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2nd Year Medicine > Endocrine (240) > Flashcards

Endocrine (240) Flashcards

1
Q

Endocrine system made up of?

A

DUCTLESS endocrine glands

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2
Q

How are endocrine signals terminated? (2)

A

Either by

  • Metabolic inactivation in liver
  • Inactivation at sites of action
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3
Q

Complementary protein actions? Antagonistic actions?

A
  • Complementary e.g. = adrenaline, cortisol and glucagon all prevent hypoglycaemia and hypokalaemia during short-term intense exercise
  • Antagonistic = insulin vs glucagon
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4
Q

Specific carrier proteins for hormones? (3)

General carrier proteins? (2)

A

Specific

  • Cortisol-binding globulin = binds cortisol
  • Thyroxine-binding globulin = binds thyroxine T4
  • Sex-steroid binding globulin = binds testosterone and oestradiol

General
* Albumin
* Transthyretin
(both bind steroids + thyroxine)

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5
Q

Why can bound hormone not cross capillary wall?

A

Too large = only free hormone can cross capillary wall to activate receptors in target tissues (i.e. BIOPHASE)

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6
Q

What controls rate of secretion?

A

HPA negative feedback loop

  • Hypothalamus (secretes CRF) -> Anterior pituitary (secretes ACTH) -> adrenal cortext (secretes cortisol) -> inhibits pituitary and hypothalamus
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7
Q

Plasma concentration of hormone equal to?

A

Plasma concentration = rate of secretion - rate of elimination

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8
Q

Half life of amines e.g. adrenaline? Proteins and peptides? Steroids and thyroid hormones?

A
  • Amines = seconds
  • Proteins and peptides = minutes
  • Steroids and thyroid hormones = hours to days (due to extensive protein binding suppressing elimination)
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9
Q

Hormone receptor types? (3)

A
  • GPCR - activated by amines and some proteins/peptides
  • Receptor kinases - some proteins/peptides e.g. insulin
  • Nuclear receptors - subdivided into class 1 (steroid hormones, located in cytoplasm bound to heat shock proteins), class 2 (activated by lipids, found in nucleus) and hybrid class (activated by thyroid hormone T3)
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10
Q

Gs and Gi protein signalling? Gq11?

A

Gs and Gi (adrenaline, CRF, glucagon) = adenylyl cyclase, cAMP + PKA
Gq (angiotensin II, thyrotropin releasing hormone, gonadotropin releasing hormone) = PLC, PKC, IP3, CICR

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11
Q

Signalling via receptor kinases e.g.?

A

Insulin!

  • Binding of insulin causes autophosphorylation of intracellular tyrosine residues
  • IRS1 proteins recruited and also phosphorylated
  • Activates protein kinase B which produces metabolic effects
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12
Q

Look at pharmacology table of endocrine glands and their secretions!

A

…

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13
Q

Cells of the pancreas? (2)

A
  • Exocrine tissue = acinar cells

* Islets = a cells, B cells, d-cells, PP- cells

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14
Q

Function of pancreatic islets? (4)

A
  • Beta cells = secrete insulin
  • Alpha cells = secrete glucagon
  • Delta cells = secrete somatostatin
  • PP cells - secrete pancreatic polypeptide
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15
Q

Explain synthesis of insulin? (2)

A
  • Synthesised in RER of pancreatic B cells as preproinsulin

* Cleaved to form insulin

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16
Q

Explain structure of insulin (2)

A
  • 2 polypeptide chains (A chain + B chain) linked by disulphide bonds
  • C peptide is connected to insulin as a byproduct of cleavage but has no known physiological function
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17
Q

Insulin preparations? (5)

A
  • Ultra shot-acting = lispro
  • Short-acting = regular
  • Intermediate = NPH + lente
  • Long-acting = ultralente
  • Ultra long-acting = glargine
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18
Q

What is lispro insulin?

A

Ultra short-acting = lysine and proline swap positions, making much more unstable (so less time spent in blood)

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19
Q

Features of lispro insulin? (5)

A
  • Monomeric
  • Not antigenic
  • Most rapidly acting insulin!!
  • Injected within 15 minutes of starting meal
  • Must be used in combination with other insulin preparations as very very short-acting!!
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20
Q

What is insulin glargine?

Administration?

A

Ultra long-acting - asparagine swapped to glycine on A chain + 2 arginine residues added to B-chain
* Administered as single bedtime dose

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21
Q

Explain process of insulin secretion (6)

A
  • Glucose enters B cells thru GLUT2 transporter and is phosphorylated by glucokinase
  • Increased metabolism of glucose leads to increase in intracellular ATP
  • ATP inhibits K+ channel (kATP) preventing K+ from exiting cell
  • Depolarisation of cell membrane
  • Depolarisation opens voltage-gated Ca++ channels
  • Increased intracellular Ca++ concentration causes release of insulin from vesicles
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22
Q

When should B cells secrete insulin?

A

Should only secrete insulin in response to blood glucose rising above 5mM (Beta cells are lost in T1DM)

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23
Q

How many phases does insulin release occur in?

Why?

A 
2 phases (2nd phase dependent on effectiveness of 1st phase)
* Reserve pools of insulin are important (i.e. only 5% of insulin granules available for immediate release) so entire insulin store isn't depleted
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24
Q

Mechanism of action of sulphonurea in T2DM?

A

Mimic the action of ATP to depolarise beta cells

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25
Q

What 2 proteins are kATP channels made up?

A
  • Kir6 and SUR1
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26
Q

What has the opposite effect of ATP (and thus sulphonourea) on beta cells?

A

Diazoxide - inhibits insulin secretion by STIMULATING kATP!!!

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27
Q

What are SURs?

A

Second line tx for T2DM

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28
Q

What is maturity-onset diabetes of the young (MODY)?

What gene mutations can cause MODY? (6)

A

Monogenic diabetes with genetic defect in β cell function (results in impaired insulin secretion!!)

  • Glucokinase
  • Hepatocyte nuclear factor-4a
  • Hepatocyte nuclear factor -1a
  • Insulin promoter factor 1
  • Hepatocute nuclear factor 1B
  • Neurogenic differentiation factor 1
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29
Q

What does impaired glucokinase activity lead to?

A

MODY2

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30
Q

Why is robust genetic screening to differentiate between MODY and T1DM important??

A

MODY can be treated with sulphonylurea rather than insulin!! Type 1 diabetics cannot

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31
Q

What is type 1 diabetes?
MODY?
Type 2 diabetes?

A
  • Type 1 = loss of B cells (req endogenous insulin)
  • MODY = defective glucose sensing in pancreas + loss of insulin secretion
  • Type 2 diabetes = hyperglycaemia and hyperinsulinaemia (reduced insulin sensitivity in tissues)
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32
Q

Biological effects of insulin? (9)

A

STIMULATES

  • Amino acid uptake in muscle
  • DNA synthesis
  • Protein synthesis
  • Growth
  • Glucose uptake in muscle + adipose tissue
  • Lipogenesis in adipose tissue and liver
  • Glycogen synthesis in liver and muscle

INHIBITS

  • Lipolysis
  • Gluconeogenesis in liver
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33
Q

What are the 2 pathways by which insulin mediates its effects? (2)

A

Pathway 1
* IRS-1 -> PI3K -> PKB -> glycogen synthesis + cell growth

Pathway 2
* IRS-1 -> Ras -> MAP kinase pathway -> gene expression + cell growth

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34
Q

What is leprechaunism (Donohue syndrome)?

S/s? (3)

A

Rare autosomal recessive - mutation in insulin receptor causing SEVERE INSULIN RESISTANCE!!

  • Elvin facial appearance
  • Growth retardation
  • Absence of subcutaneous fat + decreased muscle mass
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35
Q

Rabson Mendenhall syndrome?

S/s? (4)

A

Rare autosomal recessive - SEVERE INSULIN RESISTANCE

  • Developmental abnormalities
  • Acanthosis nigricans (hyperpigmentation)
  • Fasting hypoglycaemia (due to hyperinsulinaemia)
  • Diabetic ketoacidosis
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36
Q

Diabetic ketoacidosis symptoms? (4)

A
  • Vomiting
  • Dehydration
  • Increased HR
  • Acetone smell on breath
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37
Q

How are ketone bodies formed?

When are ketone bodies formed? (2)

A

Formed in liver mitochondria from acetyl-CoA from B oxidation of fats

  • Insulin normally inhibits lipolysis and prevents ketone body overload
  • In T1DM - DKA is a danger is insulin injection is missed!!
  • Rarer in T2DM but can occur as insulin resistance increases!!
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38
Q

Tx for DKA?

A

Insulin + rehydration

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39
Q

What is diabetes mellitus?

A

a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion/insulin action

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40
Q

Diabetes Dx? (4)

A
  • HbA1c = >48m/m
  • Fasting glucose = >7 mmol
  • 2-hr glucose in OGTT = >11.1 mmol
  • Random glucose = >11.1 mmol
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41
Q

Gestational diabetes mellitus?

A

diabetes diagnosed in the second or third trimester of pregnancy that was not clearly overt diabetes prior to gestation

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42
Q

Clinical presentation T1DM? (4)

Symptoms? (4)

A
  • Pre-school + during puberty
  • Severe weight loss
  • Acute onset
  • Ketonuria + metabolic acidosis

4Ts

  • Toilet
  • Thirsty
  • Tired
  • Thinner
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43
Q

T2DM clinical presentation? (4)

A
  • Middle-aged/elderly
  • Obese
  • Insidious onset
  • Evidence of micro-vascular disease (unlike T1DM)
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44
Q

Testing criteria for DM in asymptomatic adults? (9)

A
  • Obese
  • First-degree relative with diabetes
  • High risk race (e.g. Asian)
  • History of CVD
  • Hypertension
  • High cholesterol
  • Women with PCOS
  • Physical inactivity
  • Other clinical conditions associated with insulin resistance (e.g. Rabson Mendenhall syndrome)
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45
Q

Risk factors for T2DM? (6)

A
  • Obesity
  • FH
  • Gestational diabetes
  • Ethnicity
  • PHx of MI/stroke
  • Medications e.g. antipsychotics
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46
Q

Symptoms of diabetes mellitus? (8)

A
  • Thirst
  • Polyuria
  • Thrush
  • Fatigue
  • Blurred vision
  • Infections
  • Weight loss
  • T2DM = neuropathy + retinopathy
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47
Q

Useful discriminatory tests between type 1 and type 2? (4)

A

Type 1 associated with

  • Autoimmine markers (GAD)
  • Ketones
  • C-peptide in plasma
  • HLA association with DQA and DQB genes
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48
Q

How to differentiate between late-onset type 1 diabetes and ‘typical’ type 2 diabetes?

A

Type 1 diabetes = KETOSIS

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49
Q

Type 3 diabetes?

