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Phase 2a Medicine > Endocrinology > Flashcards

Endocrinology Flashcards

1
Q

Endocrine action depends on which three things?

A
  1. Blood level of hormone
  2. Numbers of target receptors
  3. Affinity for target receptors
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2
Q

The major endocrine system comprises of which 7 glands?

A
  1. Pituitary
  2. Thyroid
  3. Parathyroid
  4. Adrenal
  5. Pancreas
  6. Ovary
  7. Testis
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3
Q

What is the difference between endocrine and exocrine?

A

Endocrine - hormones are secreted directly into the bloodstream and then travel to their target
Exocrine - hormones are secreted into a duct, which transports them to their site of action

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4
Q

Which hormones are synthesised and then stored in vesicles?

A

Peptides and monoamines

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5
Q

Which hormones are synthesised on demand?

A

Steroids

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6
Q

What potentiates the conversion of noradrenaline to adrenaline?

A

Cortisol

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7
Q

What are the effects of amines binding to alpha receptors?

A

Vasoconstriction, pupil dilation, alertness, contraction of stomach/bowl/anal sphincter

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8
Q

What are the effects of amines binding to beta receptors?

A

Vasodilation, increased heart rate, bronchial and visceral smooth muscle relaxation

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9
Q

What compounds are measured when checking for adrenaline/noradrenaline disorders?

A

Normetanephrines and metanephrines (noradrenaline and adrenaline are broken down into these)

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10
Q

Which two amine hormones are derived from tryptophan?

A

Serotonin (5HT) and melatonin

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11
Q

What part of the nervous system is stimulated by alpha and beta adrenoreceptors?

A

Sympathetic nervous system

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12
Q

Are amines water soluble?

A

Yes

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13
Q

How do thyroid hormones travel in the bloodstream?

A

99% bound to protein - not water soluble

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14
Q

Briefly describe how thyroid hormones are synthesised

A
  • Thyroglobulin released into colloid in thyroid gland
  • Iodine incorporated into tyrosine molecules to form iodothyrosines
  • Iodothyrosines conjugated to form T3 and T4, which is stored in the colloid bound to thyroglobulin
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15
Q

Where are peptide hormone receptors located?

A

On the cell membrane

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16
Q

Where are steroid hormone receptors located?

A

In the cytoplasm

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17
Q

Where in the cell are the receptors for thyroid hormone, oestrogen and vitamin D?

A

In the nucleus

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18
Q

Progesterone, cortisol, testosterone and oestradiol are all derived from which precursor?

A

Cholesterol

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19
Q

Briefly describe the intracellular steroid pathway

A
  1. Steroid hormone diffuses through the plasma membrane and binds to the receptor
  2. Receptor hormone complex enters the nucleus and binds to GRE (glucocorticoid response element)
  3. Binding initiates transcription of gene to mRNA
  4. mRNA directs protein synthesis
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20
Q

Which hormone inhibits prolactin?

A

Dopamine

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21
Q

Which hormone inhibits growth hormone?

A

Somatostatin

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22
Q

Give 5 ways in which hormone action can be regulated

A
  1. Hormone metabolism - increased metabolism reduces hormone activity
  2. Hormone receptor induction e.g. induction of LH receptors by FSH in follicle to make sure ovary responds to LH at appropriate time in cycle
  3. Hormone receptor down-regulation (hormone secreted in large quantities causes down-regulation of its target receptors)
  4. Synergism = combined effects of two hormones amplified (e.g. glucagon with adrenaline)
  5. Antagonism = one hormone opposes another hormone (e.g. glucagon antagonises insulin)
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23
Q

Which two hormones are secreted from the posterior pituitary?

A

ADH and oxytocin

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24
Q

Which six hormones are secreted from the anterior pituitary?

A
  1. TSH
  2. ACTH
  3. FSH
  4. LH
  5. GH
  6. Prolactin
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25
Q

What disease is caused by excess cortisol?

A

Cushing’s

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26
Q

What effect does growth hormone have on the liver?

A

Stimulates the production of IGF-1 (insulin-like growth factor), which is important for cartilage formation and skeletal growth

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27
Q

Where is T4 converted to T3?

A

In the muscles and liver

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28
Q

What is the half-life of T4 and T3?

A

T4 - 5 to 7 days

T3 - 1 day

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29
Q

What is anorexia?

A

Lack of appetite

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30
Q

How is BMI calculated?

A

weight (kg) / h (m2)

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31
Q

Name 7 conditions that obese individuals are at increased risk of developing

A
  1. Type 2 diabetes
  2. Hypertension
  3. Coronary artery disease
  4. Stroke
  5. Osteoarthritis
  6. Obstructive sleep apnoea
  7. Cancer (esp breast, endometrium, prostate, colon)
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32
Q

Where is the ‘hunger centre’ in the brain?

A

Lateral hypothalamus

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33
Q

Where is the ‘satiety centre’ in the brain?

A

Ventromedial hypothalamic nucleus

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34
Q

What are the 5 central controllers that increase appetite?

A
  1. Neuropeptide Y
  2. Melanin-concentrating hormone
  3. Agouti-related Peptide
  4. Orexin
  5. Endocannabinoid
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35
Q

What are the 4 central controllers that decrease appetite?

A
  1. alpha-MSH (melanocyte stimulating hormone)
  2. CART (cocaine and amphetamine regulated transcript)
  3. GLP-1 (glucagon-like peptide)
  4. Serotonin
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36
Q

How does leptin influence appetite?

A

It inhibits NPY and AGRP and stimulates POMC/CART, decreasing appetite

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37
Q

When do blood levels of leptin increase/decrease

A

Increase after a meal

Decrease after fasting

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38
Q

How does Peptide YY reduce appetite?

A

It is structurally similar to NPY, so can bind to NPY receptors, inhibiting gastric motility and reducing appetite.

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39
Q

How does cholecystokinin influence appetite?

A

It has receptors in the pyloric sphincter, activation of which delays gastric emptying.

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40
Q

Ghrelin is expressed in the stomach and stimulates growth hormone release. What effect does it have on appetite?

A

It has a positive effect on NPY/AgRP, which increases appetite

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41
Q

POMC (pre-opiomelanocortin) is cleaved into various peptides, including melanocortin stimulating hormone. What effects does melanocortin have in the body?

A

Binds to melanocortin receptors MCR1-5.
Stimulates the production of melanocytes, resulting in pigmentation. Also stimulates the adrenal glands and signals satiety in the brain.

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42
Q

What are the effects of POMC deficiency?

A

Pale skin, adrenal insufficiency, hyperphagia and obesity.

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43
Q

How does AgRP influence appetite?

A

It has an antagonistic effect on the MC4r receptor, which is part of the POMC pathway, thereby increasing hunger.

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44
Q

What does Malonyl CoA do?

A

It is a central metabolic signal mediating energy metabolism. In the fasted state, AMPK is activated, which inhibits acetyl coA carboxylase, meaning that less acetyl coA is converted to malonyl coA, so malonyl coA levels decrease and appetite increases.
In the fed state, AMPK is deactivated, acetyl coA carboxylase is stimulated and malonyl coA levels increase, leading to decreased appetite.

