HYPERTHYROIDISM

PROF DR NK CHOPRA
CLINICAL PROFESSOR
1
FOM SEGI UNIVERSITY
Thyroid Gland Overview

2
 Quiz Question

Question:
The thyroid gland has 2 types of cells –
1. Follicular cells, which pump in Iodine and synthesize
_______ and _____ to be released into circulation to
regulate basal metabolic rate.
2. Parafollicular "C" cells - (C for clear) - synthesize and
secrete ______ which acts to reduce osteoclastic activity.

Answer:
1. Tri-iodothyronine (T3) and thyroxine (T4)
2. Calcitonin

3
4
 Thyroid Gland - Overview

The functional units of the thyroid gland are thyroid follicles - irregular
spheroidal structures composed of a single layer of cuboidal epithelial cells
bounded by a basement membrane. The follicles are filled with a
glycoprotein complex called thyroglobulin which stores thyroid hormone
prior to secretion.

Thyroid gland has 2 types of cells:

1. Follicular cells - pump in Iodine (I-), synthesize thyroid hormone (T3, T4).
2. Para follicular "C" cells - (C for clear) - sythesize and secrete calcitonin
reduces serum Ca2+ levels.

5
 Quiz Question

Question:
The first major enzyme in the production of thyroid
hormone is called thyroid peroxidase. This enzyme is
inhibited by which two medicines?

Answer:
PTU (Propylthiouracil) and Methimazole (Tapazole)

6
 Thyroid Gland - Overview

1. Iodide (I-) is pumped into thyroid follicular cells.

2. 2I- are oxidized to I2, via thyroid peroxidase, which is inhibited by
propylthiouracil and Methimazole.
3. I2 + tyrosine forms Monoiodotyrosine (MIT) and Diiodotyrosine (DIT).
4. MIT + DIT form T3 (Triiodothyronine) and T4 (Thyroxine). Note, T3 and T4
are formed on thyroglobulin, which is stored in follicular lumen.
5. Upon TSH stimulation, iodinated thyroglobulin (T3-thyroglobulin, T4-
thyroglobulin) is taken back into follicular cells. Lysosomal enzymes degrade
thyroglobulin, releasing T3 and T4 into circulation.

I-
T3-TGB
T4-TGB T3, T4

7
 Thyroid Gland – Overview (2)
6. Leftover MIT and DIT are degraded by thyroid deiodinase, releasing I2.
Deficiency of thyroid deiodinase can mimic I2 deficiency.

7. In circulation, T3 and T4 are bound to TBG (Thyroxine-Binding-Globulin). In

hepatic failure, TBG is deficient and total T3, T4 decrease. In pregnancy, TBG is
increased, and total T3, T4 are increased.

8. More T4 is synthesized than T3, although T3 is 3-4x more active than T4. In
peripheral tissues, T4 is converted to T3 or reverse T3 (rT3), which is inactive.

9. 99% of T4 is bound, and 98% of T3 is bound to protein – only the free forms
(unbound) are active. 3 proteins which bind thyroid hormone:
- TBG – Thyroid Binding Globulin
- Transthyretin (Thyroxine Binding Prealbumin)
- Albumin

8
 Hyperthyroidism - Overview

“Thyrotoxicosis” – general term for increased levels of triiodothyronine (T3)

and/or thyroxine (T4).

Hyperthyroidism refers to causes of thyrotoxicosis in which thyroid produces

too much thyroid hormone.

Thyroid autonomy – refers to spontaneous synthesis and release of T3/T4

independent of TSH levels.

We can have 2 types of hyperthyroidism – high-uptake and low-uptake.