A

Gestational diabetes = any degree of glucose intolerance arising or diagnosed during pregnancy

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50
Q

Type 4 diabetes? (4)

A
  • Pancreatic disease e.g. pancreatitis, haemochromatosis, CF
  • Endocrine disease e.g. Cushing’s, acromegaly, phaeochromocytoma
  • Drug-induced = glucocorticoids, diuretics, B-blockers
  • Genetic diseases = CF, myotonic dystrophy, Turner’s syndrome
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51
Q

Features of monogenic diabetes (e.g. MODY)? (5)

A
  • FH
  • Renal cysts
  • Young onset
  • GAD negative
  • C-peptide positive
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52
Q

What is HbA1c?

A

Measure of blood glucose over past 2-3 months

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53
Q

Complications of diabetes mellitus? (3)

A
  • Macro-vascular = heart disease + stroke (70% die from CVD)
  • Micro-vascular = retinopathy, nephropathy, neuropathy
  • Psychological = depression/anxiety
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54
Q

Pathophysiology T2DM?

A

Genetic predisposition + obesity -> insulin resistance

  • Compensatory B cell hyperplasia = normoglycaemia
  • B cell failure (early) = impaired glucose tolerance
  • B cell failure (late) = diabetes
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55
Q

What does B cell dysfunction in T2DM lead to?

What does chronic hyperglycaemia lead to?

A

Hyperglycaemia

* Microvascular disease!

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56
Q

Complications of diabetes? (5)

A
  • Macrovascular = IHD + stroke
  • Microvacular = neuropathy, nephropathy, retinopathy
  • Dementia
  • Erectile dysfunction
  • Psychiatric
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57
Q

Types of diabetic neuropathy? (4)

A
  • Peripheral = pain/loss of feeling in feet, hands
  • Autonomic = changes in bowel, bladder function, sexual response, sweating, HR, BP
  • Proximal = pain in thighs, hips/buttocks, leading to weakness in legs (amyotrophy)
  • Focal neuropathy = sudden weakness in one nerve or group of nerves causing muscle weakness or pain e.g. carpal tunnel, foot drop, bells palsy
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58
Q

Neuropathy risk factors? (8)

A
  • Increased length of diabetes
  • Poor glycaemic control
  • Type 1 > type 2
  • High cholesterol
  • Smoking
  • Alcohol
  • Genes
  • Mechanical injury
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59
Q

What is peripheral neuropathy associated with increased risk of?

A

Increased risk of focal osteoporosis due to bone resorption

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60
Q

Tx painful neuropathy? (5)

A
  • Amitriptyline
  • Duloxetine
  • Gabapentin
  • Pregabalin
  • Capsaicin cream (if cannot tolerate oral)
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61
Q

What is charcot foot?

A

Complication of peripheral neuropathy (rockerbottom feet)

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62
Q

What group is most commonly affected by diabetic proximal neuropathy?
What is proximal neuropathy associated with?

A

Elderly T2D

* Associated with marked weight loss

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63
Q

What is gastroparesis?
S/s?
Complication?

A

Associated with diabetic autonomic neuropathy - slow stomach emptying

  • Nausea
  • Vomiting
  • Bloating
  • Loss of appetite

Complications = Can make blood glucose levels fluctuate due to abnormal digestion!

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64
Q

Tx gastropesis? (5)

A
  • Glycaemic control
  • Smaller more frequent food portions (low fat, low fibre)
  • Promotility drugs like metoclopramide
  • Botulinum toxin
  • Gastric pacemaker
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65
Q

What is gustatory sweating?

Tx?

A

Caused by autonomic neuropathy, profuse sweating at night or when eating

Tx

  • topical glycopyrrolate
  • clonidine
  • botulinum toxin
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66
Q

What happens to BP and HR in autonomic neuropathy?

A
  • BP = may drop sharply after sitting or standing, causing syncope
  • HR = raised
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67
Q

Screening for neuropathy? (5)

A
  • Diabetic foot screening
  • Nerve conduction studies or electromyography
  • HR
  • Ultrasound of bladder
  • Gastric emptying studies
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68
Q

What is diabetic nephropathy?
Also known as?
Hallmark?

A

progressive kidney disease caused by damage to the capillaries in the kidneys’ glomeruli

  • Kimmelsteil-Wilson syndrome or nodular glomerulosclerosis
  • Microvascular changes (angiopathy of capillaries)
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69
Q

Complications of diabetic nephropathy? (3)

A
  • Hypertension
  • Decline in renal function (decreased GFR)
  • Accelerated vascular disease
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70
Q

What is used to screen for nephropathy?

A

albumi creatinine ratio (ACR) to screen for diabetic kidney disease

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71
Q

Tx and Ix for microalbuminuria? (6)

A
  • Monitor serum creatinine
  • Check for retinopathy
  • Screen for PVD
  • Screen for IHD
  • Smoking cessation
  • Glycaemic control
  • Tx hypertension
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72
Q

Risk factors for nephropathy progression?

A
  • Hypertension
  • Cholesterol
  • Smoking
  • Glycaemic control
  • Albuminuria
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73
Q

Tx nephropathy? (3)

A
  • BP maintained at <130/80
  • ACE-I or ARB
  • Glycaemic control
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74
Q

Diabetic eye disease e.g.? (4)

A
  • Diabetic Retinopathy
  • Cataract- clouding of the lens (develops earlier in people with diabetes)
  • Glaucoma- increase in fluid pressure in the eye leading to optic nerve damage. 2 x more common in diabetes
  • Acute hyperglycaemia- visual blurring (reversible)
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75
Q

Stages of retinopathy? (4)

A
  • Mild non-proliferative (background retinopathy) - haemorrhage
  • Moderate non-proliferative (hard exudate, haemorrhages)
  • Severe non-proliferative (IRMA, venous beading, haemorrhages)
  • Proliferative (new vessel formation)
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76
Q

Retinopathy terminology? (4)

A
  • Haemorrages: Dot/ Blot/ Flame
  • Cotton Wool Spots: Ischaemic Areas
  • Hard Exudates: Lipid break down products
  • IRMA: Intra-retinal microvascular abnormalities (abnormalities of blood vessels)
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77
Q

Complications of diabetic retinopathy? (2)

A
  • Secondary glaucoma

* Retinal detachment

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78
Q

Retinopathy tx? (3)

A
  • Laser
  • Virectomy
  • Anti-VEGF (only tx that can help regain vision)
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79
Q

What is the cause of erectile dysfunction in diabetics?

A

Vascular + neuropathy

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80
Q

Diabetic screening?

A
  • Risk assessment then fasting blood glucose
  • High risk groups (impaired glucose tolerance, previous gestational diabetes) should be recalled annually for a fasting venous (plasma) glucose measurement
  • Other high risk groups (PCOS, FH of T2DM, obese) should be screened OPPORTUNISTICALLY
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81
Q

When should you consider a diagnosis of diabetes in a patient? (7)

A
  • thirst and polyuria
  • unexplained weight loss or tiredness
  • pruritus vulvae, balanitis or recurrent UTIs
  • recurrent infections
  • blurring of vision (usually an osmotic effect and not permanent)
  • discoloured or ulcerated feet
  • Acutely unwell- vomiting/abdominal pain (children)
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82
Q

How to make diagnosis of diabetes? (3)

A
  1. Classical symptoms (e.g. polyuria, polydipsia, unexplained weight loss)plus one of thefollowing:
    * random plasma venous glucose concentration≥11.1 mmol/L or
    * fasting venous plasma glucose concentration ≥7.0 mmol/Lor
    * venous plasma glucose concentration ≥11.1 mmol/L (2 hour sample in OGTT)
  2. No symptoms i.e. incidental finding of glycosuria or hyperglycaemia
  • Diagnosis should not be based on a single venous plasma glucose measurement
  • Additional testing on another day with a value in the diabetic range is essential
  • If fasting or random values are not diagnostic, the 2-hour value should be used
  1. If ketonuria is present with:
    Severe symptoms i.e. vomiting and dehydration,urgent hospital admission is required
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83
Q

when is oral glucose tolerance test (OGTT) carried out?

Process?

A

If fasting glucose 6.1 - 6.9

  • Initial fasting glucose
  • 75g anhydrous glucose
  • Repeat plasma glucose at 2 hrs
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84
Q

What diabetics should be referred to secondary care? (5)

A
  • Definite or likely Type 1 diabetes (urgent telephone referral to on-call Paediatric or Adult Diabetes Team)
  • Patients with low or low normal BMI
  • All children
  • Patients who are pregnant or planning a pregnancy
  • Pre-existing Chronic Renal Impairment
  • Seriously consider if patient under age of 40 at diagnosis of * Type 2 diabetes (especially if strong family history of diabetes)
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85
Q

What is the golden rule of type 1 diabetes?

A

Insulin should NEVER be omitted due to the risk ofDiabetic Ketoacidosis (DKA)
ALWAYS check for ketones

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86
Q

Mx for DKA? (5)

A
  • Increase insulin dose by 10% if blood glucose levels elevated (consider STAT dose of rapid insulin i.e. 10-20% of patient’s total daily dose)
  • 100-200 ml of fluid every hour + regular intake of carbs
  • If unable to eat, consider 200 ml of sugary drink e.g. fruit juice
  • Glucose monitoring 4 times per hour
  • Ketone monitoring (after STAT delivered, recheck ketones in 1-2 hrs)
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87
Q

Clinical signs of ketoacidosis? (4)

A
  • Dehydration
  • Abdominal pain
  • Vomiting
  • Kussmaul
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88
Q

What medications should not be taken on “sick days” i.e. fever, vomiting, diarrhoea? (4)

A
  • ACEIs + ARBS
  • Diuretics
  • Metformin
  • NSAIDs
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89
Q

What is DKA?

A

disordered metabolic state that usually occurs in the context of an insulin deficiency accompanied by an increase in the counter-regulatory hormones i.e. glucagon, adrenaline, cortisol and growth hormone

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90
Q

Pathophysiology DKA?

A
  • Insulin deficiency
  • Stress hormone activation
  • Lipolysis -> ketogenesis -> acidosis
  • Decreased glucose uptake
  • Proteolysis
  • Glycogenolysis
  • Lead to hyperglycaemia -> glycosuria -> electrolyte loss -> dehydration -> decreased renal function
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91
Q

Dx DKA? (4)

A
  • Ketonaemia >3mmol/L
  • Ketonuria >2+ on dipstick
  • Blood glucose > 11 mmol/L
  • Bicarbonate <15 mmol/L or venous pH <7.3
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92
Q

Causes of death from DKA? (4)

A

Adults

  • Hypokalaemia
  • Aspiration pneumonia (vomiting)
  • ARDS

Children
* Cerebral oedema

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93
Q

Conditions associated with DKA? (2)

A
  • Sepsis

* Gastroeteritis

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94
Q

Classical biochemistry of DKA at diagnosis? (9)

A
  • Glucose - ~40 mmol/L (from 11 - 100)
  • Potassium often raised (but beware low potassium!!)
  • Creatinine raised
  • Sodium low
  • Raised lactate
  • Blood ketones >5
  • Bicarbonate <10 in severe cases
  • Amylase raised
  • Raised WCC
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95
Q

Tx DKA? (5)

A
  • Fluid 0.9% NaCL (then dextrose one glucose falls to 15)
  • Insulin
  • Potassium
  • Monitor K+
  • Prophylactic LMWH (thrombus)
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96
Q

How are ketone levels monitored? (2)

A

Blood Ketone testing

  • Optium meter
  • Measures beta-hydroxybutyrate
  • Meter range 0 - 8mmol/L
  • < 0.6 mmol/L normal

Urine ketone testing

  • Measures acetoacetate
  • Indicates levels of ketones 2-4 hours previously
  • Ketonuria persists after clinical improvement due to mobilisation of ketones from fat tissue
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97
Q

Pathophysiology of Hyperglycaemic Hyperosmolar Syndrome?