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45
Q

What effect does PTH have on the kidney?

A

Increases Ca2+ reabsorption
Decreases phosphate reabsorption
Increases alpha-hydroxylation of 25-OH vitamin D

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46
Q

What effect does PTH have on the bones?

A

Increases bone remodelling such that bone resorption is greater than bone formation, releasing calcium from the bones

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47
Q

What effect does PTH have on the gut?

A

No direct effect, but because of the increased alpha-hydroxylation of 25-OH vitamin D in the kidney, Ca2+ absorption is increased.

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48
Q

Low serum albumin results in low total serum calcium, but not low ionised calcium. How do we calculate corrected calcium levels?

A

Corrected calcium = total serum calcium + 0.02*(40-serum albumin)

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49
Q

Give six possible consequences of hypocalcaemia

A
  1. Paraesthesia
  2. Muscle spasm (hands and feet, larynx, premature labour)
  3. Seizures
  4. Basal ganglia calcification
  5. Cataracts
  6. ECG abnormalities (long QT interval)
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50
Q

What is Chvostek’s sign?

A

An indicator hypocalcaemia. Tap over the facial nerve and look for spasm of facial muscles.

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51
Q

What is Trousseau’s sign?

A

An indicator of hypocalcaemia. If a blood pressure cuff is inflated to 20mmHg above systolic for 5 minutes, the hand and wrist muscles contract involuntarily. (‘chef’s kiss’)

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52
Q

What is the major cause of hypocalcaemia?

A

Vitamin D deficiency

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53
Q

What can cause hypoparathyroidism?

A

Surgery (i.e. thyroidectomy), radiation, syndromic disorders, genetics and infiltration disorders.

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54
Q

Why does magnesium deficiency cause functional hypoparathyroidism?

A

Magnesium is required to secrete PTH

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55
Q

What is pseudohypoparathyroidism?

A

Resistance to parathyroid hormone

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56
Q

What are the signs of pseudoparathyroidism?

A

Short stature, obesity, round facies, mild learning difficulties, subcutaneous ossification, short 4th metacarpals and other hormone resistance

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57
Q

Why might you obtain a false positive result for hypercalcaemia?

A

If the tourniquet was on for too long when the blood was being taken, or if the sample is old, haemolysis could cause a false increase in serum calcium as the intracellular calcium leaks out.

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58
Q

What are the symptoms of hypercalcaemia?

A

Thirst, polyuria, constipation and confusion (could lead to coma in severe cases)

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59
Q

What are the consequences of hypercalcaemia?

A

Renal stones and ECG abnormalities (short QT)

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60
Q

What causes 90% of cases of hypercalcaemia?

A

Malignancy, e.g. bone metastases, myeloma, PTHrP (parathyroid hormone related peptide caused by some tumours), lymphoma

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61
Q

What are the less likely possible causes of hypercalcaemia?

A
  • Thiazides
  • Thyrotoxicosis
  • Sarcoidosis (excess vitamin D)
  • Benign hypercalcaemia
  • Immobilisation (increases bone turnover)
  • Milk-alkali (too much milk + renal impairment = can’t excrete calcium)
  • Adrenal insufficiency
  • Phaeochromocytoma
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62
Q

What are the consequences of primary hyperparathyroidism?

A
  1. Bones - e.g. osteitis fibrosa cystica
  2. Kidney stones
  3. Psychic groans (confusion)
  4. Abdominal moans (constipation, acute pancreatitis)
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63
Q

What signs of hyperparathyroidism might be seen in the bones?

A

Subperiosteal erosions in the phalanges

Cysts in the skull caused by osteitis fibrosa cystica

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64
Q

What two processes does the body use to increase blood glucose levels in the fasting state?

A
  1. Breakdown of glycogen

2. Gluconeogenesis

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65
Q

What happens after feeding when blood glucose levels start to rise in non-diabetic humans?

A
  • The rising glucose levels in the blood trigger release of insulin.
  • 40% of the ingested glucose goes to the liver and the other 60% goes to the periphery (mainly muscle),
  • Ingested glucose helps to replenish glycogen stores in the liver and muscle
  • High insulin and glucose levels suppress lipolysis and levels of non-esterified fatty acids and free fatty acids fall
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66
Q

From where are insulin and glucagon secreted?

A

From the islets of Langerhans in the endocrine pancreas - beta cells secrete insulin, alpha cells secrete glucagon

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67
Q

How does insulin release inhibit glucagon?

A

Via paracrine ‘crosstalk’ between the alpha and beta cells in the islets of Langerhans

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68
Q

Briefly describe how insulin is secreted by the beta cell

A

Glucose enters the cell and is metabolised, resulting in conversion of ADP to ATP. The ATP facilitates closure of the K+ channels, resulting in membrane depolarisation. Voltage-gated Ca2+ channels open, resulting in Ca2+ influx, which facilitates exocytosis of insulin secretory granules.

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69
Q

Briefly describe how insulin increases uptake of glucose into muscle and fat cells.

A

Insulin binds to the receptor, triggering an intracellular signalling cascade. GLUT4 vesicle mobilises to the plasma membrane, where it integrates, allowing glucose to bind to GLUT4 and enter the cell.

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70
Q

Give three ways in which insulin regulates carbohydrate metabolism

A
  1. Suppresses hepatic glucose output (decreases glycogenolysis and gluconeogenesis)
  2. Increases glucose uptake into insulin sensitive tissues (muscle and fat)
  3. Suppresses lipolysis and breakdown of muscle
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71
Q

Give three ways in which glucagon regulates carbohydrate metabolism

A
  1. Increases hepatic glucose output (increases glycogenolysis and gluconeogenesis)
  2. Reduces peripheral glucose uptake
  3. Stimulates peripheral release of gluconeogenic precursors (glycerol, amino acids), which leads to lipolysis, muscle glycogenolysis and breakdown
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72
Q

What three counterregulatory hormones have similar effects to glucagon?

A
  1. Adrenaline
  2. Cortisol
  3. Growth hormone
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73
Q

Diabetes mellitus is a disorder of carbohydrate metabolism characterised by hyperglycaemia. Briefly describe the two ways in which it causes morbidity and mortality.

A
  1. Acute hyperglycaemia, which can lead to acute metabolic emergencies e.g. diabetic ketoacidosis and hyperosmolar coma
  2. Chronic hyperglycaemia, which can lead to tissue complications
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74
Q

What is the main side effect of diabetes treatment?

A

Hypoglycaemia

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75
Q

Diabetes affects many different systems, often silently. Name 5 serious complications that are associated with diabetes.

A
  1. Diabetic retinopathy
  2. Diabetic nephropathy
  3. Stroke
  4. Cardiovascular disease
  5. Diabetic neuropathy
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76
Q

What are the 6 types of diabetes?

