Hyperthyroidism

Amin Shah
2016
Introduction
• Thyrotoxicosis
▫ Constellation of clinical features arising
from elevated circulating levels of
thyroid hormones

• Hyperthyroidism
▫ Raised levels of circulating thyroid
hormones
Introduction
• Disorders of the thyroid gland result primarily from
autoimmune processes that stimulate the
overproduction of thyroid hormones
(thyrotoxicosis)
• Affecting 2–5% of all females
• Sex ratio of 5 : 1 (F:M)
• Age: 20 and 40 years
• >99% caused by intrinsic thyroid disease
▫ Pituitary cause is extremely rare
Introduction
• Thyroidal production of the hormones thyroxine
(T4) and triiodothyronine (T3) is controlled via a
classic endocrine feedback loop
• Some T3 is secreted by the thyroid, but most is
produced by deiodination of T4 in peripheral
tissues
• Both T4 and T3 are bound to carrier proteins
[thyroid-binding globulin(TBG), transthyretin,
and albumin] in the circulation
• Increased T4 + normal T3
• States of increased carrier proteins (pregnancy,
cirrhosis, hepatitis, and inherited disorders)
• Decreased T4 + normal T3
• Severe systemic illness, chronic liver disease, and
nephrosis
Causes
• Primary hyperthyroidism (Graves’ disease, toxic
multinodular goiter, toxic adenoma, iodine excess)
• Thyroid destruction (subacute thyroiditis, silent
thyroiditis, amiodarone, radiation)
• Extrathyroidal sources of thyroid hormone
(thyrotoxicosis factitia, struma ovarii, functioning
follicular carcinoma)
• Secondary hyperthyroidism [TSH-secreting
pituitary adenoma, thyroid hormone resistance
syndrome, human chorionic gonadotropin (hCG)-
secreting tumors, gestational thyrotoxicosis]
 Graves’ disease
• Autoimmune disease
• Most commonly affects women aged 30-50 yrs
• Most common manifestation with or without a diffuse
Goitre
• Results from
- production of IgG antibodies against the TSH
receptor on the Thyroid follicular cells

- Stimulate thyroid hormone production and

proliferation of follicular cells
- these Ab are termed as TRAb- serum of 80-85%
Graves 'disease
• In this disease:
o Hyperthyroidism
o Diffuse enlargement of thyroid gland and a bruit or
thrill may be present
o Eye sign

• Rarely lymphadenopathy and splenomegaly may occur

• It is also associated with other autoimmune disorders such as

pernicious anaemia, vitiligo and myasthenia gravis.

• and dermopathy (pretibial myxedema) may also be found

 Eye signs
• Exophthalmos
• Lid retraction
• Chemosis
• Oedema of
eyelids
- Decreased VA and visual fields
Toxic multinodular goitre

• This commonly occurs in older women

• Large goiter with or without tracheal compression
• Nodular or lobulated on palpation
• Antithyroid drugs are rarely successful in inducing a
remission,
• Although they can control the hyperthyroidism
Solitary toxic adenoma/nodule
• This is the cause of about 5% of cases of
hyperthyroidism
• Nodule is follicular adenoma which
autonomously secrets excess thyroid hormones
• Adenoma is usually greater than 3cm
• Most pt. are female and over 40
• It does not usually remit after a course of
antithyroid drugs
 De Quervain’s thyroiditis
• This is transient hyperthyroidism from an acute inflammatory process,
probably viral in origin