A

osmotic diuresis leads to hyperosmolar state

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98
Q

Biochemical diagnosis HHS? (5)

A
  • Hypovolaemia
  • Hyperglycaemia >30 mmol
  • No ketonaemia (differentiate from DKA)
  • Bicarbonate >15 mmol/L or venous pH >7.3 (again, different from DKA)
  • Osmolality >320 mosmol/kg
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99
Q

Features of HHS? (3)

A
  • Diabetes often not known at presentation
  • Older patients (or young afro-caribbean)
  • Associated with:CVD, sepsis, medication like steroids/diuretics
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100
Q

Compare DKA to HHS? (6)

A

DKA

  • Younger
  • Type 1
  • Cause = Insulin deficiency
  • Precipitant = insulin omission
  • Mortality = <2%
  • Tx= insulin

HHS

  • Older
  • Type 2
  • Cause = diuretics, steroids, fizzy drinks
  • Precipitant = infection
  • Mortality = 10-50%
  • Tx = diet, OHA
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101
Q

Differences in tx of HHS vs DKA? (3)

A
  • Give fluids more cautiously in HHS due to increased risk of fluid overload
  • May not req insulin
  • Consider 0.45% saline to avoid rapid fluctuations of sodium
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102
Q

Tx alcohol-induced keto-acidosis? (4)

A
  • IV pabrinex (high dose vitamins)
  • IV fluids - dextrose
  • IV anti-emetics
  • Insulin usually not required
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103
Q

Biochemical dx alcoholic ketoacidosis? (4)

A
  • Dehydration
  • Ketonaemia > 3 mmol or ketonuria >2
  • Bicarbonate <15 mmol or venous pH <7.3
  • Glucose normal
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104
Q

Pathophysiology alcohol-induced ketoacidosis? (5)

A
  • Ethanol broken down ino acetaldehyde by ADH
  • Acetaldehyde then broken down into acetate by ALDH
  • Acetate then loses water and CO2 to become acetoacetate
  • Acetoacetate becomes Beta-OHB!!
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105
Q

Target in-patient blood sugar for T1DM?

A

6-10 mmol (accept range of 4-12)

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106
Q

where does lactate come from?

What does clearance require?

A

Lacate is end product of anaerobic glucose metabolism - comes from RBCs, skeletal muscle, brain + renal medulla

  • Clearance = hepatic uptake and aerobic conversion to pyruvate then glucose
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107
Q

Ion gap?

A

[Na + K] - [HCO3 + Cl]

Normal range in 10-18
useful for deeming cause of acidosis

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108
Q

Type A lactic acidosis?

A

Associated with tissue hypoxaemia e.g. sepsis, haemorrhage

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109
Q

Type B lactic acidosis?

A
  • Associated with liver disease, leukaemic states, diabetes
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110
Q

Clinical features lactic acidosis? (3)

Lab findings?(5)

A
  • Hyperventilation
  • Mental confusion
  • Coma

Lab

  • Reduced bicarbonate
  • Raised anion gap
  • Glucose often raised
  • Absence of ketonaemia
  • Raised phosphate
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111
Q

Tx lactic acidosis? (4)

A
  • Tx underlying condition e.g. sepsis, diabetes
  • Fluids
  • Antibiotics
  • Withdraw offending medication (METFORMIN)
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112
Q

What is MODY?
Ax?
Age of onset?

A

Maturity Onset diabetes of the Young - non-insulin dependent diabetes!!

  • Autosomal dominant inheritance (genetic cause rather than autoimmune destruction of B cells)
  • <25 years of age
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113
Q

Genetic defects associated with MODY? (3)

A
  • Glucokinase
  • Transcription factors - HNF1a, NHF4a, HNF1B
  • MODY X
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114
Q

What is glucokinase?

A

First step in glycolysis

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115
Q

Insulin secretion in patients with glucokinase mutations?

A

Sigmoid curve (glucose against insulin secretion) is shifted to the right so require greater volume of glucose to secrete insulin

i.e. have high fasting glucose!! (can produce plenty of insulin after a meal however so will not have high rise after meal)

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116
Q

Difference between glucokinase mutations and transcription factor mutations? (2)

A
  • Have glucokinase mutations from birth!
  • Transcription factor genes will progress over time (at birth - won’t have high glucose)
  • Glucokinase - fasting glucose is high but after meal, it decreases
  • HNF - have normal fasting glucose but is high after glucose challenge
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117
Q

Features of glucokinase mutations? (4)

Features of transcription factor mutations? (4)

A

Glucokinase

  • Onset at birth
  • Stable hyperglycaemia
  • Diet treatment - NO NEED FOR INSULIN in glucokinase MODY!!
  • Complications rare

Transcription factor

  • Adolescence/young adult onset
  • Progressive hyperglycaemia
  • 1/3 diet, 1/3 OHA, 1/3 Insulin (similar to T2)
  • Complications frequent
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118
Q

What OHA is effective in treating HNF MODY?

Why does it work?

A

Sulphonylureas e.g. gliclazide

  • the sites of defect in HNF MODY are mitochondria, L-PK and Glut 2
  • The K+ channel is unaffected so sulphonylureas work best
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119
Q

What tests are used to differentiate T1DM from MODY? (2)

A
  • Antibodies

* C-peptide level (MODY will have high C peptide compared to T1)

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120
Q

Neonatal diabetes?

Types? (2)

A

Requires insulin treatment within first 3 months of life

  • Transient neonatal diabetes (TNDM) - usually diagnosed <1 week, resolves around 12 weeks, stop insulin
  • Permanent neonatal diabetes (PNDM) - usually diagnosed 0-6 weeks, lifelong insulin
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121
Q

What mutation is associated with neonatal diabetes?

Tx?

A

KATP channel - insensitive to insulin, no insulin secretion as channel cannot close
* Therefore, best tx is sulphonylureas as they can close channel independent of insulin

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122
Q

Histology of type 1 diabetes? Type 2 diabetes?

A
  • Type 1 diabetes - lymphocytes attacking pancreatic islet

* Type 2 - amyloid deposition

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123
Q

Highest risk genetype for type 1 diabetes?

A

HLA DR3 or DR4

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124
Q

Islet auto-antibodies T1DM? (4)

A
  • IA-2
  • IAA
  • GAD
  • ZnT8
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125
Q

Maternal factors T1DM? (3)
Auto-immune trigger factors T1DM? (4)
Accelerating factors? (5)

A

Maternal

  • ABO mismatch
  • Age
  • Infection

Triggers

  • Viral infection!
  • Vit D deficiency
  • Diet
  • Environmental toxins

Accelerating factors

  • Infection
  • Insulin resistance
  • Puberty!
  • Weight!
  • Stress
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126
Q

What is checked at annual review of diabetic patients? (5)

A
  • Weight
  • BP
  • Bloods - HbA1c (monitored regularly anyway), creatinine, lipids
  • Retinal screening
  • Foot risk
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127
Q

Differential diagnoses in someone presenting under 30 years wit diabetes? (6)

A
  • Type 1
  • MODY
  • LADA
  • Mitochondrial gene mutations
  • Amylin gene mutations
  • Type 2 (unusual)
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128
Q

Describe normal secretion of insulin?

A

Biphasic in response to meal

  • rapid pase of pre-formed insulin lasts 5-10 mins
  • slow phase over 1-2 hrs
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129
Q

What are children diagnosed with diabetes under the age of 6 likely to have?

A

Monogenic rather than Type 1 Diabetes

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130
Q

What is LADA?

Also known as? (2)

A

Latent onset diabetes of adulthood - presence of elevated levels of auto-antibodies in newly-diagnosed patients who did not initially require insulin

  • slowly progressive type 1
  • type 1.5 diabetes
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131
Q

When to suspect LADA? (7)

A
  • young adults 25 to 40
  • Males
  • Usually non-obese
  • Auto-antibody positive
  • Associated auto-immune conditions
  • Non-insulin requiring at diagnosis
  • Sub-optimal control on oral agents
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132
Q

Significance of cystic fibrosis?

A

Prone to develop diabetes

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133
Q

What is DIDMOAD or Wolfram syndrome?

A

DIDMOAD (diabetes insipidus, diabetes mellitus, optic atrophy, and deafness), is a rare autosomal-recessive genetic disorder that causes childhood-onset diabetes mellitus, optic atrophy, and deafness

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134
Q

Bardet-Biedl Syndrome features? (7)

Cause?

A
  • Often very obese
  • Polydactyly
  • Hypogonadal
  • Visual impairment
  • Hearing impairment
  • Mental retardation
  • Diabetes

Cause = consanguineous parents

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135
Q

Autoimmune conditions associated with diabetes? (6)

A
  • Thyroid
  • Coeliacs
  • Pernicious anaemia
  • Addison’s disease
  • IgA deficiency
  • IPEX syndrome
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136
Q

What does thyroid gland secrete? (3)

A
  • Thyroxine
  • Tri-iodothyronine
  • Calcitonin
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137
Q

What do the 4 parathyroid glands secrete?

A

Parathyroid hormone (PTH)

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138
Q

Describe the anatomy and location of the thyroid gland (5)

A
  • Highly vascular
  • 5th cervical - 1st thoracic vertebrae (2nd-4th tracheal rings)
  • H to U shape
  • Isthmus sometimes absent (2 separate lobes)
  • Increases in size during pregnancy/menstruation
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139
Q

Describe the innervation, blood supply and drainage of the thyroid gland? (3)

A
  • Innervation = autonomic (parasympathetic from vagus + sympathetic from superior, middle and inferior ganglia of synpathetic trunk)
  • Blood supply = superior (from external carotid) and inferior thyroid (subclavian - thyrocervical trunk) arteries + sometimes thyroidea IMA!!
  • Drainage - superior, middle (internal jugular) + inferior thyroid vein (brachiocephalic vein)
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140
Q

What is the thyroid gland supported by? Posteromedial aspect?

A

Ligaments + strap muscles

* Posteromedial aspect supported by posterior suspensory ligament (Berry ligament)

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141
Q

Which cells secrete calcitonin?

A

Parafollicular C cells of the thyroid gland

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142
Q

Synthesis, storage and release of thyroid hormones? (5)

A
  • Iodine taken up by follicle cells
  • Iodine attached to tyrosine residues on thyroglobulin to form MIT and DIT
  • Coupling of MIT + DIT to form T3 - triiodothyronine
  • Coupling of 2 DITs to form thyroxine (T4)
  • Stored in colloid thyroglobulin til required
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143
Q

Percentage of thyroid hormones secreted? Significance of T3?