A
  1. Type 1 diabetes
  2. Type 2 diabetes
  3. Maturity onset diabetes of youth (MODY) - genetic condition
  4. Pancreatic diabetes
  5. ‘Endocrine diabetes’ caused by e.g. Cushing’s
  6. Malnutrition-related diabetes
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77
Q

What is the definition of diabetes in a symptomatic patient?

A

Random plasma glucose > 11mmol/l

Fasting plasma glucose > 7mmol/l

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78
Q

What is the definition of diabetes in an asymptomatic patient?

A

Glucose tolerance test - 75g glucose administered:
fasting > 7mmol/l
or >11mmol/l after 2 hours
- repeated on 2 occasions

HbA1c of 48mmol/mol (6.5%)

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79
Q

What is type 1 diabetes?

A

Insulin deficiency disease characterised by loss of beta cells due to autoimmune destruction.
- Beta cells express antigens of HLA histocompatibility system (?because of a virus), which activates a chronic cell mediated immune process –> chronic ‘insulitis’

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80
Q

What happens as a result of failure of insulin secretion in type 1 diabetes?

A
  • Continued breakdown of liver glycogen
  • Unrestrained lipolysis and skeletal muscle breakdown providing gluconeogenic precursors
  • Inappropriate increase in hepatic glucose output and suppression of peripheral glucose uptake
  • Rising glucose concentration results in increased urinary glucose losses as renal threshold (10m) is exceeded
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81
Q

What happens if type 1 diabetes is not treated with insulin?

A
  • Circulating glucagon increases due to loss of paracrine function in the islets of Langerhans, which increases glucose levels further
  • Perceived ‘stress’ leads to increased levels of cortisol and adrenaline
  • Body enters a progressive catabolic state and increasing levels of ketones–> wasting
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82
Q

What is type 2 diabetes?

A

Impaired insulin secretion and insulin resistance, leading to impaired glucose tolerance, progressive hyperglycaemia and high free fatty acids.

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83
Q

A normal glucose disposal rate is about 300mg/m2/min. What is the glucose disposal rate in a typical individual with type 2 diabetes?

A

100mg/m2/min

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84
Q

What are the consequences of impaired insulin action in type 2 diabetes?

A
  • Reduced muscle and fat uptake after eating
  • Failure to suppress lipolysis and high circulating free fatty acids
  • Abnormally high glucose output after a meal
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85
Q

Why is ketone production generally not excessive in type 2 diabetes like it is in type 1 diabetes?

A

Because even low levels of insulin are sufficient to prevent muscle catabolism and ketogenesis - insulin is not completely missing like it is in type 1 diabetes

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86
Q

What is the ‘ideal’ management for type 2 diabetes?

A

Weight loss and exercise, which can reverse hyperglycaemia if substantial enough

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87
Q

How is type 2 diabetes usually managed in practice?

A

Medication to control blood pressure, blood glucose and lipids

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88
Q

What is GLP-1?

A

Glucagon-like peptide 1 - stimulates insulin release and inhibits glucagon release

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89
Q

Why are DPP-IV inhibitors sometimes used to treat type 2 diabetes?

A

DDP-IV breaks down GLP-1. If inhibited, there is more GLP-1 available to stimulate insulin release and inhibit glucagon release.

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90
Q

How are SGLT2 inhibitors such as empaglifozin, canaglufozin and dapaglifozin used to treat type 2 (and sometimes type 1) diabetes?

A

They block the reabsorption of glucose in the kidney, increasing glucose excretion and thereby lowering blood glucose levels.

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91
Q

What two types of insulin are used to treat diabetes?

A
  • Prandial insulins = fast-acting insulin used at meal times

- Basal insulins - maintaining insulin at a constant baseline

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92
Q

Why is glucose control a ‘balancing act’ for diabetic patients?

A

Tight glucose control reduces the risk of diabetic retinopathy, but increases the risk of hypoglycaemia.

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93
Q

Why might diabetics need to take insulin half an hour before eating?

A

Because the insulin is given via a subcutaneous injection (rather than going straight to the liver, as insulin produced in the pancreas does) and has to travel through the body, which causes a delay. It is therefore possible for glucose levels to drop before the insulin gets to work, causing hypoglycaemia.

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94
Q

What are the advantages of basal insulin?

A
  • Simple for the patient, may only need to use once a day, patient can adjust themselves based on fasting glucose
  • Lower risk of hypoglycaemia at night
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95
Q

What are the disadvantages of basal insulin?

A
  • Doesn’t cover meals

- Best used with long-acting insulin analogues, which are expensive

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96
Q

What are the advantages of pre-mixed insulin?

A
  • Both basal and prandial components covered in a single insulin preparation
  • Can cover insulin requirements through most of the day
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97
Q

What are the disadvantages of pre-mixed insulin?

A
  • Requires consistent meal and exercise pattern
  • Increased risk of nocturnal hypoglycaemia
  • Increased risk of fasting hyperglycaemia if basal component does not last long enough
  • Often requires accepting hyper HbA1c of <7.5%
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98
Q

What is considered the best treatment for type 1 diabetes?

A

Intensive basal-bolus insulin therapy

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99
Q

What is ‘double diabetes’?

A

Type 1 diabetes sufferers put on weight and become resistant to the insulin they are being given.

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100
Q

How is hypoglycaemia currently classified?

A

Three levels:
Level 1: Alert value - plasma glucose <3.9mmol/l, no symptoms
Level 2: Serious biochemical. Plasma glucose <3.0 mmol/l
Level 3: Patient has impaired cognitive function and requires external help to recover.

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101
Q

What are the common symptoms of hypoglycaemia

A
  • Trembling, palpitations, sweating, anxiety, hunger
  • Difficulty concentrating, confusion, weakness, drowsiness, dizziness, vision changes, difficulty speaking
  • Nausea, headache

Can often be mistaken for intoxication

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102
Q

What are the risk factors for hypoglycaemia?

A
  1. Long duration of diabetes
  2. Tight glycaemic control with repeated episodes of non-severe hypoglycaemia
  3. Increasing age
  4. Use of drugs
  5. Sleeping
  6. Increased physical activity
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103
Q

How should hypoglycaemia be treated?

A
  1. Recognise the symptoms so they can be treated as soon as they occur
  2. Confirm the need for treatment if possible (blood glucose <3.9mmol/l)
  3. Treat with 15g fast-acting carbohydrate to relieve symptoms
  4. Re-test in 15 minutes to ensure blood glucose >4mmol/l and re-treat if needed.
  5. Eat a long-acting carbohydrate to prevent recurrence of symptoms
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104
Q

How does the hypothalamus control the anterior pituitary?

A

The anterior pituitary does not have an arterial blood supply, but receives blood via a portal venous circulation from the hypothalamus.

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105
Q

Describe the thyroid axis

A

The hypothalamus secretes thyroid releasing hormone (TRH), which stimulates the anterior pituitary to release thyroid stimulating hormone (TSH), which stimulates the thyroid gland to produce T4 and T3, which exert a negative feedback effect on the anterior pituitary and hypothalamus.