o there is usually fever, malaise and pain in the neck with

tachycardia and local thyroid tenderness
o Usually pappably enlarged and tender

• Thyroid function tests  show initial hyperthyroidism,

• ESR and plasma viscosity  raised
• Hypothyroidism, usually transient, may then follow after a few weeks.
• Treatment of the acute phase is with NSAIDS, using short-term
prednisolone in severely symptomatic cases.
Clinical Features
• Affect any system
• Vary with age and underlying etiology
• Elderly: Atrial fibrillation, tachycardias and/or
heart failure, often with few other signs
• Children:
▫ Excessive height or excessive growth rate
▫ Behavioural problems such as hyperactivity
▫ Show weight gain rather than loss
 Clinical Features: Symptoms
• Weight loss • Itching
• Increased appetite • Thirst
• Irritability/behaviour change • Vomiting
• Tremor • Diarrhoea
• Heat intolerance • Eye complaints
• Restlessness • Goitre
• Malaise • Oligomenorrhoea
• Stiffness • Loss of libido
• Muscle weakness • Gynaecomastia
• Breathlessness • Onycholysis
• Palpitation • Tall stature (in children)
• Sweating
Clinical Features: Signs
• Tremor • Proximal muscle wasting
• Hyperkinesis • Conjunctival oedema
• Tachycardia or atrial • Ophthalmoplegia*
fibrillation • Periorbital oedema
• Warm vasodilated peripheries • Weight loss
• Exophthalmos* • Psychosis
• Lid lag and ‘stare’ • Onycholysis
• Goitre, bruit • Palmar erythema
• Thyroid acropachy • Systolic hypertension
• Pretibial myxoedema • Cardiac failure
• Proximal myopathy • Graves’ dermopathy*
Investigations
• First line of investigations are T3,T4 and
TSH
• normal range for serum TSH is about 0.4 to 5.0 mU/L,
o Serum TSH is suppressed in hyperthyroidism (<0.05 mU/L), except
for the very rare instances of TSH hypersecretion.
• A raised free T4 or T3 confirms the diagnosis;T4 is almost always
raised but T3 is more sensitive
o T4 Normal ranges vary among laboratories; a typical range is 4.6 to
11.2 mcg/dL (60 to 145 nmol/L).
o T3 range is approximately 75 to 195 ng/dL (1.1 to 3 nmol/L)

• Thyroid peroxidase (TPO) and thyroglobulin antibodies are present in

most cases of Graves’ disease, TSHR-Ab are not measured routinely
 Investigation
• Serum TSH is a sensitive marker of
thyrotoxicosis caused by Graves’ disease, autonomous
thyroid nodules, thyroiditis, and exogenous
levothyroxine treatment
• Associated laboratory abnormalities include elevation
of bilirubin, liver enzymes, and ferritin
• Radionuclide uptake Scan may be required to
distinguish the various etiologies: high uptake in
Graves’ disease and nodular disease vs. low uptake in
thyroid destruction, iodine excess, and extrathyroidal
sources of thyroid hormone
• Anti-TPO antibodies: In autoimmune thyroid
disease, proteins mistakenly attack the thyroid
peroxidase enzyme, which is used by the thyroid
to make thyroid hormones.
• Thyroid ultrasound
• Thyroid biopsy: A small amount of thyroid
tissue is removed, usually to look for thyroid
cancer. Thyroid biopsy is typically done with a
needle.
Evaluation of thyrotoxicosis
Management
• Three possibilities are available:
▫ Antithyroid drugs
▫ Radioiodine
▫ Surgery
Drugs
• Antithyroid drugs
▫ Carbimazole
▫ Propylthiouracil
• Beta-blockers
▫ Provide rapid partial symptomatic control
▫ Decrease peripheral conversion of T4 to T3
Drugs used in treatment of
hyperthyroidism
Dose Regimen
• Gradual dose titration
▫ Start carbimazole 20–40 mg daily
▫ Review after 4–6 weeks and reduce the dose of carbimazole,
depending on clinical state and fT4/fT3 levels
▫ When clinically and biochemically euthyroid, stop beta-blockers.
▫ Review thyroid function regularly during the planned course of
treatment (typically 18 months OR between 6 and 24 months)
▫ Reduce carbimazole if fT4 falls below or TSH rises above normal –
and when approaching the end of the planned course
▫ Increase carbimazole if fT4 or fT3 are above normal (consider if
TSH remains suppressed after several months with a normal fT4)
▫ Stop treatment at end of course if the patient is euthyroid on 5 mg
daily carbimazole
Dose Regimen
• Block and replace regimen
▫ Full doses of antithyroid drugs, usually carbimazole 40
mg daily, to suppress the thyroid completely
▫ Replace thyroid activity with 100 μg of levothyroxine
daily once euthyroidism has been achieved
▫ Continued usually for 18 months
▫ Advantage:
 The avoidance of over- or undertreatment
 Better use of the immunosuppressive action of carbimazole
▫ Contraindicated in pregnancy as T4 crosses the placenta
less well than carbimazole
Relapse and Toxicity
• ~50% of patients will relapse, mostly within the
following 2 years
• Long-term antithyroid therapy is then used or
surgery or radiotherapy is considered