A
  • T4 (thyroxine) - 90%
  • T3 (triiodothyronine) - 10%

T3 is 4 x more potent than T4
* T3 = major biologically active thyroid hormone

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144
Q

Explain thyroid hormone release and transport (4)

A
  • TSH causes T3 and T4 to be secreted from colloid thyroglobulin
  • T3 and T4 are hydrophobic (lipophillic) so bind to plasma proteins
  • Unbound is biologically active form
  • T4 converted to T3 and binds to nuclear receptor in target cell to affect protein synthesis
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145
Q

Which plasma proteins are T3 and T4 bound to in blood? (3)

A
  • Thyroxine binding globulin (70%)
  • Thyroxine binding prealbumin (20%)
  • Albumin (5%)
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146
Q

Why is free T3 and T4 measured as opposed to total hormone concentration?

A

Metabolic state correlates more closely with the free than with the total concentration in the plasma

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147
Q

What does increased TBG result in? What causes increased TBG?

A

Increase TOTAL T4 but not free T4

  • Pregnancy
  • Hep A
  • Billiary cirrhosis
  • Acute intermittent porphyria
  • Heroin
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148
Q

What does decreased TBG result in? What causes decreased TBG?

A

Decreased TOTAL T4 but not free T4

  • Adrogens
  • Glucocorticoids (Cushings)
  • Acromegaly
  • Chronic liver disease
  • Carbamzepine
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149
Q

Physiological effects of thyroid hormones? (5)

A
  • Metabolism
  • Growth
  • Development
  • Reproduction
  • Behaviour
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150
Q

What is the effect of thyroid hormones on metabolic rate and thermogenesis?

A
  • Increase metabolic rate (increase number and size of mitochondria, increase ATP hydrolysis, increase synthesis of respiratory chain enzymes)
  • Increase thermogenesis (30% of temp regulation due to thyroid hormone)
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151
Q

Effect of thyroid hormone on carbohydrate metabolism? Lipid metabolism? Protein metabolism?

A
  • Carb = increase in blood glucose due to stimulation of glycogenolysis and gluconeogenesis, increase in glucose uptake into cells
  • Lipid = mobilise fats from adipose tissue + increase fatty acid oxidation
  • Protein - increase protein synthesis
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152
Q

How does thyroid hormone affect growth and development? (3)

A
  • Growth - growth hormone releasing hormone (GHRH) requires thyroid hormone
  • Development of foetal brain - myelinogenesis and axonal growth require thyroid hormones
  • CNS activity - hypothyroid slows intellectual functions, hyperthyroid results in nervousness + hyperkinesis
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153
Q

Sympathomimetic action of thyroud hormones?

Tx for hyperthyroidism?

A

Thyroid hormones increase responsiveness to adrenaline and noradrenaline by increasing number of receptors
* cardiovascular response also increased - increased rate and force

Note = propanolol used to treat symptoms in initial stages of hyperthyroidism

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154
Q

Thyroid hormone regulation? (3)

A
  • Thyrotrophin releasing hormone (TRH) from hypothalamus stimulates thyroid stimulating hormone from anterior pituitary
  • TSH stimulates release of T3 and T4 from thyroid gland
  • T3 and T4 exert negative feedback control of release of TRH and TSH
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155
Q

What environmental factors can affect thyroid hormone regulation? (3)

A
  • Low temperatures = stimulates TRH release so increased T3 and T4
  • Stress = inhibits TRH and TSH release
  • Circadian rhythm - thyroid hormones highest late at night, lowest in morning
156
Q

Tissue level regulation of thyroid hormone?

A

DeIodinase enymes - addition or removal of iodine atom in outer ring activates and deactivates T3 and T4

157
Q

Types of deiodinase enzymes? (3)

A
  • Type I (D1) - found in liver and kidney
  • Type II (D2) - found in heart, skeletal muscle, CNS, fat, thyroid + pituitary
  • Type III (D3) - found in foetal tissue, placenta + brain (except pituitary)
158
Q

Function of D2?

A

Activates T4 –> T3 in tissues

159
Q

Causes of thyroid hormone deficiency (hypothyroidism)? (3)

A
  • Primary gland failure - can cause goitre
  • Secondary to TRH or TSH (no goitre)
  • Lack of iodine in diet - can cause goitre
160
Q

Symptoms of hypothyroidism? (7)

A
  • Reduced metabolism
  • Slow pulse rate
  • Fatigue, lethargy
  • Cold intolerance
  • Weight gain
  • Adults = myxoedema (puffy face, hands, feet)
  • Children - cretinism (dwarfism and limited mental function)
161
Q

What can cause hyperthyroidism? What is this?

Symptoms? (2)

A

Grave’s disease

  • Autoimmune disease involving thyroid stimulating immunoglobulin (acts like TSH but is unchecked by T3 and T4)
  • Exophthalmos - bulging eyes due to carbohydrate build up behind eyes
  • Goitre - enlarged thyroid gland
162
Q

Symptoms of hyperthyroidism? (6)

A
  • Increased metabolism
  • Very fast pulse
  • Increased nervousness
  • Insomnia
  • Sweating and heat intolerance
  • Weight loss
163
Q

Describe embryological development of thyroid?

Abnormalities associated with this process?

A
  • Develops from evagination of pharyngeal epithelium
  • Descent from foramen caecum to normal location along thyroglossal duct

Abnormalities

  • Failure of descent (lingual thyroid)
  • Excessive descent (retrosternal location in mediastinum)
  • Thyroglossal duct cyst
164
Q

Explain anatomy of thyroid gland

A
  • Composed of follicles, each follicle surrounded by epithelial cells
  • Centre of each follicle contains amorphic pink material containing thyroglobulin
  • Occasional scattered C cells (parafollicular cells)
165
Q

Explain how thyroid hormones increase BMR

A
  • TSH binds to TSH receptor on surface of thyroid epithelial cells
  • G proteins activated with conversion of GTP to GDP + production of cAMP
  • cAMP increases production + release of T3 + T4
  • Bind to thyroid response element on target genes
  • Stimulates transcription of genes = increased BMR
166
Q

Thyroid pathologies? (4)

A
  • Hyperthyroidism (thyrotoxicosis)
  • Goitre
  • Neoplasia
  • Hypothyroidism
167
Q

Causes of thyroid inflammation? (6)

A
  • Grave’s disease
  • Hashimoto’s thyroiditis
  • Infection
  • subacute lymphocytic thyroiditis
  • De quervain’s thyroiditis
  • Riedel’s thyroiditis
168
Q

Autoimmune thyroiditis? (2)

A
  • CTLA-4 - negative regulator of T cell responses, polymorphism results in reduced function
  • PTPN-22 - inhibits T cell function
169
Q

Hyperthyroidism also known as? What is it?

Ax? (6)

A

Thyrotoxicosis
* excess T3 + T4

Ax

  • 85% due to Grave’s
  • Hyperfunctioning nodules
  • Tumours (adenoma, carcinoma)
  • TSH secreting pituitary adenoma (rare)
  • ectopic production (struma ovarii)
  • factitious (exogenous intake)
170
Q

Epidemiology of Grave’s disease?

A
  • Female > male

* 20-40 years old

171
Q

Antibodies involved in Grave’s disease?

A
  • Thyroid stimulating immunoglobulins (relatively specific for Grave’s disease)
  • Thyroid growth stimulating immunoglobulin
  • TSH binding inhibitor immunoglobulin
172
Q

Grave’s disease triad?

A
  • Hyperthyroidism with enlargement of thyroid
  • Eye changes (exophthalmos)
  • Pretibial myxoedema
173
Q

Histology Grave’s?

A

Scalloping

174
Q

Hypothyroidism?
Ax? (4)
Associated with?

A

Low levels of T3 + T4

  • Majority due to Hashimoto’s thyroiditis
  • Iodine deficiency
  • Drugs (lithium)
  • Congenital

Associated with HLA-Dr3 and DR5

175
Q

Hashimoto’s epidemiology?

A
  • F >M

* 40 - 50 yrs

176
Q

Histology hashimoto’s?

A

unlike Grave’s, have a lot of thyroid hormone (more retention rather than release) and no scalloping

177
Q

Goitre?

Ax?

A

Enlargement of thyroid gland

* Lack of dietary iodine

178
Q

Thyroid neoplasms? (2)

A
  • Follicular adenomas

* Carcinomas (papillary, follicular, medullary, anaplastic)

179
Q

What are follicular adenomas?
Difficulty?
What is a possible complication?

A

Benign lesions encapsulated by collagen
* They are difficult to distinguish from multi-nodular goitre + follicular carcinoma

Possible complication = thyrotoxicosis as they can secrete thyroid hormones independent of TSH

180
Q

Thyroid carcinoma epidemiology?

What are they derived from?

A

Can affect any age group - including children!!

* Derived from follicular epithelium (EXCEPT medullary - from C cells)

181
Q

Ax thyroid carcinomas?

A

Environment

  • Radiation
  • Iodine deficiency

Genetics

  • Papillary = MAP kinase
  • Follicular = P13K
  • Anaplastic = multiple mutations incl. p53
  • Medullary = MEN2
182
Q

Papillary carcinoma?
Features? (2)
S/s? (4)

A

Most common thyroid cancer

  • Solitary nodule (sometimes lymph node metastasis)
  • Psammoma bodies (calcified)

S/s
* hoarseness, dysphagia, cough, dyspnoea

NOTE = haematogenous spread is uncommon but usually to lung!!

183
Q

Follicular carcinoma?
Features? (3)
Difference from papillary?

A

Second most common thyroid cancer
* Slow-growing, painless + non-functional

Difference

  • MUCH greater potential for haematogenous spread!!! (less lymphatic spread)
  • Bone, lungs, liver
184
Q

What are minimally invasive follicular carcinomas difficult to distinguish from?

185
Q

Medullary carcinoma associated with?
Features?
S/s? (3)

A

Most cases are sporadic but can be associated with multiple endocrine neoplasia (MEN)
* Usually solitary nodules but familial cases are multi-nodular

S/s

  • neck mass
  • local effects (e.g. dysphagia)
  • Paraneoplastic syndrome = diarrhoea, Cushing’s syndrome
186
Q

Tx medullary carcinoma?

A

Total thyroidectomy

187
Q

Features of anaplastic carcinoma? (3)

Why is it dangerous?

A
  • Very aggressive, undifferentiated, tends to affect older patients (usually with a Hx of thyroid cancer)

Very poor prognosis due to rapid growth and involvement of neck structures = DEATH

188
Q

Midline swellings of the neck? (3)

How to differentiate?

A

Thyroid, thyroglossal cyst, dermoid cyst

If moves on swallowing = thyroid
If moves on sticking out tongue = thyroglossal cyst

189
Q

Anterior triangle swellings of neck? (4)

A

lymph nodes, branchial cyst, salivary glands, carotid body tumour

190
Q

Posterior triangle swellings of neck? (2)

A

lymph nodes, cystic hygroma (developmental lymphatic anomaly)

191
Q

Appearance of branchial cyst?

