Thyroid Disorders

Dr.shahad abualhamael , internal medicine

consultant
Assistant Professor, Department of Medicine

 Introduction
● Thyroid disorders:
– Hypothyroidism – Nontoxic goitre
– Hyperthyroidism and – Thyroid nodules & thyroid
thyrotoxicosis cancer
● Graves’ disease ● Benign thyroid nodules
● Thyroiditis ● Thyroid cancer
● Toxic adenoma – Papillary carcinoma
● Toxic multinodular goitre – Follicular carcinoma
● Thyrotoxicosis factitia – Medullary carcinoma
– Anaplastic carcinoma
● Struma ovarii
– Lymphoma
● Hydatidiform mole – Cancer metastatic to
● TSH-secreting pituitary the thyroid
adenoma

 Hypothyroidism
● Etiology:
– Primary:
● Hashimoto’s thyroiditis with or without goitre 8:15 AM, 7 Dec 2020

● Radioactive iodine therapy for Graves’ disease

● Subtotal thyroidectomy for Graves’ disease or nodular goitre

● Excessive iodine intake

● Subacute thyroiditis

● Rare causes

– Iodide deficiency
– Goitrogens such as lithium; antithyroid drug therapy
– Inborn errors of thyroid hormone synthesis
– Secondary: Hypopituitarism
– Tertiary: Hypothalamic dysfunction (rare)
– Peripheral resistance to the action of thyroid hormone

 Hypothyroidism
● Clinical features
– Cardiovascular signs: – Renal function:
● Bradycardia ● Impaired ability to excrete a water
● Low voltage ECG load
● Pericardial effusion – Anemia:
● Cardiomegaly ● Impaired Hb synthesis
● Hyperlipidemia ● Fe deficiency due to:
– Menorrhagia
– Constipation, ascites – Reduced intestinal absorption
– Weight gain ● Folate def. due to impaired intestinal
– Cold intolerance absorption
– Rough, dry skin ● Pernicious anemia
– Puffy face and hands – Neuromuscular system:
● Muscle cramps, myotonia
– Hoarse, husky voice ● Slow reflexes
– Yellowish color of skin due to reduced ● Carpal tunnel syndrome
conversion of carotene to vitamin A – CNS symptoms:
– Respiratory failure ● Fatigue, lethargy, depression
– Menorrhagia, infertility, hyper- ● Inability to concentrate
prolactinemia

 Hypothyroidism
● Diagnosis:
– A !FT4 and "TSH is diagnostic of primary hypothyroidism
– Serum T3 levels are variable (maybe in normal range)
– +ve test for thyroid autoantibodies (Tg Ab & TPO Ab) PLUS an
enlarged thyroid gland suggest Hashimoto’s thyroiditis
– With pituitary myxedema FT4 will be ! but serum TSH will be
inappropriately normal or low
– TRH test may be done to differentiate pituitary from hypothalamic
disease. Absence of TSH response to TRH indicates pituitary
deficiency
– MRI of brain is indicated if pituitary or hypothalamic disease is
suspected. Need to look for other pituitary deficiencies.
– If TSH is " & FT4 & FT3 are normal we call this condition
subclinical hypothyroidism

 8:18 AM, 7 Dec 2020

Hashimoto’s Thyroiditis
● Hashimoto’s thyroiditis is a commom cause of hypothyroidism
and goitre especially in children and young adults.
● It is an autoimmune disease that involves heavy infiltration of
lymphocytes that totally destroys normal thyroidal architecture
● Three different autoantibodies are present: Tg Ab, TPO Ab, and
TSH-R Ab (block)
● It is familial and may be associated with other autoimmune
diseases such as pernicious anemia, adrenocortical insufficiency,
idiopathic hypoparathyroidism, and vitiligo.
● Shmidt’s syndrome consists of Hashimoto’s thyroiditis, adrenal
insufficiency, hypoparathyroidism, DM, ovarian failure, and
(rarely) candidal infections.