• Major side effect: Agranulocytosis

▫ 1 in 1000 patients
▫ Within 3 months of treatment
• Warned to seek medical attention for WBC count if
they develop unexplained fever or sore throat
• Rashes: Common and require a change of drug.
Radioactive Iodine (RAI)
• All ages, but contraindicated in pregnancy and while
breastfeeding
• Iodine 200–550 MBq: Empirical dose
131

▫ Accumulates in the thyroid and destroys the gland

by local radiation
▫ Takes several months to be fully effective
• Patients must be rendered euthyroid before
treatment.
• Stop antithyroid drugs 4 days before; until 3 days after
RAI
• Risk of carcinogenesis has been long debated!
Surgery
• Thyroidectomy
▫ Only in patients who have previously been
rendered euthyroid
• Stop antithyroid drug 10–14 days before
operation  Give potassium iodide, 60 mg,
three times daily (reduces the vascularity of the
gland)
• Indications for surgery or radioiodine
▫ Patient choice
▫ Persistent drug side-effects
▫ Poor compliance with drug therapy
▫ Recurrent hyperthyroidism after drugs

• Indication for surgery

▫ A large goitre, which is unlikely to remit after
antithyroid medication
AF in thyrotoxicosis
• Occurs in 10% 0f patients
• Incidence increasing with age
• Ventricular rate is little influenced by Digoxin
but responds to the addition to beta blocker
 Thyroid crisis or thyroid storm
• Rare Mortality: 10%
• Most commonly precipitated by infection in a pt. previously
unrecognized or inadequately treated thyrotoxicosis
• Rapid deterioration of hyperthyroidism with hyperpyrexia,
severe tachycardia, extreme restlessness, cardiac failure and
liver dysfunction
• Precipitated by stress, infection or surgery in an unprepared
patient, or radioiodine therapy

• Treatment is urgent
• Pt. rehydrated and give broad spectrum antibiotics
▫ Propranolol + Potassium iodide + Antithyroid drugs +
Corticosteroids
Thyrotoxicosis in pregnancy
• During pregnancy is usually due to Graves’ disease
• As anovulatory cycles are common in thyrotoxic pt.
and auto immune disease tend to remit during
pregnancy- maternal immune response is suppressed
• Hence total T3 and T4 levels are increased and TSH
lower
• Since maternal thyroid hormones, TRAb, and anti
thyroid drugs all cros the placenta
• Expose the fetus to risk of thyrotoxicosis,iatrogenic
hypothyroidism and goitre
• Treated with antithyroid drug which crosses
placenta and also treat the fetus
• Propylthiouracil may be preferable to carbimazole
• TRAb level measured in 3rd trimester to predict the
likelihood of neonatal thyrotoxicosis- if not elevated
drug discontinued 4 weeks before EDD
• After delivery drug is required,
propylthiouracil is the drug of choice – is
excreted in milk
• Subtotal thyroidectomy most safely
performed in 2nd trimester
• Radioactive iodine CI as it invariably induces fetal
hypothyroidism
Long-term consequences of
hyperthyroidism
• Slight increase in overall mortality in all age
groups
• Increased risk of osteoporosis
• Increased likelihood of developing atrial
fibrillation
• References
▫ Kumar and Clark’s Clinical Medicine, 3rd Edition
▫ Davidson's Principles and Practice of Medicine,
21st Edition
▫ Harrison’s Principles of Internal Medicine, 18 th
Edition
Thank you