PBL Topic 4 Case 9 Flashcards
1
Q
Identify three hormones secreted by the thyroid
A
- Thyroxine (T3)
- Triiodothyronine (T4)
- Calcitonin
2
Q
Thyroid secretion is controlled by which hormone? Which gland secretes this homrone?
A
- Thyroid-stimulating hormone
- Secreted by anterior pituitary gland
3
Q
What is contained within the thyroid follicles?
A
- Colloid
- Which consists of thyroglobulin
- Which contains the thyroid hormone within its molecule
4
Q
Outline the process of iodide trapping
A
- Active pumping of iodine through basal membrane by Na/I transporter
- Transport through apical membrane by pendrin (I/Cl transporter)
5
Q
Outline the process of oxidation of iodide ions
A
- Conversion of iodide to iodine
- Catalysed by thyroid peroxidase in apical membrane
- And its accompanying hydrogen peroxide
6
Q
Outline the organification of iodine
A
- Iodine binds with tyrosine
- Catalysed by iodinase enzyme
7
Q
Outline the iodisation of tyrosine
A
- Tyrosine is iodised to monoiodotyrosine
- And then to diiodotyrosine
- MIT + DIT = T3
- DIT + DIT = T4
8
Q
Outline the process by which T3 and T4 are cleaved from thyroglobulin
A
- Apical surface sends out pseudopods
- Which close around portions of colloid
- Which form pinocytic vesicles that enter the apex of the thyroid cell
- Lysosomes fuse with vesicles
- Proteases digest thyroglobulin to release T3 and T4
9
Q
What happens to the iodinated tyrosine following digestion of thyroglobulin?
A
- Iodine is cleaved by deiodinase enzyme
- Which recycles iodine available again for formation of additional thyroid hormone
10
Q
What happens to the majority of T3 and T4 as it enters the blood?
A
- Combines with thyroxine-binding globulin
- Delivered to tissues where they bind with intracellular proteins
11
Q
Outline the cellular action of thyroid hormone
A
- Retinoid X receptor forms a heterodimer with thyroid hormone receptors
- Which enhances binding of thyroid hormone at the thyroid response element in the DNA of the target cell nucleus
- Activation of these receptors causes transcription followed by RNA translation
12
Q
What is the effect of thyroid hormone on mitochondria?
A
- Increases number of mitochondria
- Which increases the formation of ATP
13
Q
What is the effect of thyroid hormone on active transport?
A
- Increases activity in Na+-K+-ATPase
- Which increases transport of sodium and potassium through membranes
- Which increases body’s metabolic rate
14
Q
What is the effect of thyroid hormone on growth?
A
- Growth and development of brain
- Growth and development of bones
15
Q
What are the effects of thyroid hormone on carbohydrate metabolism?
A
- Increased rate of absorption from GI tract
- Increased insulin secretion
- Rapid uptake of glucose by the cells
- Enhanced glycolysis
- Enhanced gluconeogenesis
16
Q
What are the effects of thyroid hormone on fat metabolism?
A
- Lipids are mobilised rapidly
- Which decreases the fat stores of the body
- Which increases the free fatty acid concentration in the plasma
- And greatly accelerates the oxidation of free fatty acids by the cells
17
Q
What are the effects of thyroid hormone on fat cholesterol, phospholipids and triglycerides?
A
- Decreased concentrations of cholesterol, phospholipids and triglycerides
18
Q
How does thyroid hormone decrease plasma cholesterol concentration?
A
- Increased numbers of LDL receptors on liver cells
- With increased LDL removal from plasma
- Liver cells convert LDL to cholesterol
- Which are secreted in bile and lost in faeces
19
Q
Why does thyroid hormone cause vasodilation and increased cardiac output?
A
- Increased cellular metabolism causes rapid utilisation of oxygen
- Increasing metabolic end product release from tissues
20
Q
Why does thyroid hormone cause increased heart rate?
A
- Direct effect of TH on excitability of the heart
21
Q
What is the effect of thyroid hormone on the respiratory system?
A
- Increase in rate and depth of respiration
- Due to increased rate of metabolism (increased utilisation of oxygen and formation of CO2
22
Q
What are the effects of thyroid hormone on the GI system?