Risk of surgery?

A

Half-filled hot water bottle

* risk of injuring internal jugular vein

192
Q

Tx cystic hygroma?

A

Voluntary C-section

193
Q

Ix solitary thyroid nodule? (3)

A
  • TSH
  • isotope scan
  • USS
194
Q

What is water balance controlled by? Effect?

A

ADH

Makes you pee less as it causes water to be reabsorbed from renal tubules

195
Q

How is urine concentration measured?

A

As osmolality

High osmolality = concentrated urine
Low osmolality = dilute urine

196
Q

What is the process called by which ADH causes water reabsorption from the kidneys?

A

Countercurrent multiplication

197
Q

What is metabolic syndrome? (6)

A
  • Impaired glucose regulation or diabetes
  • Insulin resistance
  • Raised BP
  • Raised cholesterol
  • Central obesity (makes >90, females >85)
  • Microalbuminuria (>20 mcg/minute)
198
Q

Cushing’s syndrome?

A

Excess cortisol

199
Q

Lifetime risk of diabetes following gestational diabetes?

200
Q

What proportion of patients with acromegaly also have diabetes?

201
Q

What is glibenclamide?

A

Sulphonylurea

202
Q

Pioglitazone?

203
Q

Which antidiabetic medication can cause the Somogyi effect?

A

Insulin

* post-hypoglycaemic hyperglycaemia

204
Q

Which class of drug impairs the efficacy of sulphonylureas?

A

Corticosteroids

205
Q

What is the poyol pathway?

What are its effects? (3)

A

Also known as the aldose-reductase pathway
* series of biochemical reactions that occur in the prescence of raised intracellular glucose

  • Involved in retinopathy, neuropathy, and nephropathy
206
Q

Why is poyol pathway normally inactive?

A

Aldose reductase has a very high Km compared to glycolytic enzyme glucokinase (therefore will not process glucose unless there is a significant excess)

207
Q

What is the function of aldose reductase? What then happens?

A

Converts glucose into sorbitol (the glucose that isn’t converted becomes glycating sugars)
* sorbitol dehydrogenase converts sorbitol to fructose

208
Q

What are Advanced Glycation End-products?

A

Synthesised in the aldose reductase pathway (glycating sugars bind to proteins) - can cause damage

209
Q

What is sodium balance controlled by?

A

Steroids from adrenals i.e. mineralocorticoid activity

210
Q

What is mineralocorticoid activity?
Which steroids have mineralocorticoid activity?
How does mineralcorticoid activity affect Na concentation?

A

Refers to Na+ reabsorption in renal tubules in exchange for K+/H+

  • Aldosterone (main one!)
  • Cortisol

Too much mineralocorticoid activity means sodium gain

Too little mineralocorticoid activity means sodium loss

211
Q

Concentration of sodium inside cell as opposed to outside cell?

A

Outside cell = 140 mmol/L

Inside cell = 4 mmol/L

212
Q

What is the consequence of sodium loss?

A

Water loss

213
Q

Causes of hyponatraemia?

A

Either due to too little sodium or too much water

Too little sodium

  • Adrenal/kidney
  • Gut - vomiting etc
  • Skin - severe burns

Too much water

  • Decreased H20 excretion e.g. SIADH
  • Increased water intake e.g. compulsive water drinking
214
Q

Causes of hypernatraema?

A

Either too much sodium or too little water

Too much sodium

  • Increase Na+ intake (near-drowning)
  • Malicious
  • Decrease in Na+ excretion

Too little water

  • Water loss e.g. diabetes insipidus
  • Decrease water intake
215
Q

Tx hyponatraemia?

Tx hypernatraemia?

A

Hypo

  • Too little sodium = give sodium
  • Too much water = fluid restrict

Hyper

  • Too much sodium = loop diuretic
  • Too little water = give 5% dextrose
216
Q

Dx hypo/hypernatraemia?

A 
Hypo = Na <120
Hyper = Na >160
217
Q

S/s hyper/hyponatraemia? (5)

A
  • Altered consciousness
  • Confusion
  • Nausea
  • Vomiting
  • Fitting
218
Q

2 kinds of stimuli for ADH release?

Examples? (3)

A 
Osmotic = in health
Non-osmotic = in disease

Non-osmotic stimuli

  • Hypovolaemia/hypotenison
  • Pain
  • Nausea/vomiting
219
Q

How to differentiate between hyponatraemia and pseudohyponatraemia?

A

Measure serum osmolality

220
Q

Ax Addison’s disease?

S/s? (4)

A

Adrenal insufficiency so can’t make steroids (loss of sodium thus water)

  • Dizziness
  • Excess pigmentation (due to excess ACTH from pituitary, stimulates melanocyte-stimulating hormone)
  • Tiredness
  • Poor appetite
  • Postural hypotension
221
Q

What is normally the cause of too much water?

Clinical signs?

A

ADH secreted in response to non-osmotic stimulus

  • Often don’t have symptoms of hyponatraemia
  • However, U+Es show Na to be low (due to water excess)
222
Q

Ax diabetes insipidus?

Tx?

A
  • Disruption of pituitary so can’t secrete ADH from posterior pituitary
  • Lots of water lost in urine as cannot be reabsorbed by kidneys
  • Na is high reflecting water deficit

Tx = exogenous ADH

223
Q

TSH also known as?

How is it released?

A

Thyrotropin

* Released by thyrotroph cells in anterior pituitary in response to thyrotropin releasing hormone (TRH)

224
Q

What percentage of thyroid hormone released is T4? T3?

A 
T4 = 80%
T3 = 20%
225
Q

TSH and free T3/4 in primary hypothyroidism? Hyperthyroidism?

A

Hypothyroidism

  • Free T3/4 = low
  • TSH high

Hyperthyroidism

  • Free T3/4 = high
  • TSH low
226
Q

What is meant by secondary hypo/hyperthyroidism?

TSH and free T3/4 in SECONDARY hypothyroidism? Hyperthyroidism?

A

Hypothalmic/pituitary disease

Hypo

  • Free T3/T4 low
  • TSH low

Hyper

  • Free T3/4 high
  • TSH high
227
Q

What is myxoedema? What about pretibial myxoedema?

A

Myxoedema = severe HYPOthyroidism and is a medical emergency!!
* Pretibial myxoedema = rare sign of Grave’s disease, which causes HYPERthyroidism

228
Q

Causes of primary hypothyroidism? (3)

A
  • Goitrous - Hashimoto’s, iodine deficiency, drug-induced (lithium, amiodarone)
  • Non-goitrous = atrophic thyroiditis, post-ablative therapy/radiotherapy
  • Self-limiting = withdrawal of antithyroid drugs, post-partum thyroiditis
229
Q

Causes of secondary hypothyroidism? (5)

A

Diseases of hypothalamus and pituitary gland

  • Infectious
  • Malignant
  • Trauma
  • Congenital
  • Drug-induced
230
Q

What is hashimoto’s thyroiditis?

Features? (2)

A

Autoimmune destruction of thyroid gland and so reduced thyroid hormone production (most common cause of hypothyroid in Western world)

  • Antibodies against thyroid peroxidase (TPO)
  • T-cell infiltrate
231
Q

Clinical features of hypothyroidism? (9)

A

Hair and skin

  • sparse hair
  • Dull, expressionless face
  • Periorbital puffiness
  • pale cool skin that feels doughy to touch
  • Vitiligo
  • Hypercarotenaemia (jaundice-like yellowing of the skin in palms of hands and soles of feet)

Thermogenesis = cold intolerance

Fluid retention = pitting oedema

Cardiac = reduced HR, pericardial effusion, worsening of CCF

Metabolic = hyperlipidaemia, decreased appetite, weight gain

GI
* constipation

Respiratory
* deep hoarse voice, macroglossia, sleep apnoea

Neurology
* decreased intellectual/motor activities, depression muscle stiffness, carpal tunnel

Reproductive

  • Menorrhagia + later amenorrhoea
  • Hyperprolactinaemia
232
Q

Lab investigations for primary hypotheyroidism?

A
  • Raised TSH and decreased fT4/3!!
  • Increased MCV
  • Increased creatine kinase
  • Increased cholesterol
  • Hyponatraemia
  • Hyperprolactinaemia
233
Q

Thyroid autoantibodies (including Grave’s disease)? (3)

A
  • Anti-TPO
  • Anti-thyroglobulin antibody
  • TSH receptor antibody
234
Q

Mx primary hypothyroidism?

A
  • Younger patients = levothyroxine at 50-100 ug daily
  • Elderly with history of IHD = levothyroxine at 25-50 ug daily

Important notes

  • TSH should be checked 2 months after any dose change
  • Once stabilised, TSH should be checked every 12-18 months
  • Normal metabolic rate should be restored GRADUALLY - rapid restoration can cause cardiac arrhythmias
  • TSH level is irrelevant in SECONDARY hypothyroidism as there is a decrease in TSH production (titrate dose of levothyroxine to fT4 level)
235
Q

What is levothyroxine?

Pregnancy?

A

T4 (T3 therapies rarely used + no benefit with combo of T4+T3)
* Dose requirements increase in pregnancy due to increased TBG

236
Q

Myxoedema coma epidemiology?

Dx myxoedema coma?

A

Elderly women with untreated hypothyroidism (mortality up to 60% despite early diagnosis and tx)

  • ECG = bradycardia, T wave inversion, prolongation of QT interval, low voltage
  • Type 2 respiratory failure
  • Adrenal failure (10% of patients)
237
Q

Tx myxoedema coma? (6)

A
  • ABC
  • Passively rewarm
  • Cardiac monitoring
  • Monitor urine output, blood sugar, oxygen
  • Broad spectrum antibiotics (can be caused by infection)
  • Thyroxine
238
Q

What is thyrotoxicosis?

A

State arising when tissues are exposed to excess thyroid hormone

239
Q

S/s thyrotoxicosis? (10)

A

Cardiac = AF, cardiac failure (very rare)

Sympathetic = tremor, sweating

CNS = anxiety, nervousness, sleep disturbance, irritability

GI = frequent loose stools

Vision

  • Lid retraction
  • Double vision
  • Proptosis (Grave’s)

Hair and skin

  • Brittle, thin hair
  • rapid fingernail growth

Reproductive
* lighter infrequent periods

Muscles = muscle weakness (esp. in thighs and upper arms)

Metabolism = weight loss despite increased appetite

Thermogenesis = intolerance to heat

240
Q

Causes of thyrotoxicosis? (5)

A

(remember: hyperthyroidism refers to overactivity of the thyroid gland!!)

ASSOCIATED WITH HYPERTHYROIDISM

Excessive thyroid stimulation

  • Grave’s disease
  • Hashitotoxicosis
  • Thyrotropinaemia (very rare)
  • Thyroid cancer
  • Choriocarcinoma (trophoblast tumour)

Thyroid nodules with autonomous function

  • toxic solitary nodule
  • toxic multinodular goitre

NOT ASSOCIATED WITH HYPERTHYROIDISM

  • Thyroiditis (de quervain’s, post-partum thyroiditis, drug-induced)
  • Exogenous thyroid hormones (over-treatment with levothyroxine)
  • Ectopic thyroid tissue (struma ovarii)
241
Q

What can affect lifetime risk of Grave’s disease? (2)

A
  • Smoking

* Sisters and children of women with Grave’s disease have a 5-8% risk

242
Q

Lab Ix of Grave’s disease?

