Lec#15+16 Thyroid Disorders
Lec#15+16 Thyroid Disorders
Lec#15+16 Thyroid Disorders
Murad Shatnawi, MD
Assistant Professor of Endocrinology , Diabetes and Metabolism.
YU
01/11/2021
Hypothalamus make TRH
If No : Thyroid scintigraphy
If Yes : Graves
Management
Definitive treatment of thyrotoxicosis depends on the underlying cause and may
include
antithyroid drugs : Carbimazole, propylthiouracil (50% relapse) Risk of
agranulocytosis ,
radioactive iodine
surgery.
• A non-selective β-adrenoceptor antagonist (β-blocker), such as
propranolol will alleviate but not abolish symptoms in most patients
within 24–48 hours. Beta-blockers should not be used for long-term
treatment of thyrotoxicosis .
Atrial fibrillation in thyrotoxicosis
• Atrial fibrillation occurs in about 10% of patients with thyrotoxicosis. The
incidence increases with age, so that half of all males with thyrotoxicosis
over the age of 60 are affected. Moreover, subclinical thyrotoxicosis is a
risk factor for atrial fibrillation. Characteristically the ventricular rate is
little influenced by digoxin, but responds to the addition of a β-blocker.
• Thromboembolic vascular complications are particularly common in
thyrotoxic atrial fibrillation so that anticoagulation with warfarin is
required, unless contraindicated. Once thyroid hormone and TSH
concentrations have been returned to normal, atrial fibrillation will
spontaneouslyrevert to sinus rhythm in about 50% of patients, but
cardioversion may be required in the remainder
Thyrotoxic crisis (‘thyroid storm’)
• Life threatening emergency (rare) – 30% mortality even with early recognition and
management
• Signs
• Fever
• Agitation and confusion
• Tachycardia +/- AF
• Management
• IV fluids
• Broad spectrum antibiotics
• Propanolol, digoxin
• Antithyroid drugs – sodium ipodate, Lugol’s solution, carbimozole
Subclinical thyrotoxicosis
• Serum TSH is undetectable, and serum T3 and T4 are at the upper end
of the reference range. This combination is most often found in older
patients with multinodular goitre. These patients are at increased risk
of atrial fibrillation and osteoporosis, and hence the consensus view is
that they have mild thyrotoxicosis and require therapy, usually with
131I. Otherwise, annual review is essential, as the conversion rate to
overt thyrotoxicosis with elevated T4 and/or T3 concentrations is 5%
each year.
Thyroid lump or swelling
• A lump or swelling in the thyroid gland can be a source of considerable anxiety for
patients. There are numerous causes but, broadly speaking, a thyroid swelling is either a
solitary nodule, a multinodular goitre or a diffuse goitre
• Nodular thyroid disease is more common in women and occurs in approximately 30% of
the adult female population. The majority of thyroid nodules are impalpable but may be
identified when imaging of the neck is performed for another reason, such as during
Doppler ultrasonography of the carotid arteries or computed tomographic pulmonary
angiography. Increasingly, thyroid nodules are identified during staging of patients with
cancer with computed tomography (CT), magnetic resonance imaging (MRI) or positron
emission tomography (PET) scans.
• Palpable thyroid nodules occur in 4–8% of adult women and 1–2% of adult men, and
classically present when the individual (or a friend or relative) notices a lump in the neck.
Multinodular goitres and solitary nodules sometimes present with acute painful
enlargement due to haemorrhage into a nodule.
• Patients with thyroid nodules often worry that they have cancer, but
the reality is that only 5–10% of thyroid nodules are malignant. A
solitary nodule presenting in childhood or adolescence, particularly if
there is a past history of head and neck irradiation, or one presenting
in the elderly should heighten suspicion of a primary thyroid
malignancy
• The presence of cervical lymphadenopathy also increases the
likelihood of malignancy. Rarely, a secondary deposit from a renal,
breast or lung carcinoma presents as a painful, rapidly growing,
solitary thyroid nodule. Thyroid nodules identified on PET scanning
have an approximately 33% chance of being malignant.
Causes of thyroid enlargement
Diffuse goitre
• Simple goitre
• Hashimoto’s thyroiditis1
• Graves’ disease
• Drugs Iodine, amiodarone, lithium
• Iodine deficiency (endemic goitre)
• Suppurative thyroiditis
• Transient thyroiditis
• Dyshormonogenesis
• Infiltrative : Amyloidosis, sarcoidosis ..etc.
