Teaching Clinic - Hypothyroidism Flashcards by Benjamin Chan

Where is T3 and T4 from?

• All the T4 in the circulation is derived from thyroid secretion whereas only 20% to 30% of circulating T3 is of thyroidal origin
• Normal mean daily T4 secretion is between 100 and 125 nmol (80 - 100 ug) which is entirely derived from the thyroid
• At least 2/3 of daily mean T3 production is derived from peripheral conversion of T4
• In situations of environmental iodine deficiency or diseases causing a lowered intrathyroidal iodine pool, thyroidal secretion of T3 is increased

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Thyroid function test and what is the most important hormone tested?

Approx 99.98% T4 and approx 99.7% of T3 bound to specific plasma proteins (TBG, TBPA and albumin)
Log/linear inverse relationship between serum TSH and free T4 concentration produced by -ve feedback inhibition of TSH secretion by thyroid hormones
If free T4 is slight lowered, TSH will be increased greatly (TSH is very sensitive)

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What is used to screen for primary thyroid dysfunction? What are the limitation of using TSH as a screening test?

TSH is used to screen for primary thyroid dysfunction

Limitations:
Assume that hypothalamic pituitary function is intact and normal
Assume that patient’s thyroid status is stable

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What thyroid test should be used for patients with stable vs unstable thyroid status?

STABLE thyroid status:
- TSH more sensitive indicator of thyroid status than FT4

UNSTABLE thyroid status:
- FT4 is a more reliable indicator of thyroid status than TSH

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How to classify hypothyroidism based on TSH and T4?

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Hypothyroidism in adults: S/S

Slow relaxation phase in reflexes

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Risk factor of hypothyroidism

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Case 1
Secondary amenorrhoea for 8 months to private gynaecologist
No visual disturbance
Mild weight loss = intentional (ACEi) vs unintentional
Weight gain = rapid -> thinking Cushing’s; (PCOS)
Hyperprolactinemia

Hypothalamic problems
Pituitary problems
Thyroid problems
Medications which may interfere with hormonal cycle (HRT)
R/O pregnancy

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Menarche 12, regular cycle
Uncomplicated pregnancy at 28
Barrier method for contraceptives
PMH: nil
DH: Nil
FH: mother ?hx of thyroid problem

Private blood tests in gynaecologist showed prolactin 1080 mIU/L

What are the pathological DDx for hyperprolactinemia?

Drugs-induced - first thing to r/o:
a. Dopamine: anti-psychotics, antiemetics, H2, methyldopa
b. Antiemetics: metoclopramide, cimetidine, domperidone
c. Others: estrogen
Prolactinoma
Stalk effect
Renal failure (decreased prolactin clearance)
Hypothyroidism
Chest trauma
Physiological: Pregnancy / lactation

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How do we take a non-stress prolactin level?

Take the blood 15 minutes after putting needle in as prolactin may be raised during stress

This is important as venipuncture may cause stress = increase in prolactin

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Aetiology of hyperprolactinemia

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● Pulse 68, SR
● Dry skin
● No galactorrhea
● Small firm goiter
Ix

● PRL raised 1100 mIU/1 (up to 500)
● Thyroid function
○ Elevated TSH
○ Low T4

What type of hypothyroidism is this? What could be the cause?

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How do we diagnose hypothyroidism?

Dx of HypoT
● Elevated TSH and low fT4 suggest primary hypoT
● Check anti-TPO and anti-Tg Ab
● USG is NOT required in absence of additional clinical indications (goiter or palpable nodule)
● Thyroid scan is NOT useful and not necessarily: primarily used in hyperthyroidism

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What is Hashimoto Thyroiditis?

Leading cause of hypothyroidism in iodine sufficient areas
Autoimmune
M/F 1:15
May present with or w/o goitre, usually painless
Thyroid Ab titres usually measurable
Histology: Diffuse lymphocytic infiltration with lymphoid follicles, plasma cells and disruption of thyroid follicles
May be associated with other autoimmune diseases

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What is thyroperoxidase autoantibody?

