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RACP Written 2018 > Endocrine - Hyper and Hypo Thyroidism > Flashcards

Endocrine - Hyper and Hypo Thyroidism Flashcards

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1
Q

Thyroid Physiology

- embryology of the thyoroid?

A

Median ENDODERM downgrowth from BASE OF TONGUE and travels caudally with heart.

Thyroid gland duct breaks down by week 5-6

Enlargement from 4th brachial pouch

Colloid present by week 10
Thyroid functional by week 11-12

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2
Q

Thyroid Physiology

- anatomy of the thyroid?

A

Isthmus is just in front of trachea, just BELOW CRICOID CARTILAGE

Recurrent laryngeal nerve runs BETWEEN trachea and oesophagus

Pyramidal lobe (in 80%) is remnant of thyroglossal duct

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3
Q

Thyroid Physiology

- How does thyroid hormone provide negative feedback?

A

Thyroid hormone gives negative feedback via Thyroid Hormone Receptor Beta2
–> inhibits TSH and TRH

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4
Q

Thyroid Physiology

- Other than thyroid hormone what other suppressors of TSH?

A

Dopamine
Glucocorticoids
Somatostatin

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5
Q

Thyroid Physiology

- How is iodide uptaken?

A

Iodide uptake on basolateral membrane via NIS on follicular cells.
NIS is ALSO on salivary cells, placenta and lactating breasts
–> NIS is STIMULATED by low iodide levels
–> NIS is INHIBITED by high iodide levels (=Wolf-Chykoff Effect)

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6
Q

Thyroid Physiology

- What is NIS?

A

NIS is the basolateral channel on follicular thyroid cells via which iodide is uptaken.

NIS is ALSO on salivary cells, placenta and lactating breasts

  • -> NIS is STIMULATED by low iodide levels
  • -> NIS is INHIBITED by high iodide levels (=Wolf-Chykoff Effect)
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7
Q

Thyroid Physiology

- How does the iodide get into the follicular lumen of follicular thyroid cells?

A

Via PENDRIN transporter on apical membrane

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8
Q

Thyroid Physiology

- What happens to iodide once the iodide is in the follicular lumen?

A

Iodide is oxidised by TPO and HYDROGEN PEROXIDE

It is the bound to TYROSINE RESIDUES

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9
Q

Thyroid Physiology

- How does T3 and T4 form?

A

Iodised Tg is taken back into the cell and processed in lysosomes to form T3 and T4
DIT + DIT = T4
DIT + MIT = T3

Uncoupled tyrosine residues are MIT and DIT and these get recycled

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10
Q

Thyroid Physiology

- What combinations for DIT and MIT for thyroid hormones?

A

DIT + DIT = T4
DIT + MIT = T3

Uncoupled tyrosine residues are MIT and DIT and these get recycled

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11
Q

Thyroid Physiology

- How is thyroid hormone transported in blood?

A

Thyroid Binding Globulin (TBG) binds most T3/T4 but ONLY THE FREE HORMONE IS ACTIVE

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12
Q

Thyroid Physiology

- What creates high and low levels of TBG?

A

High TBG: pregnancy and OCP

Low TBG: liver failure and steroids

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13
Q

What is Pendred Syndrome?

A

Pendred Syndrome = mutation of pendrin gene (the transporter that transports iodide from follicular cells into follicular lumen in the thyroid)

Features:

  • goitre
  • sensorineural deafness
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14
Q

Which thyroid hormone is more potent?

A

T3 is more potent than T4

T4 converts itself to T3 via 5-deiodinase

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15
Q

What are the different types of 5-deiodinase and what do they do?

A

5-deiodinase Type 1 and Type 2 convert T4 to T3

Type 1: in thyroid, liver and kidneys
Type 2: in pituitary, brain, brown fat and thyroid

Type 3 inactivates T4 and T3, and makes reverse T3

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16
Q

What receptors do thyroid hormones act on?

A

Nuclear thyroid receptors TRalpha and TRbeta

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17
Q

What are the biochemical markers of thyrotoxicosis?

A

INCREASED:

  • osteocalcin
  • ALP
  • ANP
  • SHBG
  • Ferritin
  • vWF

DECREASED:

  • LDL
  • Lipoprotein (a)
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18
Q

What are the biochemical markers of hypothyroidism?