• Riedel’s thyroiditis
Solitary nodule or part of MNG
• Colloid cyst
• Hyperplastic nodule
• Follicular adenoma
• Papillary carcinoma
• Follicular carcinoma
• Medullary cell carcinoma
• Anaplastic carcinoma
• Lymphoma
• Metastasis
Clinical assessment and investigations
• Swellings in the anterior part of the neck most commonly originate in
the thyroid and this can be confirmed by demonstrating that the
swelling moves on swallowing
• It is often possible to distinguish clinically between the three main
causes of thyroid swelling.
• There is a broad differential diagnosis of anterior neck swellings, which
includes lymphadenopathy, branchial cysts, dermoid cysts and
thyroglossal duct cysts (the latter are classically located in the midline
and move on protrusion of the tongue).
• An ultrasound scan should be performed urgently, if there is any doubt
as to the aetiology of an anterior neck swelling.
• Serum T3, T4 and TSH should be measured in all patients with a goitre
or solitary thyroid nodule.
• The finding of biochemical thyrotoxicosis or hypothyroidism (both of
which may be subclinical) should necessiate further investigations
Thyroid scintigraphy
• Thyroid scintigraphy with 99m technetium should be performed in an
individual with a low serum TSH and a nodular thyroid to confirm the
presence of an autonomously functioning (‘hot’) nodule
• In such circumstances, further evaluation by fine needle aspiration is
not necessary. ‘Cold nodules’ on scintigraphy have a much higher
likelihood of malignancy, but the majority are benign and so
scintigraphy is not routinely used in the evaluation of thyroid nodules
when TSH is normal.
Thyroid ultrasound
• If thyroid function tests are normal, an ultrasound scan will determine
the nature of the thyroid swelling. Ultrasound can establish whether
there is generalised or localised swelling of the thyroid. Inflammatory
disorders causing a diffuse goitre, such as Graves’ disease and
Hashimoto’s thyroiditis, demonstrate a diffuse pattern of
hypoechogenicity and, in the case of Graves’ disease, increased
thyroid blood flow may be seen on colour flow Doppler.
• The presence of thyroid autoantibodies will support the diagnosis of
Graves’ disease or Hashimoto’s thyroiditis, while their absence in a
younger patient with a diffuse goitre and normal thyroid function
suggests a diagnosis of ‘simple goitre’
• Ultrasound can also readily determine the size and number of nodules
within the thyroid and can distinguish solid nodules from those with a
cystic element.
• It cannot reliably distinguish benign from malignant nodules but, in
experienced hands, there are some ultrasound characteristics which are
associated with a higher likelihood of malignancy. These include:
hypervascularity of the nodule, the presence of microcalcification and
irregular, infiltrative margins.
• A pure cystic nodule is highly unlikely to be malignant and a
‘spongiform’ appearance is also highly predicative of a benign aetiology.
Fine needle aspiration
• Cytological examination of a thyroid nodule, following fine needle
aspiration, is recommended for most thyroid nodules over 1 cm in
size. Smaller nodules should be aspirated if there is a high suspicion of
malignancy on clinical or ultrasound grounds, while some clinicians
will be happy to observe a nodule up to 2 cm in size with a
spongiform appearance. Individuals with a multinodular goitre have
the same risk of malignancy as those with a solitary nodule.
Sometimes, one of the nodules in a multinodular goitre is much larger
than any other (a ‘dominant’ nodule), but ultimately the choice of
nodule to biopsy should be based on ultrasound characteristics.
• Fine needle aspiration of a thyroid nodule can be performed in the outpatient
clinic using a standard 21-gauge needle and a 20 mL syringe, usually making
several passes through different parts of the lesion. Ultrasound-guided needle
aspiration is necessary for impalpable nodules and to permit targeting of the
solid component of a mixed cystic/solid nodule. Aspiration may be
therapeutic in the small proportion of patients in whom the swelling is a cyst,
although recurrence on more than one occasion is an indication for surgery.
• Cytological examination can differentiate benign (80%) from definitely
malignant or indeterminate nodules (20%), of which 25–50% are confirmed as
cancers at surgery. The limitations of fine needle aspiration are that it cannot
differentiate between follicular adenoma and carcinoma, and that in 10–20%
of cases an inadequate specimen is obtained.
Subacute (de Quervain’s)
thyroiditis
• In its classical painful form, subacute thyroiditis is a transient
inflammation of the thyroid gland occurring after infection with
Coxsackie, mumps or adenoviruses.
• There is pain in the region of the thyroid that may radiate to the angle
of the jaw and the ears, and is made worse by swallowing, coughing and
movement of the neck.
• The thyroid is usually palpably enlarged and tender. Systemic upset is
common. Affected patients are usually females aged 20–40 years.