 8:19 AM, 7 Dec 2020

Hashimoto’s Thyroiditis
● Symptoms & Signs:
– Usually presents with goitre in a patient who is euthyroid or has mild
hypothyroidism
– Sex distribution: four females to one male
– The process is painless
– Older patients may present with severe hypothyroidism with only a small,
firm atrophic thyroid gland
– Transient symptoms of thyrotoxicosis can occur during periods of
hashitoxicosis (spontaneously resolving hyperthyroidism)
● Lab:
– Normal or low thyroid hormone levels, and if low, TSH is elevated
– High Tg Ab and/or TPO Ab titres
– FNA bx reveals a large infiltration of lymphocytes PLUS Hurthle cells
● Complications:
– Permanent hypothyroidism (occurs in 10-15% of young pts)
– Rarely, thyroid lymphoma

 Management of Hypothyroidism
● Start patient on L-thyroxine 0.05-0.1mg PO OD. L-thyroxine
treats the hypothyroidism and leads to regression of goitre.
● If patient is elderly or has IHD start 0.025mg PO OD.
● Check TSH level after 4-6 weeks to adjust the dose of L-
thyroxine.
● In case of secondary hypothyroidism monitor FT4 instead of
TSH.
● Hypothyroidism during pregnancy:
– Check TFT every month. L-thyroxine dose requirement tends to go
up as the pregnancy progresses.
● If patient has concommitant hyperprolactinemia and
hypercholesterolemia, treat if not normalized after adequate
thyroid replacement.

 Myxedema Coma
● Medical emergency, end stage of untreated hypothyroidism
● Characterized by progressive weakness, stupor, hypothermia,
hypoventilation, hypoglycemia, hyponatremia, shock, and death
● The patient (or a family member) may recall previous thyroid disease,
radioiodine therapy, or thyroidectomy
● Hx is of gradual onset of lethargy progressing to stupor or coma. A hx of
amenorrhea or impotence with pituitary myxedema
● PE reveals !HR and marked hypothermia (as low as 24C)
● The pt is usually an obese elderly woman with yellowish skin, a hoarse
voice, a large tongue, thin hair, puffy eyes, ileus, and slow reflexes. An
anterior neck scar may be present. Scanty pubic or axillary hair with
pituitary myxedema
● Lab: low FT4, TSH high, normal, or low, cholesterol high or N, serum Na
low
● ECG: bradycardia and low voltage
● May be ppt by HF, pneumonia, excessive fluid administration, narcotics

 Management of Myxedema Coma

● Initiate therapy if presumptive clinical diagnosis after TSH, FT3
FT4 drawn. Also draw serum cortisol, ACTH, glucose.
● General measures:
– Patient should be in ICU setting
– Support ventilation as respiratory failure is the major cause of death
in myxedema coma
– monitors ABG`s
– support blood pressure; hypotension may respond poorly to pressor
agents until thyroid hormone is replaced
– hypothermia will respond to thyroxin therapy ; in interim use passive
warming only
– hyponatremia will also be corrected by thyroxine therapy in majority
of cases
– hypoglycemia requires IV glucose
– avoid fluid overload

 Management of Myxedema Coma

● Specific measure:
– L-thyroxine 0.2-0.5 mg IV bolus, followed by 0.1 mg IV OD until oral
therapy is tolerated
– Results in clinical response in hours
● Adrenal insufficiency may be precipitated by administration of
thyroid hormone therefore hydrocortisone 100 mg IV q 8h is
usually given until the results of the initial plasma cortisol is
known.
● Identify and treat the underlying precipitant cause

8:22 AM, 7 Dec 2020

Graves’ Disease

● Most common form of thyrotoxicosis

● May occur at any age but mostly from 20-40
● 5 times more common in females than in males
● Syndrome consists of one or more of the following:
– Thyrotoxicosis
– Goitre
– Opthalmopathy (exopthalmos) and
– Dermopathy (pretibial myxedema)
● It is an autoimmune disease of unknown cause
● 15% of pts with Graves’ have a close relative with the
same disorder