Initially described as anti-microsomal autoantibody
• TPO is involved in thyroid hormone synthesis at the apical pole of the follicular cell
• The most sensitive test for detecting autoimmune thyroid disease
• Present in >95% of subjects with Hashimoto’s thyroiditis and around 85% subjects with Graves’ disease

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What is thyroglobulin autoantibody (TgAb)?

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What is the function of TRAb (thyroid releasing antibody)?

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What is the treatment of hypothyroidism?

Levothyroxine
Generally first-line:
- Low cost
- Dose consistency
- Low risk of allergic reactions
- Potentially fewer cardiac adverse effects than T3 production

Life-long replacement with thyroid hormones
Exceptions: transient hypothyroidism due to subacute thyroiditis and drug-induced hypothyroidism
- Plasma half-life of T4 is ~7 days, once daily dosing results in a steady state being reached in about 6 weeks

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Practical tips on giving thyroxine replacement

Practical tips on giving thyroxine replacement
• Typical full replacement doses in adults are 1.6 mcg/kg/day
• Lower starting doses (25-50 mcg/day) might be used in older individuals, those with mild hypothyroidism or those with untreated cardiovascular disease
• T4 primarily absorbed in jejunum
• About 70% of the dose administered is absorbed on an empty stomach
• Should be taken on an empty stomach about 30 minutes before breakfast
• Bioavailability can vary between different brands of T4 formulations
• Calcium, iron, antacids, proton pump inhibitors, anticonvulsants, rifampicin increase T4 requirement by different mechanisms (absorption or metabolism)

When taking calcium, separate the timing for 4 hours as it may affect absorption of T4

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Hypothyroid patient with thyroxine replacement
BW = 60 kg
Started T4 at 100 mcg daily
How will you monitor her treatment response?

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Monitoring of T4 Replacement (T4 half life is 7 days)
* Adequacy of treatment monitored by TSH
* Measure FT4, TSH 4-6 weeks after commencing treatment and monitor and titrate T4 dose until a normal TSH is reached.
E.g. increase T4 dose by 12.5025ug/day if TSH remains above target
* Aim to keep TSH 0.5 to 2.5 - 3 mlU/I.
* Stable patients, measure TSH and FT4 annually.

Hypothyroid patient with thyroxine replacement
Thyroid function normalised and remained normal for 2-3 years

Recent blood tests showed

TSH 15 mIU/L (N: 0.35-4.8)
FT4 12 pmol/L (N: 12-23)

What happened? What are the common reasons for abnormal TSH levels on a previously stable dosage of thyroid hormone?

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Common reasons for abnormal TSH levels on a previously stable dosage of thyroid hormone
* Non-adherence to thyroid hormone regime
* Decreased absorption of thyroid hormone
* Taking thyroid hormone with food
* Taking thyroid hormone ≤4 hours of calcium, iron, soy products, or aluminum-containing antacids
* Given medication that decreases absorption of thyroid hormone e.g. cholestyramine, colestipol, orlistat, or sucralfate
* Significant weight change
* Pregnancy
* Changing in the formulation of thyroid hormone replacement
* Started on medications e.g. some anti-epileptics

Hypothyroid patient on thyroxine replacement. Patient is pregnant, what do you need to monitor and manage?

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Issues around pregnancy
* Goal of preconception TSH: lower reference limit to 2.5mlU/L
* Early dosage adjustment: preemptively increase T4 dose by 30% and inform their clinicians promptly upon confirmation of pregnancy
* Typical strategy: increasing dose from once daily to nine doses per week (doubling the daily dose two days each week)
* Regular monitoring of TFT every 4 weeks with dosage adjustment
* For women during pregnancy: aim
* TSH <2.5mlU/L (1st trimester)
* TSH <3.0mlU/L (2nd-3rd trimester)
* Return to pre-pregnancy dosage of T4 after delivery

Case 2:
● 45/M non-smoker, non-drinker
● Referred by GP because of impotence
● Diagnosed T2DM for 7mo
● FBG 11 mmol/L, HbA1c 8.5

Investigations
WBC 11.951 ; ANC 8.76 T
LRFT, CaP04, RG unremarkable
ESR 88 mm/hT; CRP 7.6 ng/mLT
CXR clear; XR neck - no abnormal soft tissue or gas density
Blood culture, urine culture and NPA for resp virus all negative
TSH 0.1 mIU/L (N: 0.35 - 4.8)
fT 26 pmol/L (N: 12 - 23)
What was the likely clinical diagnosis? What further investigation may support your diagnosis?

