Disorders of the Thyroid Gland Jean Abigaile Caringal, MD,FPCP,DPSEDM

THYROID GLAND L- Thyroxine (T4) vs Triiodothyronine (T3)

 R & L lobes connected by

an isthmus

 Follicular cells produce

iodine-rich T4 and T3
(T4 > T3)

 Thyroid medullary C cells

(parafollicular cells)
produces calcitonin
(calcium-lowering
hormone)

L- Thyroxine (T4) Triiodothyronine (T3)

 Produced only in the thyroid  80% are from peripheral
 gland  conversion of T4
 7-day half life  One-day half life
 99.97% protein-bound (TBG,  99.7% protein-bound
 pre-albumin, albumin)  3X more potent than T4
1. Active transport of iodide  Only free hormones are
2. Organification of iodide active
(MIT/DIT)
3. Coupling (T4/T3)
4. Release

THYROID HORMONE

Effects of T4 and T3

 increase basal metabolic rate

 increase protein, lipid and glycogen synthesis
 essential for growth, development & fertility
(permissive effect)
 increase cell responsiveness to catecholamines

Dr. S. Kho
Disorders of the Thyroid Gland Jean Abigaile Caringal, MD,FPCP,DPSEDM

THYROID FUNCTION TESTS

Disorders/Anomalies?

• Too much  thyrotoxicosis/hyperthyroidism

• Too little amount  hypothyroidism

• Primary? Secondary/Central?

• Too big in size  goiter

• Lumps and bumps: cysts, Cretinism

: nodules - benign/malignant

HYPOTHYROIDISM
 Deficiency = hypothyroidism
 Defect can be at (TRH, TSH = secondary or central
hypothyroidism) and (thyroid gland = primary hypothyrodism)
 Iodine deficiency - most common cause worldwide.
 In areas of iodine sufficiency:
o Autoimmune disease (Hashimoto's thyroiditis) and iatrogenic
causes (treatment of hyperthyroidism) are most common.

Autoimmune hypothyroidism

 Hashimoto’s or goitrous thyroiditis or atrophic thyroiditis -

autoimmune process: lymphocytic infiltation and thyroid cell
destruction
 (+) anti-thyroglobulin and (+) anti-TPO antibodies; some with TSH-
R blocking antibodies
 Goiter – hallmark of classic Hashimoto’s disease; firm, smooth or
bumpy
Disorders of the Thyroid Gland Jean Abigaile Caringal, MD,FPCP,DPSEDM

HYPERTHYROIDISM

 State of thyroid hormone excess = Thyrotoxicosis

 can be due to excess TRH  TSH  thyroid gland
(Secondary hyperthyroidism)
 Autoimmune disease – Excess thyroid hormone from the thyroid
gland (Primary hyperthyroidism)

Hypothyroidism: treatment

 Daily replacement dose of levothyroxine at 1.6 mcg/kg BW

 Measure TSH level after 6-8 weeks
 Levothyroxine should be taken on an empty stomach, 30 minutes
to 1 hour before breakfast. Once full replacement is achieved and
TSH levels are stable, follow-up measurement of TSH is
recommended at annual intervals and may be extended to every
2-3 years.
 Because T4 has a long half-life (7 days), patients who miss a dose
can be advised to take two doses of the skipped tablets at once. Primary and Secondary Hyperthyroidism

 Treated with antithyroid drugs (Thionamides)

Myxedema Coma Thyrotoxicosis without Hyperthyroidism

 Severe, long- standing hypothyroidism: reduced level of  No role for antithyroid medication (Thionamides)!!!
consciousness and sometimes associated with seizure.
 Elderly and is usually precipitated by factors that impair
respiration, such as drugs, pneumonia, CHF, MI, GI bleeding, CVA.
 Hypoventilation: hypoxia, hypercapnia; hypoglycemia and
dilutional hyponatremia
 Treatment: thyroid hormone, supportive treatment, treat the
precipitating factor

Case 1.

20-year-old female found to have a mild diffuse goiter on routine

physical examination. She is otherwise clinically euthyroid.

 What would be a good screening test to rule out thyroid function

abnormality?
Answer: TSH

 TSH came back normal. What is the next test?