 Graves’ Disease
● Pathogenesis:
– T lymphocytes become sensitized to Ag within the thyroid gland and
stimulate B lymphocytes to synthesize Ab to these Ag
– One such Ab is the TSH-R Ab(stim), which stimulates thyroid cell
growth and function
– Graves’ may be ppt by pregnancy, iodide excess, viral or bacterial
infections, lithium therapy, glucocorticoid withdrawal
– The opthalmopathy and dermopathy associated with Graves’ may
involve lymphocyte cytokine stimulation of fibroblasts in these
locations causing an inflammatory response that leads to edema,
lymphocytic infiltration, and glycosaminoglycans deposition
– The tachycardia, tremor, sweating, lid lag, and stare in Graves’ is
due to hyperreactivity to catecholamines and not due to increased
levels of circulating catecholamines

 Graves’ Disease

● Clinical features:
– I Eye features: Classes 0-6, mnemonic “NO SPECS”
● Class 0: No signs or symptoms

● Class 1: Only signs (lid retraction, stare, lid lag), no symptoms

● Class 2: Soft tissue involvement (periorbital edema, congestion

or redness of the conjunctiva, and chemosis)

● Class 3: Proptosis (measured with Hertel exopthalmometer)

● Class 4: Extraocular muscle involvement

● Class 5: Corneal involvement

● Class 6: Sight loss (optic nerve involvement)

 Graves’ Disease

● Clinical features:
– II Goitre:
● Diffuse enlargement of thyroid

● Bruit may be present

– III Thyroid dermopathy (pretibial myxedema):

● Thickening of the skin especially over the lower tibia

● The dermopathy may involve the entire leg and may extend onto

the feet
● Skin cannot be picked up between the fingers

● Rare, occurs in 2-3% of patients

● Usually associated with opthalmopathy and very "TSH-R Ab

 Graves’ Disease
● Clinical features:
– IV Heat intolerance – IX Neuromuscular:
– V Cardiovascular: ● Nervousness, tremor
● Palpitation, Atrial fibrillation ● Emotional lability
● CHF, dyspnea, angina ● Proximal myopathy

– VI Gastrointestinal: ● Myasthenia gravis

● Weight loss, "appetite ● Hyper-reflexia, clonus
● Diarrhea
● Periodic hypokalemic
– VII Reproductive: paralysis
● amenorrhea, oligo-
– X Skin:
menorrhea, infertility
● Pruritus
● Gynecomastia
● Onycholysis
– VIII Bone:
● Vitiligo, hair thinning
● Osteoporosis
● Palmar erythema
● Thyroid acropachy
● Spider nevi

 Graves’ Disease
● Diagnosis:
– Low TSH, High FT4 and/or FT3
– If eye signs are present, the diagnosis of Graves’ disease can be
made without further tests
– If eye signs are absent and the patient is hyperthyroid with or
without a goitre, a radioiodine uptake test should be done.
– Radioiodine uptake and scan:
● Scan shows diffuse uptake
● Uptake is increased
– TSH-R Ab (stim) is specific for Graves’ disease. May be a useful
diagnostic test in the “apathetic” hyperthyroid patient or in the pt who
presents with unilateral exopthalmos without obvious signs or
laboratory manifestations of Graves’ disease

 Treatment of Grave’s Disease

● There are 3 treatment options:

– Medical therapy
– Surgical therapy
– Radioactive iodine therapy

 Treatment of Grave’s Disease

● A. Medical therapy:
– Antithyroid drug therapy:
● Most useful in patients with small glands and mild disease

● Treatment is usually continued for 12-18 months

● Relapse occurs in 50% of cases

● There are 2 drugs:

– Neomercazole (methimazole or carbimazole): start 30-40mg/D for

1-2m then reduce to 5-20mg/D.
– Propylthiouracil (PTU): start 100-150mg every 6hrs for 1-2m then
reduce to 50-200 once or twice a day
– Monitor therapy with fT4 and TSH
– S.E.: 5%!rash, 0.5%!agranulocytosis (fever, sore throat), rare:
cholestatic jaundice, hepatocellular toxicity, angioneurotic edema,
acute arthralgia

 Management of Grave’s disease

● A. Medical therapy:
– Propranolol 10-40mg q6hrs to control tachycardia,
hypertension and atrial fibrillation during acute phase of
thyrotoxicosis. It is withdrawn gradually as thyroxine levels
return to normal
– Other drugs:
● Ipodate sodium (1g OD): inhibits thyroid hormone synthesis and
release and prevents conversion of T4 to T3
● Cholestyramine 4g TID lowers serum T4 by binding it in the gut