A

INCREASED:

  • CK
  • LDL
  • Prolactin
  • Lipoprotein (a)
  • Noradrenaline

DECREASED:
- vasopressin

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19
Q

Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism?

Osteocalcin

A

INCREASED in THYROTOXICOSIS

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20
Q

Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism?

CK

A

INCREASED in HYPOTHYROIDISM

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21
Q

Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism?

Noradrenaline

A

INCREASED in HYPOTHYROIDISM

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22
Q

Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism?

Vasopressin

A

DECREASED in HYPOTHYROIDISM

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23
Q

Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism?

ALP

A

INCREASED in THYROTOXICOSIS

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24
Q

Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism?

LDL

A

DECREASED in THYROTOXICOSIS

INCREASED in HYPOTHYROIDISM

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25
Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism? SHBG
INCREASED in THYROTOXICOSIS
26
Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism? vWF
INCREASED in THYROTOXICOSIS
27
Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism? Lipoprotein (a)
DECREASED in THYROTOXICOSIS | INCREASED in HYPOTHYROIDISM
28
Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism? ANP
INCREASED in THYROTOXICOSIS
29
Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism? Prolactin
INCREASED in HYPOTHYROIDISM
30
Is _____ a biochemical marker of thyrotoxicosis or hypothyroidism? Ferritin
INCREASED in THYROTOXICOSIS
31
What are the two types of Primary Autoimmune Hypothyroidism?
Hashimotos | Atrophic Thyroiditis
32
What risk factors (non-genetic) are associated with Primary Autoimmune Hypothyroidism?
Female | Older age
33
What conditions are associated with Primary Autoimmune Hypothyroidism (ie Hashimotos or Atrophic Thyroiditis)
- Pernicious anaemia - Type 1 Diabetes - Addisons - Vitiligo - Myasthenia Gravis - Pituitary autoimmunity
34
What genetic associations are with Primary Autoimmune Hypothyroidism?
HLA -DR3, -DR4, -DR5 | CTLA-4
35
What is the pathogenesis of Primary Autoimmune Hypothyroidism?
Lymphocytic infiltration of thyroid with CD4+ and CD8+ - germinal centre formation - atrophy of follicles - absence of colloid - mild-mod fibrosis
36
What diagnostic tests would you do for Primary Autoimmune Hypothyroidism?
Anti-TPO (90-95% spec and sensitivity) | Anti-TSH receptor antibody (20%)
37
How do you treat Primary Autoimmune Hypothyroidism?
``` L thyroxine (aim for TSH ~1) Start low if ischaemic heart disease ``` T3 not needed PREGNANCY: increase dose by 50%
38
What must you be cautious of when treating Primary Autoimmune Hypothyroidism? What can be unmasked?
In pituitary disease you can unmask the HPA axis with hypoadrenalism and diabetes mellitus
39
What lab markers would you expect for subclinical hypothyroidism?
Raised TSH with NORMAL T4/T3 40% have anti-TPO
40
What risk factors for subclinical hypothyroidism?
Older patients Type 1 diabetes Downs Syndrome
41
What is the progression to hypothyroidism in subclinical hypothyroidism?
If the TSH >=1 then 100% progression
42
When do you treat subclinical hypothyroidism?
Treat if symptoms or TSH >=10 If PREGNANCY: treat if TSH >=2.5 Consider if: - age <65yrs - heart failure - dyslipidaemia - anti-TPO or anti-Tg positive
43
What are the clinical features of Myxoedema Coma?
- dry coarse skin (yellow from carotene) - delayed reflexes - pericardial and pleural effusions +/- goitre - myopathy and cardiomyopathy - elevated CK - central hypothermia / bradycardia - seizures
44
What precipitates myxoedema coma?
Trauma or major illness
45
What lab findings do you expect in myxoedema coma?
TSH VERY high (>50!!!) Hyponatraemia Elevated creatinine Elevated CO2
