in 80% of cases)
Either surgery to parathyroid or recurrent laryngeal nerve
301
What are some other causes of HPPT?
DiGeorge syndrome and other genetic conditions
Can be caused by hypomagnesemia
302
Name a risk factor for HPPT that isn't surgery?
Alcoholism
303
What are the key presentations of HPPT?
Muscle twitches
Paraesthesia
Poor memory
304
What are signs of HPPT?
Irregular heart beat
Chvostek's sign
Trousseau sign
305
Name some first line investigations for HPPT
Serum calcium and albumin. Make sure PTH levels are assessed to rule out secondary hyperparathyroidism
306
What other tests would you perform for HPPT?
Low Magnesium as this exacerbates the problem
Liver function: Consider possible haemochromatosis, Wilson’s disease, or chronic alcohol abuse.
Urine calcium and creatinine suggest autosomal dominant if elevated
307
What are some differential diagnosis of HPPT?
Low Vit D
Hypomagnesaemia
Hypalbuminaemia
CKD
308
How would you manage HPPT?
If acute treat with IV calcium with ECG monitoring as too fast replacement can cause cardiac arrhythmia
Oral calcium if asymptomatic
Chronic oral calcium plus calcitriol
309
What are some complications of HPPT?
Ectopic calcifications, renal insufficiency, renal stones. Cardiac problems
Chronic hypocalcaemia impairs left ventricular contractility.
310
What is hypercalcaemia of malignancy?
When tumours in the body cause hypercalcaemia
311
In what percentage of patients with cancer does hypercalcaemia occur?
20-30%
312
What are the different types of hypercalcaemia caused by malignancy?
- Humoral hypercalcaemia (accounts for 80%)
- Local osteolytic (accounts for 20%)
- Hypercalcemia mediated by release of PTH/1,25-dihydroxyvitamin D ( accounts for less than 1%) (lymphomas or TB or sarcoidosis)
313
What tumours are the main cause of humoral hypercalcaemia?
Renal cancer, ovarian cancer, breast cancer, endometrial cancer, human T-lymphotropic virus-associated lymphoma , squamous cell carcinoma
314
What tumours are the main cause of osteolytic hypercalcaemia?
Breast and multiple myeloma
315
Describe the pathophysiology of humoral hypercalcaemia?
Tumour secretion of parathyroid hormone-related peptide (PTHrP) leads to activation of osteoclastic bone resorption and suppression of osteoblastic bone formation. This results in skeletal release of calcium and subsequent hypercalcemia.
PTHrP also acts at the level of the kidney to reduce calcium clearance, as well as to reduce the renal phosphorus threshold, leading to hypophosphaturia and hypophosphatemia.
316
Describe the pathophysiology of osteolytic hypercalcaemia?
Tumours release cytokines (e.g. IL-1 and IL-6), chemokines, and PTHrP which leads to increased osteoclastic bone resorption, and to increased release of calcium into the serum that overwhelms the kidney’s capacity to clear calcium
317
What are the key presentations of hypercalcaemia of malignancy?
History of malignancy and signs and symptoms of hypercalcemia
318
What are the symptoms of hypercalcaemia of malignancy?
- Neuropsychiatric changes e.g., fatigue, confusion,
- Muscle weakness,
- Polyuria,
- Polydipsia
- GI disturbances
319
What are some differential diagnosis of hypercalcaemia of malignancy?
Primary hyperparathyroidism
Hyperthyroidism
Sarcoidosis
TB
320
How would you treat hypercalcaemia?
If acute and severe treat with intravenous normal saline and intravenous bisphosphate
Consider use calcitonin or furosemide if severe
Treat underlying malignancy if possible
321
What are some complications of hypercalcaemia?
Bisphosphate induced flu like syndrome.
AKI
Coma
Acute pancreatitis
322
What would hypercalcaemia show on an ECG?
The ST segment is short or absent and the duration of the corrected QT interval is decreased
323
What causes hypocalcaemia?
No parathyroid/dysfunction
Following drug treatment
Severe illness, tumour lysis, acute pancreatitis
324
How would you treat hypocalcaemia?
With calcium gluconate. ECG is recommended as dysrhythmia can occur
325
What are the complications associated with hypocalcaemia?
Respiratory failure
Cardiac arrythmias
326
What effect does hypocalcaemia have on an ECG?
Hypocalcaemia typically prolongs the Q-T interval and may lead to complete heart block.
327
What is defined as moderate hyperkalaemia?
Serum potassium between 5-6 mmol/L
328
What is defined as significant hyperkalaemia?
Serum potassium greater than 6. Greater than 6.5 requires urgent intervention
329
What are the two main causes (pathophys) of HK?
1. Increased intake of potassium in association with decreased renal output. Rare for this to occur with proper renal function. But can happen with normal intake and poor renal function (especially diabetes)
2. Decreased cellular entry of potassium or increased exit of potassium from cells.
( Diabetes+ during metabolic acidosis. )
330
Name some causes of HK (diseases and drugs)?
ddison's disease due to lack of aldosterone.