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106
Q

Describe the gonadal axis

A

The hypothalamus produces GnRH (gonadotrophin releasing hormone) in pulses, which stimulates the anterior pituitary to produce LH and FSH. Testosterone and oestrogen exert negative feedback on the hypothalamus.

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107
Q

Why do FSH and LH increase following the menopause?

A

The ovaries fail, so stop producing oestrogen. FSH and LH increase due to the lack of negative feedback on the hypothalamus.

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108
Q

Describe the adrenal axis

A

The hypothalamus produces CRH (cortisol releasing hormone), which stimulates the anterior pituitary to release ACTH (adrenocorticotropic hormone), which stimulates the adrenal glands to produce cortisol, which exerts negative feedback on the pituitary and hypothalamus.

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109
Q

Describe the GH/IGF-1 axis

A

The hypothalamus secretes GHRH, which stimulates the anterior pituitary to release growth hormone in pulses, which stimulates the production of IGF-1 in the liver

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110
Q

What is IGF-1?

A

Insulin-like growth factor 1; it manages the effects of growth hormone in the body

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111
Q

Which hormone inhibits growth hormone?

A

Somatostatin

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112
Q

What is the most common condition affecting the pituitary gland?

A

Benign pituitary adenoma

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113
Q

How might trauma affect the pituitary gland?

A

If the pituitary stalk is shaken, this can break the venous supply to the pituitary and affect its function.

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114
Q

What are the three ways in which pituitary tumours can affect function?

A
  1. Pressure on local structures
  2. Pressure on normal pituitary resulting in hypopituitarism
  3. Functioning tumours, e.g. prolactinoma
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115
Q

What local structure is most likely to be affected by a pituitary tumour and what is the most common effect?

A

The optic chiasm - most common effect is bitemporal hemianopia

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116
Q

What happens if a pituitary tumour penetrates the sphenoid sinus?

A

CSF can leak from the nose

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117
Q

What 3 symptoms are associated with hypopituitarism?

A
  1. Pale skin
  2. Lack of body hair
  3. Central obesity
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118
Q

Name three conditions that can be caused by functioning pituitary tumours

A
  1. Acromegaly
  2. Gigantism
  3. Cushing’s disease
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119
Q

Why do prolactinomas sometimes cause amenorrhoea and infertility?

A

Prolactin inhibits FSH and LH, therefore hyperprolactinaemia caused by a prolactinoma can cause amenorrhoea and infertility due to loss of inhibitory effect.

120
Q

Prolactinomas are normally treated with dopamine agonists such as cabergoline. Why?

A

Prolactin is under negative control of dopamine. Dopamine agonists can therefore decrease prolactin secretion and successfully shrink the vast majority of prolactinomas.

121
Q

What are the 5 Tanner stages in boys based on?

A

Pubic hair, testicular growth and testicular volume

122
Q

What are the 5 Tanner stages in girls based on?

A

Pubic hair and breast development

123
Q

What are considered the definitive signs of puberty in boys and girls?

A

Boys - first ejaculation (may be nocturnal)

Girls - menarche

124
Q

What is the first visible change of puberty in girls and what is it due to?

A

Thelarche (breast development), which is induced by the effects of oestrogen on the breast, causing ductal proliferation, site specific adipose deposition and enlargement of the areola and nipple.

125
Q

How can maturation of the uterus and ovaries be checked?

A

Via ultrasound (transabdominal at this age). A prepubertal uterus looks like a tube and the prepubertal ovaries have not yet taken on the multicystic appearance of mature ovaries.

126
Q

What happens to the vagina during puberty?

A

The epithelium thickens and the reddish colour becomes dulled.

127
Q

What are the 6 signs of maturation in the female external genitalia?

A
  • Increase in size and thickening of the labia
  • Rugation and change in colour of the labia majora
  • Hymen thickens
  • Clitoris enlarges
  • Vestibular glands begin secretion
  • Pubic hair
128
Q

What causes growth of pubic and axillary hair in females?

A

Adrenal and ovarian androgens

129
Q

What is adrenarche?

A

Maturation of the adrenal gland, which results in activation of adrenal androgen production (DHEA and DHEA-S).

130
Q

What are the consequences of adrenarche?

A

Axillary hair, oily skin, mild acne, body odour

131
Q

What is ‘mini puberty of infancy’?

A

The HPG axis becomes active shortly after birth for a brief period, then the GnRH neurons are suppressed until puberty.

132
Q

What is the difference between true precocious puberty and precocious pseudopuberty?

A

True precocious puberty requires hypothalamic activation and therefore activation of the HPG axis. Precocious pseudopuberty does not involve activation of the HPG axis, but patients may have overactive adrenal glands, causing breast/penile growth.

133
Q

Why is it particularly important to investigate precocious puberty in boys?

A

Most female patients have idiopathic precocious puberty, but most male patients have an underlying pathological condition, such as a brain tumour.

134
Q

How is precocious puberty treated?

A

Using a GnRH superagonist to suppress pulsatility of GnRH secretion, which shuts down the HPG axis.

135
Q

How is delayed puberty usually spotted?

A

In girls - lack of menarche

In boys - late growth

136
Q

What are the consequences of delayed puberty?

A
  • Delayed acquisition of secondary sex characteristics
  • Psychological problems
  • Defects in reproduction
  • Reduced peak bone mass
137
Q

What are the indications for investigation with regard to delayed puberty in girls?

A
  • Lack of breast development by 13 years
  • More than five years between breast development and menarche
  • Lack of pubic hair by 14 years
  • Absent menarche by 15-16 years.
138
Q

What are the indications for investigation with regard to delayed puberty in boys?

A
  • Lack of testicular enlargement by 14 years
  • Lack of pubic hair by 15 years
  • More than 5 years to complete genital enlargement
139
Q

What is the most common cause of delayed puberty in both sexes?

A

Constitutional delay of growth and puberty - extreme of normal physiologic variation, diagnosis of exclusion. Frequently associated with family history of late menarche in female relatives and late growth spurt in male relatives.

140
Q

Why should karyotyping be requested for all girls presenting with short stature?

A

To check for Turner’s syndrome

141
Q

What does puberty correlate better to than chronological age?

A

Bone age. GH deficiency results in delayed bone age, whereas advanced bone age is seen in precocious puberty.

142
Q

What is Kallman syndrome and what causes it?

A

Hypogonadotrophic hypogonadism, caused by failure of migration of GnRH neurons. Occurs more in males (4:1), patients present with small genitalia.

143
Q

How is Kallman syndrome treated?

A

Responds well to hormone treatment

144
Q

What is Turner’s syndrome?

A

A chromosomal abnormality seen in girls resulting in a 45XO karyotype, affects 1 in 2000 girls. Various potential issues such as cardiovascular malformation, neck webbing, small mandible, prominent ears, high arched palate, renal malformations etc.

145
Q

What is Klinefelter syndrome?

A

A chromosomal abnormality seen in 1 in 1000 boys resulting in a 47 XXY karyotype. Reduces IQ, increases risk of breast cancer, causes primary hypogonadism with azoospermia, gynaecomastia, osteoporosis and tall stature. Often undiagnosed until patient notices infertility.