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Biochemical picture: Primary hyperthyroidism

Is it from increased production from thyroid or due to increased release of pre-formed thyroid hormones due to thyroid destruction?

Technetium thyroid scan: Primary increase in synthesis (toxic nodule, TMG, Grave’s (diffuse increase vascularity on U/S), destructive thyrotoxicosis (no increase in vascularity on U/S)

What is subacute thyroiditis?

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Painless thyroiditis DDx

- Hashimoto thyroiditis - Atrophic thyroiditis - Atrophic thyroid - Post-partum thyroiditis - Variable prognosis depending on residual thyroid reserve

How does the thyroid hormone change along with subacute thyroiditis?

What is subclinical hypothyroidism?

Subclinical hypothyroidism • High TSH with normal fT4 levels • Investigations: thyroid antibodies • Management in non-pregnant adults • Assess lipid levels and hypothyroid symptoms • Regular TFT monitoring • Start T4 replacement if persistent TSH >10 mlU/L

When do we treat hypothyroidism?

Normal TSH: no need for intervention TSH >10 mIU/L: treat with T4

Case 3: 48/F non-smoker Presented to A&E with ankle swelling for several months Mild shortness of breath on exertion; no chest pain Malaise and lethargy; generalised aches and pains in muscles ● DH: Adalat retard 20 mg qd (nifedipine) ● FH: brother has IHD ● PMHx: HT x 1 year, hyperthyroidism x 15 years treated with RAI ○ Ask hypothyroidism hx PE ● P 58/min, SR, BP 100/70 ● JVP not elevated ● Apex displaced lateral 2 cm ● HSDNO, chest clear ● Bilateral ankle edema ECG: Sinus bradycardia CXR: cardiomegaly Creatinine kinase 1080 u/L What is the approach to elevated creatinine kinase?

- Heavy exertion recently - Fall - Intramuscular injection - Hypothyroid myopathy (CK is elevated) - Inflammatory myositis (far-fetched) Check troponin T to rule out cardiac disease (causes elevated CK)

What are the DDx for generalised aches and pains in muscles?

Myalgia vs muscle injury: -

Patient with Hx of radioiodine Blood test TSH 88 mIU/L (N: 0.35-4.8) fT4 5 pmol/L (N: 12-23) What is the Dx? What should be done?

Post-radioiodine hypothyroidism Started thyroxine replacement

Post-radioactive hypothyroidism

Transient: 3.5 to 28% Pre anti 10 to 15% in first 2 years, then around 3% per year Requires long-term follow-up

Post-thyroidectomy hypothyroidism - What are considerations in the management plan? Do you just check T4 replacement?

Post-op parathyroidism: (Calcium phosphate) Patients with differentiated cancer of thyroid, we try to suppress T4 so they have a lower chance of recurrence (clarify TSH target, whether they need T4 suppressive therapy?)

Case 4 • M/45; non-smoker and non-drinker • Referred by private practitioner for erectile dysfunction • Type 2 diabetes dx 7 months ago: FG 11 mmol/L, HbA1c 8.5%

Test testosterone (gonadal status)

HbA1c 7.4% LH 0.3 mIU/L, FSH 0.5 mIU/L, Testosterone 5 mmol/L (N: 10-35) Defect is in hypothalamus Pituitary / hypothalamus is abnormal If high LH, FSH = gonads are abnormal TSH, fT4, central hypothyroidism, 9 am cortisol level (50) = low Short synacthen test Baseline ACTH 6 pg/mL Cortisol = 30 mmol/L (0’); 75 nmol/L (30’); 100 nmol/L (60’) What is the cause of this hormonal profile? What are the likely MRI findings?