A
- Increased appetite and food intake
- Increased secretion of digestive juices
- Increased motility of GI tract
- Hyperthyroid: Diarrhoea
- Hypothyroid: Constipation
23
Q
What are the effects of thyroid hormone on the CNS?
A
- Increases rapidity of cerebration
- Hyperthyroid: Nervous and psychoneurotic tendencies (anxiety, worry paranoia)
24
Q
What are the effects of thyroid hormone on muscles?
A
- Initially muscles react with vigor
- Though excessive TH causes weakened muscles due to protein catabolism
25
What are the effects of thyroid hormone on sexual function
- Men: lack of TH causes loss of libido, excess libido causes impotence
- Women: lack of TH causes loss of libido, menorrhagia
26
Identify 6 effects of TSH on the thyroid gland
- Increased proteolysis of thyroglobulin
- Increased activity of iodide pump
- Increased iodination of tyrosine
- Increase number of thyroid cells
- Increased secretory activity
27
Outline the cellular action of TSH
- TSH binds with TSH receptors on basal membrane of thyroid cells
- Which activates adenylyl cyclase
- With increased formation of cAMP
- cAMP activates phosphatidyl inositol 3-kinase
- With an increase in secretion of thyroid hormones
28
Outline the control of TSH secretion
- TSH is controlled by TRH
- Which is secreted by median eminence of hypothalamus
- Which binds to TRH receptors on anterior pituitary cells
- Which activates the phospholipase C second messenger system
- Which leads to TSH release
29
Identify factors that reduce TSH secretion
- Increased thyroid hormone causes negative feedback of TSH secretion
- Somatostatin reduces basal TSH release
30
Which cells of the thyroid gland secrete calcitonin?
- Parafollicular cells
31
What is the primary stimulus for calcitonin secretion?
- An increase in plasma calcium ion concentration
32
How does calcitonin decrease plasma calcium concentration?
- Decrease activity and formation of osteoclasts
33
Identify thyroid function tests
- TSH
| - Plus free T4 or free T3
34
What are the problems in the interpretation of thyroid function tests in serious acute or chronic illness?
- Reduced concentration and affinity of binding proteins
| - Decreased peripheral conversion of T4 to T3
35
What are the problems in the interpretation of thyroid function tests in pregnancy and with oral contraceptives?
- Greatly increased TBG levels so high T4.
| - TSH is suppressed in the first trimester
36
What are the problems in the interpretation of thyroid function tests in patients taking amiodarone?
- Amiodarone decreases T4 to T3 conversion
| - Amiodarone may induce both hyper-and hypothyroidism
37
What is the most likely diagnosis?
- TSH undetectable
- T4 raised
- T3 raised
- Primary thyrotoxicosis
38
What is the most likely diagnosis?
- TSH undetectable
- T4 normal
- T3 raised
- Primary T3 toxicosis
39
What is the most likely diagnosis?
- TSH undetectable
- T4 raised
- T3 low, normal or raised
- Sick euthyroidism
40
What is the most likely diagnosis?
- TSH undetectable
- T4 low
- T3 low
- Secondary hypothyroidism
41
What is the most likely diagnosis?
- TSH elevated
- T4 low
- T3 low
- Primary hypothyroidism
42
What is the most likely diagnosis?
- TSH elevated
- T4 normal
- T3 normal
- Subclinical hypothyroidism
43
What is thyrotoxicosis?
- Increased metabolic rate
| - Due to effect of excess T3/T4 on tissues
44
What is the commonest cause of thyrotoxicosis?
- Hyperthyroidism
45
Identify the three main pathological causes of hyperthyroidism
- Grave's Disease
- Functioning adenoma
- Toxic nodular goitre
46
What is struma ovarii?
- Teratoma
- Ovary comprising thyroid tissue
- With ectopic secretion of thyroid hormones
47
Outline the epidemiology of hyperthyroidism
- Affects up to 5% of women
- More common in women 5:1
- Most common between 20-40
- Most caused by intrinsic thyroid disease (pituitary cause is rare)
48
Outline the pathology of Grave's thyroiditis?
- IgG autoantibody called long-acting thyroid stimulator (LATS)
- Binds to thyroid epithelial cells
- And mimics the action of TSH
- Stimulating function and growth of thyroid follicular epithelium
49
Identify the three clinical features of Grave's thyroiditis
- Exophthalmos
- Pretibial myxoedema
- Thyroid acropachy
50
What is exophthalmos?