 Management of Grave’s disease

● B. Surgical therapy:
– Subtotal thyroidectomy is the treatment of choice for patients
with very large glands
– The patient is prepared with antithyroid drugs until euthyroid
(about 6 weeks). In addition 2 weeks before the operation
patient is given SSKI 5 drops BID to diminish vascularity of
thyroid gland
– Complications (1%):
● Hypoparathyroidism
● Recurrent laryngeal nerve injury

 Management of Grave’s Disease

● C. Radioactive iodine therapy:

– Preferred treatment in most patients
– Can be administered immediately except in:
● Elderly patients

● Patients with IHD or other medical problems

● Severe thyrotoxicosis

● Large glands >100g

● In above cases it is desirable to achieve euthyroid state first

– Hypothyroidism occurs in over 80% of cases.

– Female should not get pregnant for 6-12m after RAI.

 Management of Grave’s Disease

● Management of opthalmopathy:
– Management involves cooperation between the
endocrinologist and the opthalmologist
– A course of prednisone immediately after RAI therapy 100mg
daily in divided doses for 7-14 days then on alternate days in
gradually diminishing dosage for 6-12 weeks.
– Keep head elevated at night to diminish periorbital edema
– If steroid therapy is not effective external x-ray therapy to the
retrobulbar area may be helpful
– If vision is threatened orbital decompression can be used

 Management of Grave’s Disease

● Management during pregnancy:

– RAI is contraindicated
– PTU is preferred over neomercazole
– FT4 is maintained in the upper limit of normal
– PTU can be taken throughout pregnancy or if surgery is
contemplated then subtotal thyroidectomy can be performed
safely in second trimester
– Breastfeeding is allowed with PTU as it is not concentrated in
the milk

 Toxic Adenoma
(Plummer’s Disease)
● This is a functioning thyroid adenoma
● Typical pt is an older person (usually > 40) who has
noted recent growth of a long-standing thyroid nodule
● Thyrotoxic symptoms are present but no infiltrative
opthalmopathy. PE reveals a nodule on one side
● Lab: low TSH, high T3, slightly high T4
● Thyroid scan reveals “hot” nodule with suppressed
uptake in contralateral lobe
● Toxic adenomas are almost always follicular
adenomas and almost never malignant
● Treatment: same as for Grave’s disease



 Toxic Multinodular Goitre

● Usually occurs in older pts with long-standing MNG

● PE reveals a MNG that may be small or quite large
and may even extend substernally
● RAI scan reveals multiple functioning nodules in the
gland or patchy distribution of RAI
● Hyperthyroidism in pts with MNG can often be ppt by
iodide intake “jodbasedow phenomenon”.
● Amiodarone can also ppt hyperthyroidism in pts with
MNG
● Treatment: Same as for Grave’s disease. Surgery is
preferred.

 Subacute Thyroiditis
● Acute inflammatory disorder of the thyroid gland most likely due to viral
infection. Usually resolves over weeks or months.
● Symptoms & Signs:
– Fever, malaise, and soreness in the neck 8:36 AM, 7 Dec 2020

– Initially, the patient may have symptoms of hyperthyroidism with palpitations,

agitation, and sweat
– PE: No opthalmopathy, Thyroid gland is exquisitely tender with no signs of
local redness or heat suggestive of abscess formation
– Signs of thyrotoxicosis like tachycardia and tremor may be present
● Lab:
– Initially, T4 & T3 are elevated and TSH is low, but as the disease progresses
T4 & T3 will drop and TSH will rise
– RAI uptake initially is low but as the pt recovers the uptake increases 8:37 AM, 7 Dec 2020

– ESR may be as high as 100. Thyroid Ab are usually not detectable in serum

 Subacute Thyroiditis

● Management:
– In most cases only symptomatic Rx is necessary e.g.
acetaminophen 0.5g four times daily
– If pain, fever, and malaise are disabling a short course of
NSAID or a glucocorticoid such as prednisone 20mg three
times daily for 7-10 days may be necessary to reduce the
inflammation
– L-thyroxine is indicated during the hypothyroid phase of the
illness. 10% of the patients will require L-thyroxine long term