Hypopituitarism MRI: empty sella (due to damage from RT)

Post-radiotherapy Hypopituitarism - Treatment - Monitoring

Commenced on cortisol, thyroxine & testosterone replacement Start cortisol replacement first before thyroxine!!!! - Rate of turnover of cortisol is decreased in hypothyroidism because of reduction in 11 beta hydroxysteroid dehydrogenase activity = may precipitate adrenal crisis if you do it the other way round (exaggerate cortisol insufficiency) Monitor T4, don’t monitor TSH since the pituitary is gone (aim T4 to mid-level or even higher)

Case 5 M/74 Admitted for non-specific dizziness in the recent few months, worsened in the recent 1-2 weeks Blood test on admission - Na 111 mmol/L - K 3.8 mmol/L - Cr 83 umol/L How do you approach the investigation of hyponatremia?

R/O triggers Volume status: Hypervolemic then treat Plasma Osm and urine Osm Want to r/o hypocortisol and hypoACTH Pseudohyponatremia: - Hypertriglyceridemia - Hyperlipidemia - High protein Rule out: - GI causes, e.g. vomiting / diarrhoea - Renal causes, e.g. diuretics Clinically euvolemic

Plasma osmo 235; urine Osm 542; urine Na 32 mmol/L 9am cortisol 37 nmol/L TSH 0.51 mIU/LL (N: 0.35-4.8), fT4 9.5 pmol/L (N: 12-23) What Ix should be done?

LH, FSH, Testosterone, Prolactin, Cushingoid, acromegaly MRI pituitary

What was seen on MRI pituitary

Tenting of optic chiasm Suprasellar extension Pituitary macroadenoma Do a visual field perimetry = bitemporal hemianopia

What is non-thyroidal illness syndrome (NITS)?

Case 6 • F/65 • CA vulva (melanoma) requiring radical vulvectomy and lymph node dissection • Put on nivolumab since Dec 2023 • Baseline TSH, T4 normal • Developed fever, tachycardia and painful neck swelling in the same month What Ix to do?

Thyroid scan

Case 6 * F/65 * CA vulva (melanoma) requiring radical vulvectomy and lymph node dissection * Put on nivolumab since Dec 2023 * Baseline TSH, T4 normal * Developed fever, tachycardia and painful neck swelling in the same month What is the possible cause?

Thyroid will be destroyed by immune-checkpoint inhibitors --> destructive thyroiditis (with presentation of mostly hypothyroidism, some having preceding transient thyrotoxic phase) Could lead to hypophysitis ICI = upregulates T-cell response

Classes of ICI

Classes of ICl • First FDA approval in 2011: ipilimumab for melanoma • Anti-cytotoxic T lymphocyte antigen 4 (anti-CTLA4): ipilimumab • Anti-programmed cell death-1 (anti-PD-1): nivolumab, pembrolizumab

What causes immune related adverse events

Traditional cytotoxic chemotherapy or molecular target therapies rarely cause endocrine dysfunction Thyroiditis, hypophysitis, DM, primary adrenal insufficiency, hypoparathyroidism Most commonly thyroid and pituitary: - Rich vascularisation: more suspecitivle to contact with activated T lymphocytes - Direct expression of CTLA-4 in the pituitary or of PD-1/PD-L1 in the thyroid

How to differentiate between thyroiditis and Graves’ disease

Anti-TSHR (Only in graves) Technetium-99m thyroid scan (increased uptake = graves, decreased uptake = thyroiditis) Presence of thyroid eye disease (Only in graves)

Why will there be increased endocrine IRAEs?

More and more cancers More patients are prescribed immune-checkpoint inhibitors

Routine monitoring for endocrine IRAEs

- Glucose (immune-checkpoint associated DM), electrolytes (Na, K, Ca), TSH, fT4, 8-9 am coristol - At baseline - Every drug infusion for 6 months - Every 2-3 months for next 6 months - Every 6 months thereafter - Clinical investigation of symptoms suggestive of endocrine IRAEs

Central hypothyroidism: common causes

- Pituitary adenoma - Infiltrative disease - Radiotherapy - Immune-checkpoint inhibitors

In primary hyperthyroidism how can technetium thyroid scan be used to differentiate the cause?

Teaching Clinic - Hypothyroidism Flashcards

(49 cards)