Painless transient thyroiditis can also occur after viral infection and in
patients with underlying autoimmune disease. The condition can also
be precipitated by drugs, including interferon-α and lithium.
• Irrespective of the clinical presentation, inflammation in the thyroid
gland occurs and is associated with release of colloid and stored
thyroid hormones, but also with damage to follicular cells and
impaired synthesis of new thyroid hormones. As a result, T4 and T3
levels are raised for 4–6 weeks until the pre-formed colloid is
depleted. Thereafter, there is usually a period of hypothyroidism of
variable severity before the follicular cells recover and normal thyroid
function is restored within 4–6 months
• In the thyrotoxic phase, the iodine uptake is low, because the
damaged follicular cells are unable to trap iodine and because TSH
secretion is suppressed. Low-titre thyroid autoantibodies appear
transiently in the serum, and the erythrocyte sedimentation rate (ESR)
is usually raised.
• High-titre autoantibodies suggest an underlying autoimmune
pathology and greater risk of recurrence and ultimate progression to
hypothyroidism.
• The pain and systemic upset usually respond to simple measures such
as non-steroidal anti-inflammatory drugs (NSAIDs). Occasionally,
however, it may be necessary to prescribe prednisolone 40 mg daily
for 3–4 weeks. The thyrotoxicosis is mild and treatment with a β-
blocker is usually adequate. Antithyroid drugs are of no benefit
because thyroid hormone synthesis is impaired rather than enhanced.
Careful monitoring of thyroid function and symptoms is required so
that levothyroxine can be prescribed temporarily in the hypothyroid
phase. Care must be taken to identify patients presenting with
hypothyroidism who are in the later stages of a transient thyroiditis,
since they are unlikely to require life-long levothyroxine therapy
Post-partum thyroiditis
• The maternal immune response, which is modified during pregnancy
to allow survival of the fetus, is enhanced after delivery and may
unmask previously unrecognised subclinical autoimmune thyroid
disease.
• Surveys have shown that transient biochemical disturbances of
thyroid function occur in 5–10% of women within 6 months of
delivery
• Those affected are likely to have anti-thyroid peroxidase antibodies in
the serum in early pregnancy. Symptoms of thyroid dysfunction are
rare and there is no association between postnatal depression and
abnormal thyroid function tests. However, symptomatic thyrotoxicosis
presenting for the first time within 12 months of childbirth is likely to
be due to post-partum thyroiditis and the diagnosis is confirmed by a
negligible radio-isotope uptake. The clinical course and treatment are
similar to those of painless subacute thyroiditis (see above).
Postpartum thyroiditis tends to recur after subsequent pregnancies,
and eventually patients progress over a period of years to permanent
hypothyroidism.
Amiodarone
• The anti-arrhythmic agent amiodarone has a structure that is analogous to that of T4
(and contains huge amounts of iodine; a 200 mg dose contains 75 mg iodine, compared
with a daily dietary requirement of just 125 μg. Amiodarone also has a cytotoxic effect
on thyroid follicular cells and inhibits conversion of T4 to T3. Most patients receiving
amiodarone have normal thyroid function, but up to 20% develop hypothyroidism or
thyrotoxicosis and so thyroid function should be monitored regularly.
• The ratio of T4:T3 is elevated and TSH provides the best indicator of thyroid function.
• The thyrotoxicosis can be classified as either:
• type I: iodine-induced excess thyroid hormone synthesis in patients with an underlying
thyroid disorder, such as nodular goitre or latent Graves’ disease
• type II: thyroiditis due to a direct cytotoxic effect if amiodarone administration results
in a transient thyrotoxicosis.
• These patterns can overlap and can be difficult to distinguish clinically,
as iodine uptake is low in both
• Antithyroid drugs may be effective in patients with the type I form,
but are ineffective in type II thyrotoxicosis. Prednisolone is beneficial
in the type II form.
MEN Syndrome
• MEN1 : parathyroid , pituitary & Pancreatic tumors.
• MEN2A : Parathyroid hyperplasia, MTC & PHE
• MEN2B : MTC , PHE & mucosal neuroma
APS
• 1 : addison , hypoparathyroid and ch candidiasis
• 2 : addison , hypothyroidism and diabetes
Selenium
• Selenium supplementation in people with Hashimoto's thyroiditis
might reduce antibody levels and result in a decreased dosage of
levothyroxine (LT4) and may provide other beneficial effects (e.g. on
mood and health-related quality of life).
• They found that treatment with selenium, but not with
pentoxifylline, was associated with improved quality of life, less eye
involvement, and delayed progression of Graves' orbitopathy at 6
months