- Anterior bulging of eyes
| - Results from infiltration of orbital tissues by adipocytes and mucopolysaccharides
51
What is pretibial myxoedema
- Accumulation of mucopolysaccharides in dermis of skin
- Skin appears puffy
- Outer third of eyebrow is lost
52
What is thyroid acropachy?
- Clubbing
- Swollen fingers
- Periosteal knee bone formation
53
Outline the genetic component of Grave's thyroiditis
- HLA-B8, DR3 and DR2
- E.coli and other gram negatives have TSH binding sites
- Which initiates infection mimicry in genetically susceptible patients
54
What is de Quervain's thyroiditis? What are the features and treatment
- Transient hyperthyroidism from an acute inflammatory process
- With fever, malaise, neck pain, raised ESR
- Proceeded by hypothyroidism
- Treatment is with aspirin
55
What is Type 1 Amiodarone-Induced Thyrotoxicosis?
- Associated with pre-existing Graves or multi nodular goitre
- Hyperthyroidism is triggered by high iodine content of amiodarone
56
What is Type 2 Amiodarone-Induced Thyrotoxicosis?
- Not due to previous thyroid disease
- Direct effect of drug on thyroid follicular cells
- Leading to destructive thyroiditis
57
What is the effect of amiodarone on iodine?
- Inhibits the deiodination of T4 to T3
58
What are the 6 most common symptoms of hyperthyroidism?
- Weight loss
- Increase appetite
- Heat intolerance
- Palpitations
- Tremor
- Irritability
59
What are the eye signs in hyperthyroidism?
- Lid lag
| - Stare
60
What is the presentation of hyperthyroidism in the elderly?
- Atrial fibrillation, tachycardia, heart failure
| - 'Apathetic thyrotoxicosis' where clinical picture is more like hypothyroidism
61
What is the presentation of hyperthyroidism in children?
- Excessive height or excessive growth rate
| - Behavioural problems such as hyperactivity
62
What are the investigations in hyperthyroidism?
- Suppressed TSH
- Raised T4 or T3
- Thyroid peroxidase and thyroglobulin antibodies are present in Grave's disease
63
Outline the mechanism of action of radioiodine?
- Emits beta radiation
| - Which has a cytotoxic action on thyroid follicular cells
64
Why is surveillance important with radioiodine therapy?
- Hypothyroidism will eventually occur
| - Which is easily managed by replacement therapy with T4
65
Identify a contra-indication to radioiodine therapy
- Children
| - Pregnant patients
66
Identify three thioureylenes
- Carbimazole
- Methimazole (active metabolite of carbimazole)
- Propylthiouracil
67
Outline the mechanism of action of thioureylenes
- Competitively inhibits the oxidation of iodide by thyroid peroxidase
- Which inhibits iodination of tyrosine residues in thyroglobulin
68
Which chemical group is essential for the antithyroid activity of thioureylenes?
- Thiocarbamide (S-C-N)
69
Why does propylthiouracil act more rapidly than other drugs in its class?
- It has an additional effect
| - To inhibit the peripheral conversion of T4 to T3
70
Both methimazole and propylthiouracil cross the placenta, why is this effect less pronounced with propylthiouracil?
- Propylthiouracil is more strongly bound to plasma protein
71
What are the most dangerous unwanted effects of thioureylenes?
- Neutropenia
| - Agranulocytosis
72
What are the most common unwanted effects of thioureylenes?
- Rashes
73
Why is propranolol indicated in hyperthyroidism?
- Beta adrenoreceptor antagonist
| - That reduces tachycardia, dysrhythmias, tremor and agitation
74
What is the role of guanethidine in the treatment of hyperthyroidism?
- Noradrenergic blocking agent
- Used to improve exophthalmos
- By relaxing the sympathetically innervated smooth muscle
- That causes eyelid retraction
75
What is the role of glucocorticoids in the treatment of hyperthyroidism?
-Mitigate severe exophthalmia in Grave's disease
76
What is the surgical procedure used in the treatment of hyperthyroidism and what are the risks associated with it?
