Download Thyroid Disorders - University of Yeditepe Faculty of Medicine, 2011

Thyroid Disorders
Hasan AYDIN, MD
Yeditepe University Medical Faculty
Department of Endocrinology and Metabolism
Thyroid Regulation
HYPOTHALAMUS - TRH
ANT. PITUITARY - TSH
TSH -R
THYROID T4 and T3
PLASMA T4 + FT4
PLASMA T3 + FT3
TISSUES FT4 to FT3
Thyroid Hormones
THEY ARE NOT ESSENTIAL FOR LIFE,
BUT ARE EXTREMELY HELPFUL
THYROID GLAND DISORDERS

THYROID HORMONE EFFECTS:

Affects every single cell in the body

Modulates:

Oxygen consumption

Growth rate

Maturation and cell differentiation

Turnover of Vitamins, Hormones, Proteins, Fat, CHO
Thyroid Gland Disorders

Overproduction of thyroid hormones

Underproduction of thyroid hormones

Thyroid nodules

Thyroiditis

Thyroid neoplasms
Hyperthyroidism
Thyroid Gland Disorders

TSH High usually means Hypothyroidism


Rare causes:
 TSH-secreting pituitary tumor
 Thyroid hormone resistance
 Assay artifact
TSH low usually indicates Thyrotoxicosis

Other causes
 First trimester of pregnancy
 After treatment of hyperthyroidism
 Some medications (Steroids-dopamine)
Thyroid Gland Disorders

THYROTOXICOSIS:


is defined as the state of thyroid hormone excesss
HYPERTHYROIDISM:

is the result of excessive thyroid gland function
Abnormalities of Thyroid Hormones

Thyrotoxicosis
 Primary
 Secondary
 Without Hyperthyroidism
 Exogenous or factitious

Hypothyroidism
 Primary
 Secondary
 Peripheral
Causes of Thyrotoxicosis
Primary Hyperthyroidism
Grave´s disease
 Toxic Multinodular Goiter
 Toxic adenoma
 Functioning thyroid carcinoma metastases
 Activating mutation of TSH receptor
 Struma ovary
 Drugs: Iodine excess

Causes of Thyrotoxicosis

Thyrotoxicosis without hyperthyroidism



Subacute thyroiditis
Silent thyroiditis
Other causes of thyroid destruction:



Amiodarone, radiation, infarction of an adenoma
Exogenous/Factitia
Secondary Hyperthyroidism




TSH-secreting pituitary adenoma
Thyroid hormone resistance syndrome
Chorionic Gonadotropin-secreting tumor
Gestational thyrotoxicosis
Thyrotoxicosis

Symptoms:










Hyperactivity
Irritability
Dysphoria
Heat intolerance &
sweating
Palpitations
Fatigue & weakness
Weight loss with increased
appetite
Diarrhea
Polyuria
Sexual dysfunction

Signs:









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Tachycardia
Atrial fibrillation
Tremor
Goiter
Warm, moist skin
Muscle weakness,
myopathy
Lid retraction or lag
Gynecomastia
Exophtalmus
Pretibial myxedema
Manifestations of Thyrotoxicosis
Differential Diagnosis

Panic attacks

Psychosis

Mania

Pheochromocytoma

Hypoglycemia

Occult malignancy
Treatment

Reducing thyroid hormone synthesis:
 Antithyroid drugs (Methimazole, Propylthyouracil)
 Radioiodine (131I)
 Subtotal thyroidectomy

Reducing Thyroid hormone effects:
 Propranolol
 Glucocorticoids
 Benzodiazepines

Reducing peripheral conversion of T4 to T3
 Propylthyouracil
 Glucocorticoids
 Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)
Treatment: Special Considerations

Thyrotoxic crisis or Thyroid storm:
 It´s
a life-threatening exacerbation of thyrotoxicosis,
acompanied by fever, delirium, seizures, coma, vomiting,
diarrhea, jaundice.
 Mortality rate reachs 30% even with treatment
 It´s usually precipitated by acute illness, such as:
 Stroke, infection,trauma, diabetic ketoacidosis, surgery,
radioiodine treatment






Propylthyouracil IV or Nasogastric tube
Radioiodine (131I)
Propranolol
Glucocorticoids
Benzodiazepines
Iodide (Large oral or IV dosage) (Wolf-Chaikoff effect)
HYPOTHYROIDISM
Definition

A deficiency of thyroid hormones, which in turn results in a
generalized slowing down of metabolic processes.