A
  • Decreased TSH and increased fT4/3
  • Hypercalcaemia and increased ALK PHOS (grave’s associated with osteoporosis)
  • Leucopenia
  • TSH receptor antibody
243
Q

Clinical signs specific to Grave’s disease? (4)

A
  • Pretibial myxoedema
  • Thyroid acropachy
  • Thyroid bruit (associated with large goitres - but not heard in other goitrous conditions)
  • Grave’s eye disease (associated with smoking) - can be severe and sight-threatening
244
Q

Tx for Grave’s eye disease?

A 
Mild = lubricants
Severe = steroids, radiotherapy, surgery
245
Q

Features of nodular thyroid disease? (3)

Tests? (4)

A

Older patients
Insidious onset
Asymmetrical goitre

Tests

  • increased fT4/3, decreased TSH (or normal)
  • antibody negative
  • Scintigraphy = high uptake
  • Thyroid US
246
Q

Thyroid storm?
S/s? (3)
Tx? (5)

A

EMERGENCY associated with hyperthyroid patients with acute infection/illness or recent thyroid surgery

  • HYPERthermia
  • Respiratory and cardiac collapse
  • Exaggerated reflexes

Tx
* Lugol’s iodine, glucocorticoids, PTU, B-blockers, fluids

247
Q

Mechanism of hyperthyroid (antithyroid) drugs?

Examples? (2)

A

Inhibition of TPO therefore blocking thyroid hormone synthesis

  • Carbimazole (1st line)
  • Propylthiouracil (1st line only in 1st trimester of pregnancy as carbimazole has risk of aplasia cutis)
248
Q

Side effects of antithyroid drugs? (3)

A

Generally well tolerated

  • Allergic reaction
  • PTU associated with cholestatic jaundice + fulminant hepatic failure
  • AGRANULOCYTOSIS - very dangerous!! (risk highest in first 6 weeks)
249
Q

B-blockers for treatment of?
Mechanism?
Drug of choice?

A

Hyperthyroidism - especially in immediate symptomatic relief of thyrotxic symptoms

  • Reduced activity of sympathetic NS
  • Drug of choice = propanolol
250
Q

What is the 1st choice of treatment for relapsed Grave’s disease and nodular thyroid disease?
Risks? (3)

A

Radioiodine

  • Contraindicated in pregnancy
  • Contraindicated in active thyroid eye disease
  • High risk of hypothyroidism when used in Grave’s disease
251
Q

When is thyroidectomy carried out?

Risks of surgery? (3)

A

When radioiodine is contraindicated (usually treatment for relapsed Graves and nodular thyroid disease)

  • Recurrent laryngeal nerve palsy
  • Hypothyroidism
  • Hypoparathyroidism
252
Q

Ax subacute thyroiditis?

Tx?

A

May be triggered by viral infection (so will have viral symptoms like fever)
* Usually self-limiting

253
Q

Non-thyroidal illness also known as? What is it?

Course of disease?

A

Sick euthyroid syndrome

  • refers to impact of intercurrent illness on HPT axis
  • TSH typically suppressed initially then rises during recovery
254
Q

Hormone subtypes? (3)

A
  • Proteins and peptides = insulin, GH, prolactin
  • Steroids = derived from cholesterol e.g. cortisol, testosterone
  • Tyrosine tryptophan derivatives = adrenaline, thyroid hormones, melatonin
255
Q

Example of steroid hormone receptors?

A

Oestrogen + androgen receptors

256
Q

How is pituitary function assessed in thyroid disease since TSH cannot be used? (6)

A
  • 9am cortisol (random measurement is of little value)
  • FT4, FT3
  • Prolactin
  • IGF1 (may indicate GH hypersecretion)
  • LH, FSH
  • Imaging
257
Q

What is prolactin secreted by?

A

Prolactin (PRL) secreted by lactotroph cells of anterior pituitary

258
Q

Tests to check adrenal function? (2)

A
  • Synacthen Test (adrenal insufficiency)

* Dexamethasome suppression test (Cushings)

259
Q

S/s Cushing’s syndrome? (9)

A
  • Cushingoid facies (moon face)
  • Acne
  • Hirsutism
  • Abdominal striae & centripetal obesity
  • Interscapular & supraclavicular fat pads
  • Proximal myopathy
  • Osteoporosis
  • Hypertension
  • Impaired glucose tolerance
260
Q

Ax cushings syndrome? (4)

A

Cushing’s disease = pituitary cushings
* tumour from corticotroph cells of anterior pituitary

ACTH-independent Cushing’s
* adrenal tumour

Ectopic ACTH = malignancy

Exogenous steroids

261
Q

How is Cushing’s diagnosed?

A

First carry out dexamethasone suppression test
* Failure to suppress = Cushing’s

To determine cause, measure ACTH

  • ACTH low = adrenal origin
  • ACTH raised = need to distinguish between pituitary origin (Cushing’s disease) + ectopic ACTH

Rise in cortisol and ACTH on CRH test indicated pituitary source

262
Q

Endocrinology of pregnancy? (5)

A
  • Ovum = oestrogen
  • corpus luteum = progesterone
  • Implantation = HCG (pregnancy test)
  • Placenta = human placental lactogen (hPL), placental progesterone, placental oestrogen
  • Pituitary = prolactin (lactogen)
263
Q

Pathophysiology gestational diabetes?

A
  • Progesterones + hPL cause insulin resistance in the mother

* if predisposed, results in raised blood glucose + gestational diabetes

264
Q

When does foetal organogenesis occur?

A

Starts at 5 weeks

265
Q

Which complications can diabetes lead to in pregnancy? (5)

A
  • Congenital malformation
  • Prematurity
  • Intra-uterine growth retardation (IUGR)
  • Macrosomia (large foetus)
  • Polyhydramonios (too much amniotic fluid)
  • Intrauterine death
266
Q

Diabetic complications for foetus? (5)

A
  • Respiratory distress
  • Hypoglycaemia - fits
  • Hypocalcaemia - fits
  • CNS defects (anencephaly, spina bifida)
  • Caudal regression syndrome
  • Genital and GI abnormalities e.g. ureteric duplication
267
Q

How does diabetes in pregnancy lead to macrosomia?

A
  • Meternal hyperglycaemia
  • Foetal hyperglycaemia
  • Foetal hyperinsulinaemia
  • Leads to macrosomia (in 3rd trimester foetus produces own insulin which is a MAJOR growth factor!!)
  • Can lead to neonatal hypoglycaemia - fits
268
Q

Management of type 1 and type 2 diabetes in pregnancy? (6)

A
  • Optimise blood sugar control
  • Folic acid 5mg
  • Consider change from tablets to insulin
  • Regular eye checks (accelerated retinopathy)
  • Avoid ACE-I and statins (for BP use Labetalol, Nifedipine, methyldopa)
  • Monitor HbA1c, BP
269
Q

Tx during labour for mother with T1DM, T2DM or GDM?

A

Maintain good blood glucose during labour - IV insulin and IV dextrose

270
Q

Tx GDM? (2)

A
  • Lifestyle
  • Metformin

(may need insulin)

271
Q

Dx gestational diabetes?

A
  • 6 week post-natal fasting glucose or GTT

* DM should have resolves - if not, they have T2DM

272
Q

Implications of gestational diabetes?

A
  • After 10-15 years, 50% have increased risk of T2DM (especially for obese)
  • T1DM (<5%)
273
Q

Prevention of diabetes after GDM? (4)

A
  • Keep weight as low as possible
  • Healthy diet
  • Aerobic exercise
  • Annual fasting glucose
274
Q

When does gestational diabetes usually present?

A

Later in pregnancy - 3rd trimester

275
Q

Implications of thyroid disease in pregnancy?

A
  • Hypo and hyperthyroidism causes anovulatory cycles (reduced fertility)
  • Maternal thyroxine important for neonatal development
  • Increased demand on thyroid during pregnancy
276
Q

Mx hypothyroidism in pregnancy?

A
  • Increase thyroxine dose by 25mcg as soon as pregnancy suspected!
  • Check TFTs monthly for first 20 weeks then 2 monthly until birth
  • Aim for TSH <3 mU/1
277
Q

Complications of untreated hypothyroidism in pregnancy? (

A
  • Preeclampsia
  • Abruption
  • Post-partum haemorrhage
  • Preterm labour
  • Neuropsychological development (increased risk of IQ < 85)
278
Q

What is a possible effect of hCG in pregnancy?

A

hCG effect mimics hyperthyroidism biochemically (raised fT4, low TSH)

  • Increases thyroxine
  • Suppresses TSH

(because hCG and TSH have similar structures)

279
Q

What is it important to distinguish hyperthyroidism from in pregnancy?

A

Gestational hCG-associated thyrotoxicosis

  • Hyperemesis gravidarum
  • Not TRab antibody positive
  • Resolves by 20 wks gestation
280
Q

Complications of hyperthyroidism in pregnancy? (5)

A
  • Infertility
  • Spontaneous miscarriage
  • Stillbirth
  • Thyroid crisis in labour
  • Transient neonatal thyrotoxicosis
281
Q

Ax thyrotoxicosis in pregnancy? (3)

A
  • Grave’s disease
  • Toxic multinodular goitre, toxic adenoma
  • Thyroiditis
282
Q

S/s hyperthyroidism pregnancy? (4)

A

Difficult to distinguish from hyperemesis of pregnancy

  • Nausea + vom
  • tachycardia
  • warm and sweaty
  • lack of wt gain
283
Q

Mx hyperthyroidism pregnancy? (3)

A
  • Wait and see - if hyperemesis, will settle, Graves may settle as pregnancy suppresses autoimmunity
  • B-blockers if needed
  • LOW DOSE anti-thyroid drugs (propylthiouracil 1st trimester, carbimazole 2/3rd trimester, wait as late as possible)
284
Q

Why is carbimazole avoided in 1st trimester? (4)

A
  • Embryopathy
  • Scalp abnormalities
  • GI abnormalities
  • Choanal and oesophageal atresia
285
Q

Why is it important to check TRab antibodies in pregnancy?

A

TRab antibodies can cross the placenta and cause neonatal transient hyperthyroidism (ideally check during 3rd trimester)

286
Q

Post-partum thyroiditis?

A
  • Transiently thyrotoxic -> hypothyroid
  • Small, diffuse, non-tender goitre
  • Hypothyroid phase associated with postnatal depression
287
Q

Histology anterior pituitary? (4)

Posterior?