- Thyroidectomy
- Bleeding causing tracheal compression and asphyxia
- Laryngeal nerve plasy
- Transient hypocalcaemia
77
What is thyroid crisis?
- Rare, life-threatening complication
- Signs of fever, agitation, confusion, tachycardia, AF, cardiac failure
- Precipitated by infection in unrecognised thyrotoxicosis
78
How is thyroid crisis treated?
- Rehydrate
- Broad spectrum antibiotic
- Propranolol
- Sodium ipodate
79
What is the mechanism of action of sodium ipodate?
- Restores serum T3
| - Which inhibits release of thyroid hormone
80
Outline the pathophysiology of thyroid eye disease
- TSH receptor is degraded by APC
- Activation of T-cells, and B-cells
- Which activates cytokines which induces differentiation of B cells into plasma cells
- Which secrete anti-TSH receptor antibodies
81
Outline 5 clinical features of thyroid eye disease
- Soreness
- Watering
- Proptosis
- Lid retraction
- Peri-orbital oedema and inflammation
82
Outline the treatment of thyroid eye disease
- Methylcellulose or hypromellose aid lubrication and improve comfort
- Steroids reduce inflammation
- Surgical decompression may be required
- Corrective eye muscle surgery if diplopia occurs
83
What is a goitre?
- Enlargement of the thyroid without hyperthyroidism
- Cause by lack of T3 or T4
- TSH rises and causes hyperplasia of thyroid epithelium
84
Identify 3 causes of goitre
- Iodine deficiency
- Rare inherited enzyme defects
- Drugs that induce hypothyroidism
85
Identify and describe two types of goitre
- Parenchymatous goitre: hyperplasia of thyroid epithelium, fibrosis results in multinodular goitre
- Colloid goitre: Colloid forms cysts, with haemorrhage, fibrosis and calcification
86
Identify 3 indications for surgical intervention of a goitre
- Possibility of malignancy
- Pressure symptoms on trachea or oesophagus
- Causes considerable anxiety
87
What is hypothyroidism?
- Inadequate levels of T3 and T4
- Metabolic rate is lowered
- Mucopolysaccharides accumulate in dermal connective tissue
- To produce myxoedema face
88
What is the commonest cause of acquired hypothyroidism?
- Hashimoto's thyroiditis
89
Outline the pathophysiology of Hashimoto's thyroiditis
- Autoantibodies for thyroid peroxidase and thyroglobulin
- Formed from plasma cells infiltrating thyroid due to loss of Ts cells
- Colloid content reduced and increased mitochondria (oncocytes)
90
Identify 3 other causes of primary hypothyroidism
- Postpartum thyroiditis (due to modification in immune system during pregnancy)
- Dietary iodine deficiency (endemic goitre)
- Dysmorphogenesis (defective synthesis of thyroid hormones)
91
What is Prendred's syndrome?
- Defect in the transporter pendrin
- Due to deletion mutation in chromosome 7
- Reduced movement of iodide ions through through apical membrane
- Causes sensorineural hearing loss
92
What are the most common features of hypothyroidism
- Weight gain
- Cold intolerance
- Bradycardia
- Constipation
- Dry hair and thick skin
- Deep voice
93
Outline the clinical picture of hypothyroidism in children
- Slow growth velocity
- Poor school performance
- Arrest of pubertal development
94
What results from thyroid function tests would indicate hypothyroidism
- High TSH
| - Low free T4
95
Outline other abnormalities from blood tests in primary hypothyroidism
- Anaemia
- Increased AST
- Increased creatine kinase
- Hypercholesterolaemia
- Hyponatraemia
- Bradycardia, ST segment, T wave abnormalities
96
What is secondary hypothyroidism?
- Failure of TSH secretion
- With hypothalamic or anterior pituitary disease
- Characterised by low TSH, low T4
97
What is the treatment for hypothyroidism? How and when are they given?
- Levothyroxine, given orally, first line
| - Liothyronine given intravenously, reserved for myxoedema coma
98
What are the adverse effects of levothyroxine and liothryonine?
- In severe overdose:
- Angina pectoris
- Cardiac dysrhythmias
- Cardiac failure
99
What is myxoedema coma?
- Severe hypothyroidism occurring in the elderly
- Presents with confusion or coma
- High mortality (50%)
100
What is the treatment for myxoedema coma?