A number of drugs can cause this e.g., K+ sparing diuretics and ACE inhibitors
Rhabdomyolysis
Excess k+ therapy
Massive blood transfusion
Burns
Metabolic acidosis
331
What are the key presentations of HK?
Chest pain, weakness, palpitations, and light-headedness. With abnormal ECG.
332
What effect does HK have on an ECG?
- Fast irregular pulse.
- Tall tented T-waves in ECG.
- Small/no p-waves
- Wide QRS complex
333
What tests would you perform on a patient with suspected HK?
Basic metabolic panel.
Serum calcium, FBC and an ECG
334
How would you treat a patient with HK and K+ levels below 6.5 mmol/L
Polystyrene sulfonate resin (binds to K+ in gut and lowers over a few days)
335
How would you treat a patient with HK and k+ levels above 6.5 mmol/L
- First give calcium chloride (which is cardioprotective). May need to repeat in 5-10 mins. Will protect for 30-60 mins but won't lower k+ levels
- Use insulin and glucose to lower K+ levels as insulin will force K+ into cells.
- Can also use salbutamol to lower K+ levels further
336
What are the complications associated with untreated hyperkalaemia?
Myocardial hyperexcitability leading to ventricular fibrillation and cardiac arrest.
337
What is defined as moderate hypokalaemia (HPK)?
Potassium levels between 2.5-3 mmol/L
338
What is defined as severe HPK?
Potassium levels below 2.5 mmol/L
339
What can cause HPK?
- Diuretics, vomiting/diarrhoea,
- Pyloric stenosis,
- Cushing's/ steroids/ACTH,
- Conn's syndrome,
- Alkalosis,
- Renal tubular failure
340
What are the symptoms of HPK?
- Muscle weakness,
- Cramps, palpitations,
- Light headiness,
- Constipation
341
What are some signs of HPK?
Hypotonia, hyporeflexia, tetany
342
What are the effects of HPK on an ECG?
Small T-waves, with prominent U waves. A long PR interval.
343
What tests would you conduct on a patient with suspected HPK?
Basic metabolic panel (includes serum sodium, potassium, glucose, chloride, bicarbonate, urea, and creatinine).
ECG.
Urine electrolytes and creatinine can be useful for determining aetiology
344
High levels of what would indicate long standing HPK?
HC03-
345
How would you treat mild HPK?
Give an oral K+ supplement and review after 3 days. If due to diuretic consider K+ sparing one.
346
How would you treat severe HPK?
Give IV k+ no more than 20mmol/h and not more concentrated than 40mmol/L otherwise can cause cardiac arrest.
347
What is carcinoid syndrome?
A tumour of the neuroendocrine cells that results in excessive release of certain hormones
348
Where are most carcinoid tumours found?
The GI tract
349
What is carcinoid syndrome?
A build up of hormones produced by the neuroendocrine cells and the liver can no longer metabolise them
350
What are the symptoms of carcinoid syndrome?
- Diarrhoea
- SOB
- Flushing
- Itching
- Hepatic pain
- Fibrosis of heart valves
- Bronchoconstriction
Symptoms are worsened by stress and alcohol as these stimulate the neuroendocrine cells
351
What are the investigations for carcinoid syndrome?
- **24 hr urine 5-hydroxyindoleacetic acid:** show increased levels
- **Chest X-ray/ chest or pelvis MRI/ CT:** to identify location
- **Plasma chromogranin A:** reflects tumour mass
- **Ostreoscan:** injected radiolabelled somatostatin analogue, octreotide, to bind to the increased number of somatostatin receptors on tumour cells.
352
What is the management of carcinoid syndrome?
- **Decreasing emotional stress and alcohol consumption**
- **Somatostatin analogues:** e.g. octreotide, inhibit hormone release
- **Surgical resection**
- **Debulking embolisation or radiofrequency ablation of hepatic metastases:** can help with symptoms
353
What is pheochromocytoma?
A tumour arising from catecholamine-producing chromaffin cells of the adrenal medulla that classically presents with headaches, diaphoresis, and palpitations in the setting of paroxysmal hypertension
354
What are the symptoms of Pheochromocytomas?
- Headache,
- palpitations,
- resistant/young age hypertension,
- Impaired glucose tolerance.
- Cold sweats (diaphoresis)
355
What is the treatment of Pheochromocytomas?
- If hypertensive crisis give antihypertensive agents (calcium channel blockers)
- Alpha blockers **phenoxybenzamine or doxazosin**
355
Tests for pheochromocytomas?
Plasma free metanephrines
24-hour urine catecholamines
356
What can cause Pheochromocytomas?
Multiple endocrine neoplasia type 2 (MEN 2)
Neurofibromatosis type 1
Von Hippel-Lindau disease