A

Anterior

  • Islands of cells
  • Acidophils (somatophils (GH), mammotrops (PRL))
  • Basophils (corticotrophs (ACTH), thyrotrophs (TSH), gonadotrophs (FSH/LH))
  • Chromophobe

Posterior
* non-myelinated axons of neurosecretory neurons

288
Q

Pathology of anterior pituitary? (2)

A

Hyperfunction

  • Adenoma
  • Carcinoma

Hypofunction

  • Surgery/radiation
  • Haemorrhage
  • Ischaemic necrosis (sheehan syndrome)
  • Tumours
  • Sarcoidosis
289
Q

Pathology of posterior pituitary? (2)

A
  • Diabetes insipidus - lack of ADH secretion, can lead to life threatening dehydration
  • SIADH - ectopic secretion of ADH by tumours or primary disorder in the pituitary
290
Q

Pituitary adenoma derived from?
Ax? (2)
Classification?
Complications of large adenomas? (3)

A

Derived from cells of anterior pituitary

  • Ax = sporadic or associated with MEN1
  • Classify by hormone produced (prolactin, ACTH, FSH/LH)

Large adenomas

  • visual field defects
  • pressure atrophy of surrounding tissues
  • infarction can lead to panhypopituitarism
291
Q

Functional pituitary adenomas? (3)

A

Prolactinoma

  • Most common
  • Infertility, lack of libido, amenorrhea

GH

  • second most common
  • increase in insulin-like growth factors
  • gigantism or acromegaly

ACTH secreting

  • Cushing’s disease
  • Bilateral adenocortical hyperplasia
292
Q

Ax pituitary hypofunction?

A
  • Granulamatous inflammation - sarcoidosis
  • Infarction - Sheehan’s syndrome
  • Primary or metastatic tumours
293
Q

Craniopharyngioma derived from?
Features? (3)
S/s? (3)

A

Remnants of Rathke’s pouch

  • Slow growing
  • cystic
  • may calcify

S/s

  • headaches
  • visual disturbances
  • children may have growth retardation
294
Q

Tx craniopharyngioma?

Risk?

A

Great prognosis
* Tx = radiation

SCC may develop following radiation but rare

295
Q

Paired hormones? (5)

A
  • ACTH (central) -> cortisol (peripheral)
  • TSH (central) -> thyroxine (peripheral)
  • LH/FSH (central) -> testosterone/oestrogen (peripheral)
  • GH (central) -> IGF-1 (peripheral)
  • Prolactin (central)
296
Q

What is the general rule for dynamic endocrine tests?

A
  • Too much hormone = do test that tries to suppress the hormone
  • Too little hormone = test that tries to stimulate hormone
297
Q

Examples of dynamic pituitary function tests (stimulation)? (3)

A
  • Synacthen (synthetic ACTH) = if cortisol doesn’t rise to 500, adrenal insufficiency !!
  • Insulin stress test = stimulates cortisol (>500) and GH (>7ug/l), purposely trying to make patient hypo
  • Water deprivation test = if serum osmolality <2, diabetes insipidous
298
Q

What is a microadenoma? Macroadenoma?

A
  • Microadenoma = <1 cm

* Macroadenoma = >1 cm

299
Q

Complications of non-functioning pituitary adenoma? (2)

A

Too big

  • Compression of optic chiasma (bitemporal hemianopia)
  • Compression on cranial nerves 3, 4, 6 (disrupts eye movement)

Too little hormones

  • Hypoadrenalism (lack of cortisol)
  • Hypothyroidism
  • Hypogonadism (lack of FSH, LH)
  • Diabetes insipidous if affects post. pituitary
  • GH deficiency
300
Q

Physiological causes of raised prolactin? (4)

Drug-induced causes of raised prolactin? (2)

A

Physiological

  • breast-feeding
  • pregnancy
  • stress
  • sleep

Drugs

  • Dopamine antagonists e.g. metoclopramide
  • Antipsychotics
301
Q

Pathological causes of raised prolactin? (3)

A
  • Hypothyroidism (TRH stimulates prolactin)
  • Stalk lesions (prevent action of dopamine)
  • Prolactinoma!!!
302
Q

Dx prolactinoma?

A
  • MRI pituitary
  • If prolactin >5,000, nearly always prolactinoma
  • visual fields (bitemporal hemianopia)
303
Q

S/s prolactinoma? (2)

A

Females

  • EARLY presentation
  • Galctorrhoea (production from breast)
  • Ammenorrhoea
  • Infertility

Males

  • LATE presentation
  • Impotence
  • Visial field abnormal
  • Headache
  • Ant pit malfunction (other hormones squeezed out)
304
Q

Tx prolactinoma?

Side effects? (3)

A

Dopamine agonists
* Carbergoline most common (least side effects) - oral once or twice per week

Side effects

  • nausea/vom
  • low mood
  • fibrosis
305
Q

Acromegaly?

S/s? (8)

A

GH excess

  • Giant
  • Thickened soft tissues (large jaw, large hands)
  • Sleep apnoea
  • Hypertension, cardiac failure
  • Headaches (VASCULAR effect, NOT due to tumour!!)
  • Diabetes mellitus
  • Visual field disturbance
  • Colon cancer
306
Q

Tests for acromegaly? (3)

A

IGF-1
Suppression test = glucose tolerance test (remember insulin is stimulating test)
* Normal = GH suppresses to <0.4 ug/l
* Acromegaly = GH remains >1 ug/l

Visual field test

MRI pituitary scan

307
Q

Tx acromegaly? (4)

A

1st line = pituitary surgery

2nd line = somatostatin analogues (relieves headache in 1 hr)
* sandostatin, lanreotide

3rd line = dopamine agonists (only if struggling with somatostatin analogue)
* Cabergoline

Last line = GH antagonist

  • Pegvisomant
  • Blocks GH activity, however, tumour does not decrease in size
308
Q

Side effects of somatostatin analogues? (3)

A
  • Local stinging
  • Flatulence, diarrhoea, abdominal pains
  • GALLSTONES (as somatostatin stops gallbladder contracting)
309
Q

Acromegaly follow-up? (5)

A
  • Achieve clinically safe levels of GH (<0.4 post GTT and <2ug random)
  • Check other pituitary hormones, especially thyroid!!
  • Cancer surveillance (colon)
  • Cardio risk factors (BP, lipids, glucose)
  • Sleep apnoea
310
Q

Cushing’s syndrome?

S/s? (5)

A

Excess cortisol

  • protein loss - myopathy, osteoporosis, thin skin (striae, bruising)
  • Diabetes + obesity (due to altered carb + lipid metabolism)
  • Psychosis, depression
  • Excess mineralocorticoid - hypertension, oedema
  • Excess androgen = virilism, hirtuism, acne, amenorrhea
311
Q

How to differentiate cushings from obesity? (6)

A
  • Thin skin
  • Striae (rapid weight gain)
  • Proximal myopathy + central obesity (lemon on sticks)
  • Frontal balding in women
  • Conjunctival oedema (chemosis)
  • Osteoporosis
312
Q

Screening Cushing’s? (3)

A

Overnight 1mg dexamethasone suppression test (oral)

  • Normal = <50mmol cortisol next morning
  • Cushings = >100

Urine free cortisol
* Normal = <250

Diurnal cortisol variation

313
Q

Definitive test for cushings?

A

Low dose DST

  • 2 day 2mg dexamethasone suppression test
  • Normal = cortisol <50
  • Cushing’s = >130
314
Q

Ax Cushing’s? (4)

A
  • Pituitary = Cushing’s disease (all others are cushing’s syndrome)
  • Adenoma of adrenal
  • Ectopic
  • Pseudo - alcohol and depression, steroid medication
315
Q

CRH test?

A

Suggestive of pituitary disease if:

  • 50% increase in ACTH
  • 20% increase in cortisol
316
Q

Tx Cushing’s? (4)

A
  • Pituitary = hypophysectomy, external radiotherapy (if reoccurs), bilateral adrenalectomy
  • Adrenal = adrenalectomy
  • Ectopic = remove source or bilateral adrenalectomy
  • Drug tx (if other tx fails) = metyrapone, ketoconazole, pasireotide
317
Q

Pan hypopituitarism?

A

Anterior pituitary

  • Growth hormone = growth failure
  • TSH = hypothyroidism
  • LH/FSH = hypogonadism
  • ACTH = hypoadrenal
  • Prolactin

Posterior pituitary
* Diabetes insipidous

318
Q

Causes of hypopituitarism? (6)

A
  • Pituitary tumours
  • Secondary metastatic lesions (lung, breast)
  • Local brain tumours - astrocytoma, meningioma, glioma
  • Granulomatous diseases = TB, sarcoid
  • Trauma
  • Autoimmume = sheenan (post-pregnancy)
319
Q

S/s anterior hypopituitarism? (9)

A
  • Menstrual irregularities (F)
  • Infertility, impotence
  • Gynaecomastia (M)
  • Abdominal obesity
  • Loss of facial hair (M)
  • Loss of axillary and pubic hair (M&F)
  • Dry skin and hair
  • Hypothyroid faces
  • growth retardation (children)
320
Q

Dx panhypopituitarism?

A

Synacthen test and Insulin tolerance test best for steroid axis
(remember LSH and FSH should be high in post-menopausal women)

321
Q

Tx hypopituitarism? (5)

A

Replacement therapy

  • Thyroxine
  • Hydrocortisone
  • ADH
  • GH
  • Sex steroids (HRT, the pill, testosterone)
322
Q

Testosterone replacement? (3)

Risks? (3)

A
  • IM injection every month (sustanon)
  • Skin gel (testogel)
  • Prolonged IM injection every 3 months (nebido)

Risks

  • Prostate enlargement (does not cause prostate cancer but if already have cancer, can make it grow)
  • Polycytheamia - monitor FBC
  • Hepatitis (only for oral tablets) - monitor LFTs
323
Q

Causes of cranial diabetes insipidus? (3)

A
  • Familial - DIDMOAD
  • Acquired - idiopathic or RTA
  • RARE = tumour, sarcoid, meningitis
324
Q

Dx diabetes insipidus?

A

Water deprivation test

  • Check serum osmolalities for 8hr, then 4hrs after giving IM DDAVP (desmopressin)
  • If serum osmol >2 = normal
  • if not = DI (if it improves after DDAVP it is DI)

then do vasopressin stimulation test
if respond = brain problem
if dont respond = renal problem

325
Q

Tx diabetes insipidus? (3)

A
  • Desmospray - nasally
  • Desmopressin oral
  • Desmopressin injection (only used in emergencies or post-pituitary surgery)
326
Q

menopause hormones?

A

very high LH and FSH (no negative feedback as ovaries not functioning)

327
Q

what inhibits prolactin?

328
Q

anterior pituitary gland derived from? Called?

Secretes?

A

derived from Rathke’s pouch
called adenohypophysis
secretes TSH, ACTH, FSH, LH, GH and prolactin

329
Q

posterior pituitary gland called?
derived from?
secretes?

A

neurohypophysis
extension of hypothalamus
secretes ADH + oxytocin

330
Q

sheehan syndrome?

A

occurs after severe PPH

ischaemic necrosis of pituitary gland resulting in panhypopituitarism

331
Q

what can cause hyperfunction anterior pituitary?

hypofunction?