In infants and children => marked slowing of growth and
development, with serious permanent consequences including
mental retardation.

In adulthood => a generalized slowing down of the organism,
with the clinical picture of myxedema.
Causes of Hypothyroidism


Primary

Congenital

Acquired

Transient
Secondary

Pituitary

Hypothalamic
Hypothyroidism

Symptoms:






Tiredness
Weakness
Dry skin
Sexual dysfunction
Hair loss
Difficulty concentrating

Signs:





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
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Bradycardia
Dry coarse skin
Puffy face, hands and
feet
Diffuse alopecia
Peripheral edema
Delayed tendon reflex
relaxation
Carpal tunel syndrome
Serous cavity effusions.
Hypothyroidism
Special Considerations

Myxedema coma
 Reduced level of consciousness, seizures
 Hypotension/shock
 Hypothermia
 Hyponatremia

Usually in elderly hypothyroid pts.

Usually precipitated by intercurrent illnesses that impairs
ventilation

It´s an Emergency with a high mortality rate

Treatment: Lyotironine(T3) or T4, Hydrocortisone, external
warming, IV fluids
Many Causes, One Treatment

Goal : Normalize TSH level regardless of cause of hypothyroidism

Treatment : Once daily dosing with Levothyroxine sodium (1.6
µg/kg/day)

Monitor TSH levels at 6 to 8 weeks, after initiation of therapy or dosage
change
Treatment: Special Considerations

Elderly patients

Coronary Artery Disease

Poor adrenal gland reserve

Childrens

Pregnancy

Emergency surgery (Non thyroid related)
Goiter and Thyroid Cancer
Definitions
Goiter is a diffuse or nodular enlargement of the
thyroid gland resulting from excessive replication of
benign thyroid epithelial cells.
A thyroid nodule is a discrete lesion
within the thyroid gland that is palpably
and/or ultrasonog- raphically distinct
from the surrounding thyroid
parenchyma
Etiology of Nontoxic Goiter

Iodine deficiency

Goitrogen in the diet

Hashimoto's thyroiditis

Subacute thyroiditis

Inherited defect in thyroidal enzymes necessary for
T 4 and T 3 biosynthesis

Generalized resistance to thyroid hormone (rare)

Neoplasm, benign or malignant
Multinodular Goiter
Clinical Issues

Hyperthyroidism

Suspicion of malignancy

Compressive/obstructive symptoms

Cosmetic concerns
MULTINODULAR GOITER
Presentation


Asymptomatic

Neck mass discovered by patient or physician

Abnormal CXR
Symptomatic

Pressure symptoms

Hoarseness

Thyrotoxicosis
NODULAR GOITER
Suspicious Nodule or Goiter

High suspicion







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Family history of medullary thyroid carcinoma
Rapid tumor growth
A nodule that is very firm or hard
Fixation of the nodule to the adjacent structures
Paralysis of the vocal cord
Regional lymphadenopathy
Distant metastasis
Moderate suspicion





Age of either<20 or >70 years
Male sex
History of head and neck irradiation
A nodule >4 cm in diameter or partially cystic
Symptoms of compression, including dysphagia, dysphonia,
hoarseness, dyspnea, and cough
Ultrasound

Ultrasonographic Cancer Risk Factors for a
Thyroid Nodule
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hypoechogenicity,
microcalcifications,
irregular margins,
increased nodular flow visualized by Doppler,
the evidence of invasion or regional lymphadenopathy
Multinodular Goiter : Evaluation

TSH

FT4, T3

Radionuclide Scan / RAIU

US

CT Scan (without contrast)

FNA biopsy
Multinodular Goiter
Fine Needle Aspiration Evaluation

Biopsy all accessible nodule(s)

Biopsy suspicious nodule(s) cold on scan;
firm by palpation; growing in size

Results less reliable in large goiters

Most common diagnosis is “colloid nodule”
Fine Needle Aspiration Evaluation
FNA results

Malignant- pt needs to have surgical management

Benign- observation with interval ultrasounds and
clinical examinations

Indeterminate- radioisotope scan- perform
suppression scan and if cold proceed to surgical
management- if hot nodule consider observation