146
Q

What is the most common category of endocrine disorders?

A

Thyroid disorders

147
Q

What is Hashimoto’s thyroiditis?

A

An autoimmune disorder affecting the thyroid gland, which causes (in most cases) hypothyroidism.

148
Q

What is Graves’ disease?

A

An autoimmune disorder that causes hyperthyroidism

149
Q

What antibodies are found in almost all patients with autoimmune hypothyroidism?

A

Thyroglobulin and thyroid peroxidase

150
Q

Thyroid cell destruction in autoimmune thyroid disease is mediated by which cells?

A

Cytotoxic (CD8+) T cells

151
Q

What are the classical features of Graves’ disease?

A

Goitre, tachycardia, eye symptoms (swollen, red)

152
Q

What causes Graves’ disease?

A

TSH receptor antibodies (originally called Long Acting Thyroid Stimulators), which (usually) stimulate the TSH receptor, leading to hyperthyroidism.

153
Q

How can TSH receptor antibodies cause hypothyroidism in rare cases?

A

Some of them block the effects of TSH instead of stimulating the receptor

154
Q

What is the biggest risk factor for thyroid autoimmunity?

A

Being female

155
Q

Why does thyroid autoimmunity commonly manifest in the postpartum period?

A

Immune activity drops during pregnancy, but rises postpartum and can sometimes result in autoimmunity.

156
Q

Thyroid associated ophthalmopathy is seen in ~50% of patients with Graves’ disease and can also occur in autoimmune hypothyroidism. What is it thought to be caused by?

A

Swelling in the extraocular muscles, most likely due to an autoantigen in the extraocular muscles that cross reacts with (or is identical to) a thyroid autoantigen.

157
Q

What other diseases are associated with thyroid autoimmune disease?

A

Other autoimmune diseases, e.g. type 1 diabetes, Addison’s disease, pernicious anaemia, coeliac disease, chronic active hepatitis

158
Q

In which areas is goitre endemic?

A

In iodine deficient areas

159
Q

What is the single most common endocrine disorder?

A

Sporadic non-toxic goitre

160
Q

What drugs can cause hyperthyroidism?

A
  • Iodine
  • Amiodarone
  • Radiocontrast agents
  • Various cancer drugs
161
Q

What are the clinical features of hyperthyroidism?

A

Weight loss, tachycardia, hyperphagia, anxiety, tremor, heat intolerance, sweating, diarrhoea, menstrual disturbances

162
Q

What are the 3 common causes of hyperthyroidism?

A
  1. Graves’ disease
  2. Toxic multinodular goitre
  3. Toxic adenoma
163
Q

How can you differentiate between the 3 common causes of hyperthyroidism?

A

Disease specific clinical signs:
Graves’ disease - diffuse goitre, thyroid eye disease, pretibial myxoedema, acropachy
Toxic multinodular goitre - multiple nodules
Toxic adenoma - single nodule

164
Q

How is hyperthyroidism treated?

A

Antithyroid drugs (e.g. carbimazole)
Radioiodine
Surgery (partial/subtotal thyroidectomy)

165
Q

Thionamides such as carbimazole, propylthiouracil (PTU) and methimazole are used to treat hyperthyroidism. How do they work?

A

They decrease the synthesis of new thyroid hormone - PTU also inhibits the conversion of T4 to T3

166
Q

What are the disadvantages of antithyroid drugs?

A

Low remission rates (30-50%)

No definite way to predict remission/relapse for an individual patient

167
Q

Which patients with hyperthyroidism are less likely to have a good prognosis?

A
  • Those with severe biochemical hyperthyroidism
  • Large goitre
  • Male sex
  • Young age at disease onset
  • +ve for thyroid antibodies following a course of antithyroid drugs
168
Q

What is a common side effect of thionamides?

A

Rash

169
Q

What is a potential serious side effect of thionamides and how does it manifest?

A

Agranulocytosis - manifests as sore throat, fever and mouth ulcers

170
Q

How is radioiodine used to treat hyperthyroidism?

A

Iodine-131 is a stable isotope of iodine, which emits large beta particles of moderate energy, with some gamma ray emission. It is taken up into the thyroid (as iodine is required for thyroid hormone synthesis) and emission of beta particles results in ionisation of thyroid cells, which damages the DNA and enzymes.

171
Q

What is the most common type of hypothyroidism?

A

Primary hypothyroidism accounts for >99% of cases and most cases are due to Hashimoto’s thyroiditis

172
Q

What are the clinical features of hypothyroidism?

A

Fatigue, weight gain, cold intolerance, constipation, menstrual disturbances, muscle cramps, dry/rough skin, oedema

173
Q

What investigation could be performed if primary hypothyroidism is suspected?

A

TSH and T4 and T3 could be measured. Would expect increased TSH due to lack of negative feedback and usually decreased T4 and T3.

174
Q

What TSH and T4/T3 levels would we expect to see in secondary/tertiary hypothyroidism?

A

Would expect inappropriately low TSH for reduced T4/T3 levels

175
Q

Where are ADH/vasopressin and oxytocin synthesised?

A

In the paraventricular nucleus and supraoptic nucleus within the hypothalamus

176
Q

What results in secretion of ADH/vasopressin?

A

Water loss, increase in plasma osmolality, decrease in cellular hydration.

177
Q

Vasopressin binds to which G protein coupled receptors?

A

V1a in the vasculature
V1b in the pituitary gland
V2 in the renal collecting tubules

178
Q

How much urine would pass per day if vasopressin were not present to allow urine concentration?

A

20-30l

179
Q

Describe the mechanism of action of vasopressin

A

Vasopressin activates V2 receptors on cell surface membrane of principal cells of renal collecting ducts, triggering an intracellular cascade. Aquaporin-2 proteins are synthesised and inserted into the apical membrane, increasing the permeability of the collecting duct. Water can then be reabsorbed from the renal collecting duct and returned to the bloodstream, decreasing plasma osmolality.

180
Q

Name 6 endogenous solutes that may affect plasma osmolality

A
  1. Sodium
  2. Potassium
  3. Chloride
  4. Bicarbonate
  5. Urea
  6. Glucose
181
Q

Name 4 exogenous solutes that may affect plasma osmolality

A
  1. Alcohol
  2. Methanol
  3. Polyethylene glycol
  4. Manitol
182
Q

What calculation can be used to reasonably approximate plasma osmolality?

A

(Na+ x 2) + glucose + urea

183
Q

What is normal osmolality?

A

282-295mOsmol/kg

184
Q

A lack of vasopressin results in which uncommon condition?

A

Cranial diabetes insipidus

185
Q

Resistance to the action of vasopressin results in which uncommon but life threatening condition?

A

Nephrogenic diabetes insipidus

186
Q

What is SIADH?

A

Syndrome of antidiuretic hormone secretion - i.e. inappropriate vasopressin release, which can also come from an ectopic source.

187
Q

How is diabetes insipidus diagnosed?