A 
hyperfunction = adenoma or carcinoma
hypofunction
* surgery/radiation
* haemorrhage
* sheehan syndrome
* tumours
* sarcoid, TB, histiocytosis X
332
Q

posterior pituitary hypofunction vs hyperfunction

A

hypofunction = diabetes insipidus (lack of ADH that can lead to life threatening dehydration)

hyperfunction = SIADH
* ectopic secretion of ADH by tumours or primary disorder in pituitary

333
Q

pathology of adrenal gland

A

hyperfunction = hyperplasia, adenoma or carcinoma
hypofunction
* acute = waterhouse-friderichsen
* chronic = addison’s disease

334
Q

adrenocortical hyperplasia congenital vs acquired

A

congenital (CAH) = enzyme deficiency

  • autosomal recessive
  • increased androgen production = masculinisation + precocious puberty

acquired

  • pituitary adenoma (cushing’s)
  • ectopic ACTH (small cell)
335
Q

adrenocortical tumours in children?

A

li-fraumeni syndrome

336
Q

adrenocortical tumours epidemiology? S/s?

A

Adult males
(in children suspect li fraumeni)
* asymptomatic
* primary hyperaldosteronism (conn’s), cushing’s, virilisation

337
Q

adrenocortical carcinoma

A

usually small, well-circumscribed
yellow
rarely functional

338
Q

adrenococrtical carcinoma

prognosis?

A

rare
functional - conn’s, cushings, virilisation

50% dead in 2 years

339
Q

primary hyperaldosteronism Ax?

A

conn’s syndrome

adenoma

340
Q

adrenocortical hypofunction Ax

A

primary

secondary = hypopituitarism, steroids

341
Q

primary adrenocortical insufficiency Ax?

A

acute = rapid withdrawal of steroid treatment, Addison’s crisis (infection), massive adrenal haemorrhage (DIC, sepsis, anticoagulants)

chronic = Addison’s disease

342
Q

Ax Addison’s disease?

A

3 common causes = autoimmune adrenalitis, infections (TB, histoplasma, HIV), metastatic malignancy from lung or breast

unusual causes = amyloid, sarcoid, haemochromatosis

343
Q

Addison’s symptoms?

signs?

A 
weakness + fatigue
anorexia
vomiting + diarrhoea
weight loss
pigmentation (palmar creases, buccal)

signs

  • hyperkalaemia + hyponatraemia!! (hypotension)
  • hypoglycaemia
344
Q

Addison’s crisis Ax?

S/s?

A

infection, trauma, surgery

  • vomiting
  • abdominal pain
  • hypotension –> shock
  • death
345
Q

which cells secrete catecholamines?

therefore what can cause hypersecretion?

A

chromaffin cells from adrenal medulla

adrenal medullary tumours e.g. neuroblastoma, phaeochromocytoma (differentiate from adrenocortical tumours)

346
Q

phaeochromocytoma?
S/s?
Dx?
Associated with?

A

adrenal medullary tumour derived from chromaffin cells
S/s = hypertension, palpitations, sweating, headache
Dx = urinary excretion of catecholamines

associated with MEN2

347
Q

why is phaeochromocytoma called 10% tumour?

A 
10% are extra-adrenal
10% are bilateral
10% are malignant
10% not associated with hypertension
25% are familial (MEN2)
348
Q

osteoporosis?

A

progressive skeletal disease characterised by:
low bone mass
bone fragility
fracture

349
Q

risk factors osteoporosis?

A

early menopause

drugs = GLUCOCORTICOIDS, aromatase inhibitors

350
Q

Dx osteoporosis?

A

DEXA scan
normal > -1
osteopenia -1 to -2.5
osteoporosis >-2.5

severe osteoporosis -2.5 with fragility fracture

351
Q

2ndry causes osteoporosis?

A

endocrine - hyperthyroidism, hyperparathyroidism, cushing’s
GI - coeliac, IBD, liver disease, chronic pancreatitis
resp - CF, COPD
CKD

352
Q

Tx osteoporosis?

A

lifestyle advice = avoid smoking + alcohol, calcium (2-3 portions dairy)

drug Tx

  • calcium + vit D supplements
  • bisphosphonates (alendronate and risedronate)
  • denosumab
  • HRT

NOTE - calcium supplements should not be taken within 2 hours of bisphosphonates

353
Q

examples of bisphosphonates

duration of Tx?
complications?

A

alendronate, risedronate, zoledronic acid (useful if intolerant to oral bisphosphonates)

Tx = 5 years
complications = osteonecrosis of jaw, oesophageal cancer, atypical fractures
354
Q

desonumab
mechanism
side effects?

A

monoclonal antibody used in tx of osteoporosis
inhibits osteoclasts
S/E = hypocalcaemia, eczema, cellilitis (injection)

355
Q

teriparatide?

A

used in severe osteoporosis

356
Q

Paget’s disease of bone
s/s
complication?

A

affects long bones, pelvis, lumbar spine + skull (i.e. like midline bones)

  • bone pain
  • deformity
  • deafness
  • compression neuropathies

osteosarcoma is a rare complication

357
Q

Dx Paget’s disease of bone?

Tx?

A 
Dx = high ALK PHOS + high uptake on isotope bone scan
Tx = analgesia + bisphosphonates
358
Q

osteogenesis imperfecta?
S/s?
Tx?

A

autosomal dominant disorder (COL1A) affecting bone

  • blue sclerae
  • dentogenesis imperfecta
  • fractures in childhood
  • hearing loss

Tx = no cure, surgery to correct deformities, bisphosphontes

NOTE - important differential for suspected NAI

359
Q

key precursor for aldosterone, cortisol + testosterone?

where are they produced?

A

cholesterol

adrenal glands

360
Q

regulation of cortisol production?

A

HPA axis (negative feedback)

361
Q

renin angiotensin system activation?

A

regulates aldosterone

activated in response to low BP (causes vasoconstriction + release of aldosterone)

362
Q

whats likely diagnosis?

21 year old female “unwell” for few months - weight loss + amenorrhoea
acutely unwell over past 48 hours with vomiting + diarrhoea

on examination = dark skin, dehydrated, hypotensive, hyperkalaemia + hyponatraemia

A

classic presentation of Addison’s disease

363
Q

adrenal insufficiency Ax?

A 
primary = Addison's disease, CAH, adrenal TB, malignancy
secondary = lack of ACTH, iatrogenic, pituitary/hypothalamic disorder
364
Q

Addison’s disease Ax?

associated with?

A

commonest cause of primary adrenal insufficiency!!

autoimmune destruction of adrenal cortex
associated with other autoimmune diseases e.g. T1DM, thyroid, pernicious anaemia

365
Q

Dx addison’s?

Tx?

A

hyponatraemia
hyperkalaemia
hypoglycaemia

short synacthen test!!
* <550 mmol after ACTH = Addison’s

Tx = hydrocortisone (as corticol replacement), fludrocortisone (as aldosterone replacement)

366
Q

how to differentiate between addisons and secondary adrenal insufficiency?
so Tx?

A 
clinical features similar (weight loss, nausea, fatigue, weakness) except:
skin pale (no increased ACTH)
aldosterone production intact (regulated by RAS)

so only Tx is hydrocortisone (fludrocortisone is unnecessary)

367
Q 
likely diagnosis?
34 y/o male
1 year history of HTN
no other PMHx
no regular medications
O/E
* BP 168/98 mmHg
* renal function normal but plasma potassium low
A

primary aldosteronism (Conn’s or bilateral adrenal hyperplasia)

368
Q

what is primary aldosteronism?

s/s?

A

uncontrolled production of aldosterone

significant hypertension
hypokalaemia
metabolic alkalosis

369
Q

Ax primary aldosteronism?

Dx?

A

adrenal adenoma = Conn’s syndrome
bilateral adrenal hyperplasia (commonest cause)
rare causes = genetic mutations or unilateral hyperplasia

Dx step 1 = confirm aldosterone excess
* plasma aldosterone and renin ratio raised = do saline suppression test
if failure to suppress = PA

step 2 = confirm subtype
* adrenal CT for adenoma

370
Q

Tx primary aldosteronism

A

surgical for adrenal adenoma = laparoscopic adrenalectomy

drugs if bilateral adrenal hyperplasia = spironolactone or eplerenone

371
Q

congenital adrenal hyperplasia?

Dx?

A

enzyme defects autosomal recessive
* increased androgen production = virilisation
* low mineralocirticoids
Dx = 17 OH progesterone

372
Q

s/s CAH in males? females?

Tx?

A

males = adrenal insufficiency, poor weight gain, same biochemical pattern as Addison’s disease
females - genital ambiguity, acne, hirsutism

Tx in children = glucocorticoid replacement, surgical correction, achieve maximum growth potential
In adults = control androgen excess, restore fertility

373
Q

complications phaemochromocytoma?

A

LVF
stroke
shock
parlytic ileus of bowel

374
Q

biochemical abnormalities phaeochromocytoma?

Tx?

A 
hyperglycaemia
low K+
high haematocrit
mild hypercalcaemia
lactic acidosis

suspect when you have hypertension + hyperglycaemia

Tx = surgery, a-blocker, b-blocker

375
Q

endocrine causes of hypertension?

A

conn’s
cushing’s
phaeochromocytoma

376
Q

Tx DKA?

A

fluids
insulin
POTASSIUM

377
Q

Ax hyponatraemia?

Hypernatraemia?

A

hypo = SIADH, compulsive water drinking

hyper = diabetes insipidus, severe dehydration

378
Q

Tx SIADH?

A

loop diuretics - furosemide

379
Q

kallmans syndrome?
Dx?
differential?
Tx?

A

hypothalamic pituitary failure
low levels FSH/LH
oestrogen deficiency
amenorrhoea

Dx = negative progesterone challenge test

stress, anorexia, pituitary tumours, drugs (steroids/opiates)

Tx = FSH + LH injections, GnRH

380
Q

PCOS?

A 
normal FSH, excess LH
oligo/amenorrhoea
normal oestrogen
insulin resistance
increased testosterone
381
Q

high FSH/LH, low oestrogen + amenorrhoea

A

menopausal

382
Q

Turner’s syndrome

A

premature ovarian failure
wide chest
shorter than average
no puberty

383
Q

causes of primary hypogonadism in males

A

klinefelters syndrome

cryptochordism

384
Q

klinefelters syndrome
Dx?
S/s

A

most common cause of primary hypogonadism in males
it is NOT inherited
Dx = karyotyping
S/s
* small, firm testes, infetility, learning disability, breast development, wide hips

385
Q

Kallman’s syndrome?

S/s?

A

genetic disorder characterised by isolated GnRH deficiency + anosmia

associated with
small penile size +/- undescended testicles
red green colour blindness
cleft lip
unilateral renal agenesis
386
Q

Ix if suspect hypogonadotrophic hypogonadism?

Tx?

A

measure AM testosterone
if normal = reassure patient
if low = measure LH/FSH
* high = hypergonadotrophic hypogonadism (primary) e.g. klinefelter’s
* low = hypogonadotrophic hypogonadism (secondary) e.g. Kallmann’s, prader willi

Testosterone replacement therapy

2nd Year Medicine (24 decks)

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