Answer: No further test necessary. She is euthyroid.

 TSH came back elevated. What is the next test?

Answer: T4 is adequate unless you are suspecting a binding
hormone abnormality then a free T4 is a better test.

 TSH came back elevated and T4 is low. What is the diagnosis?

Answer: Primary hypothyroidism.
Disorders of the Thyroid Gland Jean Abigaile Caringal, MD,FPCP,DPSEDM

Graves’ Disease Treatment of Graves’ Disease

 Representing 60 – 80% of all cases of thyrotoxicosis 1. Medical

 Risk factor: genetics, smoking, sudden increases in iodine intake,
• Anti-thyroid drugs, Thionamides: propylthiouracil (PTU),
post-partum
carbimazole, methimazole or thiamazole
 Autoimmune (thyroid stimulating antibodies/TSI) stimulation of
 Check symptoms and Free T4 level after 4 weeks initially.
TSH receptors; TPO antibodies
• TSH often remains suppressed for several months
 Diffusely enlarged thyroid gland, commonly with a thrill or bruit
• Common side effects: rash, urticaria, fever and arthralgia
 Exophthalmos/ophthalmoplegia (30%)
• Major side effects: hepatitis, SLE-like syndrome,
 Dermopathy (<5%)
agranulocytosis (<1%)
 Thyroid acropachy (<1%)
• Beta-blockers alleviate adrenergic symptoms; propranolol
 TSH suppressed
blocks the conversion of T4 to the more active T3
 T3 is increased disproportionately more than T4 • Non-dihydropyridine calcium channel blockers may be used if
 In 2-5%: T3 toxicosis beta-blockers are contraindicated
 Thyroid RAI uptake (RAIU) is high or normal
 Uptake on RAI scan is diffused and homogenous 2. Radioactive iodine (131I treatment)

• Using the destructive effects of its radioactivity

• Takes a few weeks to months before efficacious
Thyroid scan • May lead to RAI thyroiditis; make sure patient is euthyroid
before RAI Therapy

3. Surgical

• Subtotal or near-total thyroidectomy – for patients who

relapse, allergic to thionamides, goiter is very large
• Make sure patient is euthyroid prior to surgery
• Major complications: bleeding, laryngeal edema,
hypoparathyroidism, damage to recurrent laryngeal nerves

Graves’ Disease Other causes of Thyrotoxicosis

• Destructive thyroiditis

- true hyperthyroidism is absent, low RAIU, Tg levels

increased

• Acute

• Subacute

• Chronic

• Thyrotoxicosis factitia – exogenous thyroid hormone use

• Ectopic thyroid tissue (Struma ovarii)

• TSH-secreting pituitary adenoma – rare

• Toxic multinodular goiter and toxic adenoma

Disorders of the Thyroid Gland Jean Abigaile Caringal, MD,FPCP,DPSEDM

THYROIDITIS TOXIC MULTINODULAR GOITER AND TOXIC ADENOMA

• Mutation of thyroid follicles

• High T4 &/or T3 with suppressed TSH
• RAI scan shows hot (autonomous) nodule/s with the normal gland
having decreased uptake
• Ultrasound of the thyroid is often helpful to determine size and
number of nodules

• 25 yo, female
• Anterior neck mass
• Occasional palpitation, tremors
• TSH – 0.31 (0.27-4.2)
• ? viral etiology • FT4 – 24 (12-22)
• Preceded by URTI
• Tender enlarged thyroid gland
• Leakage of T4 & T3 due to inflammation
• RAI uptake is low (<2 - 4%)
• Thyrotoxicosis is often followed by hypothyroidism before full
recovery