A

The symptoms are polyuria, polydipsia and no glycosuria.
Check urine volume, renal function and serum calcium.
Urine will be inappropriately dilute for plasma osmolality –> serum osmolality > 300 AND urine osmolality <200 is consistent with diabetes insipidus.

188
Q

What are possible acquired causes of cranial diabetes insipidus?

A 
Idiopathic
Tumours
Trauma
Infection (e.g. TB, meningitis)
Vascular (e.g. aneurysm, infarction)
Inflammatory diseases
189
Q

What are possible primary causes of cranial diabetes insipidus?

A

Genetic disorders such as Wolfram syndrome

Developmental disorders such as septo-optic dysplasia

190
Q

Describe how a water deprivation test can be used to diagnose diabetes insipidus

A

Deprive patient of water and measure osmolality and urine output. In normal individuals, osmolality increases as does urine concentration. In diabetes insipidus, osmolality increases but urine concentration will not.

191
Q

Following a water deprivation test, how can cranial DI be distinguished from nephrogenic DI?

A

By giving desmopressin and allowing access to water (or giving a hypertonic saline infusion to rule out primary polydipsia). The desmopressin mimics the action of vasopressin so in CDI osmolality will return to normal levels, whereas in NDI osmolality will continue to increase.

192
Q

What substance is cleaved from the same protein as vasopressin and can be measured as a marker of vasopressin levels?

A

Copeptin

193
Q

How is cranial DI managed?

A 
Treat any underlying condition e.g. tumour
Administer desmopressin (V2 receptor agonist) via tablets, nasal spray or injection
194
Q

How is nephrogenic DI managed?

A

Avoid precipitating drugs

Make sure water is available at all times and give very high dose desmopressin

195
Q

What is the definition of hyponatraemia?

A

Below the normal level of serum sodium i.e. <135mmol/l

196
Q

What is the definition of severe hyponatraemia?

A

Serum sodium <125mmol/l

197
Q

What are normal serum sodium levels?

A

135-144mmol/l

198
Q

What are the symptoms of moderate hyponatraemia?

A

Headache, irritability, nausea/vomiting mental slowing, unstable gait/falls, confusion/delirium, disorientation

199
Q

What are the symptoms of severe hyponatraemia?

A

Stupor/coma, convulsions, respiratory arrest

200
Q

What causes the symptoms of hyponatraemia?

A

Too much water causes the brain to swell due to low osmolality

201
Q

What actions should you take if you suspect hyponatraemia?

A
  • Stop giving hypotonic fluids
  • Review patient medication
  • Check plasma and urine osmolality
  • Check urinary Na+, glucose, thyroid function and possibly cortisol
  • Assess underlying causes e.g. via chest imaging
202
Q

How is hyponatraemia treated in fluid overloaded and normovolaemic patients?

A

Fluid restriction - 500-1000ml over 24 hours

203
Q

How is hyponatraemia treated in dehydrated patients?

A

Saline replacement

204
Q

What condition is responsible for 25% of all hyponatraemia cases?

A

SIAD - syndrome of antidiuresis, where too much arginine vasopressin is secreted when it shouldn’t be

205
Q

What normally causes SIAD?

A

Can be caused by various drugs

206
Q

What needs to be measured daily in acute SIAD and weekly to monthly in chronic SIAD?

A

urea and electrolytes

207
Q

How is SIAD managed?

A
  1. Diagnose and treat underlying condition
  2. Fluid restriction <1l/day
  3. Sometimes demeclocycline (antibiotic)/vaptan (vasopressin receptor antagonist)
  4. Increase Na+ levels if necessary - must be done slowly <8mmol/l increase over 24 hours and only if levels <115mmol/l and patient is fitting
208
Q

What serious neurological condition can be caused by hyponatraemia?

A

Osmotic demyelination syndrome - massive demyelination of descending axons

209
Q

What are the risk factors for osmotic demyelination syndrome?

A 
Serum Na+ <105mmol/l
Hypokalaemia
Chronic excess alcohol
Malnutrition
Advanced liver disease
210
Q

How is acute severe symptomatic hyponatraemia managed?

A
  1. IV 150ml of 3% saline (or equivalent) over 20 minutes
  2. Check serum Na+
  3. Repeat until 5mmol/l increase in Na+
  4. After 5mmol/l increase, stop hypertonic saline, check Na+ 6 hourly for first 24 hours, limit increase to 10mmol/l in the first 24 hours
211
Q

Where do craniopharyngiomas arise from?

A

From squamous epithelial remnants of Rathke’s pouch (part of roof of the mouth that pituitary gland arises from)

212
Q

What are the two types of craniopharyngioma?

A

Adamantinous and squamous papillary (benign, but can infiltrate surrounding structures if it grows)

213
Q

What are the symptoms of craniopharyngioma?

A

Can cause raised ICP, visual disturbances, growth failure, pituitary hormone deficiency and weight increase

214
Q

Rathke’s cysts are usually asymptomatic and small. How do symptomatic patients present?

A

Headache, amenorrhoea, hypopituitarism and hydrocephalus

215
Q

What is the second most common pituitary tumour (after pituitary adenoma), that can be a complication of radiotherapy?

A

Meningioma

216
Q

What are the symptoms of meningioma?

A

Visual disturbances (loss of acuity, visual field defects) and endocrine dysfunction

217
Q

What is lymphocytic hypophysitis?

A

Inflammation of the pituitary gland due to autoimmune reaction

218
Q

Why is lymphocytic hypophysitis more common in pregnancy?

A

Due to increased blood flow around the pituitary gland

219
Q

In men, what hormone measurements would indicate primary hypogonadism?

A

Low testosterone and raised LH/FSH

220
Q

Why do anabolic steroids cause the testes to shrink?

A

Anabolic steroids contain testosterone (or similar compound) and suppress the body’s own testosterone production in the testes due to negative feedback on the pituitary.

221
Q

What hormonal changes occur when puberty starts in girls?

A

Oestradiol (previously very low/undetectable) increases, pulsatile LH increases.

222
Q

What drug can be used to mimic the effects of ACTH?

A

Synacthen

223
Q

What condition would result in low cortisol, high ACTH and a poor response to synacthen?

A

Primary adrenal insufficiency

224
Q

What condition would result in low cortisol, low/normal ACTH and a poor response to synacthen?

A

Hypopituitarism

225
Q

How can an insulin stress test be used to test growth hormone secretion in adults?

A

By simulating a hypoglycaemic episode. Administer glucagon to make the glucose levels drop below normal. The body should then produce growth hormone in response.

226
Q

If a single blood test results in raised prolactin levels, why should the test be repeated?

A

Stress can raise prolactin levels

227
Q

Besides stress, what else can cause raised prolactin levels?

A

Drugs, stalk pressure, prolactinoma

228
Q

A CT scan may be used to visualise the pituitary when MRI is contraindicated. What are the disadvantages?

A
  1. Less optimal soft tissue imaging compared to MRI
  2. Use of intravenous contrast media
  3. Exposure to radiation
229
Q

What drug is used to treat hypothyroidism?