 Other Forms of Thyrotoxicosis

● Thyrotoxicosis Factitia:
– Due to ingestion of excessive amounts of thyroxine
– RAI uptake is nil and serum thyroglobulin is low
● Struma Ovarii:
– Teratoma of the ovary with thyroid tissue that becomes hyperactive
– No goitre or eye signs. RAI uptake in neck is nil but body scan
reveals uptake of RAI in the pelvis.
● Hydatidiform mole:
– Chorionic gonadotropin is produced which has intrinsic TSH-like
activity.
● TSH-secreting pituitary adenoma:
– FT4 & FT3 is elevated but TSH is normal or elevated
– Visual field examination may reveal temporal defects, and CT or
MRI of the sella usually reveals a pituitary tumour.

 Thyroid storm (Thyrotoxic crisis)

● Usually occurs in a severely hyperthyroid patient caused by a
precipitating event such as:
– Infection
– Surgical stress
– Stopping antithyroid medication in Graves’ disease
● Clinical clues
– fever! hyperthermia
– marked anxiety or agitation! coma
– Anorexia
– tachycardia! tachyarrhythmias
– pulmonary edema/cardiac failure
– hypotension! shock
– confusion

 Thyroid storm (Thyrotoxic crisis)

● Initiate prompt therapy after free T4, free T3, and TSH drawn
without waiting for laboratory confirmation.
● Therapy
● 1. General measures:
● Fluids, electrolytes and vasopressor agents should be used as
indicated
● A cooling blanket and acetaminophen can be used to treat the
pyrexia
● Propranolol for beta–adrenergic blockade and in addition
causesdecreased peripheral conversion of T4!T3 but watch for
CHF.
– The IV dose is 1 mg/min until adequate beta-blockade has been
achieved. Concurrently, propranolol is given orally or via NG tube at
a dose of 60 to 80 mg q4h

 Thyroid storm (Thyrotoxic crisis)

● Therapy
● 2. Specific Measures:
– PTU is the anti-thyroid drug of choice and is used in high doses:
1000 mg of PTU should be given p.o. or be crushed and given via
nasogastric tube, followed by PTU 250mg p.o. q 6h. If PTU
unavailable can give methimazole 30mg p.o. every 6 hours.
– One hour after the loading dose of PTU is given –give iodide which
acutely inhibits release of thyroid hormone, i.e. Lugol’s solution 2-3
drops q 8h OR potassium iodide (SSKI) 5 drops q 8h.
– Dexamethasone 2 mg IV q 6h for the first 24-48 hours lowers body
temperature and inhibits peripheral conversion of T4-T3
– With these measures the patient should improve dramatically in the
first 24 hours.
● 3. Identify and treat precipitating factor.

 Nontoxic Goitre
● Enlargement of the thyroid gland from TSH stimulation which in
turn results from inadequate thyroid hormone synthesis
● Etiology:
– Iodine deficiency
– Goitrogen in the diet
– Hashimoto’s thyroiditis
– Subacute thyroiditis
– Inadequate hormone synthesis due to inherited defect in thyroidal
enzymes necessary for T4 and T3 biosynthesis
– Generalized resistance to thyroid hormone (rare)
– Neoplasm, benign or malignant

 Nontoxic Goitre
● Symptoms and Signs:
– Thyroid enlargement, diffuse or multinodular
– Huge goitres may produce a positive Pemberton sign (facial
flushing and dilation of cervical veins on lifting the arms over the
head) especially when they extend inferiorly retrosternally
– Pressure symptoms in the neck with upward or downward
movement of the head
– Difficulty swallowing, rarely vocal cord paralysis
– Most pts are euthyroid but some are mildly hypothyroid
● RAI uptake and scan:
– Uptake may be normal, low, or high depending on the iodide pool
– Scan reveals patchy uptake with focal areas of increased and
decreased uptake corresponding to “hot” and “cold” nodules
respectively

 Management of Nontoxic Goitre

● L-thyroxine suppressive therapy:

– Doses of 0.1 to 0.2mg daily is required
– Aim is to suppress TSH to 0.1-0.4 microU/L (N 0.5-5)
● Suppression therapy works in 50% of cases if
continued for 1 year
● If suppression does not work or if there are obstructive
symptoms from the start then surgery is necessary