Autonomous nodule

Multinodular toxic
Subacute thyroiditis / de Quervain’s thyroiditis goiter
• Treatment directed towards pain relief which includes aspirin or
steroids
• Beta-blockers are given for hyperadrenergic symptoms
• Antithyroid medications has no role
Toxic adenoma/ toxic multinodular goiter: treatment
• Thyroid hormone for symptomatic patients during the
hypothyroid phase  RAI is preferred; preparation and precautions similar except post-
therapy hypothyroidism is rare
 Antithyroid and other medical therapy are useful but has a high
Silent thyroiditis / Painless thyroiditis recurrence when stopped
 Surgery for larger nodules and MNG esp. if with breathing or
• Pattern is similar to subacute thyroiditis except that there is is swallowing problems
little or no pain/tenderness.
• Etiology unknown
• A variant of this is post-partum thyroiditis
 2-6 months after delivery
 may recur on subsequent pregnancies
 Treatment: beta-blocker
Disorders of the Thyroid Gland Jean Abigaile Caringal, MD,FPCP,DPSEDM

THYROID STORM

Diagnostic Criteria for Thyroid Storm Work-up of nodules

 Thyroid Ultrasound
o Cyst (simple cyst or a complex cyst)
o Nodule (single or multiple)

Treatment of thyroid storm

• Treatment aims to correct both the severe thyrotoxicosis and the

precipitating illness and to provide general support.
• PTU is preferable to methimazole because it blocks conversion of
T4T3
• SSKI or the equivalent as Lugol’s solution acutely retards the
release of preformed hormone
• Dexamethasone or hydrocortisone (100 mg every 8 hours)
• Beta-blocker or calcium-channel blocker

GOITER

• Enlarged thyroid gland • Fine needle aspiration biopsy of all nodules > 1 cm except hot
• Can be HYPO-, HYPER-, EU thyroid nodules
• Thyroid function tests should be performed and treatment is • Only patients with low TSH get a RAI scan
directed towards the cause • Simple cysts are usually aspirated
• Iodine or thyroid hormone replacement has variable effects • Complex cysts should be aspirated under UTZ to make sure solid
component is biopsied

Nontoxic Multinodular Goiter

Thyroid scan
Disorders of the Thyroid Gland Jean Abigaile Caringal, MD,FPCP,DPSEDM

Nontoxic MNG: treatment Other Thyroid Cancers

• T4 therapy – response is variable, appropriate candidates are
young patients; TSH decreased to subnormal but detectable level.
• Surgery: Near-total or total thyroidectomy
• 131I treatment – reduction of thyroid volume; appropriate for
elderly patients who are poor candidates for surgery, or TSH
suppression is not advisable
• Anaplastic – extremely poor prognosis; no real good treatment
(usually only palliative)
• Lymphoma – rapid growth; radiation and chemoTX rather than
surgical
• Medullary (C cell) CA – may be familial; part of MEN 2A and MEN
2B
• No role for RAI or TSH suppression in these types

THYROID CANCER
Other Pearls of Thyroid Diseases
• Most common malignancy of the endocrine system
• Differentiated • Know “apathetic hyperthyroidism”, some elderly patients present
 Papillary – 80-90% with sluggishness and depression rather than hyperactivity
 Follicular – 5-10% • Know that there can be a transient mild hyperthyroidism in
• Poorly Differentiated pregnancy at the peak of B-hcg (10-14 wks); TSH slightly
• Undifferentiated (Anaplastic) decreased
• Thyroid C Cells – Medullary carcinoma - <10% • Know that TBG goes up during pregnancy(2nd trim.) thereby
• Mixed medullary-follicular carcinoma leading to total T4 but normal Free T4; TSH normal
• Others: • Know that in sick patients with nonthyroidal illness, there may be
 Lymphomas – 1-2% “sick euthyroid syndrome” most commonly a ”low T3 syndrome“
 Sarcomas
 Metastases

Well-differentiated Thyroid Cancer

Papillary Follicular
• Psammoma bodies, cleaved • Distinction of CA is based
nuclei with an “Orphan on the presence of
Annie” appearance invasion
• Non-encapsulated • Encapsulated
• Spreads locally and to the • Spreads hematogenously
lymphatics  Less favorable prognosis
• Better prognosis

• Staging is based on TNM (Size, Nodes and Metastasis)

• Prognosis also depends on age (worse if > 45 y/o); sex (worse in
males)
• Treatment is surgical followed by RAI ablation (majority) then,
suppressive doses of thyroid hormone
• Follow up for recurrence include RAI whole body scan and
thyroglobulin levels

| JL Deomampo

Medisina 2018