- T3 orally or IV
- Oxygen
- Monitoring of cardiac output
- Hydrocortisone IV
- Glucose infusion
101
What is myxoedema madness?
- Demented or psychotic symptoms with striking delusions
- Occurring rarely in severe hypothyroidism
- May occur shortly after T4 replacement
102
What do TFTs show subclinical thyrotoxicosis?
- TSH undetectable
- Serum T3 and T4 in upper end of normal range
- Often present with multinodular goitres
103
How is subclinical thyrotoxicosis managed?
- Annual review and treatment with radioactive iodine
104
What do TFTs show subclinical hypothyroidism?
- Raised TSH
| - T3 and T4 in lower end of reference range
105
When and how is subclinical hypothyroidism managed?
- In patients with non-specific symptoms or positive autoantibodies
- Thyroxine
106
Outline the anatomy of the parathyroid glands
- Four glands
- Located behind the thyroid gland, one behind each of the upper and each of the lower poles of the thyroid
- Contains mainly chief cells and a small to moderate number of oxyphil cells
107
Outline the synthesis of parathyroid hormone
- Ribosomes synthesise preprohormone
- Which is cleaved to prohormone and then parathyroid hormone
- By the endoplasmic reticulum
- Packaged into secretory granules in the cytoplasm
108
Outline the effects of an increase in [PTH] on the serum [Ca2+] and [PO42-]
- Calcium: Increase
| - Phosphate: Decrease
109
Identify the two main effects of PTH that increase serum calcium concentration
- Increased resorption from bone
| - Decreased excretion from urine
110
Outline the effect of PTH on bones
- PTH binds to PTH-1 receptor on osteoblasts
- Which increases osteoblast expression of RANKL
- Which binds to RANK on osteoclast precursors
- Differentiation of osteoclast precursors to mature osteoclasts
111
Outline the effect of PTH on the kidneys
- Reduced PCT reabsorption of PO42-
| - Increased DCT reabsorption of Ca2+
112
Outline the effect of PTH on intestines
- PTH greatly enhances both calcium and phosphate absorption from the intestines
- By increasing the formation in the kidneys of 1,25-dihydroxycholecalciferol from vitamin D
113
What is the difference between the three types of hyperparathyroidism?
- Types 1 and 3 are pathological and involve hyperplasia
| - Type 2 is physiological and occurs in CKD or Vitamin D deficiency
114
Identify 7 clinical features of hyperparathyroidism
- Renal stones
- Thirst and polyuria
- Muscle weakness
- Tiredness
- Anorexia and constipation
- Peptic ulceration
- Osteitis fibrosa
- Brown tumour
115
Identify three findings from investigations suggesting hyperparathyroidism
- Raised PTH levels
- Raised serum calcium
- Lower plasma phosphate
- Mild metabolic acidosis
116
What is the main cause of hyperparathyroidism?
- Secretory adenoma of parathyroid gland
117
Outline the treatment for hyperparathyroidism
- Operative inspection of all four parathyroid glands
- Followed by removal of any suspected adenoma
- Which is then submitted for intraoperative diagnosis
118
Outline five clinical features of hypoparathyroidism
- Tetany
- Convulsions
- Paresthesia
- Psychiatric disturbances
- Cataracts
- Brittle nails
119
Identify three causes of hypoparathyroidism
- Removal or damage to parathyroid glands during thyroidectomy
- Autoantibodies
- Congenital deficiency (DiGeorge syndrome)
120
Outline the clinical features of DiGeorge syndrome
- Intellectual impairment
- Cataracts
- Calcified basal ganglia
121
Outline the pathology of pseudohypoparathyroidism
- Resistance to PTH
| - Due to mutation of GNAS1 which is coupled to PTH receptor
122
Outline the clinical features of pseudohypoparathyroidism
- Short stature
- Short metacarpals
- Intellectual impairment
123
What is pseudo-pseudohypoparathyroidism
- Describes the phenotypical defects of pseudohypoparathyroidism
- But with no abnormalities in calcium metabolism
124
What is Cushing's syndrome?