Non diagnostic- repeat FNA or U/S guided FNA
Thyroid Cancers
Benign Neoplasms of the Thyroid
Thyroid adenoma is a benign neoplastic growth
contained within a capsule.
Embrional adenoma
Fetal adenoma
Microfollicular adenoma
Macrofollicular adenoma
Papillary cystadenoma
Hurtle cell adenoma
Thyroid Cancer

Papillary (mixed papillary and follicular)
75%

Follicular carcinoma
16%

Medullary carcinoma
5%

Undifferentiated carcinomas
3%

Miscellaneous (lymphoma, fibrosarcoma,
squamous cell carcinoma, malignant
hemangioendothelioma, teratomas, and metastatic
carcinomas)
1%
Papillary Carcinoma

very slowly grow and remain confined to the thyroid
gland and local lymph nodes for many years.

In older patients, more aggressive and invade locally
into muscles and trachea.

in later stages, they can spread to the lung.

Death is usually due to local disease, with invasion of
deep tissues in the neck less commonly, death may
be due to extensive pulmonary metastases..
Follicular Carcinoma

is characterized by the presence of small follicles,
colloid formation is poor.

capsular or vascular invasion.

more aggressive and local invasion of lymph nodes or
by blood vessel invasion with distant metastases to
bone or lung.

often retain the ability to concentrate radioactive iodine,
to form thyroglobulin, and, rarely, to synthesize T3 and
T4.
Follicular Carcinoma

rare ''functioning thyroid cancer'' is almost always a
follicular carcinoma.

more likely to respond to radioactive iodine therapy.

In untreated patients, death is due to local extension or
to distant bloodstream metastasis with extensive
involvement of bone, lungs, and viscera.
Medullary Carcinoma

a disease of the C cells (parafollicular cells) derived

calcitonin, histamin, prostaglandins, serotonin, other peptides

more aggressive , but not undifferentiated thyroid cancer.

locally into lymph nodes and into surrounding muscle and
trachea.

lymphatics and blood vessels and metastasize to lungs and
viscera.

Calcitonin and CEA clinically useful markers for diagnosis and
follow-up.
Medullary Carcinoma

About 80% are sporadic

the remainder are familial. four familial patterns:
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without associated endocrine disease (FMTC);

MEN 2a medullary carcinoma, pheochromocytoma, and
hyperparathyroidism;

MEN 2B, medullary carcinoma, pheochromocytoma,
and multiple mucosal neuromas;

MEN 3 : with cutaneous lichen amyloidosis, a pruritic
skin lesion located on the upper back.
Undifferentiated (Anaplastic) Carcinoma

small cell, giant cell, and spindle cell carcinomas.

usually occur in older patients with a long history of
goiter 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 tumors are very resistant to
therapy .
Lymphoma

only type of rapidly growing thyroid cancer that is
responsive to therapy

as part of a generalized lymphoma or may be primary
in the thyroid gland.

occasionally with long-standing Hashimoto's thyroiditis

characterized by lymphocyte invasion of thyroid
follicles and blood vessel walls, which helps to
differentiate thyroid lymphoma from chronic thyroiditis.

If there is no systemic involvement, the tumor may
respond dramatically to radiation therapy
Cancer metastatic to the thyroid

Cancers of the breast and kidney, bronchogenic
carcinoma, and malignant melanoma.

The primary site of involvement is usually obvious,

Occasionally , the diagnosis is made by needle biopsy
or open biopsy of a rapidly enlarging cold thyroid
nodule.

The prognosis is that of the primary tumor,
Management of Thyroid Cancer
Papillary and Follicular Carcinoma:

Low-risk group under age 45 with primary lesions under 1 cm
and no evidence of intra- or extraglandular spread.

For these patients, lobectomy is adequate therapy

All other patients high-risk, and for these total thyroidectomy
and-if there is evidence of lymphatic spread -a modified neck
dissection are indicated.

Prophylactic neck dissection is not necessary.

For the high-risk group, postoperative radioiodine ablation
Management of Thyroid Cancer

Follow-up at intervals of 6-12 months should include
careful examination of the neck for recurrent masses.

If a lump is noted, needle biopsy is indicated to confirm
or rule out cancer.

