Thyroid disease Flashcards

1
Q

Overt hypothyroidism - diagnosis

A

TSH elevation with fT4 reduction.
TSH >10imu/L regardless of fT4.

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2
Q

Hypothyroidism affect on miscarriage

A

Inc risk miscarriage
Inc preterm birth
Less consistent - LWB and fetal death
Increased GHTN/PET
Adverse neurological outcomes in offspring (3 observational trials confirm)

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3
Q

Thyroid antibodies

A

Inc risk of developing PP thyroiditis
Possible PPROM

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3
Q

Pregnancy affects on thryoxine homeostasis

A

Inc demand for thyroxine (30-50%) in early pregnancy
E2 induced inc production of TBG (and TBG increases half life)
Increased iodine renal excretion.
hCG and TSH homology - inc T4 production

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4
Q

Hyperthyroidism

A
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5
Q

Lipiodol

A

iodinated contract
Wolff-Chiakoff, high iodine load inhibit thyroid hormone synthesis. Very high iodine levels inhibit thyroid peroxidase and therefore thyroglobulin iodination can’t occur.
Transient hyperthyroidism much rarer Jod-Basedow effect - only occurs in “abnormal thyroids” i.e. people with Grave’s underlying as they are unable to respond appropriately to the negative feedback.

Selfi study - SCH developed in 38%; the majority (96%) were mild (TSH 4-10 mIU/L) and most developed SCH by week 4 (75%). Three participants met the current treatment guidelines (TSH > 10 mIU/L). Thyroxine treatment of mild SCH tended to improve pregnancy success (P = .063). Hyperthyroidism (TSH < 0.3 mIU/L) occurred in 9 participants (5%).

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6
Q

Definition of subclinial hypothyroidism

A

TSH concentration above the upper limit of normal range and a serum free T4 (thyroxine) concentration within the normal range.
Above 97.5th percentile or >4.12mIU/L used depending on lab ranges.
95% of individuals without evidence of thyroid disease were found to have a TSH level of <2.5mIU/L

First trimester threshold usually reduce by 0.5mIU/L and total T4 measured due to changes in T4 binding mainly to TGB.

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7
Q

Untreated SCH and miscarriage

A
  • It is recommended to counsel women that SCH is not associated
    with an increased risk of miscarriage (strength of evidence:
    B; strength of recommendation: moderate).
  • It is recommended to counsel women that a TSH levels between
    2.5 and 4.0 mIU/L is not associated with an increased risk of miscarriage (strength of evidence: B; strength of
    recommendation: moderate).
    ASRM guideline
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7
Q

Guideline advice for TSH screen in women attempting pregnancy

A

ASRM - universal screening not recommended, including those undergoing ART. “aggressive case finding recommended”
Non-pregnant thresholds should be used. This includes people with irregular menstrual cycles.

ATA - evaluation of serum TSH concentration is recommended for all wmen seeking care for infertility.

RANZCOG - Screening for subclinical hypothyroidism or TPO antibodies, and subsequent treatment with thyroxine is not recommended prior to pregnancy or in pregnancy

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8
Q

SCH and infertility

A

There is insufficient evidence to counsel women that SCH is
associated with infertility (strength of evidence: C; strength
of recommendation: weak). _ ASRM

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9
Q

SCH and pregnancy outcomes

A

There is moderate-quality evidence that SCH during pregnancy
is not associated with adverse obstetric outcomes.
Although some studies show an increased risk, particularly
with testing later in pregnancy, higher-quality studies with
preconception and first-trimester testing predominately do
not show an increased risk. There is insufficient evidence
that TSH levels of 2.5–4 mIU/L are associated with adverse
obstetric outcomes.

It is recommended to counsel women that SCH is not associated
with increased obstetric risk (strength of evidence B;
strength of recommendation: moderate).

It is recommended that women be counseled that SCH in
pregnancy is not associated with adverse neurodevelopmental
outcomes in offspring (strength of evidence: A;
strength of recommendation: strong).