9
 Hyperthyroidism – Hx/PE

Goitre – diffuse +/- bruie

nodular
Gastrointestinal
Weight loss with normal or increased appetite
Hyperdefaecation
Diarrohea and steatorrhoea
Anorexia, vomiting
Cardio respiratory
Palpitation, sinus tachycardia,AF
Increased pulse pressure
Ankle edema,
Angina,cardiomyopathy,cardiac failure
Dyspnoea on exertion
Exacerbation of asthma

10
Neuro muscular
Nervousness, irritability, emotional lability, psychosis
Tremor, hyperreflexia, ill sustained clonus
Proximal myopathy
Periodic paralysis
Dermatological
Increased sweating,pruritis
Palmar erythema,spider naevi
Onycolysis, alopecia
Pigmentation,viteligo
Clubing
Pretibial myxedema

11
Reproductive
Amenorrhoea / oligomenorrhoea
Infertility, spontaneous abortion
Loss of libido,impotence
Occular
Lid retraction
Grittiness,excessive lacrimation
Chemosis
Exophthalmos
Ophthalmoplegia
Papilloedema, loss of acuity

12
Others
Heat intolerance
Fatigue
Gynecomastia
Lymphadenopathy
Thirst
Osteoporosis

13
14
15
 Hyperthyroidism - Workup

(1) Hx/PE
(2) Labs
(3) Imaging
(4) Antibody tests

16
 Hyperthyroidism – Screening Labs

1. Decreased TSH
2. Increased Free T4, Free T3

3. Other lab abnormalities:

- Mild leukopenia
– Normocytic anemia
– Elevations in hepatic transaminases and bone alkaline phosphatase
– Mild hypercalcemia
– Low albumin
– Low cholesterol

17
Hyperthyroidism – TSH, T4/T3, FT4/FT3, T3RU

TSH Total T4/T3 Free T4/T3

Hyperthyroid Low High High

Excess TBG Normal High Normal

Hypothyroidism High Low Low

Low TBG Normal Low Normal

18
 Quiz Question

Question:
The first step in sorting out the etiology of
hyperthyroidism is to decide if the cause is a “high-
uptake” or “low-uptake” cause. Which test is used for
this? Be specific.
Answer:
RAIU (Radioactive Iodine Uptake) test. Note this is NOT
a thyroid scan.

19
 Hyperthyroidism - Workup
Radioactive Iodine Uptake Test – administer radiolabelled iodine (I-123)and
measure the level 24 hours later. Usually, thyroid follicles take up about 10-
30% of administered dose. If the thyroid takes up >30%, this indicates
hyperfunction. *Note - this is a FUNCTION test, not an IMAGING test.

HIGH-UPTAKE HYPERTHYROIDISM - DDX

- Graves’ dx.
– Toxic multinodular goiter.
– Solitary toxic adenoma.

LOW-UPTAKE HYPERTHYROIDISM - DDX

- Factitious hyperthyroidism
– Iodine-induced hyperthyroidism
– Thyroiditis – Disruptive, subacute, painless, post-partum

20
 Hyperthyroidism - Workup
Thyroid Scan
1. Administer a radioactive isotope that localizes in thyroid gland.
2. Image the thyroid.

DIFFUSE vs. SOLITARY IMAGE

These patterns are seen in high uptake hyperthyroidism.
1. Diffuse tracer uptake – indicates Graves’ dx.
2. Mutiple discrete nodules – toxic multinodular goiter
3. Single area of intense uptake – Solitary toxic adenoma.

NODULE EVALUATION
Cold nodule – nonfunctional. Scary, because 20% risk of carcinoma.
Hot nodule – functional. not malignant, but must be folllowed because can
cause thyrotoxicosis.

21
 Hyperthyroidism - Antibodies
Anti-Thyroglobulin Antibodies (TG)

Anti-Thyroid Peroxidase Antibodies (TPO), Anti-Microsomal

Antibodies

Thyroid Stimulating Immunoglobulins (TSI), Anti-TSH Receptor

Antibodies (TSHR-Ab)
• Formerly called LATS (Long Acting Thyroid Stimulator) in 1950s,
later discovered to be an IgG

22
 Hyperthyroidism – Antibodies

* Chart displays % of TSHR-AB TG TPO

people w/ antibodies
Graves 80-95 50-70 50-80

Hashimotos 10-20 80-90 90-100

General Population 0 5-20 8-27

Relatives of 0 30-50 30-50

Hashimoto’s patients
Type 1 DM 0 30-40 30-40

Pregnant Women 0 14 14

23
 Hyperthyroidism – Etiologies

Thyroid uptake low 4. Factitous

5. Iodine induced
high 6. Thyroiditis

Thyroid scan:
1. Diffuse tracer uptake – TPO, TG
Graves’ dx. TSHR-Ab
2. Mutiple discrete nodules –
toxic multinodular goiter
3. Single area of intense uptake – Antibody tests
Solitary toxic adenoma.