Serum TSH should be checked

Serum Tg should be < 1 ng/ml .
Thyroiditis
Definition
Infectious or autoimmune inflammatory
diseases of thyroid gland
Classification
•
Hashimoto thyroiditis
•
Subacute granulomatous thyroiditis
•
Infectious thyroiditis
•
Radiation & Trauma induced thyroiditis
•
Subacute Lymphocytic thyroiditis
•
Postpartum thyroiditis
•
Drug induced thyroiditis
•
Riedel’s thyroiditis
HASHIMOTO’s THYROIDITIS
Chronic Lymphocytic Thyroiditis
•Is the most prevalent form of thyroid autoimmune disease
(3-4 % of popul.) and most common cause of hypothyroidism
•Is characterized by gradual thyroid failure, goitre or both
•Is more common in middle age
•Clusters in families
•May be associated with other autoimmune
disorders
Dr. Hakaru Hashimoto
Subacute Granulomatous
(de Quervain’s) Thyroiditis
•Most frequent cause of thyroid pain and tenderness
•Postviral inflammatory process
(Coxsackievirus, mumps, measles, adenovirus, other)
•Strongly associated with HLA-B35, most common in
40-50 years old women
•Transient thyroiditis (thyrotoxic for 2-6 wks)
Clinical Presentation
•Previous viral infection (in 1-3 weeks)
•Pain over thyroid,upper neck, jaw,
throat,ears
•Hoarseness,dysphagia
•Fever, palpitation, nervousness,
lassitude
•Tender, enlarged, firm and often
nodular
Treatment of DeQuervain’s Thyroiditis

A nonsteroidal antiinflammatory drug

Aspirin: 2.4-3.6 g in divided doses

Naproxen: 1.0-1.5 g in divided doses

Prednisone : 30-40 mg qd

A beta blocker

Propranolol : 40-120 mg

Atenolol : 25-50 mg
Infectious Thyroiditis

Acute (with abscess formation)


Gram-positive or negative organisms (via blood
or a fistula from the piriform sinus adjacent to the
larynx)
Chronic



Mycobacterial
Fungal
Pneumocystis
Infectious Thyroiditis

Acute




Usually unilateral neck pain and tenderness
Fever, chills, a unilateral neck mass (fluctuant)
USG, FNAB, drainage and antibiotics
Chronic



Bilateral, less prominent neck pain
Some patients have hypothyroidism
FNAB
Radiation and Trauma-Induced Thyroiditis

Radiation Thyroiditis

Radioiodine treatment of Graves disease


Develops 5-10 days later and is mild
Trauma-induced Thyroiditis

Palpation, thyroid biopsy, surgery, car seat belt
Subacute Lymphocytic Thyroiditis
(Painless, Silent, Lymphocytic)
A variant form of Hashimoto’s thyroiditis
 Associated with HLA-DR3
 Postulated initiating factors :



Excess iodine intake
Various cytokines
Treatment of Subacute
Lymphocytic Thyroiditis

Most patients need no treatment

Symptomatic treatment during the hyperthyroid
phase : propranolol or atenolol

T4 ( 50-100 µg daily) given for 8-12 wks,
discontinued and reevaluated 4-6 wks later
Postpartum Thyroiditis
•Occurs in 3-16% of pregnancies (25 % in T1DM)
•Is seen within 1 year after parturition
•Is likely to recur after subsequent pregnancies
•Thyrotoxicosis is mild and transient
•Antithyroid antibodies are elevated
•RAIU is low
•Slightly increased ESR
Presentation of Postpartum Thyroiditis

Transient hyperthyroidism (2-8 wks) followed by
hypothyroidism (2-8 wks) and then recovery 2030 %

Transient hyperthyroidism alone 20-40 %

Transient hypothyroidism alone 40-50 %
Drug-Induced Thyroiditis

Interferon-alpha thyroiditis

Interleukin-2 thyroiditis

Amiodarone
Riedel’s Thyroditis

Is a fibrotic process associated with a mononuclear cell
inflammation that extends beyond the thyroid into soft
tissue

Can involve the parathyroids, the recurrent laryngeal
nerve, trachea, mediastinum, ant. chest wall

Fibrosclerosis may involve the retroperitoneal space,
mediastinum, retroorbital space, the biliary tract
Treatment of Riedel’s Thyroiditis

Thyroxine

Surgery

Glucocorticoids

Tamoxifen

Methylprednisone pulse therapy + azathioprine or
penicillamine