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10
Q

Does treatment of SCH improve pregnancy outcomes

A

It is not recommended to treat pregnant women or women
desiring pregnancy who have a diagnosis of SCH with levothyroxine,
as treatments have not been demonstrated to
reduce pregnancy loss nor to improve clinical pregnancy
or LB outcomes (strength of evidence B; strength of recommendation: moderate).
Thyroid-stimulating hormone and T4 levels should be
tested in patients with signs or symptoms of hypothyroidism
(including irregular menstrual cycles) rather than in all
patients with infertility (strength of evidence: B; strength of
recommendation: moderate).

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11
Q

TAI screening in infertile populations and early pregnancy

A

There is intermediate-quality and conflicting evidence that
is insufficient to suggest an association between thyroid
antibodies and miscarriage.
There is weak evidence that women with RPL have higher
rates of positive thyroid antibodies on the basis of limited
case-controlled studies.
There is insufficient evidence to recommend screening for
TAI in infertile or pregnant women.
Recommendation
It is not recommended to screen for TAI in asymptomatic
women with infertility or pregnancy. Targeted screening
may be considered in women with a history of RPL
(strength of evidence C; strength of recommendation
weak).

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12
Q

Overall conclusion of SCH screening and treatment in infertility and pregnancy

A

Most of the evidence advocating for screening and treatment
of SCH in women with infertility or pregnancy is based on
low-quality observational data and one clinical trial, which
should be withdrawn because of significant concerns over
data integrity. On the basis of current evidence, it is not recommended to screen or treat for asymptomatic SCH in women
with infertility or pregnancy.

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13
Q

Thyroid physiology

A

Paraventricular nucleus in hypothalamus –> TRH –> ant pit –> thyrotrophs release TSH –> thyroid gland –> T3 and T4 (transported in blood stream via Thyroid binding globulin (TBG).
Thyroid hormone affects:
Bone growth and maturation
Muscular function and development
Cellular function - increases basal metabolic rate, increases O2 usage, lipolysis, glycolysis, gluconeogenesis (breaking stuff down), LDL uptake
Promotes normal cardiac output
Promotes normal nerve development in brain - inc synapses, mylenation, dendrites
Promotes GI motility and function
Promotes skin hydration

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14
Q
A

Sits anterior neck, inferior to larynx, butterfly shape, consists of thyroid follicles - functional unit of gland.

TSH binds onto TSHreceptor (G-coupled receptor) on thyroid follicles. GDP –> GTP after binding –> activates effector enzyme coverts ATP –> cAMP –> Protein kinase A –> phosphorylates transcription factor –> stimulates genes –> mRNA –> protein synthesis –> thyroglobulin protein released into lumen of thyroid.

Iodide transported from bloodstream through thryoid follicles into luminal space of thyroid.
Thyroid peroxidase enzyme (TPO) converts iodide to iodine and then TPO iodinates the thyroglobulin.
Thyroglobulin can sit within lumen containing a store of thyroid hormone
Iodinated thyroglobuin protein is moved back into thryoid follicle and lysosomes break it into thyroid hormones.
Creates T4 - thyroxine and T3 triodothyronine (thyorid hormones).
They act like steroid hormones (not water soluble) so need transportation within a binding protein
–> 70% bound to Thyroxine binding globulin (TBG) - can transport both T3 and T4
–> 30% bound to albumin
TBG synthesised in liver and production increased by oestrogen.
Thyroid receptors on cells allow transport of T4/T3 into cells.

15
Q

Thyroid disease

A
16
Q

Thyroiditis

A

Thyroiditis: Diverse group of disorders characterised by thyroid inflammation.

17
Q

Thyroid embryology

A

Week 3 - endodermal cells proliferative creating thyroid diverticulum
Week 5 - migrates caudally crossing anterior to hyoid and laryngeal cartilage. Remains attached to tongue - thyroglossal duct. Forms into right and left lobe and follicular elements form.
Medial part forms from floor of pharynx and tongue, lateral from branchial plexus.
Week 7 - reaches final destination
Week 10 - thyroglossal duct degenerates
Week 12 - functionally mature