46
How do you manage myxoedema coma?
HDU/ICU Passive rewarming Fluid resus +/- inotropes IV hydrocortisone T4 loading VTE prophylaxis REMEMBER reduced renal clearance
47
What demographics are patients who present with Graves Disease?
Women predominant | Aged 20 - 50 years old
48
What two organisms have been proposed to contribute to a molecular mimicry as part of pathogenesis of Graves Disease?
- H pylori | - yersinia enterocolitis
49
What immune modulating therapies have been associated with developing Graves Disease?
- IFNalpha and IFNbeta - ipilumumab - HAART therapy - Alemtuzumab - lymphocyte depletion treatments
50
What genetic associations are with Graves Disease?
``` HLA-DR CTLA-4 CD25 PTPN22 FCRL3 CD226 ```
51
What are the Graves-Specific features which present in addition to thyrotoxicosis features with Graves Disease?
``` Goitre Ophthalmopathy Pretibial myxoedema Thyroid acropachy Myopathy Onycholysis Psychosis / aesthenia Osteoporosis AF with HIGH EMBOLISM RISK Heart failure and IHD exacerbation Neutropenia, lymphocytosis and thrombocytopenia ```
52
What are the Graves-Specific musculoskeletal features of Graves Disease?
Myopathy | Osteoporosis
53
What are the Graves-Specific cardiac features of Graves Disease?
AF with HIGH EMBOLISM RISK | Heart failure and IHD exacerbation
54
What gender distribution is seen in Graves Ophthalmopathy?
Male > Female
55
What are the eye features of Graves Ophthalmopathy?
``` Exophthalmos Proptosis and lid lag Periorbital lid swelling and chemosis Diplopia and poor convergence Limited upward gaze Reduced visual acuity ```
56
What causes the proptosis and lid lag seen in Graves Opthalmopathy? What causes the reduced visual acuity seen in Graves Ophthalmopathy?
Proptosis and lid lag is due to overactivity of sympathetic stimulation in levator Reduced visual acuity is due to retinal and optic nerve oedema
57
What are the risk factors for progression of Graves Ophthalmopathy?
Smoking (STRONGEST) Hypothyroidism Iodine 131
58
What is Hypokalaemic Periodic Paralysis
Transient hypokalaemia often post carbohydrates and exercise Seen in Asian males Acquired forms are seen in hyperthyroidism during THYROTOXIC phases
59
What is the natural history of Graves Disease?
25% of untreated will spontaneously remit If conservated treatmetn: 50% will remit Once remission: 25% recur 25% become hypothyroid
60
How do you manage the symptoms of Graves Disease?
Beta blockers
61
How do you treat Graves Disease?
Symptom management with beta blockers ``` Antithyroid drugs: avoid permanent ablation (propylthiouracil and carbimazole) FAVOURED IF: - age <40yrs with small goitre - during pregnancy - low titre TR-Abs ```
62
Mechanism of Propylthiouracil? Use in pregnancy? Side effects?
Propylthiouracil (PTU) - shorter half life than carbimazole Action: At Thyroid: inhibits thyroperoxidase to inhibit oxidation of iodide to iodine At peripheries: inhibits 5-deiodinase to inhibit conversion of T4 to T3 PREGNANCY: - safer than carbimazole in 1st trimester - safe in breast milk at doses <300mg/day S/E: - (rare) fulminant hepatitis - ANCA positive vasculitis
63
Mechanism of Carbimazole? Use in pregnancy? Side effects?
Carbimazole (CBZ) - 1st line in treatment due to risk for hepatitis with PTU Action: Carbimazole is a pro drug, later converted to methimazole which inhibits thyroperoxidase to inhibit oxidation of iodide to iodine PREGNANCY: - in 1st trimester causes foetal damage S/E: - rash - mild neutropenia - agranulocytosis (0.4%)
64
Use of Iodine 131 in treatment of Graves Disease?
Safe but causes hypothyroidism Can EXACERBATE ophthalmopathy Use in adults >40yrs who have failed other treatments
65
Use of surgery in treatment of Graves Disease?
Most RAPIDLY effective BEST for obstructive goitre S/E: - hypothyroidsim - hypoparathyroidsim - laryngeal nerve damage
66
TSHr mutation mediated hyperthyroidism presents similarly to, and is treated similarly as, Graves Disease. What three risk factors for TSHr mutation mediated hyperthyroidsim?