A

Levothyroxine

230
Q

What is used to treat cortisol deficiency?

A

Hydrocortisone, but does not mimic circadian rhythm and can be difficult to get up in the morning - pH microparticulate therapy recently licensed

231
Q

What features suggest type 1 diabetes mellitus as opposed to type 2?

A

More likely to have earlier onset (although can occur at any age)
Lean body habitus
Acute onset of osmotic symptoms, may only be unwell for a few weeks before presentation
More prone to ketoacidosis than type 2
High levels of islet autoantibodies

232
Q

Any 2 of which 3 features are an indication for immediate insulin treatment for type 1 diabetes?

A
  1. Weight loss
  2. Short history (weeks) of severe symptoms
  3. Urinary ketones/glucose
233
Q

What features suggest type 2 diabetes rather than type 1?

A

Usually presents in over 30s
Gradual onset
Often a positive family history
Almost 100% concordance in identical twins
Can be controlled with diet, exercise and oral medication in early stages

234
Q

What other autoimmune diseases are associated with type 1 diabetes?

A
  • Hypothyroidism
  • Addisons
  • Coeliac disease
235
Q

Why might a type 1 diabetic patient’s breath smell?

A

Reduced insulin leads to fat breakdown and formation of glycerol and free fatty acids, which are oxidised to form ketone bodies. Starvation ketones make the breath smell.

236
Q

What is the definition of diabetic ketoacidosis?

A

All three required:

  1. Hyperglycaemia (plasma glucose >50mmol/l)
  2. Raised plasma ketones (urine ketones >2+)
  3. Metabolic acidosis (plasma bicarbonate <15mmol/l)
237
Q

How does ketoacidosis result in decreased blood volume?

A

In the absence of insulin, hyperglycaemia increases and ketone levels rise. Glucose and ketones can escape in the urine, but this can lead to osmotic diuresis and therefore decrease in circulating blood volume.

238
Q

What are the clinical features of diabetic ketoacidosis?

A
  • Polyuria and polydipsia
  • Nausea/vomiting
  • Weight loss
  • Weakness
  • Abdominal pain
  • Drowsiness/confusion
  • Hyperventilation (as body tries to get rid of CO2 to limit amount of acid in blood)
  • Dehydration
  • Hypotension
  • Tachycardia
    (can eventually lead to coma)
239
Q

How is diabetic ketoacidosis treated?

A
  1. Rehydration (3l in first three hours) to dilute acidosis and glucose
  2. Insulin
  3. Replacement of electrolytes (rehydration and insulin decreases K+, which can lead to cardiac issues if too low)
  4. Treat underlying cause
240
Q

What are the possible complications of diabetic ketoacidosis?

A
  • Cerebral oedema
  • Adult respiratory distress syndrome
  • Thromboembolism
  • Aspiration pneumonia
  • Death
241
Q

What are the microvascular complications associated with diabetes?

A
  • Nephropathy
  • Retinopathy
  • Neuropathy (nerve damage in extremities due to blood vessel occlusion –> loss of sensation –> foot wounds, infection)
242
Q

Why does too much insulin result in anxiety, tachycardia, sweating, dizziness, headache, shaking, impaired vision and irritability?

A

The body releases adrenaline to try and stop glucose levels from falling too low

243
Q

What is DAFNE?

A

Dose Adjustment for Normal Eating - training people how to give their insulin in a safe way

244
Q

What devices can be used to administer insulin?

A

Injections, insulin pumps (e.g. patch pumps) and closed loop systems that measure glucose continuously.

245
Q

What is MODY?

A

Maturity-onset diabetes of the young. Autosomal dominant condition resulting in a single gene defect altering beta cell function, which results in moderately raised glucose levels.

246
Q

How is MODY3 treated?

A

Very sensitive to sulphonylurea treatment, insulin not usually required.

247
Q

How do sulphonylureas work?

A

They stimulate beta cells in the pancreas by binding to and closing the K-ATP channels. K+ cannot exit the cell, membrane depolarises, Ca2+ channels open and insulin is secreted.

248
Q

Why does MODY2 generally not require treatment?

A

Only causes mild diabetes. The mutation in the glucokinase gene (GCK) results in higher glucose levels being required before insulin is secreted, but blood glucose levels are still well controlled.

249
Q

Which patients are likely to be affected by MODY?

A
  • Those with a parent affected with diabetes
  • Absence of islet autoantibodies
  • Sensitive to sulphonylurea
250
Q

In which type of diabetes is C-peptide (which holds pro-insulin in correct conformation and is not present in synthetic insulin) negative within five years?

A

Type 1 diabetes, due to destruction of the beta cells.

251
Q

What causes permanent neonatal diabetes?

A

A mutation in the ATP-activated K+ channel, which means it is permanently open, hence the membrane cannot depolarise and insulin cannot be secreted.

252
Q

What is MIDD?

A

Maternally inherited diabetes and deafness, caused by a mutation in mitochondrial DNA, which results in a loss of beta cell mass.

253
Q

How can continuous excess alcohol intake affect insulin secretion?

A

By altering secretions, which leads to the formation of proteinaceous plugs which block ducts and encourage calculi formation (chronic pancreatitis).

254
Q

What is hereditary haemochromatosis?

A

An autosomal recessive condition that results in a triad of cirrhosis, diabetes and hyperpigmentation as excess iron is deposited in the liver, pancreas, pituitary, heart and parathyroids. Usually requires insulin treatment.

255
Q

How is pancreatic neoplasia treated?

A

May be treated with surgical resection if restricted to the tail of the pancreas only. Requires insulin, frequent small meals and enzyme replacement.

256
Q

Why is diabetes common in cystic fibrosis patients?

A

Viscous secretions lead to duct obstruction and fibrosis

257
Q

Name three potentially reversible endocrine causes of diabetes.

A
  1. Acromegaly (excess secretion of growth hormone results in increased insulin resistance)
  2. Cushings (excess cortisol, increased insulin resistance)
  3. Phaeochromocytoma (excess adrenaline, increased gluconeogenesis, decreased glucose uptake)
258
Q

Name three types of drugs that can increase insulin resistance

A
  1. Glucocorticoids
  2. Thiazides (unknown reasons)
  3. Antipsychotics (?due to weight gain)
259
Q

Describe how a pituitary tumour can cause acromegaly

A

A functional pituitary tumour can release growth hormone, which travels to the liver and stimulates the synthesis and secretion of IGF-1, which in turn mediates the peripheral effects of growth hormone, leading to an increase in size of extremities, heart etc.

260
Q

What comorbidities are associated with acromegaly?

A
  1. Hypertension and heart disease
  2. Cerebrovascular events and headache
  3. Arthritis
  4. Insulin-resistant diabetes
  5. Sleep apnoea
261
Q

What effect does acromegaly have on lifespan?

A

Overall decrease of about 10 years, higher mortality associated with higher levels of growth hormone.

262
Q

What are the clinical features of acromegaly?