7. Pregnancy

24
 Thyroid Diseases - Etiologies

Graves Disease

Thyroiditis

Pregnancy

25
 Thyroid Diseases - Graves
Etiology:
Patient produces IgG antibodies which are agonists to the TSH receptor.

Classic Triad (15-20%):

Diffuse Thyroid enlargement, pretibial myxoedema, and Ophthalmopathy

Short term:
- Beta blockers - to reduce peripheral T4T3 conversion.
Ophthalmopathy – methylcellulose eye drops, papilloedema- steroids
Pretibial myxoedema – local steroid
Long term:
- Thionamides - PTU or Methimazole - remission at 1 year in 33%, but 5-10%
have serious side fx.
- RIA (Radioactive Iodine Ablation), w/ I131. Hypothyroid in 50%.
- Surgery, but risks are greater than RIA.

26
 Thyroid Diseases - Etiologies

Graves Disease

Thyroiditis

Pregnancy

27
 Quiz Question

Question:
What is the most common cause of hypothyroidism in iodine-sufficient
populations?

Answer:
Hashimoto’s thyroiditis

28
 Thyroid Diseases – Thyroiditis
Literally, thyroiditis means inflammation of the thyroid gland.

Etiologies:
- Acute thyroiditis (Suppurative) – Staph, Strep, MTB, T.P.
– Autoimmune thyroiditis – Hashimotos, Atrophic, Juvenile
- Drug induced thyroiditis - Amiodarone
– Painless Thyroiditis
– Postpartum thyroiditis – Type I DM
– Subacute thyroiditis (Granulomatous) - Viral
- Reidel’s stroma – Fibrosis of gland

Rx:
1. In thyrotoxic stage, beta-blockers relieve adrenergic symptoms. Steroids?
2. **No ablative therapy (drugs, radioiodine ablation, surgery)
3. Watch for recovery hypothyroidism – consider synthroid.

29
Thyroid Diseases – Sub acute( De Quervain’s) Thyroiditis

Hx/PE:
Virus induced
Low-grade fever, Pain in gland, Sx of hyper or hypothyroidism.

Stages:
(1) Inflammatory destruction causes release of T4, T3 into blood, thyrotoxicosis
may ensue.
(2) Transitory period (1-2) weeks of euthyroidism occurs after extra T4 is cleared
from body.
(3) Patients become hypothyroid as gland repairs itself (6-12mo)
(4) Euthyroid state returns, with subtle abnormalities (See prognosis).

Prognosis:
Clinically patients recover fully, but serum thyroglobulin levels remain elevated
and intrathyroidal iodine content is low for many months.

30
 Thyroid Diseases – Hashimoto’s Thyroiditis
Hx:
Age 40-50s, more common in women
Auto immune
Throid peroxidase antibodies positive
Familial predisposition, associated with certain HLA haplotypes.

Pathology:
Autoimmune destruction of gland, leading to hypothyroidism.
Lymphocytic infiltration, fibrosis, thyroid will be rubbery consistency

31
 Thyroid Diseases - Etiologies

Graves Disease

Thyroiditis

Pregnancy

32
 Thyroid Diseases – Pregnancy
Normal:
TRH and TBG both increase. TBG is increased as much as twofold, thus leading
to elevated total T4 and T3. This leads to slightly increased binding of T4 and
T3, thus potentially leading to slightly low Free levels of T4 and T3. However,
the increased TRH usually increases T4 and T3 production enough to keep the
free levels within normal range or even slightly high. This can cause transient
decrease in TSH (10-20% of women).

Graves disease:
Most common hyperthyroid etiology in pregnancy (occurs in 0.2%)
Diagnosis made by TSH < 0.01 and elevated free T3 or T4 levels.

Iodine studies:
Contraindicated during pregnancy.