Older Women Iron deficiency
67
What are the two types of Amiodarone Induced Thyrotoxicosis (AIT) and how do you differentiate them?
AIT Type 1: Increased thyroid hormone due to iodine load AID Type 2: thyrocyte toxicity To differentiate: - Scan uptake is LOW in both - IL-6 is ELEVATED in Type 2 - Tg is ELEVATED in Type 2 - Vascularity: REDUCED in type 2, INCREASED/NORMAL in type 1
68
What is, and when do you treat, subclinical hyperthyroidism?
Subclinical hyperthyroidism = subnormal TSH but normal T4 and T3 WHEN TO TREAT? - TSH <0.1 - Multinodular goitre - Coexisting AF or osteoporosis
69
How do you treat subclinical hyperthyroidism?
Thionamides for young patients with subclinical Graves Radioiodine if older or multinodular goitre Surgery if LARGE multinodular goitre
70
What are the features of a thyroid storm?
``` Fever (usually >40) and diaphoretic Tachycardic and AF CCF and APO Proximal myopathy Dehydration and shock ```
71
What are precipitants of a thyroid storm?
Infection/trauma Radioiodine Noncompliance
72
What is the management of thyroid storm?
HDU/ICU Beta Blocker: IV propranolol to aim for HR 90bpm then oral 40-80mg TDS PTU preferred to CBZ as it is more rapid Lugol's drops (BUT if used >=4 days then will worsen the thyrotoxicosis) Cholestyramine will increase T4 clearance Hydrocortisone will block thyroid output and T4-->T3 conversion Plasmapheresis
73
What medication must you AVOID in a thyroid storm?
Aspirin Avoid it to prevent decreased protein binding and subsequent increases in free T3 and T4 levels
74
What demographic tend to get thyroiditis?
Females | Aged 30 - 50yrs
75
What is the implied pathogenic trigger for thyroiditis?
Viral infection
76
What genetic association with thyroiditis?
HLAB35 in 75%
77
What clinical features for thyroiditis?
PAINFUL goitre Jaw pain and hoarse voice Constitutional symptoms and fevers Symptoms of thyrotoxicosis for 2-6 weeks
78
What lab findings are expected with thyroiditis?
Elevated ESR and CRP | Elevated T3/T4 with REDUCED TSH hypothyroid phase happens post thyrotoxic phase
79
What treatment for thyroiditis? | What complications of thyroiditis?
Aspirin and NSAIDs Prednisolone Thyroxine if a prolonged hypothyroid phase 10% get permanent hypothyroidism
80
What are the clinical features for Lymphocytic and Post Partum Thyroiditis?
PAINLESS goitre | NORMAL ESR
81
What lab findings are expected for Lymphocytic and Post Partum Thyroiditis? What biopsy findings?
Anti-TPO Ab (ESPECIALLY IF POST PARTUM!) Low-zero uptake on US Biopsy: lymphocytic infiltration
82
What is the clinical course of Lymphocytic and Post Partum Thyroiditis?
Hyperthyroid for 2-4 weeks | Hypothyroid from 4-12 weeks
83
How do you treat Lymphocytic and Post Partum Thyroiditis?
Symptoms management with beta blocker Treat with thyroxine if prolonged hypothyroidism
84
Presentation and treatment of Riedel's Thyroiditis?
RARE Occurs in middle aged women ? part of IgG4 Systemic Disease Usually presents with fixed painless thyroid mass Treat with surgery, steroids and TAMOXIFEN
85
What associated features are with Riedel's Thyroiditis?
Horners Carotid stenosis Hypoparathyroidism
86
THROID & DRUGS: Lithium?
Lithium can cause both hypothyroidims and thyroiditis
87
THROID & DRUGS: Immune checkpoint inhibitor antibodies?
Ipilumumab & Tremilimumab (anti-CTLA4) - central hypothyroidism (5%) - thyroiditis (2%) Nivolumumab & Pembrolizumab (anti-PD1) - thyroiditis (4%) - central hypothyroidism (<1%)
88
THROID & DRUGS: Alemtuzumab?
Alemtuzumab (anti-CD52) - Graves (15%) - Thyroiditis
89
THROID & DRUGS: Interferon-Alpha?
Interferon alpha - anti-TPO and anti-Tg (15%) - Hypothyroidism (5%) - Graves
90
THROID & DRUGS: Tyrosine kinase inhibitors?
Hypothyroidism (25%)
91
THROID & DRUGS: Bexarotene?
Bexarotene (RXR agonist) - central hypothyroidism (impairs TSH release) and increases T4 clearance

RACP Written 2018 (167 decks)

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