- Increased circulating glucocorticoids (cortisol)
| - Usually following administration of synthetic steroids or ACTH
125
Identify the two groups of causes of Cushing's syndrome
- Increased ACTH from pituitary (Cushing's disease) or ectopic release from an ACTH releasing tumour
- Excess of endogenous cortisol secretion by an adrenal tumour or hyperplasia
126
What are the clinical features of Cushing's syndrome?
- Pigmentation with ACTH-dependent causes
- Cushingoid appearance caused by excess alcohol consumption
- Impaired glucose tolerance or diabetes in ectopic ACTH syndrome
- Hypokalaemia due to mineralocorticoid activity in ectopic ACTH secretion
- Hypertension
127
How is Cushing's syndrome diagnosed?
- Elevated plasma cortisol
- Elevated urinary excretion of 17-hydroxysteroids
- Measurements of plasma ACTH
128
What are the effects of untreated Cushing's?
- Hypertension
- Myocardial infarction
- Infection
- Heart failure
129
Identify a drug used in the treatment of Cushing's syndrome
- Metyrapone
- An 11-beta hydroxylase blocker
- Which is involved in the formation of cortisol from cholesterol
130
Identify an antifungal agent that is synergistic with metyrapone and how it works
- Ketoconazole
| - Inhibits steroidogenesis
131
Identify the treatment of pituitary-dependent hyperadrenalism
- Trans-sphenoidal removal of tumour
- External pituitary radiation
- Medical therapy to reduce ACTH (e.g. bromocriptine)
- Bilateral adrenalectomy
132
Name an adrenolytic therapy that inhibits growth of adrenal tumours
- Mitotane
133
What is hyperaldosteronism?
- Autonomous secretion of excess aldosterone
134
Identify two causes of hyperaldosteronism
- Adenoma of the zona glomerulosa (Conn's syndrome)
| - But can also be caused by hyperplasia of the zona glomerulosa
135
Outline the pathology of hyperaldosteronism
- Sodium and water retention leads to hypertension
| - Potassium loss leads to muscular weakness and cardiac arrhythmias, tetany and paraesthesia
136
What is secondary hyperaldosteronism
- Reduced renal perfusion (e.g. fall in blood pressure)
- Stimulates aldosterone secretion
- Commonest type of hyperaldosteronism
137
What investigations are used in the diagnosis of hyperaldosteronism?
- Plasma aldosterone:renin ratio (elevated aldosterone and suppressed renin)
- Hypokalaemia and urinary potassium loss
138
Outline the treatment of hyperaldosteronism
- Adenoma: Laparoscopic surgical removal
| - Hyperplasia: Aldosterone antagonists e.g. spironolactone
139
Identify 3 adverse effects of spironolactone and an alternative drug
- Gynaecomastia
- Rashes
- Nausea
- Eplerenone
140
Identify the two factors that must be balanced to maintain a stable body weight over time
- Energy intake
| - Energy expenditure
141
How is BMI calculated?
- Weight (KG) / Height (M2)
142
A BMI between which values indicates overweight?
- 25 and 29.9 kg/m2
143
A BMI over which value indicated obesity?
- 30 kg/m2
144
Identify a disadvantage of BMI measures?
- Not a direct estimate of adiposity
| - Does not take into account high BMI due to a large muscle mass.
145
Obesity is defines as [X%] or greater total body fat in men and [Y%] in females
- [X] = 25%
| - [Y] = 35%
146
What causes obesity
- Greater energy Intake than energy expenditure
147
For each [X] number calories of excess energy that enter the body, approximately 1 gram of fat is stored.
- [X] = 9.3 calories
148
How is weight lost?
- Energy intake must be less than energy expenditure.
149
What is meant by expert patient?
- People living with a long-term health condition
- Who are able to take more control over their health
- By understanding and managing their conditions
- Leading to an improved quality of life
150
Identify an advantage and disadvatnage of self-manageemtn
- Increases confidence and reduces anxiety
| - Benefits for some disease (COPD) but not others (arthritis)
151
What is meant by Shared Care?
- Enabling all patients to manage aspects of their own care that they choose to
- With added nursing support to bridge any shortfalls.
152
Outline the epidemiology of anxiety
- Highest in young women (2:1)
- Associated with alcohol use and smoking
- Associated with stress and sleep disorders
- Antidepressants are most commonly used pharmacological treatment