33
 Factitious hyperthyroidism

Intentional , psychiatric
Intake of high dose of thyroxin
T4:T3 ratio is 70:1 ( normal 30:1)
Low iodine uptake
Low thyroglobulin

34
 Thyroid Storm
• Causes
– Surgery
– Radioactive Iodine Therapy
– Severe Illness
• Diagnosis
– Clinical – tachycardia, hyperpyrexia, thyrotoxicosis symptoms
– Labs (Low TSH, High T4, FT4)
• Treatment
– Propranolol IV vs. Verapamil IV
– Propylthiouracil, Methimazole
– Sodium Iopate/ Sodium Iodide
– Acetamenophen, cooling blankets
– Plasmapheresis (rare)
– Surgical (rare)
35
 Hypothyroidism

• Prevalence is 14/1000 females and 1/1000 males.

• Other autoimmune diseases.
• Family history of autoimmune diseases

36
 Primary hypothyroidism-Causes

• Iodine deficiency
• Autoimmune thyroiditis (Hashimoto’s)
• Radioactive iodine
• Post thyroidectomy
• Anti-thyroid drugs (CMZ, PTU)
• Lithium, Amiodarone
• Sub acute thyroiditis
• Infiltrative disease
• Agenesis

37
 Secondary hypothyroidism-causes
• Hypothalamic disease
• Pituitary disease

38
 Clinical features
General and CVS
• Tiredness • Bradycardia
• Weight gain • Angina
• Cold intolerance • Cardiac Failure
• Goitre • Pericardial effusion
• Constipation

39
 Clinical Features
Neurological and Haematological
• Aches and Pains • Iron deficiency A
• Carpal Tunnel • Pernicious Anemia
• Deafness • Macrocytosis
• Hoarseness
• Ataxia
• Depression
• Psychosis
• Delayed relaxation of jerks

40
 Clinical Features
Skin and Reproduction
• Dry skin • Infertility
• • Menorrhagia
Vitiligo
• Galactorrhoea
• Alopecia
• impotence

41
 Laboratory Diagnosis

• T4/FT4 reduced
• T3/FT3
• TSH elevated
• Thyroid Antibodies may indicate aetiology.
• If TSH is reduced or normal in the presence of a low T4, pituitary
function necessary.

42
43
44
 Treatment
• Thyroxine. Usual maintenance dose is 150ug.
• Compliance and adequacy of dose checked by TSH measurements.
• Try to maintain TSH in normal range.

45
 Subclinical Hypothyroidism

• Primary thyroidal failure (Hashimotos) is a gradual

process.
• Non specific symptoms
• Reduced thyroid activity has been compensated by an
increase TSH output to maintain a euthyroid state.
• Normal T4/FT4 with elevated TSH.
• Thyroid antibodies usually positive

46
 Treatment

• Repeat tests after an interval.

• If TSH is continuing to rise in the presence of
strongly positive antibodies, the risk of
developing hypothyroidism in the future is
high. Thus treatment with thyroxine at this
early stage may be justified if symptomatic.
• Beware-Thyroxine may not cure all
symptoms.

47
 Myxoedema Coma
• Hypothermia
• Requires prompt treatment. Mortality of 50%.
• T3 20ug bd IM
• Steroids recommended
• Glucose to correct hypoglycaemia
• Rewarming
• Assisted ventilation

48
 Post-partum thyroiditis.

• Incidence is about 9%.

• Transitory or permanent.
• Early hyperthyroidism (<4/12), later hypothyroidism (>4/12),
euthyroid 10/12 later.
• Increased microsomal antibodies.
• Thyroxine

49
 Sick euthyroid syndrome

• Patients with systemic illness

• A high serum T4 due to abnormality of binding to serum proteins.
• A low/normal serum T3 due to reduced production.
• TSH low
• Clinically euthyroid.

50
 The “Triage” Approach to Thyroid Disease
Hypothyroidism:
Symptoms: Labs:
Fatigue, weight gain, + High TSH
= Start/Increase Synthroid
Dose
constipation, dry skin

Hyperthyroidism:
Symptoms: Labs:
Anxious, weight loss, + Low TSH
= Evaluation and antithyroid drugs
diarrhea, diaphoresis + Propranolol

51
Thank u
52