A
  • Enlargement of extremities
  • Arthralgias
  • Maxillofacial changes
  • Excessive sweating
  • Headache
  • Hypogonadal symptoms
263
Q

How are GH secretion patterns different in a person with acromegaly?

A

GH secretion is more continuous - still pulsatile, but does not return to low baseline and peaks not as high

264
Q

Why is it that a very low level of GH can exclude acromegaly but a single high level of GH cannot be used to diagnose acromegaly?

A

Because of the pulsatile nature of GH secretion. A normal pattern has a low baseline and high peaks, so high levels are seen in both acromegaly and normal, but low levels are not seen in acromegaly.

265
Q

What test can be used for diagnosis of acromegaly?

A

Oral glucose tolerance test with 75g oral glucose. Glucose normally inhibits GH secretion, but not in a patient with acromegaly. Therefore, a patient with acromegaly will have high IGF-1 following glucose dose.

266
Q

What are the three options for treatment of acromegaly?

A
  1. Pituitary surgery
  2. Medical therapy
  3. Radiotherapy
267
Q

What are the two important determinants for success in pituitary surgery?

A
  1. Size of the tumour (large tumour can get wrapped around carotid arteries, optic nerves etc.)
  2. Experience of the surgeon
268
Q

What is the difference between conventional and stereotactic radiotherapy?

A

Conventional radiotherapy is multi-fractional, stereotactic radiotherapy uses a finely focused single fraction.

269
Q

What three types of drugs can be used to treat acromegaly?

A
  1. Dopamine agonists (e.g. cabergoline)
  2. Somatostatin analogues (somatostatin inhibits various hormones, including GH)
  3. Growth hormone receptor antagonists
270
Q

Why is cabergoline often used to treat prolactinomas?

A

Cabergoline is a dopamine receptor agonist. Prolactin is normally under tonic inhibition from dopamine.

271
Q

What are the clinical features of prolactinoma?

A

Galactorrhoea
Menstrual irregularity/amenorrhoea
Infertility/hypogonadism

272
Q

What test is typically used to diagnose Cushing’s syndrome?

A

Dexamethasone suppression test. Dexamethasone is a steroid that inhibits the secretion of ACTH. In a normal individual, dexamethasone will decrease cortisol levels, but in Cushing’s syndrome, cortisol levels remain raised.

273
Q

What controls the cortisol circadian rhythm in response to light?

A

Suprachiasmic nucleus

274
Q

What causes primary adrenal insufficiency?

A

Addison’s disease caused by e.g. autoimmune adrenalitis

275
Q

What causes secondary adrenal insufficiency?

A

Hypopituitarism e.g. due to pituitary macroadenoma

276
Q

What causes tertiary adrenal insufficiency?

A

Suppression of the hypothalamic-pituitary-adrenal axis due to e.g. steroids switching off ACTH

277
Q

Why should patients taking steroids double their dose if they are unwell?

A

Because they are at high risk of adrenal insufficiency

278
Q

Why is dexamethasone sometimes given to covid patients?

A

Because the most damage is caused by the inflammatory response to covid

279
Q

Why does Addison’s disease cause pigmentation?

A

ACTH works at melanocortin receptors. Low cortisol levels results in a lack of negative feedback and high ACTH levels.

280
Q

What are the clinical features of primary adrenal insufficiency?

A

Symptoms: Fatigue, weight loss, adrenal crisis, headache
Signs: Pigmentation, pallor, hypotension
Biochemistry: Low Na+, high K+, borderline elevated TSH

281
Q

What is used to treat primary adrenal insufficiency?

A

Any steroid e.g. etomidate, ketoconazole

282
Q

What is the most common reason for low cortisol levels?

A

Patient taking steroids

283
Q

How is adrenal insufficiency investigated?

A

Check cortisol and ACTH first thing in the morning. Autoimmune disease likely if cortisol <100nmol/l, but unlikely if >500nmol/l. High ACTH and low cortisol suggests primary insufficiency, low ACTH and low cortisol suggests secondary insufficiency.

Can also use synacthen test –> adrenal insufficiency unlikely if cortisol >500nmol/l following administration of synacthen

284
Q

In primary adrenal insufficiency, aldosterone secretion can be affected. What can be given to replace it?

A

Fludrocortisone

285
Q

Patients with adrenal insufficiency may present with adrenal crisis (hypotension, cardiovascular collapse, fatigue, fever, hypoglycaemia, hyponatraemia, hyperkalaemia). How should this be managed?

A
  1. Take bloods for cortisol and ACTH if possible
  2. IV hydrocortisone
  3. Fluid replacement with normal saline
  4. More IV hydrocortisone (gradually)
  5. Fludrocortisone if primary adrenal insufficiency
  6. When stable, wean to normal replacement with oral medication
286
Q

What are the ‘sick day rules’ for patients with adrenal insufficiency?

A
  • Always carry 10 x 10mg hydrocortisone tablets
  • Double dose of steroids when unwell
  • If vomiting or acutely unwell, take emergency injection of hydrocortisone 100mg
  • If unable to have injection, take 20mg hydrocortisone tablet and repeat if vomiting
  • Go to A&E/call ambulance
287
Q

What is the most common cause of death in type 1 and type 2 diabetes?

A

Cardiovascular disease

288
Q

What does GLP-1 (glucagon-like peptide 1) do?

A

Released in response to food in the intestine, acts on stomach to slow gastric emptying, acts on beta cells in pancreas to stimulate insulin production, acts on liver to reduce glucagon production, acts on brain to increase satiety and reduce appetite.

289
Q

Why are DPP-4 inhibitors used to increase GLP-1 levels?

A

GLP-1 itself only has a half-life of a few minutes, as it is rapidly broken down by the DDP-4 enzyme.

290
Q

DDP-4 inhibitors only increase GLP-1 levels slightly. What can be given if a large increase is needed?

A

GLP-1 analogue injection

291
Q

How can thiazolidinediones (TZDs) be used in diabetes treatment?

A

They bind to nuclear receptors to directly reduce insulin resistance

292
Q

How can SGLT-2 inhibitors be used in diabetes treatment?

A

Sodium glucose transporter 2 inhibitors act on the kidney to reduce glucose reabsorption. This means that more glucose is excreted in the urine.

293
Q

What is a common side effect of SGLT-2 inhibitors?

A

Genitourinary candidiasis

294
Q

What are the clinical consequences of diabetic neuropathy?

A

Pain, autonomic disturbance (e.g. erectile dysfunction), insensitivity.

295
Q

What is the most common cause of foot trauma?

A

Stupid shoes, e.g. pointy ones

296
Q

How does motor nerve damage from diabetic neuropathy increase the risk of foot injury?

A

Over time, the small muscles in the foot atrophy, causing e.g. clawing of the toes and increasing friction

297
Q

How does autonomic nerve damage from diabetic neuropathy increase the risk of foot injury?

A

The loss of sweat function results in dryness, which leads to fissures and cracks, creating a point of entry for infection and increasing ulcer formation

Phase 2a Medicine (13 decks)

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