 Benign Thyroid Nodules

● Thyroid nodules are common especially among older women
● Etiology:
– Focal thyroiditis
– Dominant portion of multinodular goitre
– Thyroid, parathyroid, or thyroglossal cysts
– Agenesis of a thyroid lobe
– Postsurgical remnant hyperplasia or scarring
– Postradioiodine remnant hyperplasia
– Benign adenomas:
● Follicular
– Colloid or macrofollicular
– Hurthle cell
– Embryonal
● Rare: Teratoma, lipoma, hemangioma

 Thyroid Cancer

Approximate frequency of malignant thyroid tumours

Papillary carcinoma (including mixed papillary 75%

and follicular
Follicular carcinoma 16%

Medullary Carcinoma 5%

Undifferentiated carcinomas 3%

Miscellaneous (e.g. lymphoma, fibrosarcoma, 1%

squamous cell ca, teratoma, & metastatic ca)
 Papillary Carcinoma
● Usually presents as a nodule that is firm, solitary, “cold” on
isotope scan, and usually solid on thyroid US
● In MNG, the cancer is usually a “dominant nodule” that is larger,
firmer and different from the rest of the gland
● 10% of papillary ca present with enlarged cervical nodes
● Grows very slowly and remains confined to the thyroid gland and
local lymph nodes for many years.
● In later stages they can spread to the lung
● Death usually from local disease or lung metastases
● May convert to undifferentiated carcinoma
● Many of these tumours secrete thyroglobulin which can be used
as a marker for recurrence or metastasis of the cancer

 Follicular Carcinoma
● Differs from follicular adenoma by the presence of capsular or
vascular invasion
● More aggressive than papillary ca and can spread either by local
invasion of lymph nodes or by blood vessel invasion with distant
metastases to bone or lung
● Death is due to local extension or to distant bloodstream
metastasis with extensive involvement of bone, lungs & viscera
● These tumours often retain the ability to concentrate RAI
● A variant of follicular carcinoma is the “Hurthle cell” carcinoma.
These tumours behave like follicular cancer except that they
rarely take up RAI
● Thyroglobulin secretion by follicular carcinoma can be used to
follow the course of the disease

 Management of Papillary and

Follicular Carcinoma
● Patients are classified into low risk and high risk groups
● The low risk group includes patients under age 45 with primary
lesions under 1cm and no evidence of intra- or extraglandular
spread. Lobectomy is adequate therapy for these patients.
● All other patients are considered high risk and require total
thyroidectomy. Modified neck dissection is indicated if there is
lymphatic spread.
● Surgery is usually followed by RAI ablation therapy
● Patient is placed on L-thyroxine suppressive therapy
● Regular F/U with thyroglobulin level, thyroid US, whole body
scan etc.

 Medullary Carcinoma
● A disease of the C cells (parafollicular cells)
● More aggressive than papillary or follicular carcinoma but not as aggressive
as undifferentiated thyroid cancer
● It extends locally, and may invade lymphatics and blood vessels
● Calcitonin and CEA are clinically useful markers for DX and F/U
● 80% of medullary ca are sporadic and the rest are familial. There are 4 familial
patterns:
– FMTC without endocrine disease
– MEN 2A: medullary ca + pheochromocytoma + hyperparathyroidism
– MEN 2B: medullary ca + pheochromocytoma + multiple mucosal neuromas
– MEN 2 with cutaneous lichen amyloidosis
● The familial syndromes are associated with mutations in the ret proto-
oncogene (a receptor protein kinase gene on chrom. 10)
● Dx is by FNA bx. Pt needs to be screened for other endocrine abnormalities
found in MEN 2. Family members need to be screened for medullary ca and
MEN 2 as well.

 Undifferentiated (Anaplastic)
Carcinoma
● This tumour usually occurs in older patients with a long history of
goitre in whom the gland suddenly—over weeks or months—
begins to enlarge and produce pressure symptoms, dysphagia,
or vocal cord paralysis.
● Death from massive local extension usually occurs within 6-36
months
● These tumours are very resistant to therapy